PCP

Phencyclidine Abuse:

An Appraisal

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse, and Mental Health Administration
Phencyclidine (PCP) Abuse:

An Appraisal

Editors:

Robert C. Petersen, Ph.D.

Richard C. Stillman, M.D.

NIDA Research Monograph 21

August 1978

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

Alcohol, Drug Abuse, and Mental Health Administration

National Institute on Drug Abuse

5600 Fishers Lane

Rockville, Maryland 20857
NIDA Research Monographs are prepared by the research divisions of the

National Institute on Drug Abuse and published by its Office of Science. The

primary objective of the series is to provide critical reviews of research problem

areas and techniques, the content of state-of-the-art conferences, and integrative research reviews Its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community.

Editorial Advisors

Martin W Adler, Ph.D.

Temple University, School of Medicine

Philadelphia, Pennsylvania

Sydney Archer, Ph.D.

Rensselaer Polytechnic Institute

Troy, New York

Richard E. Belleville, Ph.D.

NB Associates, Health Sciences

Rockville, Maryland

Gilbert J. Botvin, Ph.D.

Cornell University Medical College

New York, New York

Joseph V. Brady, Ph.D.

The Johns Hopkins University School of Medicine

Baltimore, Maryland

Theodore J. Cicero, Ph.D.

Washington University School of Medicine

St. Louis, Missouri

Sidney Cohen, M.D.

Los Angeles, California

Reese T. Jones, M.D.

Langley Porter Neuropsychiatric Institute

San Francisco, California

Denise Kandel, Ph.D.

College of Physicians and Surgeons of Columbia University

New York, New York

Herbert Kleber, M.D.

Yale University School of Medicine

New Haven, Connecticut

NIDA Research Monograph Series

William Pollin, M.D.

DIRECTOR, NIDA

Jack Durell, M.D.

ASSOCIATE DIRECTOR FOR SCIENCE, NIDA

EDITOR-IN-CHIEF

Eleanor W. Waldrop

MANAGING EDITOR

Parklawn Building, 5600 Fishers Lane, Rockville, Maryland 20857
Phencyclidine (PCP) Abuse:

An Appraisal
ACKNOWLEDGMENT

This monograph is based upon papers presented at a conference

which took place on February 27-28, 1978, at the Asilomar Conference Center, Pacific Grove, California. The conference was

conducted and reported by PLOG Research, Inc. , Reseda, California

under NIDA contract 271-77-3413.

The National Institute on Drug Abuse has obtained permission from

the copyright holders to reproduce certain previously published

material as noted in the text. Further reproduction of this

material is prohibited without specific permission of the copyright

holders. All other material in this volume except quoted passages

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or reproduced without permission from the Institute or the authors

Citation of the source is appreciated.

The U.S. Government does not endorse or favor any specific

commercial product or commodity . Trade or proprietary names

appearing in this publication arc used only because they are

considered essential in the context of the studies reported

herein.

Library of Congress catalog card number 78-600095

DHHS publication number (ADM) 85-728

Printed 1978 Reprinted 1983, 1985

NIDA Research Monographs are indexed in the Index Medicus. They

are selectively included in the coverage of American Statistics

Index, BioSciences Information Service, Chemical Abstracts,

Current Contents , Psychological Abstracts , and Psychopharmacology

Abstracts

iv
Foreword

Phencyclidine (PCP), or “angel dust” as it is more commonly known

to drug users, posed until recently a relatively modest problem.

While some illicit use occurred as early as the mid ‘6Os, the drug’s

initially poor street reputation seemed to make it decidedly unlikely

that it would ever become popular as a drug of choice.

More recent events have made it abundantly clear that our initial

optimism was poorly founded. A change in mode of use from oral

ingestion to smoking or snorting, which may enable the user to better

control aversive consequences of use, together with the ease with

which PCP can be synthesized, have markedly changed the phencyclidine

abuse picture.

In one year (from 1976 to 1977) the number who had used phencyclidine

as measured by NIDA’s National Drug Use Surveys nearly doubled in the

12 to 17 year age group. Among young adults between 18 and 25, the

number of PCP users increased nearly fifty percent in that same year.

Although the level of use detected was still modest, there is good

reason to believe that the standardized indicators of the extent of

PCP use and of its adverse consequences represent significant underestimates of the seriousness of the problem. Clinical reports have

also indicated that phencyclidine use can precipitate violent acting

out and seriously self-destructive behavior as well as psychotic

thinking and behavior.

Because of the relatively recent emergence of phencyclidine abuse as

a problem of widespread proportions, our knowledge remains fragmentary. If the dimensions of the problem continue to be in doubt,

still more remains to be learned about the implications of use,

especially on a chronic basis. This volume represents an attempt to

bring together our present knowledge. It is based on a small working

conference of researchers and clinicians with extensive PCP experience which was held in late February of this year (1978). We hope

that it proves to be a useful compendium of information on the problem as well as a stimulus to further work to answer some of the

critical questions with which we are confronted. In addition,

because phencyclidine may well prove to be prototypic of a range of

easily synthesized psychoactive drugs susceptible to abuse, we hope

it will stimulate thinking about better ways both to anticipate newly

emerging drug problems and to cope with them.

The Editors

v
Contents

Foreword

The Editors . . . . . . . . . . . . . . .

Chapter 1

Phencyclidine: An Overview

Robert C. Petersen and Richard C. Stillman . . . .

Chapter 2

Neurobiology of Phencyclidine--An Update

Edward F. Domino . . . . . . . . . . . . .

Chapter 3

Neurochemical Pharmacology of Phencyclidine

Kenneth M. Johnson . . . . . . . . . . . .

Chapter 4

The Behavioral Effects of Phencyclidine in Animals

Robert L. Ealster and Larry D. Chait . . . . . .

Chapter 5

Phencyclidine Use Among Youth: History, Epidemiology, and

Acute and Chronic Intoxication

Steven E. Lerner and R. Stanley Burns . . . . . .

Chapter 6

Phencyclidine and Ketamine Intoxication: A Study of

Four Populations of Recreational Users

Ronald K. Siegel . . . . . . . . . . . . .

Chapter 7

Epidemiology of Multiple Drug Use with Special Reference

to Phencyclidine

J. Fred E. Shick . . . . . . . . . . . . .

Chapter 8

Patterns of Phencyclidine Use

David B. Graeven . . . . . . . . . . . . .

Chapter 9

The Psychiatric Aspects of Chronic Phencyclidine Use: A

Study of Chronic PCP Users

Michael A. Fauman and Beverly J. Fauman . . . . .

v

1

18

44

53

66

119

148

176

183

v i
Chapter 10

Phenomenological Aspects of Phencyclidine Abuse Among

Ethnic Groups in Hawaii

Anthony J. Marsella and Russell D. Hicks . . . . 201

Chapter 11

The Pharmacokinetics of Phencyclidine in Overdosage and

Its Treatment

Alan K. Cone, Regine Aronow, and Joseph N. Miceli . . 210

Chapter 12

Clinical Observations During Phencyclidine Intoxication

and Treatment Based on Ion-Trapping

Regine Aronow, Joseph N. Miceli, and Alan K. Done . . 218

Chapter 13

The Diagnosis and Treatment of the PCP Abuse Syndrome

David E. Smith, Donald R. Wesson, Millicent E.

Buxton, Richard Seymour, and Honey M. Kramer . . . 229

Chapter 14

The Phencyclidine Psychosis: Phenomenology and Treatment

Paul V. Luisada . . . . . . . . . . . . . 241

Chapter 15

Long Term Treatment of Adolescent PCP Abusers

Gerald G. DeAngelis and Elliott Goldstein . . . . 254

Chapter 16

Phencyclidine, Criminal Behavior, and the Defense of

Diminished Capacity

Ronald K. Siegel . . . . . . . . . . . . . 272

Chapter 17

Control of Drug Self-Administration: The Role of

Aversive Consequences

Nancy K. Mello . . . . . . . . . . . . . 289

Conference Participants . . . . . . . . . . . . . 309

List of Monographs . . . . . . . . . . . . . . 311

vii

Chapter 1

Phencyclidine: An Overview

Robert C. Petersen, Ph.D., and Richard C. Stillman, M.D.

Although phencyclidine was first abused in oral form over a decade

ago, it is only in recent years as a smoked or snorted drug that

it has become a more serious problem involving significant numbers

of users. This overview is intended to review and summarize what

is presently known about the drug with special emphasis on the contributions of the authors of this volume. By providing a relatively

brief integrated view of our current knowledge we hope to convey

the limitations of that knowledge and to encourage others to enlarge our presently modest understanding of the implications of

phencyclidine abuse.

THE MATERIAL

Phencyclidine,or PCP, one of the group of arylcyclohexylamines, is

in pharmaceutically pure form a white powder which readily dissolves

in water. In “street” form PCP is often adulterated and quite often

misrepresented as a variety of other drugs. It is highly variable

in appearance, being sold in liquid, powder, and tablet form, the

latter two in many colors. As a powder or liquid, it is often placed

on parsley or on other leaf mixtures to be smoked as cigarettes

(joints). When misrepresented, PCP is most commonly sold as THC

(the principal psychoactive ingredient in marihuana, which in reality

is not available on the street). But phencyclidine has also been

sold as cannabinol (another marihuana constituent), mescaline,

psylocybin, LSD, and even as amphetamine or cocaine. Because of

the variability in street names and its frequent misrepresentation,

the casual user may be unaware of what he or she has ingested or

may be mistaken about its true identity.

Some of the street names for phencyclidine include: angel dust,

dust, crystal, cyclones, embalming fluid, elephant or horse tranquilizer, killer weed, superweed, mintweed, mist, monkey dust,

Peace Pill, rocket fuel, goon, surfer, KW, and scuffle. The wide

range of regional names for this illicit drug, as well as variations

in its appearance, mean that the casual user may not be aware that

he or she has used PCP or may fail to report its use in surveys because

1
he or she does not know the drug by the survey designation. A further complication in user identification of PCP is the fact that

phencyclidine is sometimes also used in combination with such other

drugs as barbiturates, heroin, cocaine, amphetamine, methaqualone,

LSD, mescaline, and procaine (cf. Lerner and Burns, this volume).

Depending on the care with which the synthesis of PCP is carried out,

the street drug may contain a variety of impurities, including potassium cyanide. Although PCP is sometimes smoked after sprinkling it

on marihuana, it is apparently rarely sold in that combination. At

least one major laboratory on the West Coast which does street drug

analysis has never encountered the combination in samples submitted

to it.

In addition to phencyclidine itself, there are over thirty chemically

similar analogs, some of which are capable of producing similar psychic

effects. These also can be synthesized with varying degrees of difficulty, and some have already appeared on the street. Those reportedly

abused thus far include: PCC, PCE, PHP, TCP, and the anesthetic,

ketamine . Details of their chemical formulas and structure are given

by Domino (this volume) . The addition of these compounds, and possibly others in the future, makes the problem of “tracking" PCP and

related drug use more difficult.

Adding to the risk of PCP use, especially when it is taken orally,

is the wide variability in purity of the street drug. Even when it

is not misrepresented, the percentage of PCP contained in street

samples has been found to be quite variable.

When PCP is sold as a granular powder (“angel dust”), it is usually

relatively pure, consisting of perhaps 50-100 percent phencyclidine.

However, sold under a variety of other names and/or in other forms,

the purity is from 5 to 30 percent, with leafy mixtures generally

containing the smallest amounts of the drug. While in the past

street samples of phencyclidine have often been found on analysis

to contain other drugs as well, more recently such samples appear

less likely to contain other drugs in addition to PCP. It should,

of course, be noted that samples submitted by users for analysis are

not necessarily representative of street drugs overall. Users are

far more likely to have analyzed drugs about which they have some

doubt or from which they have had some unusual reaction. Nevertheless,

it does appear that the purity of PCP street samples has increased

in that it is less frequently sold mixed with other psychoactive

materials.

Phencyclidine can be easily synthesized. The “starting” chemicals

are widely available and because of their important industrial uses

do not lend themselves to more stringent controls. While some of

the mass media accounts have exaggerated the ease with which phencyclidine can be made. it is not particularly difficult and can be

done by individuals with only modest technical training and without

elaborate equipment.

The precise classification of PCP is presently unsettled. PCP has

stimulant, depressant, hallucinogenic, and analgesic properties

2
which are dose-dependent. One proposed classification is with

ketamine as a “dissociative anesthetic” (cf. Domino, this volume).

Phencyclidine is used legally in veterinary medicine as an animal

immobilizing agent. Although it was originally developed as an

anesthetic for use with humans, it was later abandoned for that

purpose because in some patients it produced post-operative thought

disturbances and agitation. PCP made its first illicit appearance

in 1965 on the West Coast. At that time it rapidly developed a

bad street reputation and had only limited popularity. Since then

there have been sporadic outbreaks of its use. Most recently there

is evidence from a variety of sources suggesting a marked increase

in use (cf. Extent of Phencyclidine Abuse, below).

Although originally orally ingested, PCP is now most commonly smoked

or snorted. Intravenous use is much less frequent, but has been reported. By smoking, the experienced user is better able to limit

his dose (self-titrate) to a level with which he or she is comfortable and is probably less likely to overdose. By contrast, when the

drug is taken by mouth there is a longer period before the drug takes

effect, it continues to be absorbed after the user may have concluded

he has had enough, and the dose is frequently larger--all factors

more likely to result in adverse reactions due to an overdose.

BIOLOGICAL, NEUROCHEMICAL, AND PRECLINICAL BEHAVIORAL ASPECTS

Three of the papers in this volume focus specifically on what is

presently known about the neurobiological, neurochemical, and preclinical behavioral aspects of phencyclidine. Domino (this volume)

divides and summarizes the major pharmacological properties of PCP

and related compounds as follows:

Central Nervous System Effects

a. Small doses lead to a “drunken” state with numbness of the

extremities and in some species produces excitation.

b. In moderate doses, analgesia and anesthesia are produced.

c. A psychic state somewhat resembling sensory isolation is

produced. Sensory impulses in grossly distorted form do,

however, reach the neocortex.

d. Cataleptiform motor responses occur.

e. Large doses, expecially of PCP, may produce convulsions.

f. There are marked inter-species differences in effects. Primates and especially man show predominantly depressant effects.

Autonomic and Cardiovascular System Effects

a. Sympathomimetic effects are produced including increases in

heart rate and blood pressure.

b. Catecholamines are potentiated through a cocaine-like action.

Balster and Chait (this volume) in their review of the preclinical

behavioral pharmacology of PCP emphasize several points. They too

underscore the interspecies differences in PCP effects. For example,

in rodents, unlike primates, PCP has excitatory rather than depressant

effects.

3
Unlike virtually all other hallucinogens, with which PCP is sometimes

categorized, monkeys will self-administer phencyclidine. This suggests that animal testing of other PCP analogs may be useful in

predicting their dependence liability in man. Experiments with PCP

to date do not, however, suggest that phencyclidine produces comparable physical dependence to that of the opiates or other CNS depressants. Tolerance from two to four times the original amounts develops

if the drug is administered chronically to test animals. Finally,

work done thus far indicates the PCP enhances the depressant effects

of delta-9-THC (the principal psychoactive ingredient in marihuana)

and the anesthetic effects of pentobarbital. When administered with

d-amphetamine, there is preliminary evidence that PCP increases

amphetamine stereotype in rats.

Johnson, in his review of the neurochemical pharmacology of phencyclidine (this volume), emphasizes that our knowledge in this area is

in its infancy, but that it appears unlikely that the diverse spectrum

of effects is mediated by PCP’s action on any one neurotransmitter.

He also points out that there have been virtually no studies exploring

the neurochemistry of chronic use.

EXTENT OF PHENCYCLIDINE ABUSE

Attempts at estimating the extent of PCP use are fraught with difficulty. Since the drug is often sold as any one of a variety of

other psychoactive substances, the user, especially if he or she

is inexperienced, may not realize PCP is involved. The fact that

phencyclidine is known by an unusually large number of street names

and varies widely in its physical appearance also contributes to

confusion in casual user identification. Most official reports of

drug use have in the past lumped PCP with other hallucinogens, making

trend detection from such sources difficult. Moreover, the patient

admitted for emergency treatment of PCP-induced bizarre behavior is

likely to be diagnosed as acutely schizophrenic rather than as a toxic

drug reaction. Patients admitted with injuries from automobile accidents, fires and drownings in which PCP was a cause may not be so

identified. Thus a marked increase in use and in use-related drug

emergencies may not be reflected in emergency room or medical examiner statistics.

Despite these limitations, there are a number of converging lines

of evidence suggesting increased use in recent months. These range

from reports of law enforcement agencies on disruption of illegal

laboratory production to self-reports by users. While available

survey data has definite limitations, they provide minimal estimates

of the level of phencyclidine use as well as some short term trend

indicators. In NIDA’s 1976 National Survey, 3 percent of youth

between 12 and 17 years of age at the time of the survey acknowledged

having used PCP at some time in their lives. Among young adults

18-25, the age category in which virtually all drug use peaks, nearly

one in ten reported having used PCP prior to the 1976 survey. By

contrast, data from the 1977 National Survey suggests that the percentage who had ever used in the 12-17 year-old group had nearly

doubled since the earlier survey (5.8 percent vs. 3.0 percent in 1976).

4
Use by the 18-25 age group had also increased markedly, from 9.5

percent to 13.9 percent. The likelihood that these increases were

simply the result of year to year survey sampling variation is small

(less than one in a hundred).

Some indication of the extent to which a drug poses serious problems

is provided by the Government’s Drug Abuse Warning Network (DAWN).

DAWN is a national reporting system which collects reports of drugrelated deaths and drug-related emergencies involving hospital emergency room treatment. For reasons that have already been outlined,

such figures are likely to be minimal estimates of the overall PCP

problem. They are, however, also useful in providing some indication

of trends. When data are examined from the 662 emergency rooms which

consistently reported to DAWN from November 1974 to October 1976,

the rate of PCP emergencies doubled during that period (there were 111

mentions in October 1976 contrasted with 54 in October 1974). Reports

of PCP-related deaths show nearly as great an increase when the period

from April 1976 to March 1977 is contrasted with that of the previous

year (30 PCP-related deaths vs. 17 the year before). Again, such

figures are likely to be minimal estimates of the actual extent of

PCP-related mortality.

A major reported cause of PCP deaths in California has been drowning.

In one series of 19 PCP deaths investigated in two California counties,

11 of the 19 were from drowning--one while in the shower. The PCP

user readily loses his orientation while swimming or immersed and

frequently drowns, sometimes in very small amounts of water. Unless

PCP in the body is specifically searched for under such circumstances,

it is very likely to be missed. Similarly, deaths resulting from

violent behavior and accidental deaths resulting from PCP intoxication

may not be reported as PCP-related. Suicide while under the influence

of the drug was the cause of death of three additional persons in the

California study. Another death was the result of threatening behavior leading to the individual’s being shot (Burns and Lerner 1978).

Another source of data which provides some indication of the extent

of phencyclidine use among chronically drug-using youth is the

National Youth Polydrug Study (NYPS), in which 97 drug abuse treatment

programs specializing in treating youthful drug abusers participated.

During the period from September 1976 to March 1977 interviews were

conducted collecting detailed data on patterns of drug abuse for 2750

new clients under age 19. Within this sample nearly a third (31.8

percent) reported having ever used PCP. It was more often used than

inhalants, sedatives, cocaine and opiates (other than heroin and

methadone). Females in the sample were as likely to have used PCP

as males. Whites were far more likely to report using it than either

black or Hispanic clients (42.3 percent of whites, 8.5 percent of

blacks and 9.0 percent of Hispanics). Females in the sample were

found to have first used PCP at a slightly earlier age (14.4 years)

than males (14.7 years). American Indians began use at the earliest

age (13.9) followed by Hispanics (14.0) whites (14.6) and blacks,

(15.3). Two-thirds of those who reported ever having used PCP reported continuing use at a rate of at least once a week for at least

one month. PCP users had also used twice as many other recreational

5
drugs as had non-PCPusers (6.0 vs. 2.8 substances respectively).

Half the current PCP users were using PCP once a week or more

often during the three month period that was studied. While this

data source is obviously not representative of youth generally,

it does suggest that PCP use is quite common among abusers of other

drugs.

THE SUBJECTIVE EXPERIENCE -- MOTIVES FOR PHENCYCLIDINE USE

One of the more puzzling questions about PCP use is just why users

continue to use in the light of the widely noted and even user

acknowledged negative aspects of the experience. Several of the

papers in this volume provide some insight into this important

question both on the basis of user reports and on theoretical

grounds. One answer that emerges is that initial reports both

in the clinical literature and in the mass media have stressed

the negative aspects and failed to note user-perceived more

positive aspects. In a major study of some 319 adult users

ranging in age from 21 to 38, Siegel (this volume) specifically

questioned users regarding the subjective effects of the phencyclidine experience. Interestingly enough, users in this sample

reported negative or undesired aspects on every occasion of PCP

use and positive or desired effects of use, only 60 percent of

the times used. Effects reported positively included heightened

sensitivity to outside stimuli (by 94 percent of users), stimulation (92 percent), dissociation (88 percent), mood elevation

(61 percent), inebriation (55 percent), and relaxation or tranquilization (by 55 percent of users). Only one in twelve (8

percent) reported experiencing euphoria, however. Negative effects

reported by the majority of users included perceptual disturbances

(by 75 percent), restlessness (by 76 percent), disorientation

(63 percent), and anxiety (61 percent). Approximately a quarter

to a third of users reported such troublesome effects as paranoia

(34 percent), hyperexcitability (27 percent), irritability (22

percent), and mental confusion (22 percent). Four out of five

users had speech difficulties (dysarthria) while using the drug.

Fauman and Fauman (this volume) studied twenty-five chronic

phencyclidine users under treatment in an Illinois residential

treatment program. Their average age was nearly nineteen (18.8

years), and they had used PCP for an average of 3.6 years. Half

(12) described their initial PCP experience in such positive

terms as “fantastic,” “mind blowing,” an intense high or a happy

experience. Ten of the twenty-five found the first experience

neutral or mildly unpleasant. Only seven of the twenty-five reported their typical PCP experience was positive. Eleven reported

their usual PCP experience to be unpleasant and three described

it as making them feel “rowdy” or ‘Violent.” Lerner and Burns

(this volume) in a study of 20 chronic users in the San Francisco

area, report that four out of five found their first PCP experience

“fun” “exhilarating,” and that they (the users) felt “happy” or

“euphoric.” Marsella and Hicks (this volume) emphasize the role of

drug use among native Hawaiian youth in the Job Corps as a way of

relieving boredom and the possible importance of the drug experience

6
in fostering a new sense of what is “real” in contrast to the more

usual conceptions of non-drug using groups. Given this new normative standard, continued drug use may be important in maintaining

it.

A theoretical framework for explaining the persistence of PCPusing behavior despite its obviously negative aspects is offered

by Mello (this volume). She emphasizes the reinforcement value

of the drug experience regardless of certain aversive consequences

because of its role in changing the user’s subjective state. In

practical terms this means that a drug which has the ability to

markedly alter the individual’s subjective feelings may be reinforcing even though that alteration is not always marked by positive aspects in the usual sense.

Another aspect of the PCP experience that may be important in its

continued use is the very risk taking it entails. The excitement

of not knowing just how the experience will turn out and the ability

to later boast of the risks taken, may convey a certain amount

of status, especially in drug-using peer groups (perhaps in a

way analogous to the telling of “war stories” by those who have

been in the military). Related and perhaps easier to understand

are some of the other effects reported by many PCP users: feelings

of strength, power, and invulnerability.

As indicated, difficulties with speech are common. It is frequently

blocked, sparse, and purposeless. Auditory and sometimes visual

hallucinations may occur, more frequently at higher doses, and

feelings of severe anxiety, impending doom or death may appear

and disappear. Touch and pain sensations, as might be expected

since PCP was originally developed as an anesthetic, are dulled

and, as a result, even severe injuries sometimes occur with the

user unaware or only minimally aware of their occurrence. Bizarre

behavior of many types has been reported.

Users typically describe the drug as stronger than marihuana

(“superpot”), perhaps more comparable to LSD, but basically “in

a class by itself.” As with these other drugs, a few users speak

of attaining distinctly new perspectives, of a more “philosophical

outlook” and of seeing their lives freshly with a new sense of

unity. Great variability exists in the effects from one user to

the next.

MODES OF USE

The novice user is often introduced to the drug openly or covertly

by smoking it sprinkled on such leafy materials as tobacco, marihuana, or dried parsley in a “joint” (a hand rolled cigarette).

Occasionally a manufactured mentholated cigarette is dipped in

liquid PCP and later smoked (“superkools”). Although other routes

of ingestion are sometimes used (e.g., snorting, oral ingestion,

or more rarely, intravenous injection), the effects of the differing routes are similar, differing primarily in rapidity of onset

of effects (as previously indicated, overdoses may be more likely

7
with oral doses because of the longer latency period before the

drug has an effect and the lessened ability to “self-titrate” the

dose). In typical use, the “high” from a single dose lasts from

four to six hours with an even longer “coming down” period.

Both animal data (cf. Balster and Chait, this volume) and human

reports suggest that a degree of tolerance develops, with increasing doses being required at the end of a “run” to achieve the

same effects as at the beginning. PCP is a social drug in the

sense that virtually all users report taking it in groups rather

than as a solitary experience.

Chronic users are reported (Lerner and Burns, this volume) to

take the drug in “runs” that may extend over two or three days

during which they remain sleepless. Appetite is also reportedly

suppressed, resulting in weight losses of ten to thirty-five

pounds during repeated periods of chronic use. Following a “run”

users need great amounts of sleep and may awaken feeling disoriented and depressed. In later stages of chronic use, outright paranoid and violent behavior with auditory hallucinations may appear.

The possible role of PCP in precipitating long term psychosis is

at present poorly understood. It may be that persistent psychosis

occurs in individuals who are latently schizophrenic as a result

of some “triggering” function of phencyclidine. Whatever the

cause, there is some evidence that individuals who have used PCP

in the past may later develop a more persistent schizophrenia

despite some months of abstinence from the drug (cf. Luisada,

this volume).

Having used phencyclidine repeatedly without serious adverse

effects is apparently no guarantee that more serious consequences

will not occur unexpectedly on another occasion of use. At least

one group of clinical investigators (Burns and Lerner, 1978)

believes that if use is persistent, adverse consequences will

almost invariably follow.

The premorbid personalities of PCP abusers are not consistently

described in the literature. PCP users appear to have a variety

of personalities, not fitting a single pattern. Fauman and Fauman

(1977) made the point that many of those who become psychotic with

this drug appear to resemble persons who become psychotic using

LSD. However, PCP abusers include not only socially marginal

people, but also people of substantial achievement without obvious

premorbid psychopathology.

For chronic PCP users, PCP is in fact a drug of choice. Lerner

and Bums (this volume) report that chronic phencyclidine users

experienced persistent cognitive and memory problems. Speech

difficulties included stuttering, poor speech articulation, and

difficulties in expressing themselves to others, effects lasting

6 months to a year following prolonged daily PCP use. Mood disorders also occurred; viz: depression, anxiety, and violent behavior. Purposive activity became more difficult with resultant

loss of employment or impaired school performance.

8
TREATMENT OF CHRONIC PCP USER

As with other drug abuse, the motivations of the user are crucially

important in the approach to treatment. In at least one geographic area of high PCP abuse, a downturn in emergency cases,

possibly indicating less widespread general use, followed an

intensive effort by the local community mental health center to

publicize the adverse effects of the drug. Unfortunately, numerous

case accounts suggest that the user who consistently enjoys PCP

will be reluctant to give up its use, since it is relatively

cheap, easily available, and quite powerful. Although for many

it is a particularly disagreeable drug, for others it is quite

enjoyable. Whether this reflects a psychopharmacologic difference

between these groups is not known, but its genuine appeal to some

must be taken into account in any therapeutic or educational program. Not only is the drug readily available, but so is the example of users who experience severe depression while taking the

drug, but who continue their use of it notwithstanding.

In their discussion of long term residential treatment of adolescent

PCP abusers, DeAngelis and Goldstein (this volume) emphasize the

importance of dealing with underlying emotional conflicts in their

clients rather than focusing on their phencyclidine use itself.

Discussion of drug abuse itself, they feel, is often a way in

which the disturbed adolescent can avoid coming to grips with

his or her real problems which cause drug abuse. In their population they have found that about half reported PCP use. They

report that many of their PCP users in treatment show “flattened

affect, depression, agitation, hostility, and belligerence.”

As a result, staff have lower initial expectations of PCP users’

participation in such activities as therapy, school or recreational

programs and are initially more tolerant of angry outbursts.

Chronic PCP users were found to stay in the program longer than

other types of drug abusers (DeAngelis and Goldstein, this volume).

PCP OVERDOSE (cf. Done, Aronow and Miceli; Aronow, Miceli

and Done; Luisada; Smith et al. - all in this volume)

Diagnosis

The victim of an overdose of PCP may exhibit many different

symptoms during the course of his intoxication, depending on the

dose, how recently it has been ingested, and frequency of prior

use. Some cardinal signs of PCP overdose are: ataxia, vertical

and horizontal nystagmus, assaultiveness or catatonic staring,

and generalized anesthesia. Severe convulsions may also occur

in extremely heavy overdoses, and PCP exhibits the lethal properties of a central nervous system depressant, with respiratory

depression, coma and death.

The dose of PCP which may result in a trip to an emergency room

is as varied as the presenting symptoms. A single cigarette may,

in the inexperienced (or deceived) user, produce overwhelming

feelings of acute anxiety requiring prompt but relatively

9
brief reassurance and therapeutic support. In adults, quantities

in excess of a half a gram have been used and it is particularly

in this dose range (or higher) that life-threatening effects

are likely to be manifested along with severe behavioral disturbance.

The diagnosis of PCP over-dosage is frequently missed (Fauman and

Fauman 1977). Because the presenting symptoms so often closely

resemble those of an acute schizophrenic episode, this is a common

misdiagnosis. Aronow and Done provide a useful summary (Aronow

and Done 1978) of the range of physical and psychological symptoms

likely to be encountered in the emergency room situation.

At relatively low doses (on the order of 5 mg in the adult, leading to an estimated serum level of 20-30 ng/ml) they describe

the patient as likely to show some of the following symptoms:

agitation and excitemnt

gross incoordination

blank stare appearance

catatonic rigidity

catalepsy

inability to speak

horizontal or vertical nystagmus

loss of response to pinprick

flushing

diaphoresis

hyperacusis

Psychologically the patient may have the following subjective

responses: changes in body image, estrangement, disorganization

of thought, feelings of inebriation, drowsiness and apathy. The

patient may show marked negativism and hostility as well as bizarre

behavior. Later, the patient may be amnesic for the drug episode.

At moderate doses (approximately 5-10 mg., leading in the adult

to serum levels of 30-100 ng/ml) they list the following symptoms:

coma or stupor

eyes remain open

pupils in midposition and reactive

nystagmus

vomiting

hypersalivation

repetitive motor movements

myoclonus (shivering)

muscle rigidity on stimulation

flushing

diaphoresis

fever

decreased peripheral sensations (pain,

touch, and position)

10
At still higher doses (over 10 mg, leading in the adult to serum

levels of 100 ng/ml and higher) the authors note the following:

prolonged coma (from 12 hours to many days)

eyes closed

variable pupil size, but reactive

hypertension

opisthotonic posturing

decerebrate positioning

repetitive motor movements

muscular rigidity

convulsions (at doses of 0.5 to 1 mg/kg)

absent peripheral sensation

decreased or absent gag and corneal reflexes

diaphoresis

hypersalivation

flushing

fever

(The doses cited are rough guidelines; other investigators suggest

that significantly higher doses of PCP are needed to produce

each of these clinical pictures.)

If the symptoms found are suggestive of recent PCP ingestion, a

urine or blood sample may reveal the presence of the drug. If

a large amount has been ingested, considerable quantities of PCP

will be present in urine for several days (or more). Attempts

should be trade to elicit a drug history from informants, although

it is quite possible that they may only know the drug under one

of its street names (cf. The Material) or may not even know that

the patient has taken phencyclidine if the drug has been misrepresented. Since the drug often renders the patient amnesic for

the circumstances of taking it, he or she may not remember having

taken it or may only recall it during a later period of recovery.

A history of recent ingestion of other drugs may complicate the

diagnosis and treatment. Thus the diagnosis may sometimes be

established by history, sometimes by laboratory tests, by the

physical and psychological course of the patient or by some combination of these.

Treatment of PCP Overdose

Life-support measures

The hospital management of the PCP overdose victim is divided into

phases corresponding to the time course of action of the drug.

The initial phase requires symptomatic, often intensive medical

management. It includes the most acute physical effects of the

drug, including the possibility of respiratory depression, convulsions, and coma. Treatment of this phase frequently requires

the full life-support capabilities of a good intensive care unit.

Acidification of the urine and gastric drainage (see below) will

markedly hasten the excretion of PCP. Since there is no specific

antagonist for PCP other treatments are symptomatic. PCP often

11
induces hypersecretion in the pharnyx, which must be suctioned.

Respiratory depression calls for external respiratory assistance.

Hyperthermia can be treated with external cooling. Life-threatening consequences of rapid development of hypertension can be treated

with diazoxide (Hyperstat) or hydralazine hydrochloride (Apresoline). Convulsions can be managed with IV diazepam and constant

attention to maintenance of an unimpaired airway. However, some

feel diazepam may prolong the course of the intoxication.

Isolation

Most clinicians advocate placing the patient in an isolated environment during this period, reducing sensory stimulation as much

as possible in order to minimize the phase of excitability,

irritability, anxiety, paranoia and violence which often follows

the obtunded or comatose phase. Needless to say, such isolation

of the patient (in quiet rooms, etc.) cannot be at the expense of

vigilant medical monitoring of the patient’s vital signs and his/

her response to emergency life-support management. Patients are

often so unmanageable that restraints are necessary, and the help

of four or five (not one) burly aides will often be needed to

prevent injury to staff or patients. If it is necessary to administer tranquilizing agents to keep the patient manageable, do

not use phenothiazines during this acute stage because of the

anti-cholinergic potentiation with PCP. Haloperidol (Haldol) has

been recommended (5 mg IM repeated hourly until the patient is

under control).

Detoxification

Recently ingested drugs should be removed by gastric lavage.

Done (1978) and Aronow and Done (1978) describe an emergency

detoxification procedure which achieves greatly enhanced urine

concentrations of PCP by lowering the urine pH to 5 or less.

They recommend administration of ammonium chloride by gastric

intubation or, in severe cases, intravenously. (Prior screening

must be done for the concomitant presence of such other drugs

as phenobarbital or salicylates, whose excretion might be adversely

affected by acidification; the presence of liver damage contraindicates the use of ammonium chloride.) To acidify by intubation

they use 2.75 mEq/kg ammonium chloride in 60 cc or saline solution

every 6 hours along with intravenous ascorbic acid (2 gm/500 cc

IV fluid q 6 hours) until the urine pH drops below 5. For patients

in deep coma, they advise using intravenous ammonium chloride

(2.75 mEq/kg as a 1-2 percent solution in saline) with precise

and repeated monitoring of blood pH, blood gases, BUN, blood ammonia

levels, and electrolytes. These guidelines must be adapted for

every patient individually by a medical team experienced in

electrolyte management.

The treatment of acute toxic effects usually belongs in an intensive care unit, not an emergency room. Constant gastric suctioning

is essential because PCP can pool in gastric contents, and should

be continued well past the point of awakening from coma. The

12
excretion of PCP is variable and prolonged. Ten days to two weeks

of further acidification using cranberry juice is indicated,

because of remaining body stores of PCP.

If medical treatment is successful, the patient’s coma will lighten,

only to be replaced, frequently, by delirium, paranoia, and violent

assaultiveness. This may occur at the same time as life-support

measures are still necessary, requiring constant attention from

the medical staff so that intubation and intravenous lines remain

open and intact. Any patient in whom coma is followed by a prolonged period of confusion should, as recommended by Burns and

Lerner (1978) have a psychiatric consultation prior to discharge

to evaluate residual paranoia or potentially suicidal depression.

PCP Psychosis

a. Diagnosis

Some patients experience a psychotic phase which lasts from several

days to several weeks despite abstinence from further PCP. The

psychosis may occur after single doses of PCP. Luisada (this

volume) divides these psychoses into three stages, each lasting

several days: the initial stage, characterized by violent psychotic behavior; the second stage, with restless but more controlled behavior and a lessening of delusional activity; and the

final stage, characterized by rapid improvement of thought disorders and amelioration of paranoia.

It should be emphasized that this psychotic stage may be the first

stage at which the patient enters treatment, often through a

psychiatric hospital emergency room rather than a general medical

hospital emergency service. The PCP user may at this point be

misdiagnosed as schizophrenic, especially if a drug history is

unavailable or inaccurate. He may or may not have passed through

an earlier stage of reduced consciousness or coma in the company

of friends or by himself, but presents with a psychotic-like

picture of confusion, incoherent speech, paranoia, assaultiveness,

restlessness, autism, preoccupation, mutism, auditory hallucinations, and grandiosity. An erroneous diagnosis of schizophrenia

does not complicate his or her immediate treatment, which is much

the same for acute schizophrenia, but labels him with a diagnosis

which may be quite inappropriate and misleading for future medical

contacts.

b. PCP psychosis - a psychiatric emergency

Phencyclidine psychosis constitutes, in this initial phase, a

psychiatric emergency, one often misidentified (in St. Elizabeth’s

hospital in Washington, D.C., PCP psychosis actually became for

two years the leading cause of inpatient psychiatric admission,

outstripping both schizophrenia and alcoholism). The patients

are dangerous to themselves, because of depression and suicidal

impulses, and dangerous to others, because of paranoia and strong

tendencies toward violence. For patients fitting this description,

13
psychiatric inpatient treatment is indicated. Voluntary hospitalization is seldom acceptable to the hostile, suspicious patient.

The immediate goals of treatment for this acute PCP-induced psychosis (Luisada, this volume) are:

1. prevention of injury to the patient or others

2. assurance of continuing treatment

3. reduction of stimuli

4. amelioration of psychosis

5. reduction of agitation

c. Treatment of PCP psychosis

In treating the psychosis, most clinicians prefer to use

haloperidol, 5 mg IM given hourly if needed, to avoid the

possibility of potentiation of PCP anticholinergic effects by

a phenothiazine. Chlorpromazine is also effective, but prior to

instituting any phenothiazine treatment of a psychotic patient

with a history of PCP use, it is essential to determine whether

the patient is still intoxicated with PCP. The patient should

be examined for the presence of nystagmus and ataxia, which, if

present, indicate intoxication. The pupils should also be examined

to guard against anticholinergic drug intoxication. If there is

no possibility of continuing intoxication by a cholinergic drug,

chlopromazine may be given instead, starting with 400 mg/day

orally in divided doses (after a test dose of 50 mg) and increased

as necessary by 200-600 mg/day. On the average, a daily dose of

1600 mg/day of chlorpromazine will be reached by the end of the

initial phase of treatment. The response of PCP psychosis to this

aggressive treatment is characteristically slow, distinguishing

it from paranoid schizophrenia, which usually responds much more

rapidly.

As the psychotic symptomatology abates, there are sometimes unpredictable reexacerbations. Patients will often wish to sign

out against medical advice, with encouragement from others to do

so, only to experience unexpected suicidal or homicidal impulses

following their discharge (the patient may still not realize,

because of drug-induced amnesia, that PCP was responsible for his

hospitalization). When feasible, group and milieu psychotherapy

can help.

Outpatient follow-q treatment is aimed at keeping the patient

away from resuming drug use, a task which is not always easy despite the dysphoria associated with the experience which led to

hospitalization. Luisada and Brown (1976) make the provocative

observation that “about one-fourth of the patients originally

treated for phencyclidine psychoses return about a year later

with schizophrenic ones in the absence of drug use. . . These

later episodes have lacked the characteristic violence of the

phencyclidine-induced ones, and they have been much more quickly

responsive to antipsychotic drugs.” Thus, some of the users who

became psychotic under PCP may have been “at risk” for schizophrenia, which later reappeared without the precipitating drug. (Some,

14
in fact, may have been identifiably schizophrenic prior to using

the drug.)

Profound depression is experienced by significant numbers of users

(not just overdose cases). They must be followed carefully to

monitor their suicidal potential (Smith et al. 1978).

PHENCYCLIDINE -- THE UNANSWERED QUESTIONS

Our present knowledge of phencyclidine as an abused drug is decidedly modest. Indeed, as was pointed out earlier in this account,

even the basic data pertaining to the incidence and prevalence

of its abuse are largely lacking. What information is available

represents a minimal estimate of both the extent of PCP use and

of possible adverse effects of such use. Since PCP is often

misrepresented as some other drug, inquiring about its use is

certain to represent an underestimate of such use, especially

by the less chronic user. And, as we have seen, the individual

who suffers from a schizophrenic-like reaction to the drug is

likely to be diagnosed as an acute schizophrenic reaction rather

than as a toxic drug reaction.

Our understanding of the personality characteristics of more

chronic users and the effect that phencyclidine has on their

lives is also limited. For example, there is some question whether

or not the acute schizophreniform reaction sometimes encountered

in users may not be indicative of a latent schizophrenia precipitated by the drug. Similarly, we know little of the frequency and

circumstances under which PCP potentiates aggression, although

there have been many individual clinical reports of highly destructive behavior related to drug use.

Although it is believed that PCP ultimately results in “burned

out,” dulled intellectual functioning after repeated use, this

has yet to be verified objectively. Besides possible adverse

effects on intellectual functioning, phencyclidine may also disrupt psycho-social functioning in ways that remain to be delineated.

Because it is widely used during adolescence, it is especially

important to assess its possible effects at this age.

A still puzzling paradox not yet fully explained is the apparent

increase in PCP use in recent years despite a continued poor

street reputation of the drug. This increased popularity may

reflect the improved ability of the user to avoid overdose when

the drug is smoked or snorted rather than taken orally, the desirability of simply changing one’s state (Cf. Mello, this volume),

the marked increase in PCP availability or some combination of

these and possibly other factors as well. Despite speculation,

the motives for use of phencyclidine remain poorly understood.

Lasting biological implications of use and especially of chronic

use arc largely unknown. These include possible reproductive

effects of PCP use as well as possible alterations in neurophysiological functioning that may be related to prolonged use. While

15
higher doses of this drug are unquestionably incapacitating, much

less is known about the effects of lower doses which may be more

typical of recreational use, especially when the drug is smoked.

Thus the wide range of possible dose response relationships involving

PCP needs elucidation. Carefully designed experiments which investigate the relationships between dose, tissue and fluid levels,

and pharmacological and behavioral effects of PCP and its analogs

should be conducted in man where medically and ethically possible.

Since PCP is often used in association with such other drugs as

alcohol, marihuana, and the barbiturates, it is important to know

the effects of such combinations. For example, doses of alcohol

or PCP which are not seriously toxic alone may become so when both

drugs are taken concomitantly.

Similarities and differences between PCP and other abused substances can be evaluated in animals with sensitive behavioral

techniques. Behavioral and drug-specific variables which contribute to the initiation and maintenance of PCP self-administration

should be studied. The effects of PCP on a wide range of behaviors

(e.g., aggression, punishment- induced conflict, cognitive function

and sensory discrimination) remain to be investigated. The long

term behavioral- toxicological consequences of phencyclidine administration should be examined in these contexts.

Unfortunately , phencyclidine has about 30 analogs -- drugs with

slightly different chemical structures which nevertheless have

similar effects. Little is known about the similarities or

possible differences in effects between these compounds and PCP.

Recent attention to the detection and quantification of phencyclidine

in biologic samples has provided valuable techniques, which are

based on standard and existing methods. These must be made

readily available for clinical and research purposes. There is

considerable need for detailed information on the metabolism,

disposition, and pharmacokinetics of phencyclicline and its analogs

in acute and chronic situations. This must in turn be matched

with carefully gathered clinical data and used to improve treatment methods for overdoses.

Finally it is important that we develop effective prevention

strategies to discourage PCP use. In the past, some success has

been obtained in discouraging the use of other drugs by making

widely known their harmful effects.

would not seem to work with PCP.

Unfortunately this approach

The dangers of its use -- both

short and long term -- are apparently quite well known to its

users. We will have to understand the reasons for its use and

the most effective ways to reach and dissuade the user. These

goals become particularly important for a drug, or family of

drugs, whose street availability cannot be substantially diminished

by means presently known.

16
REFERENCES

Aronow, Regine and Done, Alan. Phencyclidine Overdose: An

Emergency Concept of Management. Journal of the American College

of Emergency Physicians, 7(2):56-59, 1978.

Rums, R.S. and Lerner, S.E. The Causes of Phencyclidine-related

Deaths. Journal of the American College of Emergency Physicians,

1978. (in press)

Done, Alan, Toxic Emergency: Phencyclidine (PCP) Pin-up.

Emergency Medicine, May 1978.

Fauman, Michael and Fauman, Beverly. The Differential Diagnosis

of Organic Based Psychiatric Disturbance in the Emergency Department. .Journal of the American College of Emergency Physicians,

6(7):315-323, 1977.

Luisada, Paul and Brown, Bernard. Clinical Management of Phencyclidine Psychosis. Clinical Toxicology, 9(4):539-545, 1976.

17
Chapter 2

Neurobiology of Phencyclidine–An Update

Edward F. Domino, M.D.

INTRODUCTION

About 22 years aqo I was on a plane flying from San Francisco to

Detroit. On the same plane was Dr. A.C. Bratton, at that time the

Director of Pharmacological Research at Parke Davis Laboratories

in Detroit. It took about six hours to fly across the country so

we had much to talk about but especially about a fascinating compound that they had just discovered (Chen et al. 1959). Dr.

Bratton said that in rodents it was amphetamine-like but it also

made them drunk and ataxic. In dogs the chemical caused yelping

and convulsions. Monkeys were beautifully "tranquilized" and in

larger doses anesthetized by this agent. The Parke-Davis research

staff was confused. They really did not know what to do with this

compound. They were wondering whether they should take it into

man or drop it. Would I be interested in taking a look at it? My

response was positive and we did take a preliminary look at the

compound. Our initial studies were in the Macaca mulatta monkey.

In this species the agent was remarkable! It caused serenity,

hence the trade names Sernyl or Sernylan. As far as I was concerned, it was the best anesthetic agent I had ever seen for the

monkey. It appeared to be very safe compared to other general

anesthetics. So remarkable was this state of anesthesia that a

decision was made to file this new drug, whose code number was

CI-395 and which was subsequently called phencyclidine, with the

Food and Drug administration. Greifenstein, in Anesthesiology at

Detroit General Hospital and Wayne State University, was asked to

test it as a general anesthetic in patients. This he did (Greifenstein et al. 1958). He was so amazed at the remarkable anesthetic

state it induced that with Meyer in Neurology at Wayne State

University, he concluded that phencyclidine produced sensory deprivation (Meyer, Greifenstein and De Vault 1959). At that time

Luby, also from Wayne State, was studying sensory deprivation as

a model of schizophrenia at the Lafayette Clinic. After he heard

about phencyclidine, he decided to compare it to actual sensory

deprivation in both normals and schizophrenic patients (Luby et

al. 1959). Luby was so impressed with the findings that he recommended to Jacques Gottlieb, then Director of the Lafayette Clinic,

18
that I be asked to be their pharmacological consultant, for he

knew that I had done some of the animal studies with this drug.

So began my clinical introduction to phencyclidine and a long and

fruitful association with the Lafayette Clinic.

In 1964, when we reviewed the neurobiology of phencyclidine (Domino

1964) it impressed us that the development of a new drug provides

the pharmacologist and clinician with a number of surprises. That

conclusion is even more true today. Who would, in their wildest

imagination, predict that a dissociative anesthetic, which produced a high incidence of anesthetic emergence phenanena and was

adrugwhichmimicked the primary symptoms of schizophrenia by

distorting body image, would become the number one drug of abuse

in the United States in 1978? Yet that is what the drug culture

of our country has acomplished with phencyclidine. Surely a

schizophrenomimetic drug in low dosage, and anesthetic and a convulsant in large doses, would not seem to be reinforcing - yet

it apparently is to many people who now call it by many different

names, including PCP, synthetic THC, angel dust, hog, crystal,

animal tranquilizer, horse tranquilizer, peace pill, Pea Ce Pill,

crystal joint, CJ, KJ, sheet, and rocket fuel. People who abuse

phencyclidine have been called parsley monsters when the drug is

applied to parsley and smoked. Those who are "high" on phencyclidine are said to be "crystalized." The drug is taken by inhalation, orally, intranasally (snorted), and intravenously. Knowing what we now know, would any of us who were involved with the

early pharmacological birth and development of phencyclidine have

ventured further? What have we thought?

Depending on the dose and species, phencyclidine is a excitant or

a cataleptoid anesthetic. While it is an anesthetic in man, small

doses cause a rather remarkable psychotomimetic picture. Emergence

delirium is often seen. Phencyclidine and related compounds have

been called cataleptoid and or sympathomimetic anesthetics. During induction the patient often feels dissociated from his environment with analgesia and some amnesia.

A related congener of phencyclidine is ketamine, a valuable anesthetic agent used therapeutically throughout the world. Its anesthetic properties in humans were first described as representing

a new class of "dissociative" anesthetics because of its unique

pharmacological actions (Domino, Chodoff, and Corssen 1965; Corssen

and Domino 1966). During anesthesia, the patient may keep his

eyes open and seems "disconnected" from the environment. It seems

as if higher associational functions of the brain are markedly

depressed, a clinical impression for which there is some human

and animal physiologic data (Corssen, Miyaska, and Domino 1968;

Miyasaka and Domino 1968; Corssen, Domino, and Bree 1969; Winters

1972). During emergence from dissociative anesthesia, the patient

may go through a phase of vivid dreaming with and without psychomotor activity, manifested by confusion and irrational behavior.

Chemically, phencyclidine, ketamine and related compounds are

arylcyclohexylamines. While they have somewhat similar pharma19
cological actions, they also have important differences,both

quantitatively and qualitatively. The major pharmacological

properties of these agents can be summarized as follows:

1 . Central nervous systan

a. Small doses produce a "drunken" state with numbness of

the extremities; saw species are excited.

b. Moderate doses are analgesic and anesthetic.

C. The psychic state crudely resembles sensory isolation,

except that sensory impulses, if tested electrophysiologically, reach the neocortex but the neuronal signals

are grossly distorted.

d. Cataleptoid motor phenomena are seen.

e. barge doses may produce convulsions. This is especially

true of phencyclidine.

f. Marked species differences are present. Primates,especially man, are most susceptible to the depressant effects

which predominate.

2 . Autonomic and cardiovascular system

a. Sympathomimetic.

b. Tachycardia.

C. Hypertension.

d. Potentiation of catecholmines through a cocaine-like

action.

CYCLOHEXYLAMINES ABUSED

To date, at leasts six cyclohexylamines have been either given to

or taken by humans in the context of drug abuse. Their chemical

structures are shown in figure 1.

Kalir et al. (1969) have provided us with the best structureactivity studies of these compounds to date. Shulgin and MacLean

(1976) have described the illicit synthesis of phencyclidine and

several of its analogs as well as relative potency data of compounds now available on the street.

As described above, the first arylcyclohexylamine studied in man

as a general anesthetic was phencyclidine (Greifenstein et al.

1958). It is longer acting and has stimulant and convulsant prop

erties in man. Ketamine (Ketalar, Ketaject) has more depressant

properties than phencyclidine and is shorter acting. It is used

as a nonbarbiturate anesthetic in man. When phencyclidine is

taken by humans, it produces more emergence delirium, in which

some patients show post anesthetic psychiatric complications for

as long as two weeks after a single dose. Although phencyclidine

is no longer used as a general anesthetic in man, it is still a

veryusefulanesthetic in veterinary medicine, especially for

primates (Domino, McCarthy, Deneau 1969).

Widespread use of phencyclidine as a psychedelic agent by the

drug subculture in the United States is now generally acknowledged.

The early warning drug network (DAWN) has emphasized that phencyclidine has been a major drug abuse problem for same time. One

20
FIGURE 1

21
of the clinical problems associated with phencyclidine overdosage

is that the patients not only may be in coma but they may also

convulse and die of respiratory arrest. The prolonged emergence

delirium is observed in patients who may be psychotic for at

least several weeks or more. This may be due to metabolic or

psychiatric variables such as pre-morbid or borderline schizophrenia.

The clinical toxicology of phencyclidine is of such importance

that an entire issue of Clinical Toxicology in August of 1976

was devoted to it (Burns and Lerner, Guest Editors, 1976).

If one has a vivid imagination, there is a structural relationship between phencyclidine, amphetamines and LSD-25. I have

drawn 2-methoxyamphetamine and phencyclidine to approximate the

A and C rings of LSD-25 as shown below:

2-Methoxyamphetamine Phencyclidine

NEUROCHEMISTRY

The most recent review of the neurochemical pharmacology of phencyclidine is by Johnson in this monograph. Our own interests in

this area may provide an additional point of view and will be an

update of our own brief review (Domino and Luby 1973).

A. Monoamines, Especially Catecholamines and Serotonin.

Because of the structural similarities, one would expect phencyclidine to interact with the monoamines in the body, especially

the catecholamines (CA) and 5-hydroxytryptamine (5-HT). Chen and

his associates (1959) compared the sympathomimetic effects of

phencyclidine with cocaine and desoxyephedrine. They concluded

that it had similarities to both drugs, especially cocaine.

O'Donnell and Wanstall (1968) studied the action of phencyclidine

on the perfused rabbit ear. They postulated that phencyclidine

inhibited the uptake of both norepinephrine (NE) and tyramine by

adrenergic neurons in a manner similar to that of cocaine. High

concentrations of phencyclidine (Ki = 1.5 x 10-4M), like many

other psychotropic drugs, inhibit monoamine oxidase (MAO) activity

but this does not appear to be significant in relation to its

in vivo actions (Usdin and Usdin 1961).

The effects of phencyclidine on the pressor responses to norepinephrine (NE), epinephrine (EPI), and serotonin (5-HT) in the pento22
barbital-anesthetizeddog are consistent with a cocaine-like

action as illustrated in figure 2 below.

Note that 0.5 mg/kg of i.v. phencyclidine itself produces an

initial transient hypertensive response which is probably related

to peripheral CA release. Ketamine produces a similar hypertensive response but apparently has less of a cocaine-like potentiating action than phencyclidine.

Tonge and Leonard (1969) compared the effects of phencyclidine,

Ditran, mescaline and LSD-25 on rat brain 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), MAO and aromatic amino acid decarboxylase

activity. All four drugs in doses larger than those heeded for

behavioral effects increased brain 5-HT and decreased 5-HIAA over

a three hour period. Phencyclidine reduced 5-HT depletion after

reserpine and para-chlorophenylalanine. It had no effect on the

associated 5-HT enzymes. Tonge (1971) later pointed out that

this effect was dependent on the source of rats. Tonge and

Leonard (1970) found a small reduction in brain and plasma tryptophan levels after a small dose of phencyclidine. A parallel

study of these same investigators (Leonard and Tonge 1969) showed

that all four drugs decreased rat brain NE and slightly elevated

brain dopamine (DA). The fall in brain NE paralleled the time

course in the rise in 5-HT. Phencyclidine increased the degree

of depletion of NE by reserpine. All four psychototmimetic agents

increased the depletion of NE and DA by alpha-methyl-metatyrosine,

but strangely had no effect on depletion of these catecholamines

by alpha-methyl-paratyrosine. Normetanephrine brain levels were

unaffected by phencyclidine and LSD-25 or were decreased slightly

by Ditran and mescaline, indicating that the decrease in NE was

not due to enhanced release. Their assay for normetanephrine

was not very sensitive. In a subsequent study, phencyclidine was

shown to reduce normetanephrine levels in the fore- and hindbrain,

indicating decreased NE release from adrenergic neurons (Tonge

and Leonard 1972). Brain and plasma tyrosine are elevated after

a small dose of phencyclidine (Tonge and Leonard 1970). In the

mouse, Hitzemann, Loh, and Domino (1973) showed decreased 14C-NE

and 14C-DA levels after an intracerebral injection of 14C-tyrosine

after phencyclidine. An increase in 14C-3-methoxytyramine and

14C-normetanephrine was noted. In the mouse striatum phencyclidine

does not significantly change homovanillic acid levels (Sharman

1966).

Sung, Frederickson, and Holtzman (1973) have shown that 40 mg/kg

of ketamime increased the turnover of DA and decreased the turnover of 5-HT in rat brain four to six hours postinjection, although the behavioral effects lasted only two to three hours.

The cocaine-like actions of phencyclidine have also been reported

for ketamine. Miletich et al. (1973) have shown that ketamine

prevents the neuronal reuptake of NE in rat heart.

Leonard and Tonge (1968, 1970) looked at other putative neurotransmitters in the rat brain following phencyclidine. They found

no changes in whole brain acetylcholine, cholinesterase and

23
FIGURE 2

Effects of phencyclidine on the arterial blood pressure responses

of norepinephrine, epinephrine, serotonin in the pentobarbital

anesthetized dog.

Each agent was given us a bolus i.v. injection at 5-10 minute

intervals. Note the cocaine-like action of phencyclidine to

enhance the pressor responses of the CA in contrast to 5-HT where

the effects are more variable.

24
histamine. However, a high dose of phencyclidine decreased brain

GABA They also found an increase in 5-hydroxytryptamine decarboxylase activity. In a preliminary study, Tonge (1973) found

that chronic phencyclidine during the pre- and post-neonatal

periods produced elevated 5-HT levels in the rat hypothalamus

and pons-medulla.

B. Acetylcholine

There have not been enough studies on the complex effects of the

arylcyclohexylamines on the cholinergic system. In vitro phencyclidine (5 x 10-5M) inhibits primate serum cholinesterase using

benzoylcholine as substrate (Becker 1969). In humans, the usual

and fluoride variants of serum cholinesterase are inhibited by

phencyclidine whereas the dibucaine variant shows increased resistance. This differential inhibition suggests that phencyclidine

is useful in estimating human genotypes for cholinesterase. Apparently, phencyclidine and acetylcholine have similar charge distributions in relation to muscarinic cholinergic receptors (Weinstein

et al. 1973; Paster et al. 1974; Maayani et al. 1974). This would

account for phencyclidine having an atropine-like effect. However,

phencyclidine not only inhibits serum or butyrylcholinesterase,

it also inhibits acetylcholinesterase with a larger Ki (about 80

times greater). These mixed agonist and antagonist actions of

phencyclidine tend to antagonize each other. However, the algebraic sum of the actions of phencyclidine on guinea pig ileum is

predominantly antagonistic (Maayani et al. 1974). Amazingly, in

mice, scopolamine has been reported to prevent tolerance develop

ment to cyclohexamine (Pinchasi, Maayani and Sokolovsky 1977).

Ketamine is also reported to inhibit both serum butyrylcholinesterase (Schuh 1975) and brain acetylcholinesterase (Cohen et al.

1974). Although in large doses phencyclidine has been reported

to elevate slightly brain ACh (Giarman and Pepeu 1962), Leonard

and Tonge (1968, 1970) and Domino and Wilson (1972) have shown

that smaller but behaviorally effective doses do not alter total

ACh levels. Phencyclidine also increases the depletion of rat

brain ACh after hemicholinium-3, suggesting an increased utilization of ACh in smaller doses. Like LSD-25, phencyclidine does

not significantly alter the release of ACh fran the cat cerebral

cortex in contrast to the isomers of Ditran, which increase ACh

release, and general anesthetics like pentobarbital which decrease

ACh release (Domino and Bartolini (1972). Ngai, Cheney and Finck

(1978) measured regional ACh and Ch concentrations in the brains

of rats given halothane, enflurane and ketamine as well as the

turnover rate of ACh in vivo. ACh concentrations in various

brain areas did not change during anesthesia with any of the

anesthetics studied. This is noteworthy in itself because ketamine in vitro is a cholinesterase inhibitor (see above). Yet

in vivo steady state levels of ACh were not elevated, as would

be expected. During anesthesia with ketamine, ACh turnover rates

were reduced in the caudate nucleus and hippocampus, but not in

the cerebral cortex, thalamus and hypothalamus. Halothane decreased ACh turnover in all of the brain regions while enflurane

only decreased ACh turnover in the cortex. These investigators

25
felt that the changes in ACh turnover were related to known anesthetic-induced electrophysiologic changes in cortical and subcortical structures.

C. Energy production

Phencyclidine has still other effects on the enzymes involved

with energy production. In vitro phencyclidine (5 x 10-4M) is

an uncoupler of oxidative phosphorylation (Lees 1962, 1968). The

drug in vitro increased rat liver mitochondrial respiration in

low concentrations and depressed it in high concentrations.

ATPase activity was stimulated and the inorganic phosphate-ATP

exchange reaction inhibited. These in vitro effects of phencyclidine onrespiration, ATPase activity,and the inorganic

phosphate-ATP exchange reaction were crudely similar to-those

of chlorpromazine except higher concentrations of phencyclidine

were required. Only in even greater concentrations was the drug

inhibitory.

NEUROPHYSIOLOGY

It is clear that phencyclidine produces its own unique EEG; changes

in nomal humans. Van Meter, Owens and Hinwich (1960) using rabbits provided evidence that phencyclidine acts on the cerebral

cortex. Our own studies (Domino 1964; Miyasaka and Domino 1968)

also implicate a thalamo-cortical action of phencyclidine and its

congener, ketamine. Adey and Dunlop (1960) have pointed out

that phencyclidine and cyclohexamine in cats suppresses or

seriously interferes with learned approach in a T-maze situation.

This was correlated with EEG; spikes and abolition of normal hippocampal activity. After these drugs stimulation of the thalmic

nucleus ventralis anterior failed to elicit nomal hippocamal

theta wave activity. Drug-induced changes in the reticulo-cortical system were also seen, but the hippocampal changes were

especially apparent. Winters et al. (1967) compared the EEG;

effects of phencyclidine in cats with other general anesthetics.

They suggested that hallucinatory and epileptoid phenomena as

well as general anesthesia were in part a continuum with reticular,

thalamic, cortical and hippocampal alterations, depending upon

the class of drugs studied. Winters and Ferrar-Allado (1972)

showed that ketamine induced a catatonic state in cats which was

accompanied by intermittent or continuous hypersynchronous discharges from the cortex, limbic structures and the medial geniculate nucleus. An especially provocative viewpoint was expressed

by Winters (1972) When he suggested ketamine was causing epilepsy

instead of anesthesia in man. This point of view has been criticized by Corssen, Little, and Tavakoli (1974) and Domino (1974).

Nevertheless, Winters and his colleagues have documented extensively the stimulant and convulsive properties of both phencyclidine and ketamine, especially in animals. There is no question that given enough of each of these substances in an appropriate species, convulsions are seen. This is well documented in

human overdosage With phencyclidine in particular. The extensive

studies of Winters as well as a review of the literature on the

26
neuropharmacology of anesthetics were recently summarized by him

(Winters 1976).

Phencyclidine effects on the EEG; of chronic schizophrenics, both

lobotomized and not, were studied by Itil et al. (1967). While

the two groups showed symptoms to 0.05 mg/kg of phencyclidine

given over a 5 minute period, the lobotomized patients showed

much less alteration to both clinical symptoms and the alpha

frequency decrease in the EEG. These investigators concluded

that the inability of lobotomized patients to exhibit marked

phencyclidine effectsin comparison to the nonlobotamized patients

was because thalamcortical integrative mechanisms are necessary

to produce typical phencyclidine responses. Fink (1969) reviewed

the effects of phencyclidine along with many other psychoactive

compounds on the human EEG. Stockard et al. (1975) have reported

that the unusual delta wave activity followed by low voltage fast

wave activity we have previously reported in the monkey was observed in a 25 year old male patient who inhaled a rather large

amount of "angel dust." His serum phencyclidine levels were

reported as being 0.34 μg/ml. These investigators reported similar EEG; changes due to 2 to 4 mg/kg of ketamine given intravenously. They suggested that these EEG manifestations of

diffuse monorhythmic theta activity with superimposed periodic

events should raise the suspicion of cyclohexylamine intoxication

in comas of unknown etiology. It is not known if the other cyclohexylamines besides phencyclidine and ketamine produce similar

EEG manifestations and whether these are correlated with plasma

levels.

BEHAVIORAL STUDIES

The meager animal and human behavioral studies available until

a few years ago were reviewed by us previously (Domino 1964;

Domino and Luby 1973). Since then, the behavioral pharmacology

of phencyclidine has been reviewed by Balster and Chait (1976)

and again very recently (Balster and Chait, this monograph). Especially important is the evidence that both phencyclidine (Balster

and Johanson 1973; Pickens, Thanpson and Muchow 1973) and ketamine

(Moreton et al. 1977) are self-administered by animals. In addition, drug discrimination studies indicate that phencyclidine,

cyclohexamine, and ketamine belong to a class of their own for

they do not transfer stimulus control to morphine, chloropromazine,

Ditran, 9-tetrahydrocannabinol or pentobarbital. It is especially

important to know whether in low dosage there is stimulus generalization of phencyclidine to cocaine and amphetamine-like drugs and

in larger dosage to general anesthetics including nitrous oxide,

halothane and convulsants like phentylenetetrazol. Whether the

technical behavioral problems can be solved remains to be seen.

One extensive locomotor activity study using 5 mg/kg i.p. of

phencyclidine has been reported by Kanner et al. (1975). It was

previously known that phencyclidine produces increased locomotor

activity in mice which can be augmented by pretreatment with

iproniazide (Chen et al. 1959). Phencyclidine also enhances motor

27
activity in rats. Kanner et al. found that pretreatment with alphamethyl-paratyrosine (250 mg/kg, i.p.) decreased phencyclidineelicited activity by 43 percent (p < .05) in one hour. Iproniazid

(100 mg/kg, i.p.) increased phencyclidine-elicited activity by

61 percent. Pretreatment with phenoxybenzamine (10 mg/kg, i.p.)

decreased phencyclidine-elicited activity by 85 percent (p < .05)

while pretreatment with propranolol (25 mg/kg, i.p.) increased

phencyclidine-elicited activity by 56 percent (p < .05). Pimozide

(1 mg/kg, i.p.) decreased phencyclidine-elicited activity by 57

percent (p < .05) while haloperidol (0.5 mg/kg) decreased phencyclidine-elicited activity by 90 percent (p < .05). Trihexyphenidyl (5 mg/kg, i.p.) and atropine (10 mg/kg, i.p.) significantly increased phencyclidine-elicited activity by 93 percent

and 43 percent, respectively, while arewline (10 mg/kg, i.p.) and

physostigmine (0.4 mg/kg, i.p.) decreased phencyclidine-elicited

activity by 23 percent and 61 percent, respectively. Their data

indicate that the stimulation of locmotor activity produced by

phencyclidine can be influenced by noradrenergic, dopaminergic,

and cholinergic inputs. The major criticism of this kind of research is that most agonists and antagonists are known to alter

rat locomotor activity. Hence, interpretation of such findings

is must difficult and probably not very rewarding fran a therapeutic point of view.

Perhaps the most important behavioral study that must be done is

to answer the question, why do animals and people take these drugs?

Why is it reinforcing to mimic the primary symptoms of schizophrenia,

to be in coma, convulse, and maybe die from overdosage? I cannot

imagine that being a "parsley monster" or being "crystalized" is

really very wonderful.

BIOTRANSF0RMATION AND PHARMACOLOGICAL ACTIVITY OF METABOLITES

The biotransformation of phencyclidine is just beginning to be

understood. Some of the proposed matabolites of phencyclidine

are shown in figure 3 below.

FIGURE 3

Some Metabolites of Phencyclidine

28
Lin et al. (1975) have described some of the metabolities of phencyclidine they found in urine of intoxicated human patients. Two

conjugated hydroxylated compounds were found. These were 1-(1-

phenyl-4-hydroxycyclohexyl)-piperidine (4-OH cyclo PCP) and 1-(1-

phencyl-cyclohexyl)-4-hydroxylpiperidine (4-OH pip PCP). In addition, a dihydroxylated metabolite tentatively identified as 1-(1-

phencyl-4-hydroxy-cyclohexyl)-4-hydroxy piperidine has been found

in monkey urine. Wong and Biemann (1975) have reported that 1-

phenycyclohexylamine is also a metabolite of phencyclidine in man

and mouse. The findings of Lin et al. are in partial agreement

with those of Ober et al. (1963), who reported that monkeys excrete mainly the dihydroxy metabolite. In their preliminary report, they stated that the dihydroxy metabolite did not have any

phencyclidine activity. Our own studies (Domino 1978) indicate

that both 4-OH cyclo PCP and 4-OH pip PCP have biologic activity

in both the rat and dog. one would expect the hydroxylated derivatives of phencyclidine to be more water soluble and to penetrate the blood-brain barrier less. Although these compounds

are less potent than phencyclidine, they apparently cross the

blood-brain barrier in sufficient amounts, for they have important

convulsant components. Hence they may play a role in phencyclidine

overdosage in man. Much more work is obviously needed to determine not only the detailed biotransformation of phencyclidine but

also the pharmacological properties of its metabolites.

The biotransformation of ketamine is also imcompetely understood.

The scheme proposed by Chang and Glazko (1974) is given in figure

4 .

FIGURE 4

Biotransformation Pathway of Ketamine, proposed by Chang and Glazko

1974

29
Our own proposed scheme is based on that of Chang and Glazko (1974)

but introduces a further order of complexity, as shown in figure

5 .

FIGURE 5

One should realize how meager is our knowledge of the pharmacology

of each of these proposed metabolites. In most cases, they need

to be synthesized and studied further.

CHEMICAL ANALYSIS

Phencyclidine has been analyzed chemically from biological samples

using both qualitative and quantitative techniques. Thin layer

chromatography, gas chromatography, and gas chromatography-mass

spectrometry and radioimmunoassays have been used. Hawks and

Willette (1977) briefly reviewed these methods with the exception

of the radioimmunoassay procedure developed by Kalir et al. (1976).

The latter seems very pranising but unfortunately, has not attracted any interest in the United States to date.

30
From a practical point of view, the most available quantitative

procedures in the United States at this time involve gas chromatography using a flame ionization detector or combined gas chromatography-mass spectrometry using either electron impact or chemical

ionization. Reynolds (1976) and Marshman, Ramsay, and Sellers

(1976) have employed gas chromatographic techniques for the

quantitative assay of phencyclidine from urine, tissues, and

plasma. Reynolds used ether extraction of the urine with OV-1

and OV-17 GLG columns at a temperature of 180°C. The tissue

and blood samples were prepared with 0.5 N HCl. Mepivicaine was

used as the internal standard. After strong alkalization, phencyclidine was extracted with chloroform and assayed as above.

Marshman, Ramsay, and Sellers used a similar assay except that

ketamine was the internal standard. In addition, 3.8 percent

UCW-98 on Gas Chrom Q at a temperature of 200° C was used. Gupta

et al. (1975) used methadone as the internal standard for phencyclidine in human urine using Chromasorb W coated with Apiezon

L at 200°C. Finkle's gas chromatographic method (quoted by

Hawks and Willette 1977) uses SKF 525A as the internal standard

using a 3 percent OV-1 or OV-17 with a column temperature of 130-

270°C. It should be noted that these investigators all used

column and/or injection port temperatures of 200°C or above. We

know now that phencyclidine undergoes thermal decomposition to 1-

phenylcyclohexene at temperatures above 150oC (Lin et al. 1975;

Wong and Biemann 1975, 1976). These investigators recommend temperatures below 200°C for quantitative purposes.

Obviously, the most specific assays involve the use of gas chromatographic-mass spectrometric methods using a stable isotope as

the internal standard (MacLeod, Green and Seet 1976; Pearce 1976;

Lin et al. 1977). We have modified the gas chromatographic-mass

spectrometric chemical ionization assay of Lin et al. (1975) for

electron impact (Wilson and Domino 1978). Phencyclidine was determined by gas chromatography-mass fragmentography in six dogs

and seven monkeys. Aliquots of venous blood were taken over 4

hours in the monkey after 1.1mg/kg and over 24 hours in the dog

after 1.0 mg/kg of phencyclidine, i.v. Pentadeuterated phencyclidine was used as the internal standard. In the electron impact

mode the most abundant fragments in the mass spectrum of phencyclidine were m/e 91 and 200, and. 96 and 205 in the deuterated

phencyclidine spectrum. These fragments were used to quantify

the amount of phencyclidine present. In both species, a complex

exponential decline of plasma phencyclidine was found in sane

animals that fit a two or three compartment open model. In monkeys,

the mean biological half life (B phase) was 2.03 hours and in the

dog it was 2.1 hours. Compared to the monkey, the dog exhibited

considerable emergence delirium. The two species had rather different pharmacokinetics, which may be relevant to the observed

differences in degree of anesthesia and recovery.

After our initial analytic successes with phencyclidine, we subsequently developed a highly sensitive and specific method for

quantitation of ketamine and two of its metabolites in dog, monkey and human plasma using gas chromatography-mass spectrometry

31
operated in both electron impact and chemical ionization modes.

CL-394, the bromo analog of ketamine, was used as the internal

standard. We compared these two assays with the gas chromatographic, electron capture assay of Chang and Glazko (1972). Cur

results were in complete agreement. However, when dealing with

a limited amount of sample, the mass fragmentography assay was

superior. We concluded that the use of gas chromatography, electron capture for routine plasma analyses was adequate for ketamine

and barely satisfactory for ketamine metabolite I. However, for

ketamine metabolite II mass fragmentography was essential for the

small amounts in plasma. For urine analyses, gas chromatography,

electron capture is quite satisfactory and we recommend it for

routine assays (Lau and Domino 1977).

THERAPEUTIC CONSIDERATIONS OF PHENCYCLIDINE OVERDOSE

In our earlier studies in animals (Domino 1964), it was apparent

that the behavioral effects of phencyclidine were potentiated by

chlorpranazine. Although some of the cardiovascular effects were

antagonized by chlorpromazine, others were not. Hence, chlorpromazine was certainly not useful in treating phencyclidine overdosage in man, at least not during the state of acute intoxication. Our subsequent studies in rat and dog (Domino 1978) indicated that diphenhydramine, droperidol, diazepam, tetrahydroaminoacridine (a cholinesterase inhibitor like physostigmine),

physostigmine and scopolamine were not very useful antagonists.

The status of naloxone as an antagonist is confusing at the moment,

for it recently has been shown to antagonize the locomotor stimulant effects of both nitrous oxide and ketamine in mice (Hynes

and Berkowitz 1978) as well as to potentiate the hypersensitivity

effects of phencyclidine on electroshock in rats (Markowitz and

Komestsky 1978).

At present we have no specific antidotes to phencyclidine. Obviously much more needs to be done in this area.

Our development of a quantitative gas chromatographic-mass spectrometric assay for both phencyclidine and ketamine led to some

very interesting clinical studies. The first relates to phencyclidine. A number of years ago one of my graduate students,

Lindsay Hough, and my Research Associate, Ann Wilson, decided

to measure the pKa of phencyclidine at room temperature. I t

turned out to have a pKa of about 8.5. We really need sameone to

measure again the pKa of this and related compounds. Verbal communications to me of the pKa of phencyclidine have varied from

8.5 to 9.5.

As shown in figure 6 below, the degree of ionization of this compound varies as a function of its pKa and pH.

Pharmacologists for years have stressed the importance of urinary

pH as a functionof the amount of an ionized drug excreted. The

ionized form of a chemical does not readily cross the kidney

tubules unless there is a specific transport system for it. Hence,

32
basic drugs are ionized in an acid medium and acidic drugs in an

alkaline medium. The urinary excretion of basic substances such

as nicotine and amphetamines is enhanced in an acid urine and

that of acidic drugs such as the barbiturates in an alkaline

medium. Although urinary acidification is not the treatment of

choice for nicotine or amphetamine poisoning, there is no doubt

that this technique is of value, especially in amphetamine overdosage. Hence, this technique should work for phencyclidine.

Our task was to prove it with our new phencyclidine assay. Urinary

samples fran phencyclidine overdosage cases were obtained from

both our own University Hospital in Ann Arbor and from Children's

Hospital in Detroit. An account of our experience with the first

cases from University Hospital was recently published (Domino

and Wilson 1977) and that from Children's Hospital (Done et al.

1977; Aronow and Done 1978; Aronow, Miceli, and Done 1978; Done,

Aronow, and Miceli 1978). There is no doubt that acidification

of the urine results in enhanced phencyclidine levels, as shown

in table 1 for one of our patients from the University Hospital.

FIGURE 6

Percent Ionization of Phencyclidine at Room Temperature

as a Function of pH

35
TABLE 1

EFFECTS OF pH ON HOURLY URINARY EXCRETION OF PHENCYCLIDINE IN

A COMATOSE PATIENT

Urinary pH Range pH PCP Urine Volume Total PCP

μg/ml ml/hr Excretion

in μg/hr

5.0-5.9 5.3

5.8

5.6

5.7

5.3

5.4

5.5

5.7

Mean 5.5

± SE ±.1

6.0-6.9 6.4

6.4

6.5

6.0

6.5

6.0

6.0

6.0

Mean 6.2

± SE +.1

P Value <.001

7.0-7.9 7.5

7.5

7.2

7.3

7.5

7.9

7.9

7.6

Mean 7.5

± SE ±.1

P Value <.001

4.348

.558

.812

.799

.750

.767

.910

.426

1.171

±.457

300

520

280

320

350

650

450

450

415

+45

2.089 160

.863 40

.151 1200

.223 700

.167 550

.189 700

.255 450

.302 675

.503 559

±.237 ±127

N S NS

.026

.OlO

.032

.036

.078

.036

.034

.102

.044

±.011

<.03

65

60

150

930

570

330

30

670

351

±119

NS

1304.4

290.2

227.4

255.7

262.5

498.6

409.5

191.7

430.0

+129.9

334.2

34.5

181.2

156.1

91.8

132.3

114.8

203.8

156.1

± 31.6

<.06

1.7

0.6

4.8

33.5

44.5

11.9

1.0

68.3

20.8

± 8.9

<.01

Group comparison "t" test of each set of urine values to the most

acid urine (pH 5.0-5.9).

34
The patient was comatose for a period of time and had a great

deal of i.v. fluids pushed in order to promote diuresis. In addition, furosemide was periodically given, which accounts for

the occasional very large urine volumes obtained for the one

hour intervals. All samples were compared to the most acid urine

with a pH 5.0 to 5.9. It is abundantly clear that under acidic

urine conditions more free phencyclidine is excreted. Inaperiod

of 65 hours this patient excreted into the urine 9.46 mg of a

total of 500 mg or 1.9 percent of the phencyclidine ingested.

This suggests that the majority of this drug may be biotransformed

rather than excreted as the free base. Obviously careful quantitative studies must be done in the future.

Aronow and Done believe that urinary acidification is a most

effective therapy of phencyclidine overdosage. There are many

ways to acidify human urine including ammonium chloride, ascorbic

acid, and very dilute i.v. infusion of hydrochloric acid. What

seems crucial is that the pH be at least 3 units away from the

pKa of phencyclidine to achieve 99.9 percent ionization, which

mans a urinary pH of 5.5 or less. This may be difficult to

achieve in some patients, which is why we had to resort to i.v.

techniques to acidify rapidly. Another very important fact is

that the marked skeletal muscle movements that occur during phencyclidine overdosage in man can lead to profound increases in

serum creatinine phosphokinase and myoglobin in the urine. Meltzer,

Nankin, and Raftery (1971) reported that acute schizophrenic patients showed an increase in serum creatinine phosphokinase. This

is the isoenzyme of skeletal muscle. Phencyclidine in a biphasic

dose relationship markedly enhanced serum creatinine phosphokinase

increases produced by restraint stress in rats (Meltzer 1972).

Similar elevations in serum creatinine phosphokinase have been

observed by us in documented phencyclidine poisonings that have

been accompanied by acute rhabdomyolysis (Cogen et al. 1978). We

believe the skeletal muscle injury to be the result of excessive

involuntary isometric activity rather than a direct effect of

of phencyclidine on skeletal muscle. Our reasoning is that patients who do not have excessive skeletal muscle contractions but

still have toxic levels of plasma phencyclidine have much less

elevation of their serum creatinine phosphokinase. Skeletal

muscle restraints should not be used in patients with phencyclidine

overdosage unless the patients are very severe threats to themselves or others. This impression is supported by the study of

Goode et al. (1977) that limb restraint markedly elevates serum

creatinine phosphokinase and related muscle enzymes in normal

volunteers. It is our crude and preliminary impression that

acidification of the urine may reduce excessive muscular tonus

in phencyclidine overdosage, but this needs to be verified expermentally. What urinary acidification, which is now widely being used, does to the pharmacological actions of phencyclidine

and its metabolism is unknown.

Diazepam reduces some of the unwanted cardiovascular and emergence phenomena of ketamine when given as a pretreatment (Zsigmond,

Kelsch and Kothary 1976; Kothary and Zsigmond 1976). We have some

35
unpublished observations that diazepam may elevate the plasma

levels of ketanine in man. Borondy and Glazko (1977) reported

that diazepam interferes with the biotransformation of ketamine

in the rat. Our dog studies with diazepam (Domino 1978) indicate

that it reduced the convulsions but may have enhanced the central

nervous system depression. Hence, unless convulsions are uncontrollable, diazepam would not seem to be indicated in phencyclidine

overdosage.

Until a specific antidote for phencyclidine found, those of

us dealing with overdose cases will have to be satisfied with

symptomatic therapy and urine acidification. However,having

helped in the birth and delivery of this drug, I will not rest

until that specific antagonist is found.

36
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Excerpta Medica International Congress, Series No. 387, The

Sixth World Congress of Anesthesiology, April, 1976.

AUTHOR

Edward F. Domino, Department of Pharmacology, University of

Michigan, Ann Arbor, Michigan 48109, and Lafayette Clinic,

Detroit, Michigan 48207.

43
Chapter 3

Neurochemical Pharmacology of

Phencyclidine

Kenneth M. Johnson, Ph.D.

INTRODUCTION

Phencyclidine (PCP) is an unusual CNS active drug with general anesthetic, psychomotor stimulant, sedative-hypnotic, hallucinatory, and

local anesthetic properties. Although PCP is often classed as an

hallucinogen, it does not produce the type of visual hallucination

associated with the use of LSD or mescaline. Instead, the hallucinogenic activity of PCP is manifested primarily by body image and proprioceptive disturbances often accompanied by thought disorders and

changes in affect. The differences between the effects of PCP and

LSD are responsible for the classification of PCP as a schizophrenimimetic agent.

Although PCP itself is being abused with increasing frequency, its

primary place in the illicit drug market is as an adulterant of

other drugs of abuse. In this regard it is the most often encountered drug in analyses of suspect street drug samples. Because of

its prevalence, PCP ranks very high on the list of drugs thought to

be responsible for drug overdoses. Overdoses of PCP are thought to

account for acute psychotic episodes often lasting two or more

weeks. PCP overdose often challenges the diagnostic abilities of

the clinician, who suffers from lack of a rational pharmacological

basis for treatment. Consequently, often the treatment chosen is

to leave the patient alone and let the drug effect wear off, which

can take days to weeks.

The apparent high abuse liability of PCP and its use as an adulterant of other illicit drugs make it imperative that the scientific

community be aware of the effects of acute and chronic administration of PCP as well as the mechanism(s) of action underlying these

effects. Most of the known effects PCP administration are apparently mediated through action the CNS. since there is an excellent review of the neurobiological effects of PCP (Domino 1964),

the primary purpose of this paper is to review the results of previous studies which have measured the effects of PCP administration

on various neurochemical indices of brain function. Deficits in

either methodology or experimental design in these studies will also

44
be pointed out. In addition, those areas in which there is no information currently available will be identified.

EFFECTS OF PCP ON BRAIN NEUROTRANSMITTER SYSTEMS

Many, if not all, psychoactive drugs are believed to exert their

effects by modifying the transmission of neuronal impulses from one

neuron to another. Many neuronal systems have been identified in

the CNS which probably use small chemical molecules as mediators of

neuronal impulse transmission. Alterations in the concentration,

synthesis rate, storage, release, binding, metabolism, and reuptake

Of these neurotransmitters after drug administration have been correlated with alterations in the functioning of various neuronal systems. Information regarding the effects of PCP on these neurochemical indices of neuronal function in animals could be important

in understanding the mechanism of action of this drug, as well as

providing a rationale for treatment of the serious effects often

associated with PCP use by humans.

Effects of PCP on Brain Serotonin (5-hydroxytryptamine)

In 1969 Tonge and Leonard compared the effects of PCP, ditran, mescaline, and LSD. At behaviorally effective doses (10 mg/kg, i.p. for

PCP) all four hallucinogens elevated serotonin (5-HT) and depressed

5-hydroxyindoleacetic acid (5-HIAA) concentrations in the whole

brain of rats. Brain 5-HT concentrations were highest 10 min. after

PCP administration and remained elevated throughout the course of

the experiment (3 hours). grain 5-HIAA levels were significantly

lower than controls 20 and 40 minutes after PCP administration, but

were higher than controls 100 and 180 minutes following PCP. It is

possible, then that PCP caused a decrease and then a compensatory

increase in 5-HT turnover. The method used in this study for

assessing turnover prevented the assessment of this possibility. In

this study turnover was assessed by following the decline of brain

5-HT after inhibiting its synthesis with p-chlorophenylalanine (PCPA).

Control rats were injected with PCPA at time zero and sacrificied

either immediately or nine hours later. Experimental animals also

received PCP at time zero and were injected with PCP 0, 3, and 6

hours after PCPA and were sacrificed 9 hours after PCPA. The data

thus obtained were used to support the hypothesis that PCP reduced

theturnoverof 5-HT. Although this may indeed be the case, it is

difficult to conclude this fran data collected at two time points.

These investigators also observed that PCP had no effect upon two

enzymes involved in the synthesis (aromatic amino acid decarboxylase)

and metabolism(monoamine oxidase) of 5-HT. I am unaware of any

studies which have assessed either the effect of PCP on 5-HT turnover directly (without disturbing the steady-state) or of any which

measured the effect of PCP on the first enzyme involved in the biosynthesis of 5-HT, tryptophan hydroxylase. These studies clearly

need to be done in order to clarify the effects of PCP on serotonergic systems.

It is now fairly well established that brain 5-HT synthesis is

dependent upon tryptophan availability since tryptophan hydroxylase

is apparently not saturated with substrate (Eccleston et al. 1965).

45
In this regard, PCP has been shown to reduce the concentration of

both plasma and brain tryptophan about 20 percent (Tonge and Leonard

1970). If 5-HT. synthesis is indeed dependent on brain tryptophan,

then 5-HT levels would be decreased rather than increased as these

investigators previously indicated (Tonge and Leonard 1969). It is

possible, however, that PCP may actually increase the pool of free

tryptophan in plasma (i.e., not bound to plasma albumin) available

for transport into the brain by competing with tryptophan for

albumin binding sites, as other drugs have been shown to do (Gessa

and Tagliamonte 1974). This possibility has not been addressed.

In another study, Tonge and Leonard (1972) showed that PCP administration to rats at a dose (10 mg/kg) comparable to that used in their

1969 study, produced the opposite effects on 5-HT and 5-HIAA, i.e.,

5-HT levels were reduced and 5-HIAA levels were elevated. To further

confuse the issue, Tonge (1971) reported that PCP produced the

opposite effect on 5-HT and 5-HIAA on populations of Wistar rats

obtained from different sources. Using the 5-HIAA/5-HT ratio as

an index of serotonergic activity, PCP decreases the turnover of

5-HT in the substrain with the higher 5-HIAA/5HT ratio while

increasing the 5-HT turnover in the strain with the lower 5-HIAA/

5-HT ratio. Because of the suggestive nature of the foregoing

studies with PCP and the proposed role of 5-HT in emotional and

psychotic behavior, it is felt that a detailed biochemical study of

the effects of PCP on serotonergic function is warranted. It should

be noted here that ketamine (a structural analog of PCP) produced

either no effect or a slight increase in rat brain 5-HT levels,

depending upon the dose administered (Sung et al. 1973). These

authors showed a significant decrease in 5-HT turnover, as determined by the method of following the rate of increase in 5-HT after

inhibition of its metabolism with pargyline.

Effects of PCP on Brain Catecholamines

Tyrosine, a precursor for both dopamine (DA) and norepinephrine (NE)

synthesis, has been proposed to exert some regulatory influence on

the synthesis of catecholamines (Wurtman et al. 1974). Tonge and

Leonard (1970) have shown that rat brain tyrosine levels were elevated 30 to 40 percent after the administration of PCP. Plasma

tyrosine levels, however, were little affected.

In an experimental design which employed the conversion of 14C-tyrosine into 14C-catecholamine, Hitzeman et al. (1973) reported that

PCP resulted in significant decreases in the amount of 14C-DA and

14C-NE synthesized, whereas the accumulation of the O-methylated

metabolites of DA and NE (

14C-3-methoxytryamine and 14C-normethanephrine, respectively) appeared to be increased over control. However, when 14C-DOPA was used as the precursor, no effect of PCP was

observed. It was then concluded that PCP probably acts at the level

of tyrosine hydroxylase (the enzyme which converts tyrosine to DOPA).

Unfortunately, these authors neglected to measure the specific activity of tyrosine. dopamine and norepinephrine. In light of the

report by Tonge and Leonard that PCP elevates brain tyrosine, it is

entirely possible that these results are the artifactual consequence

of a diluted precursor specific activity, rather than an actual

decrease in synthesis. The increase in accumulation of the O-methylated metabolites observed suggest that PCP either increases the

46
release or decreases the reuptake of the catecholamines from the

extraneuronal space, However, it should be noted that the presumed

extreneuronal localization of catechol-O-methyltransferase is presently under dispute.

In a study similar to their study of the effects of PCP on serotonin,

Leonard and Tonge (1969) described the effects of PCP on DA and NE.

They report that 10 mg/kg PCP produced a substantial decrease in

whole brain NE concentration, no charge in normethanephrine, and a

slight increase in DA levels. Whereas previously it was demonstrated

that PCP protected against reserpine-induced serotonin depletion,

in this study PCP was found to potentiate the reserpine-induced

depletion of NE. PCP was found to have no effect on the turnover

of NE as estimated by inhibiting its synthesis with -methyl-ptyrosine ( -MPT) and measuring NE levels at 0 and 3 hours after -

MPT. As was the case with the studies of the effects of PCP on

serotonin neurochemistry, the ones on catecholamine neurochemistry

suggest that a more rigorous approach would yield less ambiguous

data and allow a more meaningful interpretation of the effects of

PCP on catecholamine function.

In spite of the studies just discussed which suggest that PCP my

have little or no effect on DA or NE function, there are several

studies which suggest there may be profound effects of PCP on both

of these systems. Taube et al. (1975) reported that PCP inhibited

the uptake of 3H-NE by rat cortical slices by 50 percent at 5 x 10-6

M. Interestingly, ketamine was about 100 times less potent. This

effect of PCP on NE uptake was verified by Garvey and Heath (1976)

who used a synaptosomal preparation. These workers demonstrated

that PCP is a competitive inhibitor of both 3H-NE uptake by hypothalamic synaptosomes (Ki = 4.7 x 10-7M) and of 3H-DA uptake by

striatal synaptosomes (KI = 4 x 10-7M). Very recently these observations were verified and the list of putative neurotransmitters

whose synaptosomal uptake is competitively inhibited by PCP was

extended to include serotonin (Smith et al. 1977). Ketamine has

been shown to be a much weaker competitive inhibitor of synaptosomal

uptake of 3H-NE (Smith et al. 1975).

Another interesting study which suggests the involvement of DA in

the action of PCP utilized the turning behavior of rats after unilateral electrolytic lesions of the substantia nigra (Finnegan,

Kanner, and Meltzer 1976). These authors found that PCP produced a

dose-related increase (maximal at 10 mg/kg) in ipsilateral rotation.

This effect was attenuated by -MPT and haloperidol (a DA antagonist),

thereby suggesting that this action of PCP is mediated by DA. Unfortunately, in contrast to turning behavior after unilateral 6-

hydroxydopamine lesions, this model apparently does not distinguish

between presynaptic and postsynaptic drug actions (Costall and

Naylor 1971). A cholinergic component of this action of PCP was

also identified by the observation that the ipsilateral turning was

blocked by the cholinomimetic drug arecoline and was slightly potentiated by the anticholinergic agent trihexyphenidyl. There is considerable evidence that turning behavior (as well as other functions

mediated by the striatum) is regulated by a reciprocal relationship

between dopaminergic neurons and cholinergic neurons. For example,

4 7
both direct and indirect dopaminergic agents and anticholinergic

agents can induce ipsilateral rotation in this model. Thus PCP may

induce rotational behavior by potentiating dopaminergic transmission,

by blocking cholinergic transmission, or both.

Effects of PCP on Acetylcholine (ACh)

There has bee-n surprisingly little work done on the effects of PCP

on central cholinergic systems, despite the ample evidence obtained

in vitro that PCP both antagonizes the ACh receptor and has potent

antiacetylcholinesterase activity. One research group from Israel

has presented both theoretical and experimental evidence that PCP

and ACh have a very similar electrostatic charge distribution pattern

when they are considered in the vicinity of the muscarinic receptor

(Weinstein et al. 1973; Paster et al. 1974; Maayani et al. 1974).

PCP, however, appears to be an antagonist of ACh in the isolated

frog rectus abdominis and guinea pig ileum preparations, rather than

an agonist. This group has proposed theoretical considerations to

account for the antagonistic activity based upon the cyclohexyl

ring-induced rigidity of the molecule. Maayani et al. (1974) also

demonstrated that PCP competitively inhibits butyrylcholinesterase

(Ki = 1 x 10-6M) and acetylcholinesterase (Ki = 80 x 10-6M). The

ACh antagonist and anticholinesterase activities would, of course,

tend to offset each other. The overall activity of PCP tends to be

anticholinergic, however, as evidenced by the observation that PCPinduced anesthesia in the guinea pig and hyperactivity in the muse

were both significantly antagonized by tacrine, a potent anticholinesterase (Maayani et al. 1974). Recently this group of investigators reported that scopolamine blocked the development of tolerance

in mice to the effects of cyclohexamine, a structural analog of PCP

(Pinchasi et al. 1977). In contrast, ketamine was shown to produce

a relatively weak reversible mix inhibition of acetylcholinesterase

from beef caudate (Ki = 500 x 10-6M) (Cohen et al. 1974). It is

unclear whether or not this concentration is physiologically significant since the slight (25 percent) increase in whole brain ACh

levels observed by these authors was found to last less than ten

minutes. In a study utilizing a cholinergic antisynthesis agent

(hemicholinium-3), Domino and Wilson (1972) reported that PCP (10

mg/kg) slightly increases the turnover of ACh but is without effect

on the whole brain levels of ACh. Leonard and Tonge (1970) also

observed no effect of PCP on whole brain levels. These authors also

failed to observe any change in brain cholinesterase activity following the administration of PCP (10 mg/kg).

It is now evident that the synthesis of ACh is dependent upon the

high-affinity, sodium-dependent uptake of choline (Yamamura and

Snyder 1973; Haga and Noda 1973). An altered choline uptake could

conceivably play a role in the cholinergic effect of PCP. To my

knowledge no one has studied the effects of PCP on this system.

Effects of PCP on Other Biochemical Parameters

Tonge and Leonard (1970) found that PCP (10 mg/kg) resulted in no

change of whole brain levels of histamine or glutamic acid. However,

they did detect a decrease in whole brain concentration of -aminobutyric acid (GABA) which persisted for two hours after PCP injection.

48
They observed no effect on GABA after 3 mg/kg of PCP. Interestingly,

ketamine has been demonstrated to competitively inhibit glutamate

decarboxylase in vitro, but to produce no change in either brain

glutamate or GABA levels when administered in vivo (Dye and Taberner

1975).

There are several other studies documenting effects of PCP on ketamine on a wide variety of biochemical parameters which may be relevant to this review. I will briefly describe two of them. Some

studies have previously demonstrated that subgroups of psychotic

patients of all diagnostic types exhibit increased serum levels of

type III (skeletal muscle) isoenzyme of creatinine phosphokinase

(Meltzer et al. 1971). Interestingly, phencyclidine, in a biphasic

dose-response fashion, significantly enhanced the increase in serum

creatinine phosphokinase levels produced by restraint stress (Meltzer

1972). The magnitude of this effect was rather dramatic in male

Sprague-Dawley rats, but not at all evident in guinea pigs. The significance of these studies is uncertain, but at the very least they

emphasize that the effects of PCP varies markedly between species.

Anesthetic doses of ketamine have been demonstrated to elicit an

increase in rat plasma corticosterone levels similar to that produced by a pharmacological dose of ACTH (Fahringer et al. 1974).

This response to ketamine was blocked by hypophysectomy and administration of dexamethasone, and partially blocked by propranolol and

haloperidol, but not by atropine or phentolamine. Aside from supporting the notion that this response may be mediated by ß-adrenergic

or dopaminergic systems, it brings up the possibility that PCP may

also elicit a similar corticosterone response. In light of the

observation that tryptophan hydroxylase activity can be increased

by corticosterone treatment (Azmitia and McEwen 1969), it is possible

that some of the effects of PCP on the serotonergic system may be

mediated by this pituitary-adrenal response.

SUMMARY

In view of the diverse pharmacological spectrum of PCP, it is unlikely

that the effects of PCP are caused by an alteration in the function

of a single neurotramsmitter. Previous studies have suggested that

the central biogenic amines, 5-HT, DA and NE, as well as ACh and

GABA may be involved either directly or indirectly with the mechanism(s) underlying the behavioral effects of PCP. The information

currently available on the neuropharmacological actions of PCP is

found to be deficient in many respects. In spite of the several

studies which have examined the effects of PCP on neurotransmitter

substances in the brain, relatively little is known in an unambigous

my. Most of those studies used whole brain for analysis of neurotransmitter concentration. Increases, decreases, or no change in

a neurotransmitter concentration for whole brain reveals little or

nothing about the functional aspects of the particular neurotransmitter. Interpretation of many of these studies was made extremely

difficult by the concomitant use of relatively nonspecific drugs

such as tetrabenazine, reserpine, imipramine, etc. Many of these

studies failed to correlate their findings temporally with behavioral

activity and almost all of these studies neglected to establish a

basic dose-response relationship for the observed effect. Further49
more, the effects of chronic administration of PCP, heretofore, have

been totally neglected in regard to neurochemical studies. In summary, these studies have only suggested that 5-HT, DA, NE, ACh, and

GABA may be involved in sane way in the mediation of the behavioral

effects produced by PCP.

As can be seen from the foregoing review of the state of knowledge

on the neurochemical pharmacology of PCP is in its infancy. It is

felt that future research in this area can provide valuable information about the mechanism(s) of action of PCP only if each neurochemical variable is examined as a function of both dose and time

and then correlated with the behavioral effects of the drug. In

addition to measuring the effects of PCP on neurotransmitter concentration in discrete brain areas, future studies should not neglect

to measure the concentration of neurotransmitter precursors and

metabolites. In addition, techniques for determining the turnover

of neurotransmitter pools are available Which do not disturb the

existing steady-state of the neurotransmitter. It is felt that the

proper utilization of such techniques would result in a significant

increase in our understanding of the way this important and interesting drug affects the CNS.

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Costall, B., and Naylor, R.J. Cholinergic and neuroleptic induced

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Domino, E.F. Neurobiology of phencyclidine (sernyl), a drug with an

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Maayani, S., Weinstein, H., Ben-Zui, N., Cohen, S., and Sokolovsky,

M. Psychotomimetics as anticholinergic agents-I: Biochem Pharmacol,

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Meltzer, H.Y. Muscle toxicity produced by phencyclidine and restraint

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AUTHOR

Kenneth M. Johnson, Ph.D.

Department of Pharmacology and Toxicology

University of Texas Medical Branch

Galveston, Texas 77550

52
Chapter 4

The Behavioral Effects of

Phencyclidine in Animals

Robert L. Balster, Ph.D., and Larry D. Chait

INTRODUCTION

Study of the behavioral pharmacology of phencyclidine (PCP) has

accelerated concurrently with the increased public health concerns

associated with its illicit use. Some important aspects of the

pharmacology of this unusual compound have been revealed by this

research, although there remain many more questions than answers.

At the conclusion of this paper we will point out some of the

future directions which behavioral research with PCP might profitably take. Before doing this, we will describe the current status

of knowledge of the behavioral effects of this drug, focusing on

research which has appeared since the two previous reviews of this

area (Domino 1964; Balster and Chait 1976) and on recent research

in our laboratory. Our research has recently been most concerned

with two aspects of the behavioral effects of PCP: tolerance

development and interactions between PCP and other drugs. Before

reporting our results on these two topics, we will briefly summarize some of the important results of prior behavioral work

with this drug.

SPECIES DIFFERENCES IN THE BEHAVIORAL EFFECTS OF PCP

One of the most interesting aspects of the behavioral pharmacology

of PCP is the obvious species differences in its gross behavioral

effects. These differences were noted in the early preclinical

studies of PCP by Chen and his coworkers (1959) and are consistently seen in our laboratory. In rats and mice, PCP produces

behavioral effects qualitatively similar to those of psychomotor

stimulants such as the amphetamines. In rats, for example,

intraperitoneal doses above 3 mg/kg produce increased motor activity, while doses between 5 and 10 mg/kg result in repetitive

movements, including cage circling, side to side head movements,

and repetitive sniffing not unlike the stereotyped behaviors seen

with stimulant administration in this species. These behaviors

differ from the effects of stimulants, however, in that the

animals also are markedly ataxic. A similar constellation of

53
behavioral effects occurs in mice, although mice are, if anything,

more stimulated. At intraperitoneal doses above 3 mg/kg they

race around the cage, and in the range of 10 mg/kg they run off

the edge of any flat surface they are placed on. Convulsions

are not uncommon at doses above 20 mg/kg. In our experience,

there is no dose of PCP which will produce anything resembling

surgical anesthesia in the mouse.

The amphetamine-like properties of PCP in mice have also been

seen in schedule-controlled behavior. Wenger and Dews (1976)

compared the effects of PCP to the effects of d-amphetamine,

pentobarbital and ketamine using a multiple fixed interval fixed

ratio (mult. FI-FR) schedule of food reinforcement. The effects

of PCP were qualitatively more similar to those of d-amphetamine

than pentobarbital in that at some dose both PCP and d-amphetamine

increased FI response rate and decreased FR response rate. Interestingly, the effects of ketamine were also very similar to

PCP and d-amphetamine. A very similar effect of PCP and ketamine

on mult. FI-FR performance has also been reported in the pigeon

(Wenger 1976).

Chen et al. (1959) reported that the effects of PCP were different

in the guinea pig than in the mouse and rat. Only "calming"

effects were seen until cataleptoid or convulsant doses were

reached. We, on the other hand, have seen more typical rodentlike effects of PCP in the guinea pig. Intraperitoneal doses

in the range of 2 to 4 mg/kg result in increased movement in the

normally sedentary guinea pig. At the higher doses repetitive

movements can be seen, and ataxia also occurs. One animal exhibited obstinate progression, a continuation of walking movements after reaching the cage wall. In a pilot study, PCP increased motor activity of guinea pigs in a circular runway apparatus (Kenneth M. Johnson, personal communication) .

In rodents, PCP shares other pharmacological properties with

psychomotor stimulants. Like methamphetamine and cocaine, PCP

increases blood pressure, promotes urination, and decreases

electrically induced tonic extensor seizures (Chen, Ensor, and

Bohner 1965). In short, PCP looks a great deal like a sympathomimetic which produces ataxia when studied. in rodent species.

This similarity of PCP to stimulants led us to suspect that PCP

may enhance the behavioral effects of amphetamine in rats. We

have found this to be the case (Balster and Chait 1978) and will

describe these results in more detail later in this paper.

The gross behavioral effects of PCP in subhuman primates are

substantially different from those we described for rodents. In

the rhesus monkey, for example, intramuscular doses between 0.2

and 0.4 mg/kg produce mild ataxia and a calming effect. Normally

agressive monkeys became easier to handle. Signs of repetitive

or stereotyped behaviors are not seen. At doses above 0.8 mg/kg

the animals are cataleptic. Nystagmus is frequently seen, and

occassionally marked salivation occurs. Although the monkeys are

immobile, they may show exaggerated limb and mouth movements,

54
their eyes remain open and most reflexes remain intact. The

animals, however, are unresponsive to enviromental events. The

sequences of unresponsiveness, gross ataxia, motor restlessness

and nystagus is very similar to the effect of large doses in

humans.

The gross behavioral effects of PCP in squirrel monkeys are

qualitatively similar. Squirrel monkeys, however, are somewhat

more sensitive to the effects of PCP on motor coordination. For

example, an intramuscular dose of 0.2 mg/kg in the rhesus

monkey produces marginal gross behavioral effects. Slight ataxia

is seen but the animals are able to grasp objects between their

fingers and maintain normal posture with little difficulty. In

the squirrel monkey, an even lower dose (0.16 mg/kg/ intramuscularly) producesmarkedincoordination, inability to grasp objects,

and inability to sit on their perch without support. In general

the effects of PCP in monkeys are quite reliable from animal to

animal. We have, however, observed one rhesus monkey who was

quite insensitive to the effects of PCP, always requiring doses

at least three times higher than normal to produce sedation adequate for handling. We are unable to explain this insensitivity,

but it suggests that there are substantial individual differences

to the effects of PCP can occur.

In spite of the differences between the effects of PCP on gross

behavior of rodents and monkeys, its effects on schedule controlled

operant behavior appear qualitatively similar. There has been

no systematic research comparing the effects of PCP on operant

behavior in various species, but some generalizations can be

made based on studies using similar schedules in different laboratories. The most consistent finding so far is that PCP produces

a rate dependent effect on fixed interval performance in mice,

pigeons and squirrel monkeys (Wenger and Dews 1976; Wenger 1976;

Chait and Balster 1978a). Low rates of responding during the

early portions of each interval tend to be increased by PCP,

whereas higher rates during the later portions of each interval

tend to be decreased. During the fixed interval component of

complex schedules in mice, pigeons, and squirrel monkeys, overall

response rate increases can be seen at low doses. These increases are considerably more dramatic in the mouse than in the

pigeon or squirrel monkey, even though average baseline rates

in all three species were comparable (0.56 to 0.74 responses/sec.).

PCP produces only dose related decreases in fixed ratio response

rates in all three species. Although the parameters in these

experiments differed somewhat, rough estimates can be made of

relative potency of PCP for disruption of fixed ratio performance.

These are shown in table 1 along with a comparable value for the

rhesus monkey (Balster and Chait 1976).

55
TABLE 1

DOSES OF PHENCYCLIDINE PRODUCING 50% DECREASES IN FIXED RATIO

RESPONDING IN VARIOUS SPECIES OF LABORATORY ANIMAIS

Species ED 50

Mouse 10.00 mg/kga

Pigeon 0.70 mg/kgb

Squirrel Monkey 0.27 mg/kgc

Rhesus Monkey 0.08 mg/kgd

a. by inspection of dose response curve in Wenger and Dews (1976)

b. by inspection of dose response curve in Wenger (1976)

c. reported in Chait and Balster (19785)

d. by inspection of dose response curve in Balster and Chait (1976)

One interesting point fran this table is the relative sensitivity

of the two species of monkey. Even though the squirrel monkey

appears slightly more sensitive to the effects of FCP on observable behavior, it is about 3 times less sensitive to its disruptive effects on food-reinforced fixed ratio responding. The

significance of this is unclear but it suggests that something

different from nonspecific disruption of gross behavior is responsible for the disruption of operant behavior in one or both

of these species.

STIMULUS PROPERTIES OF PCP

The stimulus properties of PCP were discussed in our earlier review (Balster and Chait 1976) and there has been very little

published on this topic since then. Two studies have demonstrated

that PCP can serve as an effective discriminative stimulus in a

variety of response choice situations (Jarbe, Johansson, and

Henriksson 1975 ; Overton 1975). One of the applications of

drug discrimination studies is that they allow drug groups to be

classified by virtue of similar discriminative effects using

stimulus generalization procedures (Barry 1974; Schuster and

Balster 1977). Drug classifications based on discriminative

stimulus properties generally follow traditional pharmacological

classifications. Stimulus generalization studies with PCP suggest

that phencyclidine and related arylcyclohexylamines belong in a

class by themselves in that they do not transfer stimulus control to morphine, chlorpromazine, ditran, 9-tetrahydrocannabinol

and pentobarbital (Jarbe, Johansson, and Henriksson 1975; Overton

1975). Ketamine appears to be qualitatively similar to PCP, and

another related compound, N-ethyl-phenylcyclohexylamine (PCE),

also transfers stimulus control from PCP. This suggests that

PCE may produce effects similar to PCP and ketamine in humans,

and we have heard reports of confiscation of street samples of

this drug. The classification of arylcyclohexylamines on the

basis of their stimulus properties may be a useful way of providing evidence of potential PCP-like abuse in human populations.

56
Two papers published in 1973 reported that PCP can serve as a

reinforcing stimulus in intravenous drug self-administration

studies in rhesus monkeys (Balster et al. 1973; Pickens, Thompson,

and Muchow 1973). This is particularly interesting in view of

the fact that although most drugs of abuse will serve this function, drugs classified as hallucinogens (Deneau, Yanagita, and

Seevers 1969; Hoffmeister and Wuttke 1975) and 9-tetrahydrocannabinol (Harris, Waters, and McLendon 1974; Camey, Uwaydah,

and Balster 1977) generally do not. This emphasizes the uniqueness of PCP as a "hallucinogen." Recently it has been demonstrated that ketamine is also reliably self-administered by rhesus

monkeys (Moreton et al. 1977). This represents another example

of the similarity between PCP and ketamine in behavioral studies

in animals. A behavioral pharmacological basis for differences

in the abuse liability of these two compounds has yet to be

found.

PCP INTERACTIONS WITH OTHER DRUGS OF ABUSE

It is important to study the effects of PCP in combination with

other drugs of abuse, as multiple drug use is widespread. This

may be a particularly important consideration with PCP since

street samples of PCP are often mixed with other drugs. The use

of PCP concurrent with the use of nicotine, alcohol and marihuana

undoubtedly occurs frequently, the former and latter being more

common because PCP is often administered by adulteration of

smoking materials. PCP combinations with other drugs of abuse

are also likely to occur. The possibility of increased toxicity

associated with these combinations should be thoroughly investigated.

There have been no behavioral studies of the interaction between

PCP and nicotine or alcohol. Such studies are clearly indicated.

Pryor et al. (1977) have completed an extensive series of experiments on the interaction between PCP and 9-tetrahydrocannabinol

(THC) in rats. In general, PCP enhanced the depressant properties

of 9-THC. For example, acute doses of PCP which had little or

no effect when given alone, enhanced the effects of 9-THC (1.25

to 2.5 mg/kg intraperitoneally) on conditioned avoidance responding, photocell activity, heart rate and body temperature.

On the other hand 9-THC antagonized the motor activity increases

produced by a high dose of PCP (5.0 mg/kg).

PCP Interactions with Pentobarbital

We have completed a series of experiments on the interactions

between PCP and sodium pentobarbital (PB). We have used a PCP-PB

canbination for anesthesia with rhesus monkeys for years. The

advantage of this canbination for short surgical procedures is

that the dose of PB necessary to reach a surgical plane of

anesthesia is reduced 2 to 3 fold. As a consequence the animals

recover consciousness in substantially less time than when PB is

given alone at higher doses, reducing the risk of postsurgical

complications. This use of PCP-PB combinations obviously suggests

57
that PCP enhances the depressant effects of PB; therefore we

have sought to examine this interaction in a number of species

using a variety of measures.

The results of study (Chait and Balster 1978b) of the effects of

PCP on PB lethality in mice are presented in table 2.

TABLE 2

EFFECTS OF PHENCYCLIDINE ON PENTOBARBITAL LETHALITY IN MICE

Phencyclidine Pretreatment

Dose (mg/kg i.p.)

LD50a mg/kg i.p.)

of Pentobarbital (±95% C.L.)

0 110 (±23)

80 (±16) 3 b

30 53 (±12)c

a. calculated by the method of Litchfield and Wilcoxon (1949)

b. significantly different from Pentobarbital + Saline (p<.05)

c. significantly different from Pentobarbital + Saline and Pentobarbital + 3.0 mg/kg Phencyclidine (p<.05)

A dose-dependent enhancement of PB toxicity was observed. The

animals appeared to die fran respiratory depression.

We also looked at this interaction in two species of monkeys

(Chait and Balster 1978b). A rating scale was designed which

reflects degrees of CNS depression produced by pentobarbital.

Scale values were: 0- normal movement and posture, l-does not

take offered food pellet, 2- unable to climb or maintain a sitting posture without support, 3- unable to sit, 4- unconscious

with corneal reflex present, 5- unconscious with no corneal reflex, 6- unconscious with no corneal or pain reflexes (surgical

anesthesia). In the squirrel monkey, doses of 0.16 mg/kg PCP

and 12.5 mg/kg PB were studied alone and in combination. In the

rhesus monkey, doses of 0.2 mg/kg PCP and 25 mg/kg PB were studied

alone and in combination. Injections were given simultaneously

intramuscularly. The results are summarized in figure 1.

58
FIGURE 1

Phencyclidine (PCP) -- Pentobarbital (PB) interactions in rhesus

and squirrel monkeys

In the rhesus monkey it can be clearly seen that a dose of PCP

which has very little effect when given alone markedly potentiates

the anesthetic effects of PB. The dose of PB used in this study

when given alone only results in some difficulty maintaining a

sitting position without support, but combined with PCP produces

a surgical level of anesthesia of approximately one hour's duration. The results with squirrel monkeys were quite different.

Although the dose of PCP and of PB used both produced greater

effects in this species when given alone, there was no evidence

of potentiation. This is an interesting and unexpected species

difference that warrants further investigation, particularly in

light of other data we have collected in the squirrel monkey

using schedule controlled behavior in which PCP failed to enhance

the response rate decreasing effects of PB (Chait and Balster,

unpublished data).

In spite of our failure to find evidence for a PCP enhancement of

PB effects in the squirrel monkey, the data from mice and rhesus

monkeys raises the question of potential toxicity which may re59
sult from combined use of these drugs in human populations, On

the basis of the greater phylcgenetic similarity to man of rhesus

monkeys, we would, other factors being equal, place more weight

on this result. Another question we would raise concerns the

specificity of this interaction to PB. Does PCP enhance the

depressant effects of other barbituates, nonbarbituate sedatives,

benzodiazepines, and alcohol as well? Clearly, further research

in this area is indicated.

Phencyclidine Interactions with d-Amphetamine

One benefit of studying drug interactions with PCP is that the

results may provide clues concerning the neurochemical mechanism

of action of PCP. This is the case with PCP and d-amphetamine

interactions. There is some evidence that PCP may possess

dopaminergic activity. PCP has been shown to be a potent competitive inhibitor of dopamine uptake in rat striatum (Smith et

al. 1975; Garey and Heath 1976). It has also ken shown to produce ipsilateral rotation in rats with unilateral lesions in the

substantia nigra, and this effect can be reversed by pretreatment with alpha-methyl-para-tyrosine, haloperidol and pimozide

(Kanner et al. 1975; Finnegan et al. 1976). Ipsilateral rotation

is generally considered to be indicative of an indirect acting

dopamine agonist and is also produced by amphetamines. Since

stereotyped behavior produced by amphetamine (and perhaps the

amphetamine psychosis as well) is generally considered to be a

dopaminergic effect, it might be postulated that PCP would enhance amphetamine sterotypy. We have found this to be the case

with low doses of PCP in the rat (Balster and Chait 1978).

In two separate experiments a 9 point rating scale was used to

study the effects of various doses of PCP on stereotypy produced

by d-amphetamine. PCP at 2.5 mg/kg, which had no effect when

given alone, potentiated the stereotypy produced by 1 and 3 mg/kg

d-amphetamine. Higher doses of PCP produced ataxia and stereotypies when given alone. These higher doses did not enhance the

effects of d-amphetamine. Although these results are preliminary,

they are consistent with the hypothesis that PCP has dopaminergic

activity and suggest that PCP may enhance the behavioral toxicity

associated with stimulant abuse. They may also serve as a starting point in the investigation of commonalities among the model

psychoses elicited by amphetamines (Snyder 1972; Ellinwood and

Kilbey 1978) and PCP (Luby et al. 1959).

TOLERANCE AND DEPENDENCE WITH PCP

There is conflicting evidence on the degree of tolerance develop

ment associated with chronic PCP administration. There is some

evidence from the veterinary use of PCP that the duration of

anesthesia decreases with repeated use (Martin et al. 1972). We

have reported a preliminary study of tolerance development in

rhesus monkeys (Balster and Chait 1976). PCP was given daily,

seven days a week, over a period of four months at doses beginning

at 0.2 mg/kg/day increasing to 1 mg/kg/day. Dose effect curves

60
for PCP effects on food reinforced operant behavior were obtained

before and after this chronic regimen. In two of the three monkeys a greater than 4-fold shift in dose effect curve was obtained;

in the third monkey, however, there was less evidence for tolerance development. In addition, the duration of observable motor

disruption in these three animals after chronic PCP administration

was shorter than in untreated monkeys. These same monkeys were

observed carefully for signs of withdrawal after discontinuation

of PCP. There was no clear evidence of any withdrawal symptomatology.

A more systematic study of the behavioral effects of chronic

PCP administration has recently been completed in squirrel monkeys (Chait and Balster 1978a). In this study five squirrel

monkeys were given chronic PCP at doses beginning at 0.2 mg/kg

once a day increasing to 0.6 mg/kg four times a day (2.4 mg/kg/

day) over a period lasting from 82 to 126 days. The regimens of

PCP doses more individualized for each subject to maximize tolerance development. Pre- and post- chronic dose effect curves for

the effects of PCP on operant behavior revealed approximately a

two-fold tolerance development. The most dramatic indication of

tolerance was in the duration of PCP-suppressed responding following a dose of 0.6 mg/kg given before and after chronic dosing.

At this dose operant behavior was suppressed for an average of

125 minutes before chronic PCP and only 35 minutes after chronic

PCP.

As in the study with rhesus monkeys, there was no evidence for

disruption of operant behavior after the discontinuation of PCP

administration which might indicate a withdrawal syndrome. We

had a subjective impression that four of the five subjects demonstrated unusually high excitability and apparent fearfulness

(biting, screaming, etc. with handling) during the first or,

more commonly, the second day of the withdrawal period, although

no systematic attempt was made to quantitate these observations.

No changes in body weight or food intake occurred during withdrawal.

On the basis of our studies of chronic PCP administration in two

species of monkeys the following conclusions can be drawn. Tolerance can develop to the behavioral effects of PCP: this tolerance

is most easily observed as a shortened duration of effect. Tolerance development appears to be in the range of 2 to 4 fold. We

have been unsuccessful in pushing the extent of tolerance further.

It is important to keep in mind that the chronic regimens we

used were designed to maximize tolerance development and would

probably represent the upper limits of human abuse pattern. Consequently the degree of tolerance to be expected with less vigorous

dosage conditions remains to be seen. At this point we also do

not know the mechanism for this tolerance. Pharmacokinetic,

pharmacodynamic and behavioral factors may all play a role. Experiments designed to assess the relative contribution of each

of these mechanisms are indicated.

61
A second conclusion to be drawn from our research is the lack of

evidence for development of physical dependence. Clear behavioral

or autonomic signs of withdrawal comparable to those seen with

chronic administration of opioids, barbituates or alcohol have

not been observed. Sane suggestion of irritability was observed

in the squirrel monkey, however. Systematic studies of potential

physical dependence development in various species would be useful

in clearly establishing the role dependence may play in chronic

PCP abuse.

SUMMARY AND CONCLUSIONS

We have reviewed the current status of our knowledge of the behavioral effects of PCP in subhuman species and have pointed to

some areas where more information is most critical. The following tentative conclusions can be drawn: (1) There are marked

species differences in the effects of PCP on grossly observable

behavior. Various species of rodents show a pattern of response

to PCP which is most similar to that of psychomotor stimulants,

suggesting that catecholaminergic effects may predominate in

these species. The effects in subhuman primates appear to be

more "depressant" and qualitatively more like effects in humans,

although differences also exist in the response of rhesus monkeys

and squirrel monkeys to this drug. In spite of species differences in gross behaviors, the effects of PCP on operant behavior

have not been shown to differ qualitatively in different species;

however, very little research has been completed that bears upon

this. (2) PCP represents a unique class of psychopharmacolcgical

agents. The discriminative stimulus properties of PCP do not

generalize to drugs fran other pharmacological classes and, unlike other hallucinogens, PCP is self-administered by rhesus

monkeys. Studies of the discriminative and reinforcing properties

of analogues of PCP in experimental animals may be a useful way

of evaluating their dependence liability. (3) PCP has been

shown to interact with 9-THC, pentobarbital and d-amphetamine.

It enhances the depressant effects of 9-THC, the anesthetic

effects of pentobarbital and the behavioral toxicity associated

with d-amphetamine administration. (4) With frequent high dose

chronic administration 2- to 4-fold tolerance can develop to some

of the behavioral effects of PCP, particularly resulting in a

shortened duration of action. (5) Preliminary data suggest that

PCP does not produce physical dependence comparable to that of

opioids or CNS depressants.

62
ACKNOWLEDGMENT

The research described in this paper was supported by N. I. D. A.

Research Grant DA-01442. Larry D. Chait is a predoctoral fellow

supported by N. I. D. A. Training Grant DA-07027.

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of phencyclidine. Clin Toxic, 9(4):513-528, 1976.

Balster, R. L., and Chait, L. D. The effects of phencyclidine on

amphetamine sterotype in the rat. Eur J Pharmacol, in press,

1978.

Balster, R. L., Johanson, C. E., Harris, R. T., and Schuster,

C. R. Phencyclidine self-administration in the rhesus monkey.

Pharm Biochem Behav, 1:167-172, 1973.

Barry, H. III. Classification of drugs according to their discriminable effects in rats. Federation Proc, 33:1814-1824, 1974.

Carney, J. M., Uwaydah, I. M., and Balster, R. L. Evaluation of

a suspension system for intravenous self-administration studies

of water-insoluable compounds in the rhesus monkey. Pharmacol

Biochem Behav, 7:357-364, 1977.

Chait, L. D., and Balster, R. L. Behavioral interactions of

phencyclidine and pentobartital. Federation Proc, in press,

1978b.

Chait, L. D., and Balster, R. L. The effects of acute and

chronic phencyclidine on schedule-controlled behavior in the

squirrel monkey. J Pharmacol Exp Ther, 204:77-87, 1978a.

Chen, G., Ensor, C. R., and Bohner, B. An investigation on the

sypathomime tic properties of phencyclidine by comparison with

cocaine and desoxyephe drine. J Pharmacol Exp Ther, 149:71-78,

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Chen, G., Ensor, C. R., Russell, D., and Bohner, B. The pharmacology of 1-(1-Phenylcyclohexyl) Piperidine HCl. J Pharmacol

Exp Ther, 127:241-250, 1959.

Deneau, G., Yanagita, T., and Seevers, M. H. Self-administration

of psychoactive substances by the rhesus monkey. Psychopharmacologia, 16:30-48, 1969.

Domino, E. F. Neurobiology of phencyclidine (Sernyl), a drug

with an unusual spectrum of pharmacological activity. Int Rev

Neurobiol, 6:303-347, 1964.

63
Ellinwood, E. H., Jr., and Kilbey, M. M. Chronic stimulant intoxication models of psychosis. In: Hanin, I., and Usdin, E.,

eds. Animal Models in Psychiatry and Neurology. New York:

Pergamon, in press, 1978.

Finnegan, K. T., Kanner, M. I., and Meltzer, H. Y. Phencyclidineinduced rotational behavior in rates with nigrostriatal lesions

and its modulation by dopaminergic and cholinergic agents.

Pharmacol Biochem Behav, 5:651-660, 1976.

Garey, R. E., and Heath, R. G. The effects of phencyclidine on

the uptake of 3H-catecholamines by rat striatal and hypothalmic

synaptosomes. Life Sciences, 18:1105-1110, 1976.

Harris, R. T., Waters, W., and McLendon, D. Evaluation of

reinforcing capability of delta-9-tetrahydrocannabinol in rhesus

monkeys. Psychopharmacologia, 37:23-29, 1974.

Hoffmeister, F., and Wuttke, W. Psychotropic drugs as negative

reinforcers. Pharmacol Rev, 27:419-428, 1975.

Jarbe, T. U. C., Johansson, J. O., and Henriksson, B. G. Drug

discrimination in rats: The effects of phencyclidine and ditran.

Psychopharmacologia, 42:33-39, 1975.

Kanner, M., Finnegan, K., and Meltzer, H. Y. Dopaminergic

effects of phencyclidine in rats with nigrostriatal lesions.

Psychopharmacology Communications, 1(4):393-401, 1975.

Litchfield, J. T., and Wilcoxon, F. A simplified method of

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96:99-113, 1949.

Luby, E. D., Cohen, B. D., Rosenbaum, G., Gottlieb, J. S., and

Kelley, R. Study of a new schizophrenanimetic drug -- Sernyl.

A.M.A. Archives of Neurology and Psychiatry, 81:363-369, 1959.

Martin, D. P., Darrow, C. C. II, Valerio, D. A., and Leiseca,

S. A. Methods of anesthesia in nonhuman primates, Lab Animal

Sci, 22:837, 1972.

Moreton, E. J., Meisch, R. A., Stark, L., and Thompson, T. Ketamine self-administration by the rhesus monkey. J Pharmacol Exp

Ther, 203:303-309, 1977.

Overton, D. A. A comparison of the discriminable CNS effects of

ketamine, phencyclidine and pentobarbital. Arch Int Pharacodyn,

215:180-189, 1975.

Pickens, R., Thompson, T., and Muchow, D. C. Cannabis and phencyclidine self-administration by animals. In: Goldberg, L., and

Hoffmeister, F. eds Psychic Dependence. Bayer-Symposium IV.

New York: Springer-Verlag, 1973, pp. 78-86.

64
Pryor, G. T., Husain, S., McKenzee, C. E., Carr, J. D., Braude,

M. C. Interactions between delta-9-tetrahydrocannabinol and

Phencyclidine hydrochloride in rate. Pharmacol Biochem Behav,

6:123-136, 1977.

Schuster, C. R., and Balster, R. L. The discriminative stimulus

properties of drugs. In: Thompson, T., and Dews, P. B., eds

Advances in Behavioral Pharmacology. Vol. 1. New York: Academic

Press, 1977, pp. 85-138.

Smith, R. C., Meltzer, H. Y., Dekirmenjian, H., and Davis, J. M.

Effects of phencyclidine on biogenic amines in rat brain.

Neurosci Abstracts, 1(468), 1975.

Synder, S. H. Cathecholmines in the brain as mediators of

amphetamine psychosis. Arch Gen Psychiat, 27:169-179, 1972.

Wenger, G. R. The effect of phencyclidine and ketamine on

schedule-controlled behavior in the pigeon. J Pharmacol Exp

Ther, 196(1):172-179, 1976.

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AUTHORS

Robert L. Balster, PhD., and Larry D. Chait, Pharmacology Department, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298.

65
Chapter 5

Phencyclidine Use Among Youth: History,

Epidemiology, and Acute and Chronic

Intoxication

Steven E. Lerner, M.S., and R. Stanley Burns, M.D.

INTRODUCTION

The growing popularity of phencyclidine throughout the United

States parallels the early histories of LSD and marihuana. The

initial passage of phencyclidine through the drug subculture in

1967 resulted in "bad reviews," attributed to the relative inexperience of drug experimenters. However, during the past three

years its popularity has rapidly increased among the now more

experienced drug users. In addition, the extensive use of clandestine drug canbinations containing phencyclidine has resulted in

part in a marked rise in acute phencyclidine intoxications.

The medical problems emerging from the illicit use of this entirely

new class of psychoactive drugs are compounded by its myriad analogs.

With the advent of the polydrug abuse phenomenon, the widespread experimental and long-term use of phencyclidine has expanded at an

alarming rate. The large quantities of phencyclidine that have been

recently confiscated by law enforcement officials in California alone, commensurate with the reported Drug Abuse Warning Network

"mentions" and associated deaths, are convincing indicators of a

new major drug problem.

This paper will present an overview of the pharmacology of phencyclidine, including its. effects on animals and humans, and the history of its illicit use which is highlighted by factors related to

phencyclidine's increasing popularity. Data from three major Federal sources are compared with the results of the authors' hospitalbased youth study. The increased problems and deaths seen in a

community where phencyclidine has been continuously available are

presented and discussed.

A profile of chronic phencyclidine use includes a description of

the patterns of use, the phencyclidine experience, tolerance, psychological dependence and side effects, chronic toxicity, and laboratory and neurological findings.

A review of the acute intoxicated state caused by phencyclidine

66
encompasses the presentation, clinical picture and course, laboratory and toxicological findings, diagnosis, management and treatment.

AN OVERVIEW

Phencyclidine hydrochloride (Sernyl), discovered in the mid

1950's (Domino and Luby 1972) is a white, stable solid with a melting point of 234 - 236°C (Domino 1964). It is a weak base that is

readily soluble in water (Domino 1964) and highly lipid soluble at

physiological pH (James and Schnoll 1976). Animal studies reveal

low cellular toxicity and high potency for inducing surgical anesthesia without respiratory or cardiovascular depression in monkeys

(Greifenstein et al. 1958).

The drug was first tested on humans in 1957 (Greifenstein et al

1958; Rodin, Luby and Meyer 1958), and when given in doses of 0.25

mg/kg intravenously produced anesthesia sufficient for minor and

major surgery (Greifenstein et al. 1958). Phencyclidine was also

used as a preanesthetic agent for postoperative analgesia, for pain

syndromes, burn dressing, as an abreactive agent, and for the

treatment of psychoneurosis. Since the drug produced postanesthetic

confusion and delerium of prolonged duration in some cases, clinical

investigations were discontinued (Domino and Luby 1972; Chen, Ensor

and Bohner 1966).

Phencyclidine hydrochloride in solution was legally manufactured by

Parke, Davis and Company for use in humans as a short-acting analgesic and for general anesthesia under the trade name Sernyl (Munch

1974). In 1967 the patent was changed to permit the manufacture by

Philips Roxane of the drug in solution as an analgesic for monkeys

and other primates under the trade name Sernylan. The Comprehensive

Drug Abuse Prevention and Control Act of 1970 classified phencyclidine with the barbiturates and LSD in Section 202(c), Schedule

III(b) (7) as . . . "having a depressant effect on the central nervous

system" (Munch 1974).

Phencyclidine and its better known derivative ketamine belong to

the arylcycloalkylamine group (Chen and Weston 1960) and have a

similar spectrum of activity. Administered to animals in increasing doses, these drugs produce excitation, ataxia, catalepsy, general anesthesia and convulsions. The characteristic autonomic

actions of these agents, hypertension and tachycardia, appear to

be due to central sympathetic stimulation (Chen and Weston 1960).

The degree of central nervous system stimulation and depression and

the anesthetic potency vary among the species (Chen and Weston

1960; Chen et al. 1959; and Chen 1965). Based on behavioral criteria, phencyclidine and ketamine act primarily as central nervous system depressants in both humans and monkeys. Immediate excitation

does not usually occur, whereas surgical anesthesia is more readily

induced in human than in other species (Domino 1964; Chen and

Weston 1960; and Chen 1965). Ketamine is less potent, has a shorter

duration of action, and produces convulsions less frequently (Chen

67
et al. 1959; Domino, Chodoff and Corssen 1956; and Corssen and

Domino 1966).

Phencyclidine is active orally as well as parenterally (IM, IV) in

humans (Domino and Luby 1972; and Domino 1964). In several studies

involving normal subjects, comparable subanesthetic doses of phencyclidine of 0.1 mg/kg given intravenously over 2 - 12 minutes or

7.5 mg orally consistently produced decreased touch, pain and position sense associated with nystagmus, ataxia and hyperreflexia

(Domino 1964; Luby et al. 1959; and Davies and Beech 1960).

Impairment or increased threshold of audiometry, perimetry, visual

acuity and taste is seen (Danino 1974). Touch sense and two-point

discrimination were found to be the earliest, most pronounced and

persistent sensory effect in one study. Changes in muscle tone

ranging from a slight increase to catatonia and rhythmic motor

behavior have been reported (Luby et al. 1959). An increase in the

diastolic blood pressure of less than 10 mm with an increase in

pulse rate of generally 20 - 30 beats per minute were also noted.

Side effects included nausea with repeated vomiting, vertigo, ptosis

and diplopia.

With intravenous administration over five minutes, effects are immediate, with prominent symptoms; lasting 1 - 2 hours (Luby et al.

1959). Following oral administration, subjects have reported

changes in their physical or psychological state within 45 minutes

with maximum effects at 90 minutes (Beech, Davies and Morgenstern

1961). In a similar study of five obsessional patients,given 5

to 10 mg phencyclidine orally, the point of onset at 30 - 60 minutes

and a duration of 1 - 3 hours were reported (Davies 1961).

Given intravenously in anesthetic doses of 0.25 mg/kg (or a total

dose of 17.5 mg) over thirty-five minutes, phencyclidine increases

the minute volume, rate and depth of respirations of law order. A

mean increase in minute volume of 1140 cc was measured in seven

normal patients. Their tidal volume and respiratory rates increased

a mean of 15.3 and 2.57 cc, respectively. A consistent and significant mean increase of 26 mm Hg in systolic and 19 mm Hg in diastolic

pressure was observed. The pulse rate change was significantly increased in three subjects and decreased in three subjects (Greifenstein et al. 1958).

In surgical patients given 20 mg of phencyclidine intravenously

following premedication with pethidine and atropine, no response

to pain appeared after a few minutes, and most patients were completely unresponsive for periods up to ninety minutes without respiratory depression (Greifenstein et al. 1958). Intravenous doses

of 0.275 mg/kg to 0.44 q/kg produced anesthesia for an average of

25 minutes in 735 patients. The duration of surgical anesthesia

with 0.5 - 0.75 mg/kg of ketamine is less than 5 minutes with recovery in l/2 to 1 hour (Chen, Ensor and Bohner 1966).

As a local anesthetic, phencyclidine is approximately equal to

procaine. However, the analgesic activity of the arylcyclohexyl68
amines cannot be assessed in animals by standard testing procedures.

It has been suggested that their mechanism of action may differ from

the narcotic or the analgesic and anesthetic doses are too close to

differentiate (Chen, Ensor and Bohner 1966).

In subanesthetic doses there is general impairment of sensory function with a decrease in the appreciation for touch and pain the

earliest and most pronounced effects. Subjects are awake and able

to communicate with movement preserved and impaired only by ataxia

and occasional catatonia until consciousness is lost when higher

anesthetic doses are administered. Dissociation between sensory

and motor functioning at subanesthetic doses, implying a disturbance

of sensory-motor coordination, appears to occur.

Electrophysiologically, phencyclidine and ketamine induce a continuum of subcortical and cortical (EEG) changes in animals, with

catatonia or immobility, consistent with central nervous system

stimulation. In animals and epileptic human subjects with implanted

depth electrodes, limbic arid temporal electrical seizure activity

has been observed following ketamine administration. The electrical

seizure activity is not always substantiated by convulsive behavior

or reflected in the conventional surface EEG (Ferrer et al. 1973;

and Winters et al. 1972).

The arylcyclohexylmines also have anticonvulsant properties, antagonizing electrically induced tonic extensor seizures in mice in

doses causing ataxia and excitation, and suppressing pentylenetetrazol-induced, initial clonic seizures only at doses approaching

anesthetic levels. These properties are related to effectiveness

against generalized motor seizures in humans (Chen 1973).

Electroencephalographically, phencyclidine causes diffuse theta

and delta slowing in humans. In subanesthetic to anesthetic doses

paroxysmal activity is not evident. Changes induced by intravenous

infusion ranged from slight theta slowing in one of four volunteers

at 0.03 mg/kg to marked theta activity with a dominant medium voltage of 4 - 5 Hz rhythm in two volunteers given 0.2 mg/kg. The onset of frequency changes and their restitution in the electroencephalogram were either gradual and stepwise or abrupt. These effects

ranged in duration from 15 to 60 minutes depending on the dose administered and the magnitude of the changes induced.

In six persons given intravenous infusions of phencyclidine, a

decrease in fast activity occurred after 2 - 3 mg. At approximately

7 - 10 mg, a diffuse predominant slowing in the occipital, temporal

andparietal regions was observed. In the initial clinical trials,

doses of 1.0 mg/kg intravenously produced clinically observed

seizure activity (Greifenstein et al. 1958).

In humans, phencyclidine has psychotomimetic properties. The toxic

psychosis induced by low doses is characterized more by the overt

symptoms of schizophrenia than by hallucinations. Reproducing more

of the primary symptoms than other drug models, the psychosis produced in normal volunteers is difficult to distinguish from

69
schizophrenia (Domino and Luby 1972; Collins, Gorospe and Rovenstine 1960; and Luisada and Reddick 1975). Extreme exacerbation

of existing psychoses followed the administration of phencyclidine

to chronic schizophrenic patients (Collins, Gorospe and Rovenstine

1960; and Luisada and Reddick 1975). The drug intensified disorder

in thought processes and stimulated considerable affect. Patients

acted out sexually and became more active, assertive and hostile.

These behavioral changes continued for one month (Luby et al. 1959).

Phencyclidine produces unique and profound alterations of thought,

perception and mood in subanesthetic doses. The mental effects in

normal volunteers include changes in body image, loss of ego boundary, and depersonalization associated with feelings of estrangement,

isolation and dependency (Luby et al. 1959; and Davies and Beech

1960).

Affectively charged experiences are often evoked and some subjects

exhibit negativism and hostility or apathy (Luby et al 1959; and

Davies and Beech 1960). Thinking is slowed with disruption of

attention span, inability to sustain organized directed thought

(Davies and Beech 1960), and impairment of learning. Subjects are

distractible and perseverate. Time appreciation is disturbed, with

underestimation of time intervals. Echolalia, neologisms, and

word salad may be observed with a loss of time "boundness." Some

subjects manifest echopraxia and repetitive motor behavior (Luby

et al. 1959).

Reaction time, tapping speed, rotatory pursuit performance and

weight discrimination have been reported to be impaired (Davies

1961).

The oral "sedative" dose for humans is considered to be between 1 -

5 mg. Following oral administration of a subanesthetic dose of 7.5

mg, subjects report changes in their psychological or physical state

within 45 minutes and maximum effects at 90 minutes (Beech, Davies

and Morgenstern 1961).

Under conditions of sensory isolation or reduced visual, auditory

and tactile stimulation, less disturbances of behavior and psychological processes are evident. Subjects experienced only minimal

body image changes and felt more in control and less anxious. They

were less productive verbally and appeared quieter and calmer. They

reported experiencing "nothingness" or "emptiness." When the sensory isolation was stopped, subjects were immediately aware of the

perceptual distortions and became more disturbed. Some subjects

then experienced nausea or exhibited catatonia.

Following anesthetic doses of phencyclidine, patients were amnesic

for both surgery and the recovery period.

The psychotomimetic effects of phencyclidine are most apparent following administration of low doses. The anesthetic properties of

the drug associated with changes in the level of consciousness predominate after high doses.

70
Profouud behavioral effects are seen in several species following

phencyclidine administration (Balster and Chait 1976). In the

monkey, reinforcing properties have been demonstrated by the initiation and maintenance of lever-pressing for injections of phencyclidine. The drug is self-administered in amounts producing a

state resembling general anesthesia (Balster and Chait 1976; and

Balster 1976). It is the only "hallucinogen" reliably self-administered by monkeys, which suggests a potential for abuse (Domino

and Luby 1972; Luby et al. 1959; and Balster and Chait 1976).

Learned behavior in animals is sensitive to impairment or disruption

by phencyclidine (Danino and Luby 1972; Rodin, Luby and Meyer 1958;

Chen, Ensor and Bohner 1966; Munch 1974; and Balster and Chait 1976).

Discrimination studies indicate that the arylcyclohexylamines produce effects in animals different from other psychoactive substances

and probably constitute a distinct class of drugs (Chen and Weston

1960; Chen et al. 1959; Domino, Chodoff and Corssen 1965; Balster

and Chait 1976; and Corssen and Domino 1966).

Repeated administration of phencyclidine to monkeys and primates

has resulted in shortened periods of effective anesthesia after

several weeks or months of use. A similar tolerance to the anesthetic effect of ketamine has been reported (Luisada and Reddick

1975). In monkeys receiving ketamnie 3 - 5 times per week for 6

months, the duration of anesthesia was decreased by 40 percent.

Juvenile chimps receiving 3 doses in a one-week period required 50

percent more ketamine to maintain the anesthetic effects (Luisada

and Reddick 1975). Similar observations have been made in humans

with repeated use of ketamine anesthesia in the treatment of burns

(Chen and Weston 1960).

There is some recent evidence of tolerance development to the duration and intensity of the effects of phencyclidine on operant behavior in monkeys with daily administration over a 4-month period.

Studies examining physical dependence to phencyclidine associated

with the chronic intoxicated states do not appear in the literature

(Balster and Chait 1976).

In various animal species, phencyclidine has a relatively short duration of action (Domino 1964). In the monkey, for example, it is

rapidly metabolized and excreted in the urine as conjugated di- and

mono-hydroxy metabolites (Ober et al. 1963; and Glazko 1967).

After single intravenous doses, 60 percent of the radioisotope labels were recovered in the urine within twelve hours, and approximately 75 percent in eight days (Ober et al. 1963). In humans, the

relative concentrations of mono-hydroxy metabolite and the parent

compound phencyclidine recovered in urine after acid hydrolysis and

assayed by gas liquid chromatography were 68 percent and 32 percent,

respectively. No di-hydroxy metabolite was evident (Ober et al.

1963). Subsequently, two mono-hydroxyl metabolites were detected in

urine from patients acutely intoxicated with phencyclidine after enzymatic hydrolysis (Lin et al. 1975). There is no evidence that

these two compounds possess cataleptic anesthetic activity.

7 1
Tissue distribution studies in animals demonstrate relatively high

and persistent concentrations in adipose and brain tissue with lower

and rapidly falling blood concentrations (Lin et al. 1975; and

Corssen and Domino 1966). These results are consistent with the

drug's pKa of 8.5 and lipid partition coefficient at physiological

pH (Done et al. 1977). The half life in rat blood after IP injection

is approximately 3 l/2 hours. The drug concentration half life in

the dog followed intravenous administration is approximately one

hour (Lin et al. 1975).

No evidence of acute cellular toxicity was reported in the first

1,000 patients who received phencyclidine as an investigational

drug. However, phencyclidine with restraint stress produced increased muscle enzyme (CPK, aldolase) levels and skeletal muscle

pathology in rats. One of seven human subjects had an increased

CPK level following phencyclidine administration.

In acute phencyclidine intoxication with coma, CPK levels greater

than 500 units are frequently found. In several cases where CPK

has been above 20,000 units, rhambdomyolis preceded myoglobinuria

and renal failure. Whether this represents direct muscle toxicity

or is secondary to coma and muscle compression is unknown.

Evidence of hematologic, hepatic or renal toxicity was not found by

the authors in their study of chronic use of phencyclidine for

periods greater than 6 months andupto 5 1/2 years by history.

Several female patients seen by the authors have by history used

phencyclidine regularly preceeding and during pregnancy with their

infants being in apparent good health. One infant born to mother

who used phencyclidine regularly just prior to delivery exhibited

poor feeding, a poor sucking reflex and irritability.

Phencyclidine can be detected in concentrations of 1:1000 after

extraction with an organic solvent fran an aqueous solution by a

color reaction with gold branide or potassium permanganate (Munch

1974). The drug has been identified and quantitatively determined

in extracts of body fluid (blood, urine, CSF) and. tissues by thin

layer chromatography, gas liquid chromatography with flame ionization detection, and with gas chromatography - chemical ionization

mass spectrometry (James and Schnoll 1976; Reynolds 1976; and

McLeod, Green and Seet 1976).

The History of Illicit Phencyclidine Use

Street preparations of phencyclidine have continuously changed in

name, physical form, and content.

Phencyclidine is sold on the West Coast by such labels as Angel Dust,

Cannabinol, Crystal, PCP and THC (Lundberg, Gupta and Montgomery

72
1976; Radcliff 1975; Perry 1975; Burns et al. 1975; and Burns and

Lerner 1976). In the Midwest, among its street names are DUST, TAC

and TIC (Drug Enforcement Administration 1975). On the East Coast

phencyclidine is sold as Angel Dust, Erth, Green, KW and Sheets.

Recently phencyclidine has been identified as being present in

samples sold under 46 different names (See Table 1). Many of these

street nomenclatures are regional while others arenationalin scope.

Although phencyclidine is represented under a multitude of names,

the most consistent misrepresentation is "THC" (Burns et al. 1975;

Burns and Lerner 1976a, Burns and Lerner 1976b, and Lerner and

Burns 1978).

When sold as THC in tablet or powder form the color may be beige,

brown, blue, green, orange, pink, red, strawberry, white or yellow.

Phencyclidine sold as PCP usually appears beige, gray brown, orange,

speckled pink, tan white, white gray or white yellow in color.

Physical form varies fran the frequent tablet, powder, crystalline,

and granular amorphous solid to the rare liquid.

Phencyclidine has appeared on the illicit market as a powder, a

tablet, a leaf mixture (Lundberg, Gupta and Montgomery 1976; and

Radcliff 1975), a liquid, and one gram "rock" crystals. The crystalline or granular form is found most frequently in capsules.

Phencyclidine on parsley, mint, oregano or other leaves is usually

found in the form of a joint. Most street preparations contain the

hydrochloride salt, although phencyclidine as the free base has been

seen (Shulgin and MacLean 1976).

Since 1975, only 25 percent of the street drug samples containing

phencyclidine have contained additional drugs, a smaller percentage

than in earlier years. In 1971 - 1974, other drugs were found in

40 - 60 percent of street samples analyzed at the Street Drug Information Program at the University of Southern California of

Medicine. LSD was present in 86 percent of all combination preparations, with the "caine" drugs accounting for another 4 percent.

Four percent of the samples contained two or more additional drugs.

Phencyclidine was mixed with marihuana in only two of 317 samples

(Lundberg, Gupta and Montgomery 1976). This trend has also been

reflected in other street drug analysis programs across the United

States. Recently, phencyclidine and its thienyl analog (TCP) have

been identified in over 10 percent of all samples analyzed at the

University of Southern California. Only 3 percent of the samples

containing phencyclidine were actually sold under the designation.

The crystalline or granular powder form is found most frequently as

Crystal or Angel Dust, which usually contain 50 - 100 percent phencyclidine. Found under other names, the purity drops to a range

of 10 - 30 percent. Most tablets contain approximately 5 mg and

tend to range from 1- 6 mg (Lundberg, Gupta and Montgomery 1976;

Radcliff 1975; and Drug Enforcement Administration 1975). Leaf

mixtures have been found to contain between 0.24 - 7.9 percent phencyclidine, averaging 1 mg phencyclidine per 150 mg leaves (Lundberg,

73
TABLE 1

NAMES GIVEN FOR MATERIAL CONTAINING PCP-TCP

Name

Amphetamine

Angel Dust

Belladonna

Cocaine

Cadillac

Cannabinol

Crystal

Cyclones

Detroit Pink

DMT (N,n-dimethyltryptamine)

Dust

Elephant tranquilizer

Erth

Gocn

Green

Hashish

Hog

Horse tranquilizer

Killerweed

KJ crystal

KW

LSD (lysergic acid diethylamide)

Marihuana

MDA (3,4-methylenedlaxyamphetamine)

Mescaline

Mintweed

Mist

Monkey Dust

PeaCe Pill

PCPA (para-chlorophenylalamine)

Peaceweed

Peyote

Psilocybin

Rocket fuel

Scuffle

Sheets

Snorts

Soma

STP (3-methyl-2,6-dimethoxyamphetamine)

Superweed

Surfer

T

TAC

THC (tetrahydrocannabinol)

TIC

TT-1

74
Gupta and Montganery 1976).

Phencyclidine is taken orally, by inhalation (smoking), insufflation

(snorting), and rarely by the intravenous route.

Street samples analyzed have contained phencyclidine in combination

with other drugs (barbiturates, ethyl alcohol, heroin, cocaine,

amphetamine, methaqualone, LSD, mescaline, procaine). Combination

preparations which contained phencyclidine (phencyclidine-procaine,

phencyclidine-marihuana, phencyclidine-caffeine, phencyclidinecocaine, phencyclidine-doxepin, phencyclidine-LSD, phencyclidineLSD-mescaline, phencyclidine-LSD-aspirin, phencyclidine-LSD-procaine

and some 4-5 drug combinations) have also appeared on the illicit

market. In addition the presence of PCC (1-piperidinocyclohexanecarbonitrile) as a contaminant in some illicit phencyclidine preparations has been detected (Helisten and Shulgin 1976).

The information needed for the preparation of phencyclidine was

reported over 50 years ago with descriptions of the reaction of

1-piperidinocyclohexanecarbonitrile (PCC) with Grignard reagents

(Shulgin and MacLean 1976). The majority of the illicitly synthesized phencyclidine is prepared according to the general directions of Kalir and modified in details as required by the availability of chemicals and equipment. Until recently most batch

operations were limited by the amount of piperidine to be used

(usually a maximum of 500gms) and would produce on a 3 - 5 mole

scale (Shulgin and MacLean 1976).

Piperidine was felt to be the most guarded reagent and the easiest

to trace and for these reasons manufacturers would pay as much as

$1,000/kg for a non-traceable bottle. Now piperidine is no longer

the "limiting step" as it has become readily available, leading to

the manufacture of larger quantities of phencyclidine.

In addition, a new solvent for distillation that should prevent

fires and explosions is now available. Manufacturing is now done

in larger, better equipped laboratories that are capable of producing great quantities of phencyclidine. Illegal laboratories containing as much as 25 million dollars worth of phencyclidine have

been raided. The last major seizure (in the Los Angeles area)

of an illicit laboratory in 1977 yielded 900 pounds of phencyclidine.

Recently an illegal laboratory was raided by the Drug Enforcement

Administration in the Michigan area. Officials estimated that the

$200 investment in chemicals could produce phencyclidine worth approximately $200,000 on the street.

According to the Drug Enforcement Administration, major production

centers have been discovered in Washington, D.C., Detroit, Los

Angeles and San Francisco.

Complex and formal distribution systems now exist which mirror the

heroin connection. In some areas phencyclidine has surpassed heroin

in street price. The same criminal elements that are selling

75
opiates are now also selling phencyclidine. Phencyclidine sold as

THC or Angel Dust is usually worth from $25 - $200 per gram and

upwards of $1000 an ounce. Individual phencyclidine joints vary

from $1 - $20 or more.

Various patterns of phencyclidine use have emerged over the past

several years. First time users report stoking a cigarette containing phencyclidine unknowingly or in an experimental fashion.

Although the occasional or recreational use pattern is seen, its

development is mediated by an initial experience of unexpected and

unpleasant effects (Burns et al. 1975; and Burns and Lerner 1978).

In areas where the drug has been continuously available, it has

gained a preferred drug status with small cluster groups of individuals who have used it on a chronic, daily basis for periods

of six months to six years (Burns et al. 1975; and Bums and Lerner

1978). Requests for the authors services through a national consultation service (Lerner, Bums, Linder and Associates) reveal

chronic users in California, District of Columbia, Hawaii, Kansas,

Kentucky, Maryland, Nevada, and Washington.

In the San Francisco - Oakland area chronic users purchase phencyclidine in gram amounts ranging from $85 - $125 per gram. Money

for the purchase of phencyclidine is generally provided by a partner through dealing, hustling, or Social Security Insurance (SSI).

Wholesale dealer's costs average fran $40 - $50 per gram, $200 -

$300 per quarter ounce, and from $700 - $1,000 per ounce.

Factors Related to Increased Phencyclidine Popularity and Use

When phencyclidine made its illicit debut in 1965 it was marketed

as a mild psychedelic. Dealers described this new drug as a mild

psychedelic, "a little stronger than marihuana," and sold it in

tablet and capsule form. The effects were often unexpected. Since

the dosage could not be titrated, users often experienced an adverse

reaction. Hence, phencyclidine gained a bad reputation and subsequently was not seen on the streets.

By 1972, a change was observed in both themethodof use and the

attitude of users about the drug. A conversion had taken place

from using phencyclidine orally in tablet or capsules to smoking

it on leaf material. By this newly discovered method the user was

able to more effectively control the dosage, thus decreasing the

chance of overdose. Experienced users for the first time were able

to inform new users how to take it effectively and to describe what

the effects would be like. As first time users were now being

prepared for this unique experience and with better methods of controlling the dosage, the popularity of phencyclidine spread rapidly.

Illicit laboratories increased in proportion to the new demand for

material.

Because of the ease of manufacturing phencyclidine in clandestine

laboratories, its availability has dramatically increased. Youth

are now using phencyclidine in social settings in a similar fashion

to marihuana. As other drugs of abuse become difficult to obtain,

76
phencyclidine in many areas is continuously available. Hence,

groups of users are likely to select phencyclidine as their drug

of choice and to share it with their friends.

Due in part to the lack of full infomation about the effects and

dangers associated with phencyclidine,the drug continues to expand in popularity among youth. In general, users are still under

the misconception that phencyclidine is merely "a little stronger

than marihuana." Young users who were questioned about the differences between LSD and phencyclidine uniformly responded that

LSD was a much more dangerous drug and that they would not use it.

Phencyclidine, however, does not have this connotation. until

this is changed, usage is likely to continue to increase.

The abuse of phencyclidine and other arylcyclohexylamines has

emerged over the past 12 years. As stated earlier, phencyclidine

was first seen illicitly in 1965, in Los Angeles (MacLean 1977).

Two Years later it appeared in San Francisco under the guise of

the "PeaCe Pill" (Bums et al. 1975). With media coverage of the

adverse effects, phencyclidine disappeared from the street scene

in the San Francisco area in 1968, at which time it surfaced on

the East Coast under the guise of "Hog." Since then it has been

seen with increasing frequency throughout the United States.

In 1969, the N-ethyl analog of phencyclidine, PCE, cyclohexamine

appeared on the streets in Los Angeles (Shulgin and MacLean 1976).

By 1972, due to the "ripple effect," phencyclidine appeared in five

states, from California to New York (see Table 2). It should be

noted that the PharmChem Research Foundation, which provided this

data, is only one of many street drug analysis programs operating

in the United States. Therefore, the epidemiology of its abuse

is riot necessarily reflected by these figures. Louisville, Kentucky,

and Eugene, Oregon presented the greatest increases in street drug

samples containing phencyclidine.

In 1974, the Thiophene analog of phencyclidine, TCP, was first

identified in Hawaii. That same year phencyclidine had spread into

another four states.

By 1975 the use of both phencyclidine and TCP had spread to 22

states. TCP was sold on the West Coast in Los Angeles, Newport

Beach, Santa Cruz and Sacramento. Outside of California, TCP was

being sold in Eugene and Coos Bay, Oregon, and Seattle and Tacoma,

Washington.

In 1976 phencyclidine appaared in another two states. The use of

TCP decreased slightly, although it remained popular in Oregon and

Washington

During the first eleven months of 1977, phencyclidine was identified

in 28 states, exceeding all prior years. For the first time samples

of phencyclidine were received from Indiana, Kansas, and Nevada.

Since these samples were in the powder form, the possibility of

77
TABLE 2

DISTRIBUTION OF PCP-TCP BY STATE*

78
sophisticated chronic use was evident. Although they were PharmChem's first samples from these states, it is unlikely that phencyclidine had not been available previously. For example, although

PharmChem's first sample from the Kansas area was received in 1977,

the number of cases seen by the District Attorney's Office in

Plathe, Kansas, had doubled during that year.

Recently PHP 1-(1-phenylcyclohexyl)pyrrolidine was identified on

autopsy in the body of an individual who was shot and killed by

a police officer in Los Angeles - the first documented street appearance of this analog.

Demography - Epidemiology of Illicit Use

A dearth of literature exists on the nature and extent of use of

phencyclidine and its 30+ analogs. The major Federal sources for

determining changes in emerging drug trends are the Client Oriented

Data Acquisition Process (CODAP), the Drug Abuse Warning Network

(DAWN), and the National Youth Polydrug Study (NYPS).

The CODAP system provides the largest available national data

base of patients in treatment. All drug abuse treatment and rehabilitation programs receiving Federal funds are required to

collect and report data.

Drugs of abuse are divided into 14 categories. Phencyclidine is

classified incorrectly as a hallucinogen, with LSD, mescaline,

MDA, DMT, musuhrooms, peyote, and other drugs. Since CODAP has no

flexibility in identifying and analyzing phencyclidine independently

from the other drugs, this data source is not useful for our purposes.

The DAWN system has been in operation since the spring of 1973.

Hospital emergency rooms and inpatient units, crisis centers and

medical examiners (coroners) in 24 selected Standard Metropolitan

Statistical Areas (SMSA's) are contracted to report incidents of

adverse drug reactions to the DAWN central office. In each report,

the victim's age, sex, race, employment and treatment status are

noted, as well as the drug used, the route of administration, the

source of the drug, and the form in which it was acquired.

DAWN data, however, includes only those phencyclidine users who

hadadversereactions that required agency intervention. There

is no record of the user who ingests phencyclidine without an adverse reactionor who handled such a reaction without agency intervention.

Also, the DAWN data are collected only in the major SMSA's. As an

example, in California, DAWN data are collected only for the Los

Angeles, San Francisco - Oakland and San Diego areas. Data are not

available fran 51 of California's 58 counties. Even within these

reporting counties the DAWN reporting system- emergency rooms,

inpatient units and crisis centers - is not complete. That is,

within these communities many phencyclidine-related problems are

79
treated that are never reported to DAWN.

Those phencyclidine cases which are reported frequently lack complete information. The victims are often not in sufficiently

stable condition to respond properly to questions and are not

commonly reinterviewed upon recovery.

Fran September 1972 through March 1973, phencyclidine was ranked

as the twenty-third most abused drug in the DAWN system. During

the period fran April 1973 through March 1974, it rose to the

twenty-first position. By the following year, April 1974 through

April 1975, phenyclidine use had increased to the fifth position.

For the reporting period from May 1975 through April 1976, phencyclidine continued to rank overall as the sixteenth most frequently abused drug. For the youth population between 12 and 18

years of age, however, it was in tenth place.

For this youth population between February and May 1976, there

were 294 patients treated in emergency rooms, 330 patients seen

in crisis centers, and 2 patients seem by coroners. During the

same period phencyclidine ranked as the eleventh most frequently

abused drug in Philadelphia and Washington, D.C.; seventh in

Chicago and Cleveland; fifth in Minneapolis and Los Angeles; fourth

in Detroit; and first in the San Francisco - Oakland area.

White males (61 percent) are twice as likely as white females

(32 percent) to report to DAWN emergency room. For crisis centers,

however, white males and females are reported at approximately the

same rate, 42 percent. The use of phencyclidine by minorities accounts for only 6 percent of the mentions from crisis centers and

7 percent from emergency rooms.

Ninety-one percent of phencyclidine users seen in crisis centers

reported their source as a "street buy," whereas with emergency

rooms only 49 percent reported "street buys" as their source.

The prime motivation for phencyclidine use among patients seen in

both crisis centers and emergency rooms is for the "psychic effects," which account for 73 percent of the mentions. Phencyclidine

users from the crisis centers are much more prone (28 percent) to

report dependence as their motivation than are the users from

emergency rooms (2 percent).

Crisis centers data indicate that the age group of 12 to 13 years

for white females seems to be at particularly high risk. Furthermore, 42 percent of the phencyclidine mentions in this age group

reported dependence as their prim motivation for use.

Fran September 1976 to March 1977, youth from 12 to 18 years of age

were interviewed on admission for drug treatment as part of the

NYPS. In all, 2750 patients from 97 treatment program in 39 States

participated in this study.

These patients represented a national sample of youth in treatment

80
from all regions, and from the major treatment modalities. They

were sampled selectively for sex, race, and ethnic grouping by

geographic region. Information contained in this new data base is

the most comprehensive data available on youthful abusers.

There is a high degree of similarity between the NYPS sample and

the CODAP youth subsample. Hence, information obtained from the

NYPS on drugs of abuse such as phencyclidine that are not reported

separately in CODAP may now best estimated using this new data source.

PCP Use Within the NYPS Sample

Of the 2750 clients under 19 years of age in the NYPS sample, 857

(31.8 percent) reported having ever used PCP, with 561 reporting

the use of PCP during the three months prior to admission. The

prevalence of PCP in this sample is the highest reported in any

national sample for adults or for youth. PCP ranked seventh in

prevalence among the fourteen types of drugs in the sample, and

it was abused more frequently than many other well known substances

such as inhalants (abused by 28.9 percent of the sample), other

sedatives (abused by 28.8 percent), or cocaine (abused by 25.8

percent). A comparison of PCP users with clients who never used

PCP (see Table 3) indicates that similar proportions of both males

and females use PCP (32 percent); that proportionately more whites

use it than other racial groups (42 percent of whites compared to

8 percent of blacks, 13 percent of American Indians, and 9 percent

of Hispanics); that PCP use is more frequent in the suburbs (44.1

percent of all suburban clients compared with about 30 percent

from urban and rural settings); that PCP users are slightly older

at admission, with somewhat more years of education and have a

higher Socio-Econcmic Status than users of other drugs.1

Frequency of Use of PCP. Among the 561 current users of PCP (see

Table 4) approximately 50 percent were found to be using it at an

average frequency of at least once per week during the three months

prior to admission.

The Onset of PCP use. The man age of first PCP use was 14.6 years

of age and the mean age of first continuous use was 14.8 years.

Females reported the earlier mean age of first use for PCP: 14.4

years compared to 14.7 years for males. This finding is consistent

with most other drug types in this study (except alcohol, marihuana,

and inhalants).

In the comparison of age of first use of PCP across ethnic groups,

American Indians were noted to have the earliest mean age of first

use (13.89) closely followed by Hispanics (14.00). (The number of

PCP users in these two groups, however,was too small to draw any

inferences.) Whites reported the third earliest age of PCP use

with a man of 14.58, and blacks were the oldest (15.25).

Regional Distribution of PCP Use. The National Youth Polydrug Study

divided the United States into seven sampling regions. It should

be stated that the sample was not stratified by region, which mans

81
TABLE 3

COMPARISON OF SUBJECTS WHO “EVER USED” WITH THOSE WHO “NEVER USED”

PCP, ON DEMOGRAPHIC AND BACKGROUND CHARACTERISTICS

used PCP Did not use PCP Total

sex

Males 534 (31.9%) 1138 (68.1%) 1672 (100%)

Females 336 (31.6%) 725 (68.4%) 1061 (100%)

= .02(N.S.)

dfs = 1

Race

White 784 (42) 1068 (58) 1852 (100%)

Black 33 (8) 354 (92) 387 (100%)

American Indian 18 (13) 116 (87) 134 (100%)

Hispanic 27 (9) 274 (91) 301 (100%)

= 282.3

dfs = 3

p<.0001

Residence

Urban 544 (29.9) 1274 (70.1) 1818 (100%)

Suburban 194 (44.1) 246 (55.9) 440 (100%)

Rural and

Small Town 131 (29.6) 312 (70.4) 643 (100%)

= 34.2

dfs = 5

p<.001

Age

Education

Socioeconomic

status

S.D. N x S.D. N t p<

16.2 1.4 875 15.8 1.3 1874 7.1 .001

9.4 2.6 873 9.0 2.5 1853 3.7 .001

45.4 13.8 875 41.0 15.1 1874 7.6 .001

82
TABLE 4

CURRENT FREQUENCY* OF PCP USE BY SUBJECTS

CURRENTLY USING PCP

Less than once a month

Once a month

Two to three times a month

Once a week

Two to three times a week

Four to six times a week

Daily

Twice a day

Three or more times a day

N

97

6 9

112

83

99

28

41

12

20

561

%

17.3

12.3

20.0

14.8

17.6

5.0

7.3

2.1

3.6

TOTAL 100.

* "Current" frequency is defined as the average frequency of use

during three-month period before admission

83
the proportion of the youth population in treatment in each region

was not a criterion for inclusion in the sample. It may be that

certain states are overrepresented in proportion to their population, e.g., the relatively large number of cases in the sample

from Illinois and Florida. Conversely, we know from the DAWN

system that the San Francisco Bay area is one of the centers of

PCP use, and is underrepresented in this sample.

The regional prevalence of PCP in the NYPS sample indicates that

the Great Lakes and the Midwest regions show the highest rate of

PCP use with 46.6 percent (N = 270) and 46.4 percent (N = ll6) of

each region's clients ever using PCP. Since the number of clients

from these regions is fairly large and these clients were adimitted

to 29 different treatment programs these data seem to be a valid

representation of PCP use in these regions. They exceed the rates

reported in DAWN and probably reflect the increased trend of PCP

use among youth during the past two years. Other regions show PCP

to be used by 31.5 percent of the clients from the Southeast

(N = 153); by 27.2 percent of the clients from the West Coast; by

24.2 percent of clients from the Northeast; and by 23.8 percent of

clients from the Southwest.

The PCP User vs. the Nonuser. Perhaps one of the most notable

differences those who ever used PCP and those who did not

is the greater involvement of the PCP users in polydrug abuse: PCP

users reported using twice as many substances as the nonuser of PCP,

with PCP users reporting a mean of 6.0 substances ever used (S.D. =

2.6), while nonusers of PCP reported a mean of 2.8 substances ever

used (S.D. = 1.8), (t = 33.4, p < .0001). PCP users also reported

a higher mean number of drugs used during the three months prior

to admission to treatment: 5.8 substances (S.D. = 2.6) compared to

a man of 2.6 substances (S.D. = 1.8) by nonusers of PCP (t = 28.1,

p < .0001). Thus, for this youth population seeking treatment for

drug abuse, PCP use is an integral part of a larger polydrug abuse

problem that is more serious and complex than for the nonuser of

PCP.

It is of particular interest that not a single subject who used PCP

in this study used only this substance. All PCP users used other

substances either at other times or concurrently with PCP. Almost

all of them users used marihuana: 99.5 percent. other drugs

reported used by PCP users were: alcohol (by 97.7 percent of PCP

users); hashish (by 77.8 percent of PCP users): amphetamine (75.8

percent); hallucinogens (72.2 percent). Aside from alcohol and

marihuana, which are almost universally used in this sample, and

aside from hashish, PCP is next most often used by users of amphetamines and hallucinogens.

When looking at the use of multiple drugs from the other direction,

we find that the users of other sedatives (61.7 percent), over-thecounter drugs (61.6 percent) and other opiates (61.1 percent) were

most likely also to have ever used PCP.

84
A Profile of the PCP User

A correlational profile of the PCP user was developed from analysis

in which PCP use was correlated with each of 33 demographic, social

history, and background variables. A three points scale measure was

utilized for PCP use, as follows: a score of 1 was assigned for no

PCP use, a score of 2 for irregular PCP use, and a score of 3 for

regular PCP use. Table 5 presents the list of the 18 variables

(from among the 33) which had a bi-variate correlational value of

+ .10 or greater with PCP use. The profileof the PCP users (compared to the nonusers), which was derived from this analysis, is

as follows, (listing the descriptors in rank order of magnitude of

the correlation): (1) used regularly a greater number of different

drugs; (2) white; (3) more often took more than one drug at a time

(in combination) "to boost, balance or counteract the effects" of

one drug; (4) became drunk from drinking alcohol more often; (5)

had more arrests for substance related offenses; (6) were picked up

more times by the police; (7) had more overdose episodes (OD's);

(8) reported more obstacles to school attendance; (9) had more

arrests for violent and weapons offenses; (10) listed more types

of problems as reasons for contacting a treatment program; (11)

more arrests for property offenses; (12) higher socio-economic

status; (13) older; (14) adjudicated delinquent; (15) tended to

reside in suburbia; (16) more often was admitted to treatment in

hospitals and residential settings than to outpatient settings:

(17) more often made suicidal attempts; and (18) less often were

referred to treatment by peers.

Predicting "Regular" use of PCP. The variables employed in constructing the profile of the PCP users were also used to "predict"

regular use of PCP. Clients were divided into two groups, regular

PCP users (those using PCP at least once a week for a period of

at least one month) and those who did not use PCP at all. Clients

who had used PCP minimally, but never at a frequency of at least

once per week for a period of one month, were excluded from this

analysis. The analysis was composed of two steps: first, a bivariate correlation of all the variables includied in the analysis;

second, a step-wise multiple regression in which the dependent

variable is the regular use of PCP and the independent variables

are a subset of the variables appearing in the correlation.

The bivariate correlation of the variables employed to predict

regular PCP use showed that the strongest association of regular

use of PCP is the number of substances regularly used ("Regsum"):

r = .63. Since it seems reasonable to consider the relationship

of demographic and other variables to PCP use separately from the

question of how many other drugs the subject has used, we did not

include this variable, "Regsum," in the equation of the step-wise

multiple regression. The other background variables accounted for

16.8 percent of the variance in the differentiation of the regular

PCP users from the nonusers (see Table 6). It might, thus, be said

that it provides only one-sixth of the information that would be

needed to "predict" accurately regular PCP use. The rank order of

these variables, according to their relative abilities to "predict"

to regular PCP use is as follows: (1) Race, (being white), accounts for 9.1 percent of the variance; (2) "the number of times

85
TABLE 5

CORRELATIONS OF CLIENT DESCRIPTORS WITH REGULAR USE OF PCP

Correlation With

Regular PCP Use

Number of drugs regularly used .63

Race (white) .31

Used more than one drug at a time .31

Number of times became drunk .22

Number of arrests for drug offenses .19

Number of O.D.'s .18

Number of times "picked up" by the poice .18

Number of obstacles to school attendance .17

Listed more types of problems as reasons

for entering treatment

Number of arrests for violent and

weapons offenses

Socioeconomic status

Number of arrests for property offenses

Age of admission

Adjudicated delinquent

Treatment program located in the suburbs

Admitted to outpatient drug

treatment program

Referred to treatment by peers

Number of suicide attempts

.16

.16

.14

.14

.12

.12

.11

-.11

-.10

.10

86
TABLE 6

THE REGRESSION OF DEMOGRAPHIC AND OTHER HISTORY VARIABLES

ON REGULAR USE OF PCP

(STEP-WISE MULTIPLE REGRESSION PROGRAM)

(DEPENDENT CRITERION VARIABLE: REGULAR USE OF PCP)

Variable Beta Significance Variance(R2) Simple

Race (1 = white; 0 = other) .22 p = .0001 .091 .30

Frequency of Getting Drunk .12 p = .0001 .025 .22

# of O.D.'s .11 p = .0001 .02 .18

# of Obstacles to School

Attendance .12 p = .0001 .012 .17

Age .08 p = .0001 .004 .12

Suburban (1 = from the suburbs

0 = other) .06 p = .001 .004 .11

Referred by Peer -.06 p = .002 .002 -.10

Socio Economic Status .03 p= .20 .001 .13

Months Employed Last Two Years .02 p = .21 .001 .11

Death of a Parental Figure -.03 p = .13 .001 -.03

Intact Family Structure

(0 = Intact; 1 = broken) -.02 p = .20 .001 -.02

Sex .02 p=.37 .00

# of Suicide Attempts .01 p= .68 .09

87
the client got drunk" was the next variable in the equation, and

added 2.5 percent to the explained variance, after controlling for

race; (3) the number of OD's added 2.0 percent to the explained

variance, after controlling for the two previously indicated variables; (4) "the number of obstacles to school attendance" added

1.2 percent to the explained variance, after controlling for the

above-listed variables: (5) age added 1 percent; (6) suburban residence (versus living in an urban or rural location) added .4 percent.

The variables that did not enter into the equation to a statistically significant degree in explaining or predicting regular PCP

use were sex, socioeconomic status, education, the number of months

employed in the last two years, intactness of the family, and the

number of suicide attempts. Some of these variables did not enter

into the equation since they are significantly correlated with

variables that had already been entered into the regression equation. For example, SES and employment are related to being white

(race) and living in the suburbs (residence). Suicide attempts

may have been excluded from the equation since they are correlated

with OD's (r = .15). Education, which is highly related to age,

was not included in the regression for the same reason. However,

the sex variable was excluded from the regression equation because

it was not associated with regular use of PCP; there is no difference between the sexes in their predisposition to be regular users

OF PCP.

The PCP User in the NYPS-A Summary. The above review of PCP use

in the NYPS indicates that the spread of this substance into the

youth population occurs primarily among the white suburban population and that PCP has not as yet reached the same level of use

within the inner city or among the underprivileged minorities. PCP

is being added to an already existing pattern of multiple substance

use and is not used by youth who do not use other drugs.

Two thirds of those young clients in the NYPS sample who ever tried

PCP used it at least weekly. PCP is likely to be used by clients

who have a previous history of treatment either for substance use

or emotional problems. Self-destructive behavior is also much more

prevalent among the PCP users as compared with nonusers of PCP.

The PCP users were also found to have a more extensive involvement

in the criminal justice system and more dysfunction in the education

system. Lastly, the PCP users were found to be characterized by

their low level of heroin use. Whether the dependence of adults on

heroin is also associated with a lower prevalence of PCP, as found

among youth, is yet to be determined.

Hospital-Based Youth Study

The authors conducted a study of 179 youthful (age 12 - 18 years)

phencyclidine users seen at one county hospital in the San Francisco

Oakland area between 1968 and 1976.

During the eight year period the majority of these patients (76.3

8 8
percent) were males, with a mean age of 16.8 years. The races

represented were 96.1 percent Caucasian, 2.8 percent black and

.6 percent Asian.

A large proportion of these patients were transported to the hospital by public transportation. The majority were brought to the

emergency room by police vehicle (43.0 percent) or ambulance (31.8

percent). In most cases these patients were accompanied by police

(39.1 percent), emergency service attendants (32.4 percent), perents (11.7 percent), friends (5.0 percent) and rarely by drug

treament staff (2.8 percent).

Reasons for hospital contact were primarily treatment (75.4 percent), a medical check for juvenile hall (12.3 percent), public

service evaluation (4.5 percent), or a medical check for police

(3.9 percent). In most cases these phencyclidine users were retained for observation (43.6 percent), admitted to the emergency

room (35.2 percent), or admitted to a service (2.2 percent). Only

16.8 pat-cent of these patients were immediately checked and released.

At the time of hospital contact, about half (49.2 percent) of the

patients were disoriented, a third (31.8 percent) were uncooperative, and a quarter (26.8 percent) were either awake with decreased

consciousness or were stuporous or comatose.

The majority of these patients (80.4 percent) had taken only phencyclidine prior to hospital presentation. The most popular substance taken in combination with phencyclidine was alcohol (15.1

percent), followed by barbiturates (1.1 percent).

Among this youthful population, a quarter (24.0 percent) were

chronic users of phencyclidine. These patients qualified as chronic

users by having taken phencyclidine on a regular basis for greater

than a six month period with multiple hospital admissions for phencyclidine-related problems. The youngest chronic user was a 15-

year-old female.

Similarities in Drug Study Findings

A number of consistent patterns appear from an analysis of the

data from the DAWN, NYPS, and the authors studies' on phencyclidine.

There is an overrepresentation of Caucasians among phencyclidine

users, accounting for more than 90 percent of all identified patients. This trend is observed in all of the major data sources.

However, it should be noted that in certain geographic areas

phencyclidine use appears to be limited to other specific groups,

such as blacks (Washington, D.C., Watts) and Mexican Americans

(San Jose).

The majority of the individuals report the "psychic effects" as

their primary reason for continued use of phencyclidine. Among

all individuals exposed to this drug, approximately 23 percent

89
become chronic users. Males represent the highest number of chronic

users as well as hospital emergency room contacts for problems related to phencyclidine.

Phencyclidine users utilize and apparently need more medical treatmentservices than other drug users.

Problems Seen Where Phencyclidine is Continuously Available

As the availability of phencyclidine increases in a commnity, there

is a direct relationship with the number of emergency room contacts

and community problems such as driving under the influence and violent and bizarre behavior - behavioral toxicity.

In San Jose, California, the police department has gathered data on

seizures of phencyclidine for the past three years. During the

first quarter of 1975 (January - March), 69.7 grams of phencyclidine

were confiscated. The following year during the same period, 125.1

grams of illegal material were collected. For the first quarter

of 1977, 3,951 grams of phencyclidine have been recovered.

In 1976 for the first quarter there were 69 patients treated for

phencyclidine-related problems; in 1977, 100 patients were seen

during this same period.

New problems have surfaced in communities (Alameda, Santa Clara,

and Los Angeles) in direct proportion to the frequency and regularity of phencyclidine abuse. Violent and bizarre behavior is seen

in the home, in public places, and in schools, often disrupting

education. Young people exhibit unexplained speech problems, menory loss, thinking disorders, personality changes, anxiety, severe

depression, and suicidal and homicidal tendencies.

An increasing number of young people appearing violent, bizarre,

unresponsive, extremely confused, or acutely psychotic are being

seen in local emergency rooms. With increased use of phencyclidine,

an upsurge in violent crimes that culminate in homicide is observed.

Police report erratic driving and inappropriate behavior following

automobile accidents in individuals who have no apparent evidence

of alcohol or sedative hypnotic ingestion. On toxicological examination only the isolated presence of phencyclidine is often discovered.

Young people who are observed to be highly intoxicated in public

are often arrested for sale, possession, and being under the influence of phencyclidine. In addition, an increasing number of referrals by family, friends, and the criminal justice system are made

to community drug abuse programs in an effort to deal with this new

drug problem.

The following are typical cases that illustrate the problems seen

in youth on phencyclidine.

90
CASE 1

A 15-year-old Caucasian male with no clothes on was found by police

in a field, hanging on to a barbed wire fence. He was disoriented

and incoherent upon questioning. A physical examination revealed

a confused, disoriented youth with inflamed eyes, bloody mouth with

an upper incisor missing, multiple scratches of the trunk, and

scratches and lacerations of extremities. Fluctuations in orientation were observed over the next seven hours ranging from cooperative and alert to unrousable. Prior to being discharged the patient

stated that he had "smoked some phencyclidine and got awfully

stoned."

CASE 2

A 17-year old Caucasian male arrested by police had allegedly ingested several phencyclidine joints, and over a 1 hour 45 minute

period became progressively uncommunicative and withdrawn. The

youth was transported from jail to a local emergency room. On admission he was observed lying quietly, eyes wide open, with a broad

smile on his face. Although responsive to commands, he was only

able to mouth words rather than speak. When given ipecac, he

vomited green parsley flakes. Over the next six hours he alternated

between quietly staring at the ceiling and being abusive, agitated,

combative, and fighting restraints. Upon regaining normal orientation, he was observed for two additional hours and released.

CASE 3

An 18-year old Caucasian male ingested tablets and capsules in his

possession prior to a police traffic stop. Immediately after the

officers departed he was driven to an apartment where the other

occupants of the automobile induced vomiting of what they believed

was all of the ingested material. Later he began screaming and

having convulsions. He was driven to a local hospital where he

was pronounced dead on arrival. The coroner ruled that death was

caused by aspiration of gastric contents due to phencyclidine ingestion. Phencyclidine (urine level of 0.5 mg/ml) was the only

drug found on toxicological examination.

CASE 4

A 15-year old Caucasian male reported to be "out of hand" was seen

at a local medical center for bizarre behavior. He had been involved with drugs and talked about "getting it all over." Later

that month, he was found hanging by an electrical cord from a

beam in his garage. Toxicological examination revealed a phencyclidine blood level of 0.10 mg/ml. No other drugs were detected.

CASE 5

During the summer a youth gave a pool party while his parents were

away on vacation. A 17-year old Caucasian female guest was discoveredatthe bottom of the swimming pool. Post mortem examination

91
revealed no head or neck trauma and the isolated presence of phencyclidine in the urine (0.5 mg/ml).

CASE 6

Distressed over a college setback, a 17-year old Caucasian male

snorted phencyclidine for the first time, with friends. He lost

consciousness, becoming apneic and cyanotic. On admission to the

emergency room this semiconscious patient was agitated, had writhing movements of all extremities, vomited, and had copious nasal

and oral secretions. Within three hours he appeared alert; three

hours later he was cooperative and completely oriented.

CASE 7

A 16-year old Caucasian female smoked "a crystal joint" while at

school and began acting bizarre. School authorities notified her

mother who brought her to a local hospital. On admission she was

dazed and unable to recall who gave her the drug or how much she

had taken. The patient was oriented to person and place. A blood

sample taken on admission was negative for sedative hypnotics.

Urine obtained at the same time for toxicology was positive only

for phencyclidine, with a value of 0.5 mg/ml. The patient became

fully oriented 2 1/2 hours later and was discharged.

Case 8

A 16-year old male, acting belligerent and combative, was brought

to the hospital from a party where he had smoked "crystal" and

drunk beer. On admission he was drowsy but responsive to verbal

stimuli. There were abrasions on his right arm and face. Over

the next three hours he became verbally abusive, belligerent, and

uncooperative and was transferred to the county hospital. Initially

violent, he alternated between periods of sleep and moaning. Toxicology screen obtained at this time revealed a phencyclidine urine

value of 1.1 mg/ml. Over the next 15 1/2 hours the patient became

alert and oriented and was subsequently discharged.

Homicides

In addition to hospital presentations for complications related to

phencyclidine intoxication, recently there have been several homicides committed by youth in which phencyclidine was implicated

(San Jose and Los Angeles, California; Las Vegas, Nevada; Kansas

City, Kansas). The defense attorneys in the majority of cases

claim that their clients were not guilty either by reason of diminished capacity or of insanity (drug-induced psychosis). With

defendants showing bizarre and violent behavior and sometimes defendants claiming amnesia to the event, (given the unique properties of phencyclidine) and the circumstances of many of these

homicides, it appears that the legal issues raised will require

much further debate and study.

92
Deaths

A large number of deaths have occurred in association with phencyclidine intoxication. In the majority of cases the immediate

cause of death was asphyxia by drowning, or trauma, circumstantial

evidence suggesting that death was secondary to the "behavioral

toxicity" of phencyclidine. The user could not indicate where his

limbs were in relation to three dimensional space or could not respond appropriately to imminent danger.

Other individuals have been found dead without apparent cause, the

presence of phencyclidine in high concentrations constituting the

only positive finding. The most probable cause of death in high

dose phencyclidine intoxication is primary respiratory depression.

Phencyclidine users report going swimming while intoxicated because

they experience an unusual but pleasant sensation from the water.

Sensory disturbances, incoordination, and muscle rigidity resulting

from "street" doses of phencyclidine may seriously interfere with

the user's ability to swim, drive, climb at heights, flee from a

fire, or sense imminent danger.

Suicide by self-inflicted trauma or a massive oral overdose of

phencyclidine has occurred in the chronic user who became moody or

severely depressed. It is the chronic user who is in possession of

large amounts of phencyclidine. Threatening behavior or violence

has resulted in provoked homicide.

Blood levels of phencyclidine as low as 100 mg/ml may be associated

with behavioral effects leading to death by injury or trauma.

Levels greater than 1.0 mg/ml are associated in most individuals

with coma and may result in death secondary to medical complications

or respiratory depression and seizures. Doses of 2.0 to 2.5 mg/ml

and greater are probably uniformly fatal, producing primary respiratory depression and seizures.

Phencyclidine deaths nationally appear to be on the increase. In

 Los Angeles alone the Coroner's Office reported 26 phencyclidinerelated deaths during 1977.

CHRONIC PHENCYCLIDINE USE

Phencyclidine became available on the illicit market in 1965 and

initially was taken orally in the form of tablets and capsules.

Around 1972, it became available primarily in the form of a leaf

mixture in California, with crystalline phencyclidine sprinkled on

parsley, mint, or marihuana and sold as "joints."

After experimenting with phencyclidine, increasing numbers of young

people began using it on a regular basis. This trend peaked around

1972 and subsequently declined until 1974 when the incidence of

phencyclidine abuse again rose. Where phencyclidine became continuously available, it gained a preferred drug status with several

"cluster" groups who smoked it on a regular daily basis in Northern

and Southern California. Chronic use of phencyclidine was first

reported in 1972.

93
Chronic User Study

A study designed to describe chronic phencyclidine use patterns

and determine evidence of chronic toxicity was carried out by the

authors in the San Francisco Bay Area in February 1975. Individuals

who had been treated for phencyclidine "overdose" at various music

concerts were invited to participate. They in turn brought other

known phencyclidine users into the study and in particular friends

who had used large amounts over the longest period of time.

The final study group of twenty had used phencyclidine regularly

(3 or more days per week) over a period greater than six months

without concurrent, heavy use of other drugs. Phencyclidine was

present in the urine samples obtained on both the initial and

followup visits.

The 15 male and 5 female chronic users ranged in age from 20 - 43

years old with a mean age of 25. All were Caucasian. Eighteen

(90 percent) were single and 19 (95 percent) had a heterosexual

preference.

Patterns of Use

The mean age at first use was 19.2 years, with half the group

(10) individuals 18 years old or younger. The majority (80 percent) had first used phencyclidine between 1967 and 1970 at 15 to

21 years of age, with a second group (20 percent) starting in 1972

and 1973.

Most users were introduced to phencyclidine by friends (85 percent)

in a social setting, and took the drug out of curiosity (55 percent) or to get "high" (45 percent). Within one year, half were

using phencyclidine regularly 3 or more times per week; by three

years, 75 percent used phencyclidine regularly.

The cumulative period of regular use from first exposure to the

time of the study ranged from 6 months to 5 1/2 years, with a mean

of 27 1/2 months. The longest period of daily or almost daily (5

or more days per week) use averaged 10.3 months and the maximum

period of abstinence averaged 5.9 months. The period of recent uninterrupted use of phencyclidine prior to the study averaged 9.9

months. Two to four times per month, users would go on 2 - 3 day

"runs," taking phencyclidine repeatedly without sleeping. Seventy

percent continued to use marihuana and 50 percent used alcohol on

a regular basis during their use of phencyclidine.

By 1972 the availability on the illicit market of nearly pure phencyclidine in amounts of 1 gram or more allowed the individual to

prepare joints for smoking of chosen strength, guarantee a long term

or continual supply for the user. With possession of large amounts

of phencyclidine, users started taking the drug on a regular basis.

The razor shavings from the "rock" crystal or the powder is sprinkled on parsley and smoked in the form of a joint. The amount of

94
street-purchased material used in the preparation of one joint

varies from 50 mg for a "street" joint to about 100 mg for a

"regular" or "good" joint. Up to 1/4 gram was used in a "killerdiller," "heavy" or "party joint," which is often shared by many

people.

The primary mode of taking phencyclidine was by smoking (90 percent)

or snorting (10 percent) the drug. All the chronic users had taken

phencyclidine at least once by smoking. The majority had also

snorted phencyclidine (75 percent) and taken it by mouth (60 percent). Only 6 (30 percent) individuals had used phencyclidine

intravenously. Five out of the 6 used. it intravenously not more

than five times.

Smokers reported using the equivalent of 1 to 2 street joints or

about 80 mg of street-purchased material 2 to 3 times per day. The

average daily intake was about 216 mg by smoking. The reported

maximum amounts used in a 24 hour period ranged from 1/4 to 1 gram

and averaged 500 mg . The two individuals who regularly snorted

phencyclidine estimated the 2 "lines" dose to be about 5 mg of

street-purchased material. They would snort the drug 4 to 6 times

per day. Toward the end of a prolonged period of daily use of

phencyclidine, these 2 individuals would place amounts of up to

1/4 of a gram of powder (layered with parsley or as a crystal) in

a pipe, and smoke it in one sitting.

Phencyclidine users reported that the subjective effects "come on"

within 1 to 5 minutes of smoking a typical "street" joint and reach

a "peak or a plateau" over a 5 to 30 minute period. They report

staying "loaded" or "high" for 4 to 6 hours, followed by the "come

down" which lasts 6 to 24 hours after taking the drug. Following a

2 - 3 day "run," the time before the user felt normal again was approximately 48 hours to one week. A more rapid onset of 30 seconds

to 1 minute followed insufflation of a street dose in powdered form.

The time course of the subjective effects otherwise did not appear

to differ.

The Phencyclidine Experience and Why It Is Repeated

Eighty percent of the chronic users considered their first phencyclidine experience to be pleasantandwanted to take the drug

again. They found it "fun," "exhilarating," and felt "happy" or

"euphoric." It seemed to be a "perfect escape" or "a dream world."

Fifteen percent disliked their first experience feeling "scared" or

finding it "terrible," while one individual (5 percent) characterized the experience as "strange," "weird, but interesting."

In 95 percent of the cases, first use occurred in a social setting,

with 70 percent smoking and sharing a joint at a party or with a

small group of friends (mean of 5) at someone's house. Four users

(20 percent) related minor injuries, repeated vomiting, or arrests

by the police as problems occurring with the first use. Three of

these individuals had either snorted phencyclidine or taken it by

mouth.

95
The phencyclidine "high" was reported to be very intense, several

times stronger than marihuana, comparable to LSD, although shorter

in duration. Most individuals compared it with LSD, but insisted

that it was different, "in a class by itself."

The drug had a pronounced effect on the subjects' thinking, time

perception, sense of reality, and mood. Thinking was described as

"speeded" or "wired," the mind going faster while time was slowed

down, with "no more reality." Everything was reported as being

different, in another dimension, and seen from a new point of view.

Life was dramatized, a fantasy world where "you don't have to dream,

your wishes are fulfilled" and "what you want to happen comes true."

Everything was felt to be complete and make more sense. The mind

could focus on one object and see beauty in the smallest thing. A

sense of commnunity, oneness with others and with animals was reported. Religious thoughts and the experience of death were frequently

mentioned. Mood states were also intensified, with users in most

cases feeling happy or euphoric, although everyone had also experienced severe depression and had recognized the drug's potential

for bringing one to either "the heights or the depths of being."

Music was "absorbed" light was "felt," and space and depth were

"distorted," "seen in 2D." Frequently users reported feeling like

they were "floating." Rarely did they relate visual hallucinations.

Users also experienced a feeling of strength and endurance. They

described feeling "powerful," "superior," "arrogant," with "bursts

of energy," "like God was with you, and you could move mountains."

There was also a loss of inhibitions. It was felt to be difficult

to do things; one had "to think about moving or talking." In addition, they described feeling restless and nervous.

Chronic use of phencyclidine also took place in a social setting

with the sharing of joints. Individuals would join in with 2 to 5

others at a friend's house or at home. The membership of a group

who shared in the use of phencyclidine remained quite stable over

long periods of regular use. They would listen to music, talk,

dame, and enjoy sex together while "high." Less often they would

go to a rock concert or go out in public. They took phencyclidine

as frequently during the daytime as in the evening.

The majority (60 percent) continued to use phencyclidine because

they enjoyed or liked the "high." Frequently all their friends

used phencyclidine and "it had become a life style." At times the

availability of phencyclidine or making money from phencyclidine

sales played a role. For 80 percent of the users, phencyclidine

was their drug of choice. Three individuals preferred heroin and

one preferred seconal. Nonavailability, incarceration, or hospitalization were the major factors interrupting the regular use of phencyclidine. Participation in a drug treatment program or moving out

of the area also interrupted the pattern of phencyclidine use.

96
Tolerance, Psychological Dependence, and Side Effects

Tolerance to the psychic effects of phencyclidine was reported by

chronic users. Initially they would get "high" after 2 or 3 puffs

on a phenyclidine joint; following a one week period of daily use

they required 1/2 to 1 joint. After smoking for a period of 2 to

6 weeks, most individuals used 1 or 2 joints at a time. Some users

reported being able to smoke up to 1/4 gram of street-purchased

material at one sitting, following several months of regular, daily

use. Psychological dependence, described as craving, was noted by

chronic users, but no withdral symptoms were reported.

Phencyclidine taken in typical "street" doses was reported to prevent sleep for 8 to 12 hours, decrease appetite, and to cause constipation and urinary hesitancy. Chronic users averaged one meal

or less per day and lost 10 to 35 pounds during periods of regular

use.

Chronic Toxicity

Chronic phencyclidine users reported persistent problems with memory and speech, and difficulty with thinking following long periods

of regular use of the drug. Recent memory capability appears to be

primarily affected. Users complain of stuttering, inability to

speak or blocking, and difficulty with articulation. Speech and

memory difficulties lasted as long as 6 months to 1 year following

prolonged daily use of large doses of phencyclidine.

Several chronic users complained of anxiety or nervousness during

and following periods of regular phencyclidine use and sought

psychiatric care. Some individuals became severely depressed, and

attempted suicide on repeated occasions after chronic exposure to

phencyclidine.

Chronic users reported personality change, social withdrawal, social

isolation, and divorce resulting from their use of phencyclidine.

In some cases, violent behavior was one of the effects.

Employment has been lost and education disrupted as a result of the

effects of phencyclidine with chronic patterns of use. Frequent

arrests for being under the influence of phencyclidine or for possession result in a criminal status.

Chronic phencyclidine use has culminated in a picture of violent

and aggressive behavior, paranoia, delusional thinking, and auditory

hallucinations. In most cases no known behavioral disturbance or

psychiatric problems preceded the use of phencyclidine. Typically,

the individual had used phencyclidine over several months or a few

years with the same group of friends. Form apparent reason a

sudden development of paranoia and auditory hallucinations was accompanied by violent, unpredictable behavior. Friends and family

often became fearful and brought the user to medical attention.

97
Laboratory and Neurological Findings

Fourteen (70 percent) individuals reported using phencyclidine within 24 hours of the clinical examination and 85 percent within 48

hours (see Table 7). All mine samples obtained just prior to the

physical examination were found to contain detectable levels of unchanged phencyclidine by gas chromatography-mass spectrometry and

the majority of serum samples (85 percent) obtained were also positive for phencyclidine. Phencyclidine levels were higher in cases

where the last use of phencyclidine by history was within a 48 hour

period (see Table 8).

Eight (40 percent) individuals reported using phencyclidine within

6 hours of the examination and had a "blank stare" appearance and

slurred speech. Ptosis, conjunctival infection, and vertical and

horizontal nystagmus were present. They had an ataxic gait and

were unable to tandem walk. One third appeared lethargic and were

disoriented for time and place.

Individuals reporting no phencyclidine use for 24 to 48 hours prior

to the examination had unsustained vertical and horizontal nystagmus

and difficulty with tandem gait (see Chart A).

On electroencephalographic study, one chronic user showed bursts of

spike and slow wave activity associated with observed myoclonic

twitching in response to photo-stimulation (see Photograph A).

Three chronic users selected for electroocculographic study showed

jerk nystagmus, saccadic pursuit, and hypometric slowed saccades

(see Photographs B,C,D). Urine samples concurrent with test procedures were positive for phencyclidine.

98
TABLE 7

HISTORY OF PCP USE PRIOR TO PHYSICAL EXAMINATION

LAST USE NO. CASES CUMULATIVE PERCENTAGE

<6 hours 7 35.0

7 - 24 hours 7 70.0

25 - 48 hours 3 85.0

49 - 72 hours 1 90.0

97 -120 hours 2 100.0

TABLE 8

CHRONIC USERS' URINES COLLECTED PRIOR TO P.E.

LAST USE NO. CASES URINE LEVEL

1 - 12 hours 8 1.73 ug/ml

13 - 24 hours 4 0.85 ug/ml

25 - 48 hours 4 1.24 ug/ml

> 48 hours 4 0.13 ug/ml

99
Chart A

Physical Examination Findings

Vital Signs <6 hours 7 - 24 hours 25 -48 hours >48 hours

B.P. - SYST. 132 132 115 109

- DIAST. 79 71 65 65

PULSE 88 79 78 72

RESPIR. RATE 15 17 14 16

ALTERED STATE OF

CONSCIOUSNESS

(Lethargic, somnolent,

'high'_

Disorientation

(time, place)

SPECH (slow, slurred,)

repetitive, intermittently unable)

E.O.M.M.

'Stare' appearance

Disconjugate gaze

Nystagmus

H

V

Sustained

PUPILS

Size

Light Reaction

(Sluggish, decreased

amplitude)

Corneal reflex

(Decreased or absent)

MOTOR SYSTEM

Movements:

Repetitive

Restlessness

Catalepsy

Rigidity

Hyperreflexia (L/e)

Gait (Ataxic, broad

based)

COORDINATION

Tandem standing

(Difficulty or unable)

100
Photograph A

Chronic Phencyclidine User Electroencephalogram

This abnormal electroencephalogram shows a positive photoconvulsive response. Intermittent pkotic

stimulation at botk Slow and fast flash frequencies induces bursts of spike and slow wave activity.

With sustained 20 cycles per second stimulation, involuntary myoclonic twitching is noticed on the

left face, arm and leg. This recurs with repeat pkotic stimulation, and is again clinically focalized to the Zeft side, although electroencephalographically bilateral spike and slow wave discharges occur.
Photograph B

PCP-Induced Oculomotor Disorders

These records were obtained from photoelectric cells placed about

each eye in the horizontal plane and then from EOG electrodes

placed about each eye in the vertical plane.

FIXATION: Jerk nystagmus at the gaze limit of the photocell

technique, 15°.

102
Photograph C

SMOOTH PURSUIT: Ramp pursuit grossly saccadic (staircase) in horizontal and

vertical planes.
Photograph D

SACCADES: Grossly abnormal horizontal and vertical hypometric Slowed saccades.
THE ACUTE STATES OF PHENCYCLIDINE INTOXICATION

History and Presentation

The spectrum of signs and symptoms and the pattern of recovery in

acute intoxication with phencyclidine vary with the dose and route

of administration

Individuals are most frequently brought to a hospital emergency room

when found unresponsive or when exhibiting bizarre or violent behavior (see Table 9). Others are brought in after having been

cbserved to be grossly incoordinated, driving erratically, or acting inappropriately after an automobile accident. Some individuals

present with minor or major trauma.

Clinical Picture and Course

A confusional state delirium lasting less than 8 hours appears to

follow a typical street dose after smoking one "joint." Individuals who either smoke greater amounts or take a higher dose orally

or by "snorting" may present in stupor or coma. This initial state

lasts less thanthreehours in most cases and a confusional doserelated state follows for 24 to 72 hours. Massive oral "overdose"

involving up to one gram of street-purchased material has resulted

in periods of stupor or coma of several hours to two weeks in duration. This initial stage is followed by a prolonged recovery with

a confusional state persisting up to two weeks (see Table 10).

The confusional state delirium induced by phencyclidine is characterized by immobility and a "blank stare" appearance in a-patient

who is noncommunicative. The patient is disoriented and apprehensive, becoming easily agitated or excited. These patients are

grossly ataxic and exhibit horizontal and vertical nystagmus and

catalepsy on testing. Muscle rigidity may be present. Most patients are communicative within 1 - 2 hours, and appear alert, oriented, and exhibit normal behavior within 5 hours of admission

to the emergency room.

In phencyclidine stupor or coma, the eyes may remain open although

the patient is responsive only to deep pain. Hypertension and

tachycardia are present, and in all but the more massive oral

"overdoses" respiration is normal. The pupils are initially miotic

but reactive to light. Spontaneous nystagmus, 'purposeless" movements, facial grimacing, and muscle rigidity on stimulation are

characteristic findings. Repeated episodes of vomiting, increased

bronchial and oral secretions, and profuse diaphoresis are frequently

observed. An initial stage of stupor or coma lasting less than four

hours my be followed by a period of confusion or delirium lasting

up to 2 1/2 days (refer to Table 11).

105
TABLE 9

PRESENTING PICTURE AMONG 18 CASES

OF ACUTE PHENCYCLIDINE INTOXICATION

PRESENTING PICTURE CASES PERCENT

Unresponsive 11 61.0

Bizzaare behavior 4 22.0

Automobile accident 2 11.0

Violent behavior 1 6.0

TABLE 10

COURSE OF RECOVERY OF 16 INDIVIDUALS

BY STATE OF CONSCIOUSNESS ON ADMISSION

PRESENTATION CASES DURATION OF PERIOD OF DELIRIUM TIME REQUIRED

INITIAL STATE OR CONFUSION UNTIL "NORMAL"

Group I:

Confusional

state and

history of

smoking 1

street joint 4 5 hours ------ 5 hours

(3-8 hours) (3-8 hours)

Group II:

Initial

state of

stupor or

coma 6 3 hours 34 hours 37 hours

(1-4 hours) (5-62 hours) (14-66 hours)

GROUP III:

Initial

state of

stupor or

coma (>

6 hours 4 50 hours 163 hours 212 hours

(6-103 hours) (75-288 hours) (114-360 hours)

106
TABLE 11

SUMMARY OF CLINICAL HISTORIES OF 18 CASES OF ACUTE PHENCYCLIDINE INTOXICATION

ACUTE CONFUSIONAL STATE

OR DELIRIUM (N=7) STUPOR OR COMA (N=11)

PART I: VITAL SIGNS

A. Respiratory rate (normal or)

slightly increased 24 mean 21 mean

B. Blood pressure (increased) 18-32 mean 16-25 mean

Systolic 142 mean 155 mean

116-160 range 100-180 range

Diastolic 85 mean 94 mean

76-100 range 60-110 range

C. Pulse (increased) 105 mean 88 mean

88-140 range 60-112 range

D. Temperature (normal or 100.1°F 99.3°F

slightly increased) 98.8°-101.4°F range 97.0°-100.8°F range

PART II: CLINICAL FEATURES

A. Responsiveness Appears awake; initially uncommunicative, Unresponsive to verbal

may respond to commands or respond to stimuli, responds with

simple questions with nodding or eye movement to deep pain

movement later incomplete verbal responses

and then becomes communicative/talkative
TABLE 11 (Continued)

ACUTE CONFUSIONAL STATE

OR DELIRIUM (N=7) STUPOR OR COMA (N=11)

B. Orientation

C. Behavior

D. Speech

EYE SIGNS

A. Eye lids

B. Eye position & movements

C. Nystagmus

Disoriented for time and place; appears

confused and fearful; amnesia for episode

Agitated, excited, combative; regressive;

self-destructive or "bizarre" behavior;

insomnia, anorexia, incontinence; followed

by depression, irritability and emotional

lability

Dysarthria (slurred), perseveration; may

be intermittently anarthric

Eyes open ("stare" appearance) with

ptosis

Paucity of spontaneous eye movements

appearance, may be fixation instability

dysconjugate gaze or hypometric saccadest

Bilateral horizontal jerk nystagmus;

may be vertical nystagmus (upward-downward)

Vocalizations; "moaning,"

"groaning," "grunting;"

followed by anarthria and

dysfluency, initially with

automatic speech

Eyes open ("awake" appearance) or eyes closed

May be roving eye movements;

dysconjugate gaze; doll's

eye movements present

Interittent horizontal and

vertical nystagmus at rest
TABLE 11 (continued)

ACUTE CONFUSIONAL STATE

OR DELIRIUM (N=7) STUPOR OR COMA (N=11)

D. Corneal reflex

MOTOR SYSTEM

A. Gait

B. Muscle tone

C. Movements

D. DTR's

E. Seizure activity

OTHER

A. Vomiting (central)

Decreased or absent

Grossly ataxic (sensory), unable to

tandem stand/walk; may be component

of muscle rigidity

Rigidity (catatonia), catalepsy

(waxy rigidity)

Motor restlessness, repetitive movements, facial grimacing

Increased

Repeated episodes over 1/2 to 3 hours

period

Decreased or absent

Muscle rigidity, on stimulation, opisthotonic posturing, decerebrate rigidity

Spontaneous "purposeless

movement;" muscle tremor,

muscle twitching, fasiculations

Increased

Generalized motor seizures

may be early or delayed in

appearance and repetitive

Repeated episodes
TABLE 11 (continued)

ACUTE CONFUSIONAL STATE

OR DELIRIUM (N=7) STUPOR OR COMA (N=11)

B. Increased secretions

(lacrimation, salivation,

diaphoresis, bronchorrhea)

C. Evidence of minor trauma

"Drooling," diaphoretic

Abrasions, lacerations, ecchymoses

Secretions in posterior

pharnys at nares and mouth;

tearing, diaphoresis

Abrasions, lacerations,

ecchymoses
Urine phencyclidine levels of 26.2 - 151.9 mg/ml were found in

samples collected within 12 hours of admission in four patients

who remained in coma for greater than 6 hours and required between

7- 15 days for recovery to normal (see Table 12).

Status epilepticus followed by cardiopulmonary arrest without recovery has been reported with a blood phencyclidine level of 7.0

mg/ml.

Diagnosis

Drug use is frequently considered to be the etiology of symptoms

when a young person presents acutely confused or delirious with no

focal neurological findings. But encephalitis, head injury, postictal state, and metabolic causes must be ruled out.

The "blank-stare" appearance and catatonia-catalepsy appear to be

unique to phencyclidine as effects of commonly abused drugs. The

absence of mydriases, and the presence of ataxia and nystagmus rule

out the central nervous system stimulants and LSD when considering

the acutely excited and confused patient.

In coma with or without respiratory depression, hypertension and

hyperreflexia differentiate phencyclidine intoxication from a

sedative hypnotic "overdose." If, in addition, decerebrate posturing or repetitive generalized seizure activity is observed

phencyclidine intoxication should be suspected, although other

serious causes producing a similar clinical picture must be ruled

out.

Cases involving the ingestion of large doses of phencyclidine present with coma which may last several hours or days. The prolonged

recovery with a confusional state lasting up to two weeks is characteristic of phencyclidine intoxication. If persistent paranoid

or depressive psychosis follows recovery, phencyclidine intoxication

should be suspects.

In combined intoxications involving phencyclidine and barbiturates,

normal or low blood pressure, hyperreflexia and respiratory depression may be observed.

Management

The acutely confused patient is best managed by sensory isolation

with observation at a distance. Minimizing verbal and tactile

stimulation does not preclude the monitoring of vital signs. Important functions to monitor are respiration, blood pressure,

muscle tone and activity, renal function, and temperature. Ideally,

the patient would be placed on a cushioned floor in a "quiet room"

with a monitor present. In most settings, protection of the patient and staff necessitates the use of restraints.

The early management of the stuporous or comatose patient involves

gastric aspiration-lavage and nasopharyngeal suctioning. In view

111
TABLE 12

CLINICAL HISTORIES OF TWO CASES OF ACUTE PHENCYCLIDINE INTOXICATION

Age

Sex

Estimated dose

Route

Coma

Confusion delirium

and somnolence

Depression, irritability

and emotional lability

alert and oriented

Cardiovascular system

blood pressure (mean)

pulse (mean)

Repiratory status

Seizure and motor

activity

Toxicology

Day 1

2

3

4

5

6

CASE 1

22

Male

One gram "street" material

by mouth

25 hours

71 hours

84+ hours

Transferred to psychiatric

unit

147/92 (84 hours)

94

Excessive mucous/secretions

on admission; hypoventilation

x15 ours, Tidal; volume

tions with 5 sec. periods of

100 cc's; irregular respiraapnea x15 ours; required

ventilatory assistance x27

hours; complications; right

upper lobe pneumonitis

Decerabrate rigidity;

opisthotonic posturing;

muscle tremors, twitching;

generalized motor seizures

at 66 and 78 hours;

treatment: Valium and

Dilantin

On admission: 26.2 μg/ml

PCP (urine)

26.2 μg/ml

18.2 μg/ml

15.9 μg/ml; 18.0 μg/ml

18.5 μg/ml; 20.0 μg/ml

4.7 μg/ml;

0.5 μg/ml;

1.3 μg/ml

1.2 μg/ml;

0.4 μg/ml;

0.1 μg/ml

0.3 μg/ml

CASE 2

22

Male

One gram+ "street" material

By mouth

103 hours

77 hours

32 hours

178 hours

151/98 (108 hours)

111

Excessive Mucous/secretions,

hypoventilation on admission;

hypoventilation x60 hours,

Tidal; Volume 50 cc's; apnea

x4 hours; required ventilatory

assistance x107 hours; complications: bilateral basilar

pneumonitis

Decerbrate rigidity;

opisthotonic posturing;

muscle tremors; twitching;

focal motor seizures at 3 and

21 hours; generalized motor

seizures at 3-1/2 & 89 hours;

treatment: Dilantin

On admission: 151.9 μg/ml

PCP (urine)

151.9 μg/ml

112
of the recovery of large amounts of phencyclidine from the stomach

contents in fatal "overdoses," gastric lavage is indicated in oral

ingestions.

Intubation is often difficult because of increased muscle tone.

Laryngeal reflexes are maintained and active and attempted endotracheal intubation may precipitate laryngospasm. More responsive

patients fight intubation by biting the tube off or spitting it out.

However, respiratory depression may be delayed in appearance and

necessitate a prolonged period of ventilatory assistance. Positioning and intermittent suctioning will preclude respiratory distress

secondary to secretions in the posterior pharnyx.

Urine and blood samples should be collected at the time of admission

and screened for phencyclidine, sedative hypnotics, ethyl alcohol,

opiates and amphetamines. Urine samples should be capped to prevent loss of phencyclidine, which is volatile.

The Recovery Phase

Most acutely confused patients are communicative within 1-2 hours

and alert and oriented within 6 to 8 hours of admission after ingesting the usual street dose. After they are alert and oriented,

patients should be monitored for a minimum of two hours. Patients

who remain oriented and alert and exhibit normal behavior can then

be discharged.

If a patient remains stuporous or comatose, responding only to deep

pain for greater than two hours, a minimal observation period of 24

hours is indicated. The recovery phase may vary from several hours

to days depending on the route and the dose ingested.

Suicide has been reported during the "come down" period, 6 to 24

hours after taking phencyclidine. Patients should be informed about

depression, irritability, feelings of isolation and nervousness that

often accompany this period, and may last up to 48 hours.

All patients in whom coma is followed by a prolonged period of confusion should have a psychiatric evaluation prior to discharge.

Persistent paranoia or depression may require transfer to a psychiatric unit.

Treatment

No agent is known to be specific for antagonizing the toxic effects

of phencyclidine. However, some experience has been gained in the

symptomatic treatment of seizures, hypertensive crisis, and aggressive and violent behavior.

Intravenous diazepam (Valium) in doses of 10 - 15 mg followed by

intravenous diphenylhydantoin (Dilantin) has been effective in the

control of seizures. In some cases it has been necessary to give

an acutely confused patient 10 - 20 mg. of Valium orally to prevent injury to both the patient and staff. During the confusional

113
phase of the prolonged recovery period, some patients have received

repeated doses of 10- 15 mg of Valium to control motor restlessness and agitation. These therapeutic doses of sedative hypnotic

agents do not appear to produce significant respiratory depression

in phencyclidine intoxication.

Diazoxide (Hyperstat) has been used to reduce blood pressure during

a hypertensive crisis associated with acute phencyclidine intoxication. Hydralazine hydrohloride (Apresoline) has also been suggested as a possible substitute agent.

Phenothiazines are contraindicated in acute phencyclidine intoxication where a confusional state is associated with hypertension,

tachycardia ataxia and nystagmus. It has not been demonstrated

that phenothiazines shorten the recovery phase or antagonize the

behavioral effects of phencyclidine. In some cases they have produced prolonged, severe hypotension.

SUMMARY

Phencyclidine use appears to be in a growth phase nationally. Factors contributing to the increasing popularity include the user's

ability to control the dosage, an understanding of the immediate

effects, and its availability. Those most at risk appear to be

young Caucasian males.

Phencyclidine-related problems are often like tips of icebergs, the

underlying causes of which are hidden from public view. The problens often surface in the form of speech difficulties, memory loss,

thinking disorders, personality changes, paranoia, severe depression,

violence, accidents, suicides and homicides. Of particular concern

to law enforcement personnel is the upsurge in phencyclidine-related

violent crimes and carrying of weapons by users to protect themselves

from their imagined persecutors.

The evidence currently available supports the assumption that if

there is a solution to the problem of phencyclidine abuse, that

solution is prevention. Therefore, medical personnel and others

within the helping professions must be alerted to the fact that

phencyclidine is not just another drug problem. The findings from

users we have already studied strongly suggest that phenyclidine

is not an "upper" or a downer,"I but perhaps an "insideouter," with

long term implications.

FOOTNOTE

1The SES measure employed in this analysis was based on a formula

which was especially developed for this analysis, and which was

found to be more discriminating than the Hollingshead-Redlich formula. It included educational level of both parents, rather than

only that of the head of the household, and also included codnsideration of the subject's income, and whether or not the family was on

welfare, in addition to the occupational level of the head of household.

114
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S.H. Phencyclidine - states of acute intoxication and fatalities.

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1975.

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patterns seen in street drug analysis. Clin Toxicol, 9(4):503-511,

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on Narcotics, 26(4):131-133, October-December, 1974.

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findings associated with sernyl infusion. EEG, Clin Neurophysiol,

11:696-798, 1958.

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Shulgin, A.T., and MacLean, D. Illicit synthesis of phencyclidine

(PCP) and several of its analogs. Clin Toxicol, 9(4):553-560, 1976.

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The cataleptic state induced by ketamine: a review of the

neuropharmacology of anesthesia. Neuropharmacology, 11:303-315,

1972.

AUTHORS

Steven E. Lerner, M.S.

R. Stanley Burns, M.D.

Steven E. Lerner, R. Stanley Burns, Ronald L. Linder, & Associates

350 Parnassus Avenue, Suite 304-A

San Francisco, California 94117

118
Chapter 6

Phencyclidine and Ketamine Intoxication:

A Study of Four Populations of

Recreational Users

Ronald K. Siegel, Ph.D.

The time is 1926. In his laboratories at the University of Chicago

psychologist Heinrich Kluver is just beginning the first experimental studies of the hallucinogen mesacaline. Derived from the

peyote cactus which had been used by indigenous Indians throughout

the New World for thousands of years, mescaline had only recently

been isolated and synthesized, and was rapidly capturing the attention of researchers in Germany. But before this "classic"

hallucinogen was fully investigated, other newer ones were being

developed. Elsewhere in Germany, Kotz and Merkel (1926) had just

reported the chemical groundwork for the preparation of a new

compound, phencyclidine.

The time is 1959. Chen and his colleagues at the Research Laboratories of Parke, Davis and Company in Detroit have just "discovered"

phencyclidine and observed its anesthetic effectiveness in animals.

That announcement added one more drug to the rapidly growing list

of psychoactive compounds, both natural and synthetic, which affect

behavior. Yet science was just beginning to dwelop techniques

for studying the effects of drugs on behavior. That year witnessed

the publication of a new journal, Psychopharmacologia, officially

announcing the pursuit.

It is now 1978. With such an evolutionary, albeit natural, lag

between the emergence of a new drug and its scientific investigation, it is not surprising that today, a generation after phencyclidine's discovery, those people born when the drug was first

developed are using and exploring its psychoactive properties

while scientific investigations still lag behind. Nonetheless,

reports fromuserswho first experiment with and experience the

drug effects (the street drug users) provide a rational basis

for the questions which researchers must ultimately attempt to

ask and answer. Kluver's original studies of mescaline were based

upon and guided by reports from people using the drug at that time.

Similarly, present day studies of phencyclidine and its derivatives

may be helped by examination of the patterns of use and intoxicationin contemporary nonmedical users. It is in this spirit that

the following studies with phencyclidine and its derivative

ketamine were conducted.

119
Phencyclidine and ketamine are chemical compounds known as arylcyclohexylamines. While many psychoactive drugs can be easily

classified as either stimulants, depressants, or hallucinogens,

the arylcyclohexylamines defy convenient classifications as they

appear to have mixed excitatory, sedative, cataleptoid-anesthetic,

and hallucinatory properties. The major questions concerning the

use of these compounds by man are: (1) Why do humans initiate

use of arylcyclohexylamines? (2) Why is such use maintained?

and (3) What are the consequences of such continued use? These

questions are addressed in this chapter. It will be presently

seen that the psychological intoxication resulting from arylcyclohexylamines is a primary reason for their continued use.

The nature and extent of thisintoxicationin several groups

of contemporary users Will also be explored. Furthermore, it

will be shown that the phenomenology of intoxication with these

compounds warrants their classification as true hallucinogens.

I. PHENCYCLIDINE

STREET DISCOVERY AND INITIAL USE

Phencyclidine (PCP) or 1-(1-phenylcyclohexyl) piperidine hydrochloride was first reported in the context of nonmedical street

use in the Haight-Ashbury district of San Francisco in 1967. At

that time the drug was marketed as the PeaCe Pill or PCP (an

abbreviation of the complete chemical name). While the HaightAshbury Free Medical Clinic reported that "use of the drug....

virtually ceased" by early 1968, it has remained consistently

available under a wide variety of names. Such names include

Hog, Angel Dust, Dust, Crystal, Crystal Joints, CJ, KJ, Peace,

Peace Weed, Supergrass, Superweed, Rocket Fuel, Elephant Tranquilizer, Horse Tranks, Sheets, Seams, Surfer, Snorts, Scuffle,

Cadillac, Cyclones, Sana, Mist, and Goon (cf. Perry 1975). Other

more recent common names include Amoeba, Angel Hair, DOA (dead on

arrival), Killer Weed, and Synthetic Marihuana (Young et al. 1977).

This author has also doctumented the terms Lovely, Lovely High,

and Super Kools. PCP is also the most prevalent drug in misrepresented street drugs (Perry 1977) and has recently appeared under

the names THC, psilocybin, mescaline, and other hallucinogens

Which are rarely available in pure form on the illicit market.

Cases of adverse reactions, unpleasant subjective experiences,

poisoning, and prolonged psychoses are well known (e.g., Liden,

Lovejoy, and Costello 1975; Rainey and Crowder 1975) and have

probably attenuated some street use since 1971. However, the

low costof PCP and its ease of production have contributed to

its reappearance on the street (Burns and Lerner 1976). Indeed,

one gram of PCP can make more than 24 "street joints" and doses

as low as 3 mg are behaviorally effective. PCP's subjective

effects include distortions in body image, hallucinations and

dissociation. There can also be a preoccupation with death

or death-related thoughts (meditatio mortis) and this has been

120
the basis for numerous criminal defenses of diminished capacity

(see "Phencyclidine, Criminal Behavior, and the Defense of Diminished Capacity," this volume). The prolonged and fluctuating

effects are believed to be due to PCP's affinity for adipose

tissue, its slow release from such tissue, and its subsequent

selective uptake by brain tissue (Bums and Lerner 1976). Some

adverse reactions are believed to be caused by related compounds

TCP (1-(1-2-thienylcyclohexyl) piperidine) , and PCC (1-piperidinocyclohexanecarbonitrile), often produced in illicit syntheses.

Related compounds such as PHP, which is 1-(1-phenylcyclohexyl)

pyrrolidine, may also contribute to adverse reactions.

Nonetheless, users initially experiment with the drug primarily

out of a curiosity about it and a desire to experience the anticipated drug effects of tranquilization, dissociation, and hallucinations. More often than not, initial use of PCP comes about as a

result of users self-administering what they believe to be THC,

psilocybin, or some other alleged drug. In these latter instances,

PCP is often combined with LSD.

MAINTENANCE OF USE

The street users' initial encounters with PCP would have brought

them into contact with both the unpleasant and pleasant effects of

the drug. Independent of adverse reactions and even "schizophrenomimetic" or "psychotomimetic" effects, many users found the

drug to have highly reinforcing properties. Indeed, the preclinical

animal literature is rich with examples of PCP's powerfully

psychoactive and reinforcing effects (Balster and Chait 1976),

and PCP represents one of the only hallucinogens that monkeys will

reliably self-administer. While it is difficult to determine the

unique properties that reward such animal behavior, the euphoria,

inebriation, and hallucinatory effects are undoubtedly responsible

for maintaining PCP use in man. The effects can be interpreted as

a state of intoxication with high reinforcement potential. While

many nonpharmacological factors (e.g., easy and inexpensive

illicit synthesis) may affect man's use of a drug such as PCP,

psychological intoxication appears to be the primary reinforcing

effect.

These PCP intoxications can vary greatly among users. Pollard,

Uhr, and Stern (1965) examined the effects of 10 mg (p.o.) in

a modified sensory deprivation situation. One of their college

student subjects described a typical experience marked by a preoccupation with abnormal bodily sensations, lack of visual imagery,

and marked feelings of depersonalization:

I feel like I can't think anything even. And I can't

express myself even if I can think because it's hard

for me to talk. My lips are numb. It's so uncomfortable. My perception is very bad. Nothing is clear

. . . . My mind is just a complete blank....I have such

a strange feeling. I can't explain it. Like I'm still

asleep, yet I'm not asleep. I'm awake (pp. 89-90).

121
Other subjects in this study described these sensations as "I

feel dissociated with the world" (p. 131) and "I feel dead"

(p. 134). Luby and co-workers (1959) administered 1 mg/kg, i.v.,

to normal subjects who reported body image changes, estrangement,

disorganization of thought, negativism and hostility, drowsiness

and apathy, hypnagogic states, feelings of inebriation, and repetitive motor behavior.

These authors described the hypnagogic states as resembling

pseudohallucinations wherein subjects "reported feeling as

though they were in some specific setting and were able to

describe it in detail. While the reports typically had reference

to past events, they were expressed as though the experiences

were taking place at the moment. The lack of time-boundedness

was reminiscent of dreaming. As in dreams, multiple shifts

occurred in the settings experienced by the subjects, sometimes

in rapid succession" (p. 366). Sometimes the subjects reported

euphoria and feelings of inebriation: "When it occurred, the

subjects would often smile vacuously and compare their feelings

to those resulting from several Martinis" (p. 366).

Most users have difficulty in describing this intoxication and

simply report a state of oblivion and fantasy. Perry (1975)

summarizes some of the psychological effects of this state:

The high continues for 4-6 hours, during which time

the user often becomes very talkative, having sincere

and sympathetic conversations, usually with others

similarly intoxicated. This gradually develops into

a state of mild depression as the high wears off; the

person is irritable, feels isolated and sometimes

paranoid. These users generally require 24-48 hours

to completely return to what they consider normal

(p.2).

Many users find the experience a positive one and emphasize the

rewarding aspects of the same symptoms that other users cite as

negative. Consider the following account provided by one of

the author's respondents:

Immediately after smoking the Dust (PCP) I started

experiencing the effects. All my troubles seemed to

go away. I felt a little drunk and had some trouble

walking around the apartment. Objects appeared either

very far away or very close and I couldn't really

judge distance at all. This reminded me a lot of

Acid (LSD). I closed my eyes for a while but didn't

see much more than a few colored geometric patterns.

Not nearly as trippy as other psychedelics, but it

was clearly a psychedelic. I liked being apart from

things, and felt outside my body for most of the

trip. That was fun. Before I smoked I had been

troubled about some exams coming up and felt I wasn't

really prepared. All that anxiety vanished with the

122
Dust. I even looked at my books and work but

couldn't get excited about it. I felt at peace. It

was a good feeling. When I started coming down, I

felt sad that I was leaving such a lovely place. I

think I even cried. I hadn't done that in years.

But most of all, I remember the peace and tranquility.

Everything was good. I want to be there always.

That's why I like to call Dust PPP - Perpetual Peaceful Place.

Recent studies of phencyclidine users are beginning to uncover

an increased occurrence of these pleasurable and positive effects

among those who continually self-administer the drug. For example, Walters (1978) has studied a group of multiple drug users

in Philadelphia, primarily intranasal PCP users, and found that

PCP use is rarely involved with PCP-related emergencies or

clinical crises:

Our respondent population is small, somewhat transient

and currently just under 50 youths ranging in age from

14 to 24 years, divided about evenly between males and

females. Of these, 34 have some history of PCP use,

with 15 of them using it between five and 10 times per

week. Finally their histories of PCP use range from

between one and seven years, with three years' use

being average. Yet by far, most of the drug-using

youths with whom we have had contact are not dulled,

depressive, anomic bundles of pathology described in

the literature and the media. Rather, they are bright,

level-headed and stable and eager and willing to

experience life, including drugs that are a part of

that life (p. 9).

Stickgold (1977) has recently commented on the emergence of PCP

as a drug of choice among may users. He describes this population

of users:

Those who are today using PCP, tend to come from a

different place, both socio-economically and in their

drug-taking behavior. Rather than the middle class

seekers of the new sensate worlds to explore, PCP is,

today, becoming the drug of choice of the lower class

oppressed minority group member seeking an escape from

persecution. In the past s/he has found this escape

in other depressant drugs such as heroin and barbiturates. Today PCP not only provides that escape, but

also produces a degree of increased awareness that is

different enough to be interesting, and mild enough

not to be too frightening (p. 2).

CONSEQUENCES OF CONTINUED USE

Despite the obvious negative effects, and the apparent attractiveness of the positive effects, the consequences of continued

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phencyclidine use are still largely unknown. The rather prolonged

recovery time from acute intoxication, sometimes lasting as long

as 15 days (Burns and Lerner 1976), confuses the issue of longterm effects. In addition, the persistent psychoses seen in a

very small number of cases (Burns and Lerner 1976; Fauman et al.

1976) may represent either a psychopharmacological effect from

the drug or an individual sensitivity to it. Nonetheless, most

investigators agree that these psychiatric sequelae of continued

phencyclidine use can be serious and represent classic schizophrenic symptoms. With still other chronic users, there is both

preclinical (e.g., Balster and Chait 1976) and clinical (e.g.,

Burns and Lerner 1976) evidence to suggest tolerance to the

psychological effects of phencyclidine requiring use of increasing

doses. Psychological dependence, albeit not physical addiction,

appears prominent among long-term users.

Recently, Ashley (1978) has commented on the consequences of

continued use among PCP users or "peepheads":

Chronics users clearly enjoy PCP and experience it in

a positive way . . ..Most say it takes a few days to return to normal, but many of them don't bother to and

use the drug every day.... (they) almost always complain

of being spaced and worry about turning into 'vegetables'. They are noticeably depressed when not high,

so much so that some have committed suicide at this

point. Serious accidents are commonplace among users.

Almost all report having been in an automobile accident

or knowing someone who was, while on PCP. Falls are

common, even off cliffs or out of boats and windows.

Impairment of motor and sensory functions makes many

normal physical activities dangerous (p. 64).

VARIABLES AFFECTING USE AND INTOXICATION

The precise description of the state of phencyclidine intoxication requires information about concomitant variations between

the characteristics of the behavior and the drug (cf. Siegel

1977a). Information about the behaviors should be specific

with-respect to individual variability, type of behavior and

behavioral history. Information about the drug should be

specific with respect to dose, adulterants, routes of administration, dose-response and time-response relationships, among

others. Such variables can be further modified by environmental

variables such as set and setting. While a full understanding

of these interactions is presently restricted by limited knowledge concerning arylcyclohexylamines, the presence of such a

myriad of interacting variables should temper a desire to simplify

use and intoxication with succinct labels such as "lovely high,"

"perpetual peaceful place," "psychotic," or "schizophrenomimetic."

The studies described below were undertaken in an attempt to

elucidate some of these variables in relation to the psychological

intoxication.

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THE SAMPLE

A large population of recreational drug users, recruited through

advertisements in several Los Angeles area newspapers, was initially

screened. by a telephone interview and a subsequent drug history

questionnaire. A total of 319 phencyclidine users (referred to

as Adult Group) were eventually selected for study. All subjects

in the sample met the initial requirement of having used PCP

more than once in the last year. All subjects were male, 21-38

years old, and were examined and tested in the Neuropsychiatric

Institute at UCLA. Examination procedures included a personal

history questionnaire, drug history questionnaire, mental status

examination, Minnesota Multiphasic Personality Inventory (MMPI),

Experiential World Inventory (El-Meligi and Osmond 1970), indepth interview, physical examination (for most subjects) and

visual imagery and perception tests.

One additional group of chronic PCP subjects was also recruited

for study. This latter group (referred to as Juvenile Group)

consisted of 20 juvenile males, 14-17 years of age, who were

initially referred to the author for evaluation by the courts

or law enforcement officials. All subjects in this sample met the

initial requirement of having used PCP at least once per week for

the previous 6 months.

MULTIPLE DRUG USE

All subjects in the Adult Group had past or present histories of

multiple drug use. Concomitant with their use of PCP, 86 percent

were using caffeine preparations; 81 percent were using alcohol;

81 percent were using cannabis preparations: 62 percent were using

hallucinogens other than cannabis; 58 percent were using tobacco

products; and 20 percent were using cocaine, amphetamine and other

stimulants. Prior to their PCP use, subjects reported experiences

with barbiturates (11 percent), tranquilizers (10 percent), and

opiates (2 percent).

All subjects in the Juvenile Group had past or present histories

of multiple drug use. Concomitant with their use of PCP, 100

percent were using caffeine preparations (mostly cola beverages

and chocolate); 40 percent were using alcohol: 40 percent were

using cannabis preparations: and 15 percent were using barbiturates. Prior to their PCP use, some subjects (20 percent) reported

experiences with stimulants while one (5 percent) used heroin

intranasally. Interestingly, none of the Juveniles had tried

hallucinogens other than cannabis, while 16 (80 percent) had

used volatile solvents in the past.

PREPARATIONS AND PURITY

All subjects used PCP in the form of either tablets, capsules,

powders, botanical mixtures, or liquids. It should be noted that

Helisten (1977) has reported that 88 percent of street THC samples

contain either PCP, PCP and PCC, or PCP and other drugs. Almost

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5 percent of street THC samples are combinations of TCP and PCC.

Since these are all arylcyclohexylamines, whenever subjects in

these studies reported use of street THC, it was recorded as PCP

use. Lundberg, Gupta, and Montgomery (1976) have identified the

quantitative and qualitative aspects of street PCP in the Los

Angeles area. They report that tablets contained 1.O-6.4 mg

each (mean of 5.3 mg); powder averaged 88-100 percent PCP; botanical

leaves (usually mint or parsley leaves) varied from 0.2-7.9 percent; and prerolled cigarettes ranged from 1.0-3.0 mg total for

each cigarette. Another street drug assay laboratory in California (PharmChem, Palo Alto) has found some parsley "joints"

of PCP containing from 3.2-28.3 mg of PCP (Perry 1975). The

most common adulterants for samples received by these laboratories

are LSD and TCP. Recently, NIDA (DuPont 1977) has noted that

street preparations of PCP may be combined with other psychoactive

drugs including heroin, cocaine, methaqualone, methylenedioxamphetamine (MDA), aspirin, and caffeine. Liquid forms of PCP

are usually diverted licit vials of Sernylan (formerly called

Sernyl, phencyclidine hydrochloride, from Bio-Ceutics Laboratories

in Missouri). These vials are usually 10 ml each with each ml

containing either 20 or 100 mg. Illicit PCP in liquid form is

often seen in small "cokevials" or similar glass bottles.

The most common street preparation is in the form of botanical

mixtures sometimes referred to as leaf mixtures. These consist

of PCP mixed with mint leaves, oregano, or parsley. Rarely catnip

is used and, because of the hallucinogenic nepetalactone oils

present in this material, the resultant mixture may be more

hallucinogenic than PCP alone. Lundberg, Gupta, and Montgomery

(1976) also report that marihuana or other cannabis products are

sometimes present in street PCP material.

The Juvenile Group often employed a special preparation called

"Super Cools." This consisted of a mentholated tobacco cigarette

that had been dipped in liquid PCP and dried. The additive effects

of nicotine and PCP in such preparations often resulted in states

of extreme intoxication.

ROUTES OF ADMINISTRATION

In the Adult Group, 280 subjects (88 percent) had experience with

smoking PCP preparations, 38 subjects (12 percent) had orally

ingested tablets or capsules, 15 subjects (5 percent) had used

PCP intranasally via snuffing or snorting, and three subjects

(0.9 percent) had injected PCP intramuscularly.

All 20 Juvenile subjects (100 percent) used PCP exclusively via

the smoking route.

DOSAGES

A number of researchers have attempted to calculate dosages employed in recreational use of PCP. Burns and Lerner (1976) have

estimated that the average amount smoked "per episode" is 35-75 mg,

126
usually delivered in one or two cigarettes or "joints." When

PCP was used intranasally, subjects usually self-administered one

"cokespoonful" per nostril or one "line" per nostril. The amount

of pure PCP in commercially available "cokespoons" has been determined (by this author) to range from 3.5-7.1 mg for a level cokespoon. Assuming an average street purity of 95 percent (cf. Burns

and Lerner 1976), this amounts to an average intranasal dose of

approximately 10 mg (total for both nostrils) per administration.

The average line of PCP is about 0.5 x .15 inches and amounts to

approximately 5 mg of PCP if pure or 4.75 mg if street PCP is

used. Since two lines are used per administration, this amounts

to approximately 9.5 mg, considerably more than previously estimated (cf. Burns and Lerner 1976). when PCP is taken by mouth,

the average dosage is estimated to be 5 mg.

DOSE REGIMES

Subjects in both the Adult and Juvenile Groups fell into several

patterns of PCP use (discussed below). In general, when smoking

the drug, Adult subjects tended to "titrate" or adjust their

dose intake to what was perceived to be an optimal level of intoxication. Most subjects (Adults) used approximately one cigarette

per week in this manner (range = 0.3-4.0). This amount was

generally consumed in one episode per week. When Adults used PCP

intranasally or orally, a single administration would occur approximately once every 8 weeks. In the Juvenile Group, 10 subjects (50 percent) reported that they always attempted to titrate

their use but these users consumed approximately 28 grams of leaf

mixture per month each. However, doses were not evenly distributed

across time. Generally, Juveniles consumed their supply within

a few days, but such use was marked by much sharing and selling

among peers. The remaining 10 Juvenile subjects reported that

they always attempted to stay chronically intoxicated and used

approximately 5 cigarettes per day (range = 2-20).

These doses and dose regimes have created what researchers have

generally agreed are three distinct levels of intoxication: low

(5-10 mg), moderate (10-20 mg), and high (100 + mg). (See Burns,

Lerner, and Corrado 1975 for discussion of dose-effect relationships).

PATTERNS OF USE

The dose regimes together with the set and setting define the

pattern of drug use. Five patterns of drug use have been designated

by The National Commission on Marihuana and Drug Abuse (1973)

and will be used for discussion here.

Experimental Use

Of the 319 Adult subjects, 267 (84 percent) were classified as

experimental users engaged in short term, nonpatterned trials

of PCP with varying intensity and a maximum frequency of 10 times

in their entire drug history. These users were primarily motivated

127
by curiousity about PCP and a desire to experience the anticipated

drug effects of tranquilization, euphoria, inebriation, dissociation, and hallucinations. Their use was generally social and

among close friends. Most did not enjoy the experience and did

not express a desire to repeat the drug use. Interestingly, most

of the Adult users endorsed the street myth that PCP is a "bad"

drug that inevitably produces adverse reactions. Only those experimental users who expressed a belief that their PCP was really

THC or some other drug also expressed a desire to continue using

it beyond the experimental stage. These latter users typically

claimed that PCP was simply "strong marihuana and something you

could probably learn to handle." This latter finding suggests

the importance of psychological set and setting in determining

drug reactions.

None of the Juveniles were classified as expertimental users.

Social-Recreational Use

The remaining subjects in the Adult Group (52, or 16 percent) were

classified as social-recreational users who engaged in more regular

use than experimenters. Use generally occurred in social settings

among friends or acquaintances who wished to share an experience

perceived by them as acceptable and pleasurable. These users

were primarily motivated by social factors and their use was

always voluntary. It did not tend to escalate to more individually

oriented patterns of uncontrollable use. Many of these Adult

subjects started as expermental users but only 12 of them (23

percent) engaged in episodes of more frequent use (see below),

although their primary pattern was the social-recreational one.

In the Juvenile Group, 10 subjects (50 percent) were classified

as social-recreational users. Unlike their Adult counterparts,

these Juveniles all tended to engage in more frequent patterns

of use.

When asked to rank all drugs in terms of recreational drugs of

choice, the Adult social-recreational users ranked cocaine first,

cannabis second, and, surprisingly, PCP third. This may be related to the findings that both PCP and cocaine share similar

sympathomimetic effects (Chen, Ensor, and Bohner 1965). When

asked to rank all drugs in terms of potency in producing intoxication, 93 percent ranked PCP first. Other drugs ranked above

PCP in this category included LSD and Ketamine (discussed in the

second part of this chapter). Juveniles ranked marihuana first

as a recreational drug of choice and PCP second. All Juveniles

also ranked PCP first in potency.

PCP retained popularity as a recreational drug among may Adults

and Juveniles for several reasons:

1) PCP was viewed by Adult users as a misunderstood drug

which opened new altered states of consciousness for exploration. These states were considered to be unobtainable

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or less easily reached via conventional hallucinogens.

2) PCP was viewed by Juvenile users as economical and readily

available.

3) PCP was viewed by both Adults and Juveniles as an extremely

effective and different hallucinogen that could induce intoxication quickly and with such rapid onset of action allow

one to titrate dose. It was considered by these users to

be a "social hallucinogen" which, because of the paucity of

visual effects, allowed the user to be more social than with

the more "visual" psychedelic hallucinogens like LSD.

most social-recreational users felt that the possibility of unpleasant and adverse reactions was a rate-limiting determinant

of PCP use. Consequently, they engaged in stable, low frequency

patterns of use which did not escalate to individually oriented

patterns of uncontrollable use. They also felt that PCP was not

physiologically harmful but rather "expanded consciousness" in

long-lasting ways. Indeed, many of the Adults felt that the drug

took the user "to places that LSD only suggested were there" and

"with PCP the afterglow stays with you for a long time."

Circumstantial-Situational Use

Only three Adult users and four Juveniles engaged periodically in

circumstantial-situational use, defined as a task-specific, selflimited use which was variably patterned, differing in frequency,

intensity, and duration. This use was motivated by a perceived

need or desire to cope with a specific condition or situation.

The motivations cited by users, in order of decreasing frequency,

were: to alleviate the dysphoria associated with situation depression (81 percent); to enhance appreciation of social situations

or musical events (73 percent); and as general entertainment when

other recreations were unavailable (56 percent).

Intensified Drug Use

Nine Adult users (3 percent) and 10 Juvenile users (50 percent)

engaged in episodes of intensified use characterized by long term

patterned use of at least once a day. Such use was motivated

chiefly by a perceived need to achieve relief from a persistent

problem or stressful situation, or a desire to maintain a certain

self-prescribed level of intoxication. Nonetheless, users here

referred to their intensified use as "too much," "loaded most of

the time," "really Dusted," or "bombed." or "toasted" and were

aware of negative effects including unpleasant feelings. For most

intensified users this subsequently curtailed such patterns of

intensified use for varying periods of time.

Compulsive Drug Use

None of the subjects studied engaged in compulsive use, which is

characterized by high frequency and high intensity levels of

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relatively long duration, producing some degree of psychological

dependence. Two Adult users did appear to become compulsive users,

but they dropped out of the study before adequate assessments of

their behavior could be made.

PHENOMENOLOGY AND INCIDENCE OF INTOXICATION EFFECTS

The acute physiological and psychological effects reported by

users did not differ substantially from these described in the

literature (e.g., Burns and Lerner 1976) or elsewhere in this volume. Briefly, subjects (Adults and Juveniles are combined here)

repeatedly sought and experienced heightened sensitivity to

stimuli (94 percent), stimulation (92 percent), dissociation (88

percent), mood elevation (61 percent), inebriation (55 percent),

relaxation or tranquilization (53 percent), hallucinations (30

percent), increased sociability (14 percent), increased cognitive

activity (11 percent), and euphoria (8 percent). A number of

untoward effects were also reported by the users: perceptual

disturbances (78 percent), restlessness (76 percent), disorientation (63 percent), anxiety (61 percent), paranoia (34 percent),

hyperexcitability (27 percent), irritability (22 percent), mental

confusion (22 percent), and partial amnesia (18 percent). Dysarthria was not assessed in the questionnaire but roughly 80

percent of the respondents in the interviews admitted having

experienced this effect as well.

Taken together, individuals reported experiencing negative or

untoward effects in all intoxications and positive or desired

effects in only 60 percent of the intoxications.

The chronic effects reported by the Intensified Drug Users were

also similar to those reported elsewhere in the literature. In

addition to acute intoxication phenomena, users experienced both

desired and undesired effects. The desired effects included:

a generalized feeling of well-being and detachment from worldly

tensions and anxieties (65 percent), heightened perceptual sensitivity in some modalities (43 percent), and psychedelic or transcendental reactions (8 percent). The undesired effects included:

disturbances in time perception (38 percent), nervousness and

irritability (38 percent), perceptual disturbances (31 percent),

fatigue or lassitude (27 percent), and memory disturbances (25

percent).

Overall, chronic negative effects experienced in all intoxications, while positive effects were experienced inapproximately

74 percent of the intoxications.

HALLUCINATIONS AND PSYCHOSES

Of the phenomena reported above, the changes in perception,mood,

and thinking are perhaps the least understood but also among the

most important in determining the precise nature and form of PCP

intoxication. Indeed, Domino and Luby (1972) have suggested that

these abnormal states induced by PCP strongly resemble schizo130
phrenia, especially in creating profound perceptual and cognitive

disorganization and occasionally catatonic immobility. Furthermore,

the presence of perceptual changes such as hallucinations is a

key diagnostic criterion in the determination of the psychotic

phase. Therefore, these perceptual changes were the subject of

concentrated examination and testing in the study.

The definition of the word hallucination (which comes from the

Latin Hallucinari, meaning to prate, to dream, or to wander in

mind) is far from precise. However, a widely accepted definition

in psychiatry is: "A false sensory perception in the absence of

an actual external stimulus. May be induced by emotional and

other factors such as drugs, alcohol and stress. May occur in

any of the senses." By this definition, it is not surprising

that most PCP users have experienced hallucinations. For most

such subjects (94 percent) these consist of a wandering in mind

or attention which is manifested as lapses in attention, mental

confusion, clouding, and related phenomena. Such experiences

include difficulty in maintaining attention during complicated

tasks: difficulty in maintaining thoughts during conversation;

and general preoccupation with subjective sensations. These

effects are similar to those Domino and Ludy (1972) have described

as "attention disorder," "withdrawal," and "clouding delirium."

The most common perceptual disturbance was a change in body image.

Luby and co-workers (1959) have described this state as "accompanied

by loss of 'ego boundaries', impaired ability to distinguish self

and nonself stimuli, feeling of depersonalization, and a sense

of unreality" (p. 364). Generally, subjects reported that their

bodies felt strange and distorted and these feelings were usually

coupled with changes in tactile sensations. Visual changes included macropsia and micropsia, while tactile changes included

numbness and paresthesias.

The most common mood disturbance was a blanding of affect, although

many users tended to admit that this made them somewhat euphoric

in light of pre-existing dysphoria. Previous researchers have

described this as "ambivalence" and "affect disorder." Undoubtedly,

these changes in mood contributed to the feelings of dissociation

or estrangement from self and body which were commonly reported.

The most common thinking disturbances have been described in

the literature as "loosening of association," "overinclusive

thoughts," "concreteness," "delusional thinking," and general

"disorganization" Associated with these phenomena are "negativism"

and "hostility." In order to assess these states, the MMPI and

the Experiential World Inventory (EMI) were administered. Only

the intensified Adult and Juvenile users manifested abnormal

profiles on these tests. The most consistent high point on the

EMI was the ideation scale, which strongly suggests thought

disorder including unbridled fantasy activity, inability to connect

experiences purposefully, flights of ideas, and serious loss in

the capacity to select and resist thoughts and to produce and

connect new thoughts. Other consistently high scores were seen

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on both sensory perception, time perception, and body perception

scales. Surprisingly, the impulse regulation scale, an indicator

of hostility and violence, was usually the lowest point on the

profile. The MMPI profile for these intensified users indicated

a large number of experiences and symptoms which are characteristic of psychotic thinking, including hallucinations, delusions,

paranoia, feelings of unreality, and a general sense that things

are wrong. The MMPI content scales also indicated a large number

of symptoms of the type sometimes associated with organic involvement of the central nervous system. Complaints here included

skin sensations, nausea, dizziness, and difficulty with speech,

memory, concentration, ability, coordination and motor control.

Unlike the EWI results, the MMPI profile indicated that most of

these users were distractable and when faced with frustration

might become irritable, aggressive, or impulsive, often out of

proportion to the reality of the situation. Taken together, these

findings indicate that PCP produces many of the symptoms characteristic of schizophrenia, although it most be emphasized that the

correlation of symptoms does not imply a direct causal relationship.

II. KETAMINE

In the 1959 horror film, The Tingler, actor Vincent Price injected

himself with the little-known drug LSD in order to produce a

state of fear and panic. That single cultural incident heralded

a much wider phenomenon of LSD use during the psychedelic revolution of the Sixties. In the 1976 film, Family Plot, Alfred

Hitchcock depicted a kidnap victim sedated with a little-known

drug called ketamine. Once again the cultural productions of

man acted as a barometer of the social times, as the Seventies

are witnessing a growing problem of ketamine abuse.

DISCOVERY AND INITIAL USE

Dissatisfied with the clinical experience of PCP as a surgical

anesthetic druq (the duration of action and emergence excitement

were too great to recommend use of the drug), Parke Davis and

Company developed a congener of PCP for anesthesia in man. The

drug was called ketamine hydrochloride or 2-orthochlorophenyl,

2-menthylamino cyclohexanone hydrochloride (original code name

CI-581). Marketed under the names Ketalar (Parke Davis and

Company), Ketaject (Bristol Laboratories and Ketavet (for

veterinary purposes), ketamine is rapidly emerging recreational street drug.

Ketamine was enthusiastically described as a nonbarbiturate anesthetic that is a "rapid-acting general anesthetic producing an

anesthetic state characterized by profound analgesia, normal

pharyngeal-laryngeal reflexes, normal or slightly enhanced

skeletal muscle tone, cardiovascular and respiratory stimulation,

and occasionally a transient and minimal respiratory depression"

(Bristol official package circular for Ketaject). Anesthesiologists endorsed its use initially because surgical patients remained

132
physiologically very strong and required little support of vital

processes. Surgeons were also impressed with the rapid action

but somewhat disturbed when patients appeared responsive to stimuli

in the operating room. Gradually the clinical experience demonstrated that ketamine produced a number of complications from

which it was originally claimed to be free. The complications

included: "severe laryngospasm and respiratory arrest in neonates,

cardiac arrest secondary to respiratory depression in an adult,

severe airway obstruction with vaniting and aspiration in children,

and hysterical postanesthetic reaction" (Clin-Alert 1971). Indeed,

these latter emergence reactions have been variously described as

"confusional states," "vivid dreaming," "hallucinations," and

"preseizure and seizure activity."

Nonetheless, the drug produced extremely effective analgesia

which was still judged useful in certain situations such as for

burn dressings and radiotherapy, in emergency field work, and in

war conditions. Indeed, the drug enjoyed popularity among surgeons

as the most widely used battlefield anesthetic in Vietnam. The

analgesia is probably achieved through the drug's dissociative

action in that it appears to selectively interrupt association

pathways of the brain before producing somesthetic sensory blockade (Sparks et al. 1973; Weingarten 1972; Winters 1975). Some

observers (e.g., Young et al. 1977) attribute the present popularityof the drug to experiences gained among patients in Vietnam

and elsewhere during the late 1960's.

Street use of ketamine hydrochloride solutions was first noted in

1971 in San Francisco and Los Angeles (Siegel, personal observation), while other forms of ketamine (e.g., powders, tablets,

etc.) were first noticed on the street in 1974 (Ashley 1978).

Solutions go under a variety of street names including: Ketalar,

Ketaject, Ketavet, K, Kay, Jet, Super Acid, 1980 Acid. Powder

forms of ketamine on the street as: Green, Purple, Mauve,

Special LA Coke, Super C, and K. For both medical and nonmedical

users, the emergence reaction characterized as adissociative

hallucinatory period is probably the most dramatic aspect of the

ketamine experiencee.

MAINTENANCE OF USE

The ketamine dissociative reactions, while producing analgesia,

also produce classic hallucinogenic reactions which undoubtedly

motivate recreational users. These reactions were originally

described in the anesthesiology literature (e.g., Kreuscher 1969)

as emergence reactions that could be quickly "managed" or suppressed via treatment with a variety of agents such as diazepam,

droperidol, fentanyl, pentobarbital, or meperidine (e.g., Wantz

1977). Doenicke and co-workers (1969) reported on the phenomenology

of this reaction when it was not suppressed by other medications.

Both their patients and experimental subjects experienced analgesia

concomitant with depersonalization, derealization, changes in

body imagery, nausea, dizziness, dreams, and hallucinations.

Most of their subjects stated that the dream period and hallucina133
tory phase was "pleasant" and a typical description of the intoxication follows:

During the first subjective experience, I imagined

myself in a complicated system of pipes which reminded

me of an oil refinery. A driving force shot me

through the colorful, occasionally angled, pips. I

was wondering about the provenance of these strange

circumstances and believed I had been hexed by relatives . Now this seemed to be my eternal fate, which

made me very sad. Some time later, I was first able

to perceive acoustic impressions from my surroundings,

which previously had been missing. The voices of the

people present in the room sounded distant, but yet

loud and resounding. I could hear the sounds, but I

could not understand them. I thought that they were

voices of relatives who had hexed me. Later I was

able to perceive visual impressions. The room appeared dusky-foggy to me. In the distant opening of

a pipe appeared the head of a colleague. Now I understood a few words and began to answer. My speech

sounded babbling and booming to me. Intermittently

the hallucination of being hexed returned. Later I

was told that I had uttered strange sounds. My

tongue seemed to me to be extremely big, but very

light. In my extremeties, too, I felt a striking

lightness. Shortly before awakening, I was again able

to understand what was said around me and I saw my surroundings again, though greatly blurred and constantly

revolving around me (pp. 149-150, translated from the

German by R.K. Siegel).

Rumpf and colleagues (1969) found their subjects described ketamine hallucinations as "utopic," "phantastic," "unreal," or

"mysterious." Only one out of their 18 subjects considered the

dream experiences normal and ordinary. The experience was termed

pleasant by 6 subjects, unpleasant by 8, and neutral by 4. Experiences reported by these test subjects included dreams of

recent memories, feelings of floating in space or falling or riding

in various vehicles, vividly colored (primarily red) geometric

patterns and designs, and were in general similar to the phenomenology of other drug-induced hallucinations (see Siegel 1977b).

Unexpectedly, Rumpf and colleagues reported that fully one third

of the experimental group (6 subjects) had true hallucinations

with the concomitant delusions that their dreams were not dreams,

but, in point of fact, real events! Such intense hallucinations

are rare in drug-induced experiences (Siegel and Jarvik 1975).

In a well controlled study, Collier (1972) demonstrated that most

ketamine dreams or hallucinations were judged by subjects as pleasant and of unusual intensity. One dream sequence was markedly

transcendental as "the patient ascended to Heaven, saw God and was

re-incarnated in Italy. Luminosity, green colour, tranquility and

marked euphoria predominated. This these continued for over 2 hours

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into the awake phase during which he thought that he was speaking

Italian. A central object blindness occurred. Six months later

he had not experienced any similar dreaming or spontaneous phenomena but still remembered the episode vividly" (p. 125).

Current recreational users of ketamine appear to be motivated to

achieve these dissociative hallucinatory states. Young et al.

(1977) likens this state to an LSD trip, only the ketamine tripper

"feels as if he is floating in a dreamlike state while experiencing

vivid visual images" (p. 107). Stafford (1977) has recently cited

a report from a current recreational ketamine user which illustrates the romantic appeal of the state similar to the "perpetual

peaceful place" described by PCP users:

And when I closed my eyes a lot of information started

to happen. Colors, patterns, cross-connections in

sensory perception. Like sound and inner visions sort

of got confused. I got deeper and deeper into this

state of realization, until at one point the world

disappeared. I was no longer in my body. I didn't

have a body. And I reached a point at which I knew I

was going to die.... .And what incredible feelings that

evoked! . . . . . .I just yielded. And then I entered a space

in which . . .there aren't any words.....I mean, at-onewith-the-universe, recognizing-your-godhead.....The

feeling was: I was home. That's really the feeling of

it. And I didn't want to go anywhere, and I didn't

need to go anywhere. It was a bliss state. Of a kind

I had never experienced before. I hung out there awhile,

and then I came back. I didn't want to come back. I

guess in the deep state it was no longer than half an

hour (pp. 348-349).

CONSEQUENCES OF CONTINUED USE

During the acute intoxication with ketamine, there is significant

impairment in attention, learning, and memory functions (Harris et

al. 1975). In particular, subjects have impairment in organizing

and understanding the enviroment during emergence reactions. But

few, if any researchers have documented the long term consequences

of continued use of this drug. In preclinical animal studies,

chronic ketamine administration results in abnormal brain wave

activity, and withdrawal is marked by progressive increases in

epileptiform activity without gross behavioral manifestations

(Manchar, Maxwell and Winters 1972). Since such abnormal electrical

activity in the brain is not correlated with observable changes in

behavior, it is not surprising that clinical studies have failed to

detect any long term impairment of behavior or personality functioning. Nonetheless, "bad trips" are frequent can result in

paranoia and fear of subsequent similar intoxications (see Johnstone

1973).

A number of studies have documented recurrent hallucinations following ketamine anesthesia as well as flashbacks (Fine and Finestone

135
1973; Perel and Davidson 1976), and some have even suggested, albeit

weakly, resulting psychoses (Johnson 1971). While the incidence of

ketamine flashbacks far exceeds that for other hallucinogens

(Siegel and. Jarvik 1975), the presence of flashbacks and allied

perceptions does not normally present psychological problems; for

the patients or users. Indeed, a number of psychiatric investigators have utilized continued treatment with ketamine to create

abreactive effects in psychotherapy and research settings (e.g.,

Khorramzadeh and Lofty 1973; Lilly et al. unpublished).

VARIABLES AFFCTING USE AND INTOXICATION

The variables affecting intoxication with ketamine are similar to

those discussed above with reference to phencyclidine. In addition,

because of the more profound hallucinatory quality of the ketamine

experience, intoxication is greatly influenced by set and setting.

Because ketamine induces an extreme sensitivity to environmental

stimuli, the physical surroundings are particularly important.

Indeed, recovery personnel in hospital operating rooms have long

since learned the importance of isolating the ketamine patient

from intense light, noise, and other stimulation. The intrusion

of even the most innocent stimuli such as monitoring the patient's

vital signs can trigger hyperexcitability, psychomotor activity,

and even seizures. Accordingly, recovery from ketamine anesthesia

is usually handled with minimal verbal and tactile stimulation in

medical settings, but rarely is this precaution observed in nonmedical situations. Furthermore, since ketamine is often injected

either intramuscularly or intravenously, such factors as sterile

procedures and instruments, purity of the solution, and site of

injection are especially important determinants of the intoxication.

Respiratory depression may occur from overdosage and the presence

of sedative drugs (barbiturates, opiate narcotics, etc.) in the

body may also influence the intoxication and risk of overdosage.

THE SAMPLE

Two separate populations were sampled for studies of recreational

ketamine use. One population (referred to as the Intranasal Group)

consisted of recreational users recruited from a previous study

of cocaine use (Siegel 1977a). Another population (referred to as

the Injection Group) consisted of recreational hallucinogen users

recruited from a previous study (Siegel and Jarvik 1975). A total

of 10 Intranasal users and 13 Injection users were eventually

selected for study. All subjects in the sample met the initial

requirement for having used ketamine more than once in the last

year. Subjects were approximately equally divided between men and

women, 21-45 years of age, and were examined and tested in the

manner described in the phencyclidine section of this chapter.

MULTIPLE DRUG USE

All subjects in the Intranasal Group had past or present histories

of multiple drug use. Concomitant with their use of ketamine, 100

percent were classified as social-recreational users of cocaine

136
(see Siegel 1977a). All subjects in the Injection Group also had

past or present histories of multiple drug use. Their use of

ketamine ran parallel to their use of other hallucinogens and

fully 77 percent were currently using LSD. Interestingly, none

of the Intranasal or Injection users were using phencyclidine, although two subjects from each group had experimented with it in

the past.

PREPARATIONS AND PURITY

All subjects used ketamine hydrochloride in the form of capsules,

powder, crystals, tablets, or solutions. Solutions are usually

diverted legal vials of ketamine available in concentrations of

10 or 50 mg/ml (Ketaject) or 10, 50 or 100 mg/ml (Ketalar). An

occasional street adulterant of these solutions is vitamin B12

due to a common street myth (partially true) that this attenuates

adverse reactions. Capsules (usually clear, red, or black/yellow),

powders (green, mauve, or white), crystals (white), or tablets

(usually white) are usually mixtures of ketamine hydrochloride

and various nonpsychoactive compounds such as lactose, flour, talc,

and vitamins. The most common psychoactive adulterant found in

powders or crystals is cocaine hydrochloride, although others including amphetamines and caffeine are also found. At the present

time no quantitative information is available on these preparations.

ROUTES OF ADMINISTRATION

By definition, all subjects in the Intranasal Group employed the

intranasal route of self-administration, and none of these users

had ever experimented with other routes of ketamine administration.

Similarly, all subjects in the Injection Group employed the intramuscular (i.m.) route of self-administration. However, of the 13

subjects here, four subjects experimented with intravenous (i.v.)

injection and one subject had experimented with smoking ketamine.

DOSAGES

Little reliable information on recreational intranasal dosages of

ketamine is available. Young and colleagues (1977) estimate that

"the normal abuser's dose is 50 mg" (p. 107). However, judging

from the reactions and intoxications reported by users (see below)

it is estimated that intranasal doses range from 60-100 mg. For

Injection users, the surgical anesthetic dosages range from 6.5 to

13.0 mg/kg (i.m.) and 1.0 to 4.5 mg/kg (i.v.). Recreational

Injection users employ dosages of approximately 1.0 to 2.0 mg/kg

(approximately 0.5 to 1.0 mg/lb.) for both intramuscular and

intravenous administration.

DOSE REGIMES

Subjects in both the Intranasal and Injection Groups fell into

several patterns of ketamine use (discussed below). In general,

when using the drug intranasally, subjects tended to administer

the drug only once in any given episode and to repeat episodes

137
of administration less than once per month. Injection users also

tended to administer the drug cnly once per episode. However,

repeated injections were usually self-administered once per hour

until a desired level or period of intoxication was achieved.

PATTERNS OF USE

The five patterns of use previously designated by The National

Commission on Marihuana and Drug Abuse (1973) will be used for

discussion here.

Experimental Use

Six subjects (60 percent) of the Intranasal Group and one (8 percent) of the Injection subjects were classified as experimental

users and engaged in short term, nonpatterned trials of ketamine

with varying intensity and a maximum frequency of 10 times or less

in their entire drug history. These users were motivated by curiosity about ketamine (or its advertisement as a different type of

drug such as "Green" or "K") and a desire to experience the anticipated effects of euphoria and hallucinations. Their use was generally social and among close friends or intimate others. Most

subjects enjoyed the experience but did not express a desire to

continue regular use because of the street myth that "something

that strong must have some harmful effects on the brain." Other

subjects desired to repeat the self-administration but found cost

to be prohibitive (the drug is in short supply).

Social-Recreational Use

In the Intranasal Group, four subjects (40 percent) were classified as social-recreational users. Ten subjects (77 percent)

in the Injection Group were also classified in this way, but three

of these subjects (23 percent) engaged in episodes of more frequent

use (see below). In general, social-recreational use occurred more

regularly than experimental use and was primarily motivated by individuals seeking to share with others an experience they judged to

be pleasant and fun. Such users describe their ketamine use as

"absolutely safe" and "better than LSD." The set and setting for

recreational use parallels that observed with other more conventional hallucinogens. The Intranasal users tended to employ low

dosages (probably less than 50 mg) and found the experience to be

similar to cocaine but more "trippy." This comparison to cocaine

is probably related to ketamine's cocaine-like effects on vascular

adrenergic neurons (Nedergaard 1973). The use of the term

"trippy" refers to ketamine's hallucinatory and dissociative

effects.

Injection users tended to employ sufficient dosages to produce the

"psychedelic" effects. When asked to rank all recreational drugs

in terms of potency, all social-recreational ketamine users ranked

ketamine as the most potent hallucingen and 71 percent rated it

as the hallucinogen of choice. The remaining subjects were equally

divided between LSD and psilocybin mushrooms as their hallucinogen

138
of choice. When asked to rank all drugs in terms of general recreational preference, Intranasal Users ranked cocaine first, while

Injection Users ranked LSD first. Ketamine was consistently described in several ways which contributed to the maintenance of

social-recreational patterns of use:

1 ) Ketamine was perceived by users to be a safe, nontoxic, potent hallucinogen with a short duration of

action and few adverse reactions or bad trips.

2) Ketamine was perceived by most users as the only

hallucinogen that did not produce anxiety or fear

reactions.

3) Ketamine was considered to have unique euphorichallucinogenic properties that enabled a user to experience, with varying dosages, effects similar to

either cocaine, amyl nitrite, phencyclidine, or LSD.

4) Ketamine was considered to be a glamorous avantgarde drug and had associations with cotemporary

folk heroes of high status (see Duncan 1976).

Circumstantial-Situational Use

Only two subjects in the Injection Group (15 percent) engaged

periodically in circumstantial-situational use, defined as a

task-specific, self-limited use which was variably patterned, differing in frequency, intensity and duration. This use was motivated by a desire to explore new states of consciousness and work

through personal problems. Such use is similar to that of ketamine in experimental psychotherapy situations (Khorramzadeh and

Lofty 1973).

Intensified Drug Use

Only two subjects in the Injection Group (15 percent) engaged in

intensified use characterized by long term patterned use of at

least once per week for several months. Such use was motivated

chiefly by a perceived need to achieve relief from a persistent

problem or stressful situation or a desire to maintain a certain

self-prescribed level of intoxication. Nonetheless, users here

still referred to their use as "experimental" in the sense that

they were exploring new altered states.

Compulsive Drug Use

Only one subject (8 percent) in the Injection Group characterized

herself as a compulsive ketamine user with high frequency and high

intensity levels of relatively long duration. This user admitted

to both psychological and physical addiction to the drug, although

this latter claim could not be substantiated. Indeed, she was able

to "withdraw" repeatedly from the ketamine use which continued

intermittently for several years.

139
PHENOMENOLOGY AND INCIDENCE OF INTOXICATION EFFECTS

The acute physiological and psychological effects reported by

ketamine users did not differ substantially between the Intranasal

and Injection Groups. Therefore, the users are combined (total N

= 23) in discussion here. In general, most users recognized that

they were using a hallucinogen, and considered the hallucinogenic

and psychotomimetic properties to be positive effects. This attitude (set) contrasts sharply with most phencyclidine users who

only recognized that they were using an intoxicant similar to

marihuana, which is commonly not considered a hallucinogen in

street usage.

Ketamine users repeatedly sought and experienced a number of positive effects, including: floating sensations and dissociation

(87 percent), stimulation (83 percent), hallucinations (78 percent),

increased cognitive or mental associations (74 percent), euphoria

(26 percent), and transcendental or religious experiences (17

percent). Despite the widespread beliefs among users about the

lack of adverse reactions, a number of untoward effects were also

reported: ataxia (100 percent), slurring of speech (70 percent),

dizziness (61 percent), mental confusion (35 percent), hyperexcitability (26 percent), unpleasant imagery (26 percent), blurring of

vision (17 percent), negative hallucinations, or the inability to

see things that were really there (17percent), decreased sociability (17 percent), anxiety (13 percent), nausea (13 percent),

insomia (13 percent), and decreased sexual motivation (9 percent).

Interestingly, one subject also experienced several episodes of

psychomotor seizures as a result of acute intoxication.

Taken together,ketamine users experienced more negative effects

than positive effects as a result of acute intoxication. Nonetheless, they continued to rate the overall experience as positive

and rewarding.

The long term effects resulting from ketamine use are similar to

those reported for many other hallucinogenslike LSD. Typically,

the ketamine users claimed a chronic elevation of mood (43 percent),

deeper insights into self and others (35 percent), and positive

changes in attitudes personality (17 percent). The undesired

long term effects included: flashbacks (57 percent), attentional

dysfunction (22 percent), and decreased sociability (9 percent).

Overall, long-term effects appeared equally divided between positive

and negative experiences.

HALLUCINATIONS

Of the phenomena reported above, the hallucinations appeared to be

conspicuous as both positive effects resulting from acute intoxication and as important determinants of positive/negative long term

effects. Therefore, the ketamine hallucinations among these nonmedical users were the object of concentrated examination and study.

In general, the nature of ketamine hallucinations in recreational

140
users was similar to that reported in both surgical and experimental

subjects (e.g., Collier 1972; Siegel and Jarvik 1975). One subject

from the Injection Group described her prototypical hallucinations

in a session that she tape-recorded for the author:

I see Mexico City when I close my eyes. Crazy. I've

never been there before. Now it's just black. It

reminds me of a cave. I see people moving about in

some sort of kaleidoscope pattern. I don't know where

I am. (Laughter) The crowd of people are all having

a good tine and they're laughing. My sister has got

her Sunday blue dress on, although she's always

dressed in black. I don't recognize anyone except her

and her husband. Now they're gone. They disappeared.

Now I just see commercials from TV and lots of geometric

patterns. There's someone's stereo hanging on the wall.

(Laughter) I feel a little childish. Happy. Very

happy. (Laughter) Now I see kitty cats. Striped ones

like out of a child's coloring book.

Another Injection subject described a similar experience, also

tape-recorded for the author:

I see flowers. All colors, blue and green and purple,

yellow. And now a weird looking nightclub. Now stars.

Everything happening very fast.....vegetables, pictures,

a house, a pinwheel, there's a man sitting on a chair.

It's just like a movie or a dream. There's an igloo

and a tepee. And some more flowers. (Laughter) Now

I feel like I'm in church. Really, it's really a

church. My tongue hurts. And in the church is a tiny

dot in the middle and some black space and then from

the middle comes a white light. Surrounded by flowers

like lilacs, rippling like in the wind. And pink

flowers and white picket fence. Now I see Jesus. And

I see a man and a woman kissing. NoW I see white

flowers and just green leaves. And there is an old man

on the other side and he is waving his hand and he's

gotasuitonandahat. That must be God. Now I see

a little girl. (Laughter) That's me. She's laughing.

This is all very clear. I can even see their features

and everything.

Even Intranasal users experience similar, albeit weaker, hallucinations as exemplified by one subject's report:

The first thing that happens when I snort Green (ketamine) is that I start to get speedy like with coke

(cocaine). I feel a rush of good feelings, almost

euphoric. Then things get a little blurry. I feel

like I'm floating and sometimes dizzy. But I usually

lie down and float along with the trip. When I close

my eyes I see the "retinal circus" that Tim Leary described with kid (LSD)--lights, colors, patterns, even

141
cartoons and memory pictures. If it's dark in the

room and I open my eyes I can sometimes project things

onto the wall or ceiling. But most of the time I just

lie there thinking great thoughts and solving lots of

problems. It's a lot like nitrous oxide only it's a

more intense body trip as well. When you snort it you

come down very quickly.

As suggested above, experienced users of ketamine can learn to

utilize the state of intoxication for personal growth and exploration. This use is similar to that underlying long term recreational use of other hallucinogens, and Lilly et al. (unpublished

manuscript) describe the unique aspects of ketamine in this regard.

In our group we symbolize this by saying that this

chemical induces a state in which you live in a well

of neutral reinforcement. Typical tasks are simplified and made more efficient, condensed, abstracted,

and the nonsense removed from the computations involved in carrying them out. Mental processes in a

similar way sharpen out. It looks as if the contrast

enhancement of such as edges, colors, thoughts, ideas

and so forth is forthcoming. Colors seem brighter

and yet more meaningful. Objects contain their own

meanings. People are read very readily and with

great ease and evaluated in their current state anrd

dealt with in the most efficient and energetic manner possible. After some weeks of training to get

through the initial phases of the emergence symptoms

so-called, these states occur. The subject learns to

centrally control, integrate and use the neutral energy

afforded by the ketamine and becomes that which he potentially could become otherwise without the chemical

at his best performance (p.4).

III. OVERVIEW

The nonmedical use of phencyclidine (PCP) and ketamine has been

examined in four populations of recreational users. The first

population sample consisted of 319 Adult users of PCP while the

second population sample consisted of 20 Juvenile users of PCP.

Both groups used PCP primarily by smoking in social-recreational

patterns and settings. However, Juveniles tended to be more

intensified users than Adults, many of whom were only experimenting with the drug. PCP was viewed as a potent hallucinogen by

users, who tended to titrate dosages in order to achieve desired

levels of stimulation, dissociation, and inebriation. Such positive effects were achieved in approximately 60 percent of the

intoxications. Despite the fact that negative effects such as

perceptual disturbances, dysarthria, and hyperexcitability were

common in nearly all intoxications, a substantial number of individuals maintained continued use of and preference for the drug.

These patterns of use are probably related to the dissociation and

estrangement from self and others induced by PCP, as well as the

drug's euphoro-hallucinogenic properties.

142
!The third population sample consisted of 10 Intranasal ketamine

users while the fourth population sample consisted of 13 Injection

users of ketamine. Use of ketamine was primarily experimental or

social in nature and the drug was viewed by users to be a safe,

potent hallucinogen with a short duration of action and few if any

adverse effects. Ketamine users tended to titrate their use in

order to achieve desired effects of dissociation, stimulation,

hallucinations, and transcerdental experiences. Despite the users'

beliefs that the drug was totally safe, negative effects were reported; these included ataxia, dizziness, mental confusion, and

hyperxcitability.

Long term intensified use of PCP tended to be associated with

abnormal personality profiles indicating the drug's psychotomimetic

actions. Long term use of ketamine was marked by a high incidence

of flashbacks as well as attentional dysfunction. Nonetheless,

recreational users of both drugs tended to experience generalized

feelings of well-being, heightened perceptual sensitivity, and

positive and rewarding experiences which reinforced and maintained

drug use. Some tendency toward transient psychosis was noted in

the PCP groups, while the ketamine users manifested some decreased

sociability with no concomitant personality changes as measured by

standard psychometric tests. An important caveat is that these

effects are neither uniformly negative nor uniformly predictable.

The number of variables affecting their production is presently

unknown.

143
ACKNOWLEDGMENTS

The author thanks Dr. Murray E. Jarvik for numerous helpful services

in the research and preparation of this study. The author is indebted to Ada Hirschman for superlative research assistance.

Arthur Stickgold provided valuable research materials.

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AUTHOR

Ronald K. Siegel, Ph.D.

Department of Psychiatry and Biobehavioral Sciences

School of Medicine

University of California

Los Angeles, California 90024

Mailing Address

Ronald K. Siegel, Ph.D.

Psychopharmacology unit

Research Trailer 350

Brentwood VA Hospital

Los Angeles, California 90073

147
Chapter 7

Epidemiology of Multiple Drug Use

with Special Reference to Phencyclidine

J. Fred E. Shick, M.D.

Recently we have witnessed growing concern about the illicit use

of phencyclidine (PCP) among this nation's youth. Epidemiological

data has been difficult to assemble quickly, since most surveys

either have included PCP within the category of hallucinogens"

or have anitted questions about it altogether (Johnston 1973;

Abelson and Fishburne 1976; O'Donnell et al. 1976). The primary

source of descriptive data, useful in estimating the range of

usage patterns and adverse reactions, has been studies of youth

in crisis from PCP use -- usually samples from hospital settings

and drug abuse programs (Burns et al. 1975; Burns and Lerner 1976;

Fauman et al. 1976; Fauman et al. 1975; Linden et al. 1975; Tong

et al. 1975).

The focus of my research has been to develop a fieldwork methodology to locate and gain access to heavy, multiple drug-using

youth at their congregation sites. These youth -- generally the

underemployed and undereducated 16 to 26 year old age group --

are at risk for a variety of adverse outcomes, including progression to intensified drug use, experimentation with intravenous

administration, as well as acute and chronic adverse drug reactions

My research has borrowed concepts and methods from participant

observation fieldwork methodologies (Becker 1970; Habenstein 1970;

Weppner 1977) and the work of Hughes and coworkers with heroin

addict communities in Chicago (Hughes 1977; Hughes and Crawford

1972; Hughes et al. 1971; Hughes and Jaffe 1971; Hughes, Senay,

and Parker 1972).

Our previous studies (Shick, Dorus, and Hughes 1978; Shick and

Wiebel 1978) utilized fieldwork techniques to identify sites popularly known as "hangouts" where youthful multiple drug users

congregated to buy, sell and use drugs. We also used these techniques to study intensively the social organization and activities

of groups of youth at certain sites. Particularly remarkable

were the relative geographic stability of these locations during

the warmer months, the regularity with which particular groups

frequented a given site, the preponderance of males, and the recreational and social quality of the groups' activities, including

148
drug use. These studies suggested that youthful drug user hangouts

may be conceptualized as "neighborhood" or "regional." Neighborhood hangouts were frequented by smaller numbers of visitor who

lived in the immediate neighborhood, attended the same high school,

knew one anothers' brothers and sisters,and were from similar

ethnic and socioeconomic backgrounds. Drugs available at these

sites appeared to be limited in both quantity and variety by the

small number of dealers a who generally residents of the neighborhood. By contrast, regional sites were characterized by large

number of visitors who came from an extremely wide area and were

not organized into cohesive friendship groups on consisting of longterm neighborhood friendships established during grade school and

high school. Regional sites appeared to attract the heaviest drug

users and dealers, and a wide range of drug types were regularly

available. Regional sites were well known to most visitors to the

neighborhood locations but were avoided by them and visited only

occasionally when drugs were available at their usual neighborhood hangouts. Observation and informal interviews suggested that

violence among individuals and groups was more common at regional

sites, particularly those of wide social and economic diversity,

and areas frequented by delinquent gangs.

This work demonstrated that fieldworkers who themselves had been

multiple drug users and who were residents of and regular visitors

to the area under investigation were able to locate and characterize drug user congregation sites and could be trained to gain access to users to perform epidemiologic field research activities.

We were fortunate in these studies to have the foresight to include in our fieldinterviewsa separate category of questions

about drugs generally analyzed to contain phencyclidine (PCP).

In this paper we report the epidemiological drug use data collected

from regular visitors to two regional congregation sites in the

Chicago area: (1) the largest congregation and drug distribution

site in the south Chicago suburbs, active during warm weather, and

(2) the largest urban congregation and drug distribution on the

near month side of Chicago, which was active throughout the year.

METHODS

The field team for each site consisted of two fieldworkers who were

regular members of the drug-using community being stuied and who

themselves occasionally used illicit drugs. They were trained in

fieldwork and interview techniques andregularly supervised by the

research sociologist and the author. A more detailed discussion

of the recruitment procedures, selection criteria, and training

for fieldworkers is presented in a forthcoming report.

We began by asking the fieldworkers for each location,who were

familiar with the area, to identify all known hangouts for multiple

drug users. Fieldworkers then made several visits to each site on

different days at different hours, and in fieldnotes they estimated

the number of visitors present, their age range, and other demographic characteristics, the drugs available, and whether visible

149
dealing or use occurred. They discussed the local drug scene with

individuals they met at these sites and asked about additional dtug

user hangouts, which then were visited. The research sociologist

and the author verified the fieldworkers' observations by personal

visits and informal interviews on a regular basis.

From this data, early in the Summer of 1975, we identified for

intensive study, the largest and most popular congregation sites

in each area. Informal interviews with regular visitors to these

and other locations confirmed fieldworkers' reports that these sites

were the primary hangouts for the heaviest multiple drug users and

dealers from surrounding areas.

At the suburban forest preserve (Site one) during July through

November, 1975, fieldworkers administered structured field interviews detailing demographic characteristics, drug-using habits,

and service needs to 71 subjects who were selected by word–ofmouth chains of referral from approximately 100 regular visitors

to this site. The interviews were conducted at the site in an

area away from the greatest activity or in the fieldworker's car.

At the urban congregation site (Site two) we rented a field office

in the area, and there fieldworkers administered the same interviews to 236 subjects similarly selected from approximately 300

regular visitors, between July 1975 and December 1976. Each

subject was paid $5 for his participation in the interview.

To minimize the effect of seasonal variation in drug availability,

popularity, and visitor attendance, in this paper we compare epidemiological drug use data from Site one with that from 118 of the

236 subjects selected from site two who were interviewed during

the same period -- July through November 1975.

RESULTS

Intensive Study Sites

The south Chicago suburbs include approximately 40 incorporated

cities and towns ranging in population from 1,500 to 60,000 in

the highly industrialized 180 square mile area. Most of the households consist of white, blue collar, working class families, less

than 1 percent are nonwhite, and less than 10 percent are defined

as white collar. The site of intensive study was a forest preserve

visited in the late afternoon and evening hours during good weather

by 100 to 300 youth, who arrived in cars from an extremely wide geographic area. Drug dealing and use was open and uninhibited,and

regular police patrolling seemed to have little effect (Shick and

Wiebel 1978). The drugs available at this site varied with the

attendance; on slow days only marihuana was available, but on

busy days a wide variety of drugs, including occasionally heroin,

was sold.

The near north side of Chicago is a heavily populated area surrounded by affluent whites along Lake Michigan and Latino and

150
TABLE 1

DEMOGRAPHIC CHARACTERISTICS OF THE

STUDY SAMPLES COMPARED

Age Forest Preserve Sample Urban Sample

(Years) (N=71) (N=118)

Males Females Total Males Females Total

< 18 17%(9) 72%(13) 31%(22) 26%(26) 16%(3) 25%(29)

18-20 34%(18) 17%(3) 30%(21) 42%(42) 53%(10) 44%(52)

> 20 49%(26) 11%(2) 39%(28) 31%(31) 32%(6) 31%(37)

Total 75%(53) 25%(19) 100%(71) 84%(99) 16%(19) 100%(118)

Mean Age

Modal Age

Median Age

Ethnicity

19.9 years 20.9 years

17 years 18 years

19.2 years 18.9 years

White 98% (70) 82% (97)

Black 2% (1) 8% (9)

Latin (0) 8% (9)

other (0) 2% (3)

Religious Training

Catholic

Protestant

Jewish

other

None

52% (37) 50% (59)

28% (20) 25% (29)

1% (1) 7% (9)

12% (8) 12% (14)

7% (5) 6% (7)

Marital Status

Single 86% (61) 89% (105)

Married or

Common-law

Partner 13% (9) 1% (1)

Separated 1% (1) 1% (1)

Divorced (0) 9% (0)

Children 11% (8) 18% (21)

Education

currently

Attnd'g

School 34% (24) 14% (17)

151
TABLE 1 (cont'd.)

DEMOGRAPHIC CHARACTERISTICS OF THE

STUDY SAMPLES COMPARED

Age

(years)

Forest Preserve Sample

(N=71)

Urban Sample

(N=l18)

Last year of

School Completed

8th Grade

or less

9th

10th

llth

12th

Some College

Grad'd College

High school

Equivalency

Exam

Currently

Employed

1% (1) 15% (18)

10% (7) 19% (22)

23% (16) 19% (22)

34% (24) 16% (19)

20% (14) 20% (23)

13% (9) 10% (12)

(0) 1% (2)

3% (2) 8% (9)

25% (18) 27% (23)

Area Grew up

(to age 13)

Chicago

Chicago Suburban Area

Other Part of Illinois

Out of state

No Answer

Employment Status of Family's Major Provider

Higher Exec.,

Professional 2% (1)

Lesser

Managerial 34% (22)

Adm'n., Small

B'sns.Owner 9% (6)

Clerical

Technical 34% (22)

Skilled Manual 8% (5)

Semi-Skilled

Man'l. 13% (8)

Unskilled (0)

Public Assistance,

(0)

57% (67)

7% (8)

5% (6)

30% (35)

1% (2)

5% (6)

9% (10)

11% (13)

14% (17)

19% (22)

16% (19)

12% (14)

Orphan 14% (17)

152
and lower class whites to the northwest.It is also a popular

shopping and nightlife district among young singles. The several

drug user hangouts here were within walking distance from One

another and attracted drug users from a wide area. These hangouts

were an integral part of an urban neigborhood and were active

throughout the winter months, in contrast to the isolated sites

such as parks, beaches, or forest preserves, which were active

only during warmer weather. Furthermore, the urban site attracted

diverse types of multiple drug users various ethnic and socioeconomic backgrounds and numerous adolescent runaways.Our sample

included regular intravenous users of amphetamine and heroin who

frequented the pool hall, intravenous experimenters using various

drugs, and a large number of daily or weekend users of pharmaceuticals, psychedelics, PCP, alcohol, and marihuana who "hung out"

regularly at the restaurants. Subjects' occupation ranged from

legal employment to careers of crime: illegal activities included

drug dealing, male and female prostitution, pimping, shoplifting,

burglary, and con games. The full range of drugs was regularly

available from many sources including many of the youth themelves,

several large quantity dealers who lived in the nearby hotels,and

about five pathological prescribers.

Table one displays the demographic characteristics of the two

samples. Both samples included substantially more males than

females, which accurately reflected the composition of the regular

visitors, verified by fieldwork. In contrast to the suburban

forest preserve sample, there were more nonwhite subjects and a

greater number of older subjects among the urban sample.

Subjects from the suburban forest preserve sample had grown up

near the area where they presently lived. By contrast, only 64

percent of the urban sample subjects had grown up in Chicago or

its suburbs, and 30 percent had grown up outside the state of

Illinois (5 percent had grown up in Illinois outside the Chicago

metropolitan area). A greater proportion of urban samples subjects

had dropped out of school (many during grade school or early high

school), had left home at an early age, and were no longer living

with parents (78 percent). Two-thirds of the suburban sample and

86 percent of the urban sample were no longer attending school,

and threer-quarters of both samples were unemployed.

Epidemiologic Data

In contrast to the epidemiologic assessment of heroin addiction

(Hughes 1977; DuPont and Greene 1973; Greene et al. 1974) the study

of trends and patterns of drug use among multiple drug users is

complicated by the wide variety of drug types used, the various

definitions of "multiple drug use" (Elinson and Nurco 1975; Single,

Kandel, and Faust 1974), and the questionable purity of many of

these drugs (Cheek, Newell, and Jaffe 1970; Kealy and Webber 1975).

The drug use reported by subjects reflects the alleged content and

must be interpreted in the light of the prevalence of misrepresentation and the considerable variability in potency of some drug

types.

153
In our analysis, the drug category representing phencyclidine

(PCP) is labeled "dust." Fieldworkers were trained to question

users in detail about substances which might have contained PCP.

Preliminary fieldwork and results from the Chicago Drug Analysis

Network indicated that in Chicago during 1975-1976 the preperations most likely to contain a substantial amount of phencyclidine

were marketed under the street names "PCP, dust, angel dust, TIC,

TAC, and THC." Thus, these street names were incorporated into the

structured field interview to obtain the subject's self-report of

PCP use.

Results published by PharmChem laboratories during the period of

our study were consistent with the results from the Chicago Drug

Analysis Network (Helisten 1977; Perry 1977; Rainey and Crowder

1974; Kealy and Webber 1975). (Four percent of subjects from Site

one and 11 percent from Site two reported having utilized the

services of a drug analysis service.) Practically 90 percent of

the drugs marketed as PCP, dust, angel dust,THC,TIC, and TAC

contained phencyclidine, and drugs sold as amphetamines, cocaine,

or psychedelics had a much higher misrepresentation rate. The

amount of PCP in samples varied from less than 5 percent to almost

100 percent. Generally less than 10 percent of the drugs sold

under these street names were analyzed to contain no identifiable

drug. Other drugs occasionally found in admixture included small

quantities of cocaine, and psychedelics such as LSD or MDA.

Although reports from the West Coast (Burns and Lerner 1976)

suggest a recent increase in smoking materials represented as marihuana but adulterated with PCP, fieldwork data indicated that in

Chicago during thetimeperiod studied, very seldom did this type

of use occur -- PCP was rarely marketed surreptitiously. Although

some users thought they were getting cannabinol when buying "THC,"

the majority of subjects, most of whom were experienced and "street

wise" users, knew of -- and sought -- the "animal tranquilizer"

contained in these substances.

Incidence (First Use)

Incidence data, the number of "new cases" in a particular year,

were derived from questions about season and year of first use, and

results from each sample were remarkably similar. At each site

first experimentation with every drug type (except heroin and

cocaine; see below) was declining due to the artifact of "saturation." Incidence is a one-time occurrence, and by 1975, from 70

to 90 percent of subjects in both samples had tried every type of

drug surveyed except codeine, cocaine, heroin, methadone and

solvents, seriously depleting the pool of those still eligible for

"first use" (Hughes, Schaps, and Sanders 1973).

Data from both sites indicated that among every age group (<18

years; 18-20 years; > 20 years) peak incidence of PCP use occurred

more recently than any other drug type.

At Site one, peak incidence for sedative-hypnotics (1971-1972) and

154
dust (1973-1974) was separated by two years. Among younger subjects, peak incidence of psychedelic use occurred two years before

peak incidence of dust; among older subjects, peak psychedelic

incidence occurred four years before peak incidence of dust.

At Site two, among subjects less than 18 years old, incidence for

dust peaked in 1972 and again in 1975. This bimodal curve may be

an artifact or may represent local variations in popularity, availability, or sample selection factors (Richman and Abbey 1977). If

this bimodal incidence is considered artifactual and the curve is

interpolated, peak incidence of PCP use among younger subjects appears to have occurred very recently, 1974-1975, approximately one

year following the peak incidence of sedative-hypnotic use, and two

years following the peak incidence of psychedelic experimentation.

Among the 18 to 20 year olds at Site two, peak incidence of PCP

use occurred between 1973 and 1974, again approximately one to two

years following the peak incidence of sedative-hypnotic use, and

one to two years following peak incidence of psychedelic experimentation. Among subjects over 20 years old at site two, peak incidence of dust use occurred about 1972; peak incidence of sedativehypnotic, amphetamine, and psychedelic use occurred between l967-

1969.

Among subjects less than 18 years old at both sites, heroin and

cocaine use displayed a recent rising incidence during 1972-1974.

Among the urban sample (Site two) a similar rising heroin incidence

was observed among the 18-20 year olds; among subjects older than

20 years at this site, heroin incidence peaked between 1970-1972.

Whether the mean, modal, or median age that subjects had first tried

each drug type was inspected, results from each site suggested that

the drugs subsumed under the category of "dust" were first tried

relatively late in the sequence of use. Generally subjects had

tried alcohol, marihuana, (solvents, glue, and codeine in a minority), sedative-hypnotics, amphetamines, and psychedelics prior to

their first trial of dust. Trial of opiates, when it occurred,

appeared to follow trial of dust. Among older subjects (Site two)

the age at which they first tried dust was most closely associated

with, and generally followed, their first trials of sedativehypnotics and amphetamines. The younger users' first trials of

dust were more closely associated with subjects' first trials of

psychedelics and amphetamines which followed their first trials of

sedative-hypnotics.

Results suggested that younger users who regularly frequent regional drug user hangouts such as these may be more likely than older

users to try a variety of drugs shortly after their initial trials

of marihuana. Data from both sites suggested that in contrast to

subjects 18 years or older, whose first use of each drug was more

widely spaced in time, most of the younger subjects had tried several different drug types within a brief period of six to 18 months.

This tendency of younger users to try "any drug available" was also

characteristic of the subjects we studied (Shick, Dorus, and Hughes

1978) on the far north side of Chicago (frequenting a much smaller,

155
neighborhood site) and is consistent with our impressions from work

in adolescent drug treatment programs. Whether adolescent experimentation with a variety of substances within a brief span of time

reflects a different attitude about drug use among younger adolescents and is predictive of eventual heavy use deserves further

study.

Prevalence, Remission, and Frequency of Use

In Hughes and Crawford's work (1972) in heroin-copping areas, heroin

prevalence data was relatively easily collected by ex-addict fieldworkers. Weekly logs of the number of addicts visiting a copping

area reflected prevalence of active addiction because most addicts

must make daily visits in order to obtain drug supplies and to

avoid the distress of withdrawal symptoms. At youthful multiple

drug user sites prevalence of drug use must be determined by selfreport, since the majority of users are not physically dependent.

There is a recreational quality to drug use at these sites, and a

visitor's mere presence does not indicate what drug(s) s/he may

be using.

Computer analysis determined the prevalence, remission and frequency of use of each drug type for each of the two samples from

self-reports of frequency of use during the 12 months prior to

interview.

Figure one compares the prevalence and remission rates for the

two samples. Prevalence of drug use was defined as the percentage

of subjects who had used a particular drug type at least once during the prior 12 months. Remission was defined as the percentage

of subjects who had tried a given drug type but had not used the

drug during the 12 months prior to interview. The percentage of

subjects reporting ever having used each drug type is the sum of

the prevalence percentage plus the remission percentage (see figure

one) .

Marihuana and alcohol displayed the greatest prevalence of use and

least remission among both samples. In rank order, sedativehypnotics, amphetamines dust, and psychedelics registered the

next greatest prevalence rates at both sites: prevalence rates for

these drugs were consistently greater among subjects from the suburban forest preserve than among subjects at the urban site. At

both sites the magnitude of the remission rates for these drugs was

the reverse order of their prevalence: psychedelics, dust, amphetamines, and sedative-hypnotics, in that order. The prevalence of

cocaine use was approximately the same for subjects from both

sites, but the remission rate for cocaine was slightly greater at

the suburban forest preserve than at the urban site. The same was

true for heroin. The slightly lower remission rates for heroin

and cocaine among the urban sample may reflect the greater number

of heroin addicts in the urban sample, and possibly their concomitant use of cocaine. Solvents and glue had greater remission

rates than any other drug type among both samples; however, the

prevalence of solvent use was much greater at the suburban forest

156
FIGURE 1

PREVALENCE AND REMISSION RATES OF TWO SAMPLES

COMPARED: F = 71 REGULAR VISITORS TO A CHICAGO

SUBURBAN FOREST PRESERVE DRUG USER SITE, SUMMER

1975; U= 118 REGULAR VISITORS TO A CHICAGO URBAN DRUG

USER SITE, SUMMER 1975.

157
FIGURE 2

FREOUENCY OF DRUG USE DURING THE 12 MONTHS

PRIOR TO STUDY OF TWO SAMPLES COMPARED: F = 71

REGULAR VISITORS TO A CHICAGO SURBURBAN FOREST

PRESERVE DRUG USER SITE, SUMMER 1975; U = 118 REGULAR

VISITORS TO A CHICAGO URBAN DRUG USER SITE, SUMMER

1975

158
preserve than at the urban site. The high remission rates reported

for psychedelics may reflect users' unpleasant experiences with

these drugs, indicated by the large number of adverse reactions

reported for psychedelics. In fact, remission rates for psychedelics, dust, amphetamines, and sedative-hypnotics approximate the

rank order of the number of adverse reactions reported for them.

Figure two compares the frequency of use of each drug type for the

two samples. Frequency data was obtained by asking each subject

to estimate the number of times during the past 12 months s/he

had used a particular type of drug and whether her/his use occurred

on a periodic basis, for example, daily, or on weekends. Because

these subjects reported high rates of use, the following frequency

intervals were calculated: use of the drug once a month or less;

more than once a month to once a week; more than once a week to

three times a week; four times a week to almost daily use;and

daily use.

Although prevalence of marihuana and alcohol use was approximately

the same for the two samples, a greater number of subjects reported

daily use of these two drugs among the suburban forest preserve

sample. Although the prevalence rates for sedative-hypnotics,

amphetamines, dust, and psychedelics were lower among subjects in

the urban sample, there were more daily users of amphetamines (ten

subjects), sedative-hypnotics (five subjects), dust (three subjects), and psychedelics (one subject) among the urban sample.

Although approximately the same percentage of subjects at both

sites had used dust and psychedelics more than once a month,

there was a greater number of heavier users among the urban sample

than among subjects at the suburban forest preserve. Frequency of

heroin, amphetamine, and cocaine use was greater among the urban

sample, reflecting the greater number of near-daily intravenous

users among these subjects (see table two).

There are numerous definitions of multiple drug use (Elinson and

Nurco 1975). We used a method modified from that described by

Hughes, Schaps, and Sanders (1973) to assess the number of drug

types (excluding alcohol and marihuana)used by each subject at

least once during the 12 months prior to interview. The results

are displayed in table three. Sixty-six percent of the subjects

from Site one and 44 percent from Site two had used between four

and six different types of drugs. There was a tendency for the

15 to 17 year olds among the forest preserve sample to have used

a wider variety of drugs than older subjects; among the urban

sample, this tendency was displayed among the 18-20 year olds. We

compared the variety of drugs used by both samples with a sample

of 216 heroin addicts entering treatment (Senay and Shick 1976)

and a 1970 sample of 13,412 Chicago suburban high school students

(Hughes, Schaps, and Sanders 1973). Results indicated that both

field samples of youthful multiple drug users had used a much

wider variety of drugs with greater frequency than did heroin

addicts entering treatment or the high school students.

159
TABLE 2

MEAN FREQUENCY OF DRUG USE DURING THE PAST TWELVE

MONTHS AMONG ACTIVE USERS OF TWO SAMPLES COMPARED

Mean Frequency of Use During the Past 12 Months*

Drug

Type Al. Mh. Sol. Cd. S-H Am. Co. Dust Pd. H . O.O. Mth.

F

U

231.5 264.3 26.7 3.7 60.7 37.5 5.1 22.2 16.1 28.9 10.3 96.0

148.6 206.3 22.0 8.6 57.7 102.1 17.3 48.1 36.5 133.5 42.6 59.9

F = Forest Preserve Sample (N=71)

U = Urban Sample (N=118)

Key to Abbreviations

Al.=Alcohol;Mh.=Marihuana; Sol.=Solvents; Cd.=Codeine; S-H=

Sedative-Hypnotics; Am.=Amphetamines; Co.=Cocaine; Dust=Phencyclidine; Pd.=Psychedelics; H.=Heroin; O.O.=Other Opiates; Mth.=

Methadone.

* Includes only "active users," that is, subjects who used at

least one drug one time during the 12 months prior to interview.

Frequency is expressed as the mean number of days used per year

over the past 12 month interval.

160
TABLE 3

VARIETY OF DRUG USE* OF TWO SAMPLES COMPARED

Suburban

Forest Preserve

Variety of Use Category Sample Urban Sample

N = 71 N = 118

% N % N

Nonuser 0 ( 0) 0 ( 0)

Alcohol only 0 ( 0) 1 ( 1)

Marihuana and/or Alochol 1 ( 1) 6 ( 7)

One of 6 ( 4) 13 (15)

Two of 11 ( 8) 15 (17)

solvents

Three of Sedative-Hypnotics 8 ( 6) 1 1 (13)

amphetamines

Four of Dust 20 (14) 17 (20)

Phychedelics

Five of Cocaine 2 3 (16) 18 (21)

Codeine

Six of Heroin 23 (16) 9 (11)

Methadone

Seven of Other Opiates 4 ( 3) 5 ( 6)

Eight of 4 ( 3) 3 ( 3)

None of 0 ( 0) 2 ( 2)

* Adapted with modification from a method devised by Hughes, Schaps,

and Sanders (1973). Subjects included have used a drugtype at

least once during the 12 months prior to interview.

161
Intravenous Drug Use

Intravenous experimentation is of particular concern since it appears to signify a "quantum jump" in drug using habits and attitudes, often heralds a change in friendship group, increases the

primary drug reinforcement effects (the "rush"), places users at

risk for adverse medical consequences such as serum hepatitis, and

is a precursor to heroin (or intravenous amphetamine) addiction.

Furthermore, as deAlarcon (1971) discussed, the injecting ritual

itself is communicable."

At Site one, 40 (56 percent) of the 71 subjects, including six of

the 22 subjects 15 to 17 years old, had experimented at least once

with the intravenous route of administration. The diversity of

drugs injected was the same for every age group. In rank order,

the drugs most frequently injected were opiates (generally heroin),

amphetamines, dust, cocaine, psychedelics, and sedative-hypnotics.

Intravenous experimentation was morecommon among males (66 percent) than among females (22 percent); intravenous amphetamine

and cocaine use was more common among subjects 18 years or older

than younger subjects.

The urban sample (Site two) included a larger nunber of daily intravenous users of heroin and amphetamines. Sixty-nine (58 percent) of the 118 subjects (including eight of the 29 subjects less

than 18 years old) had experimented at least once with intravenous

injection. In contrast to the suburban forest preserve sample,

intravenous drug use was more common among the females (84 percent)

than among males (54 percent). In rank order, the drugs most frequently injected (of those who had ever tried the drug itself)

were heroin (81 percent), other opiates (29 percent), amphetamines

(52 percent), cocaine (27 percent), sedative-hypnotics (25 percent),

"dust" (23 percent), and psychedelics (18 percent). The relatively

greater percentage of subjects at Site two who had tried cocaine

and sedative-hypnotics intravenously than at Site one my reflect

the slightly older age of the sample, the association of intravenous

cocaine and heroin use among heroin addicts, or the use of intravenous sedative-hypnotics to substitute for heroin when unavailable

or to "come down" from amphetamine intoxication among habitual

users.

Adverse Reactions

Table four displays the total number of adverse reactions reported

by subjects from each site. There were a greater number of adverse

reactions reported at the suburban forest preserve than at the

urban site, but this was a function of the larger number reportedly

due to alcohol at site one.

Table five displays the adverse reactions reported by subjects from

Site one. Fifty-six percent of the 127 adverse reactions reported

were of a physiological nature, generally nausea, headaches, and

vomiting, and 41 percent of these were reportedly due to alcohol.

"Bad trips," predominantly acute anxiety reactions or unpleasant

162
TABLE 4

NUMBER OF SELF-REPORTED ADVERSE REACTIONS

OF TWO SAMPLES COMPARED

Including Alcohol

Number of

Adverse Forest Preserve Urban

Reactions Sample Sample

Subjects Subjects

% N % N

None 10%(7) 34%(40)

one 31%(22) 35%(42)

Two 34%(24) 24%(28)

3 or more 25%(18) 7%(8)

Total 100%(71) 100%(118)

Excluding Alcohol

Forest Preserve Urban

Sample Sample

Subjects Subjects

% N % N

20%(14) 35%(42)

39%(28) 35%(41)

28%(20) 24%(28)

13%(9) 6%(7)

100%(71) 100%(118)

163
TABLE 5

DRUGS SELF-REPORTED TO HAVE PRODUCED ADVERSE REACTIONS,

SUBURBAN FOREST PRESERVE SAMPLE

(N=71)

Nature of

Adverse Reaction Drugs Said to Have Caused Adverse Reaction

AlC. Pd. Dust H. Am. S-H Cd. Mh. Solv. Comb. TOTAL

Physiological

"Bad

trip"

Overdose

Withdrawal

other

Total

Number

% of

29 9 87 5 432

0 25 2 1 5 1 0 1

0 1 2 4 2 210

0 0 0 1 0 000

0 0 1 4 1 000

29 35 13 13 13 11 4 3

Total 23% 28% 10% 10% 10% 9% 3% 2%

Key to Abbreviations:

2

1

0

0

0

3

2%

Alc.=Alcohol; Pd.=Psychedelics; Dust=Phencyclidine; H.=Heroin;

2 71 56%

1 37 29%

0 1 2 9%

0 1 1%

0 6 5%

3 127

2% 100%

Am.=Amphetamines; S-H=Sedative-Hypnotics; Cd.=Codaine; Mh.=

Marihuana; Solv.=Solvents; Comb.=Combinations.

164
experiences of hallucinations, accounted for an additional 29

percent of the adverse reactions, and 68 percent of these were due

to psychedelics such as LSD and MDA. Dust accounted for ten percent of the 127 adverse reactions; eight were physiological, two

were "bad trips," and two were reported as "overdoses," a term

which included from overdoses requiring emergency room treatment

and less severe episodes of passing out.

Table six displays the total number of adverse reactions reported

by subjects at Site two. Although the prevalence and frequency of

alcohol use were similar at the two sites, alcohol accouuted for a

considerably smaller percentage of adverse reactions at the urban

site (four percent) compared to the suburban forest preserve (23

percent) . Psychedelics accounted for the greatest number of adverse

reactions (31 percent), predominantly "bad trips." Amphetamines,

sedative-hypnotics, and heroin were said to be responsible for a

slightly greater percentage of the adverse reactions at Site two

than Site one; the percentage of reactions due to dust was the same

in both samples (ten percent at Site one and 12 percent at Site

two). Dust was not mentioned in reactions said to be due to a combination of drugs. At both sites a greater number of “bad trips"

was reported for psychedelics than for dust; but compared to

psychedelics dust was said to be responsible for a greater percentage of adverse physiological reactions and those labeled by

subjects as an "overdose."

Treatment of adverse reactions reported at Site two, displayed in

table seven, was practically identical to the data from Site one.

At Site two, 31 percent of the adverse reactions were treated by

friends, 32 percent were treated at hospitals, 23 percent received

no treatment, eight percent were treated by the subject himself,

four percent were treated by parents, and two percent at drug rescue

Services.

If we compare the type of drugs accounting for the adverse reaction

and the nature of treatment reported at site two (see table seven),

of all the drugs, psychedelics and dust had the greatest number of

adverse reactions treated by friends (46 percent each). Twentythree percent of the adverse reactions reported for dust, but nine

percent of the adverse reactions reported for psychedelics, were

treated in a hospital setting.

The data suggest that most reactions from dust and psychedelics are

treated by friends, receive no treatment, or are managed by the

individual himself. Hospitals appear to get subjects suffering from

sedative-hypnotic and heroin overdoses, and overdoses and physiological reactions due to amphetamine abuse, more frequently than

reactions said to be produced by other drugs, including dust.

Twenty percent of subjects at Site one and 34 percent at Site two

had been treated at a hospital for a drug-related problem. The

rank order of types of problems was the same among both samples:

overdose, problems related to "heavy usage," adverse drug reactions,

hepatitis, "to dry out," vehicle accidents due to drug intoxication.

165
TABLE 6

DRUGS SELF-REPORTED TO HAVE PRODUCED ADVERSE REACTIONS,

URBAN SAMPLE

(N=118)

Nature of

Adverse Reaction Drugs Said to Have Caused Adverse Reaction

Physiological

"Bad

trip"

overdose

Withdrawal

Other

Total

Number

% of

Total

Alc.

3

0

1

0

0

4

4%

Pd. Dust H. Am. S-H Cd. Mh. Solv. Comb. TOTAL

7 3 8 12 3 2 1 2

27 6 0 3 0 0 2 0

0 4 7 1 5 0 0

0 01 0 1 0 0 0

100 00 0 0 0

1 42 38%

2 40 37%

5 2 3 21%

0 2 2%

1 2 2%

35 13 16 16 9 2 3 2 9 109

31% 12% 15% 15% 8% 2% 3% 2% 8% 100%

Key to Abbreviations:

Alc.=Alcohol; Pd.=Psychedelics; Dust=Phencyclidine; H.=Heroin;

Am.=Amphetamines; S-H=Sedative-Hypnotics; Cd.=Codeine; Mh.=

Marihuana; Solv.=Solvents; Comb.=Combinations.

166
TABLE 7

SELF-REPORTED TREATMENT FOR ADVERSE REACTIONS, URBAN SAMPLE

Drug Reported

Producing

Adverse Reaction

None Friends

% N % N

Alc. (0) 75(3)

Mh. 33(1) (0)

S-H 22(2) 11(1)

Am. 31(5) 19(3)

Dust 23(3) 46(6)

Pd. 26(9) 46(16)

H. 13(2) 19(3)

Oth. 23(3) 15(2)

Total 23(25) 31(34)

Key to Abbreviations:

(N=118)

Reported Treatment

Hospital

% N

25 (1)

33 (1)

67 (6)

31 (5)

23 (3)

9 (3)

63 (10)

46 (6)

32 (35)

Self

% N

(0)

33(1)

(0)

13(2)

(0)

11(4)

6(1)

8(1)

8(9)

Parents

% N

(0)

(0)

(0)

(0)

8 (1)

6 (2)

(0)

8 (1)

4 (4)

Drug

Prog.

% N

(0)

(0)

(0)

6(1)

(0)

3(1)

(0)

(0)

2(2)

Total

% N

4 (4)

3 (3)

8 (9)

1 5 (16)

12 (13)

32 (35)

15 (16)

12 (13)

(109)

Alc.=Alcohol; Mh.=Marihuana; S-H=Sedative-Hypnotics; Am.=

Amphetamine; Dust=Phencyclidine; Pd.=Psychedlics; H.=Heroin;

oth.=other drugs: Drug combinations and codeine, cocaine and

glue.

167
Seven percent of Site one subjects and 23 percent of those at

Site two had been hospitalized for psychiatric problems at least

once. Approximately one-quarter of subjects at both sites considered themselves to have a "drug problem," but only ten percent

wanted help with that problem. Approximately 20 percent of both

samples had previously had some contact with a drug abuse treatment

agency.

DISCUSSION

This study suggests that by utilizing a field team research model,

public health agencies and drug treatment facilities could efficiently perform case finding and identify popular congregation

areas for epidemiologic and ethnographic studies of drug use and

as target areas for intervention. Incidence trends at these sites

suggest that field intervention activity should be directed primarily toward reducing prevalence and frequency of use, case identification and early intervention with younger users prior to experimenting with intravenous use and opiates, and should place less

emphasis on prevention approaches to reduce incidence of new cases

experimenting with pharmaceuticals and psychedelic drugs (Hughes,

Schaps, and Sanders 1973; Shick and Freedman 1975).

Regional congregation sites, such as we have described, attract

a large population of heavy, multiple drug users, many of whom

would not be included in studies conducted in schools, drug abuse

treatment centers or industry. The large number of subjects

neither employed nor attending school, the large number of grade

school and high school droputs, and the numerous adolescent runaways identified suggest that field studies at such sites can contribute an added dimension to the study of multiple drug use.

Furthermore, only about one-half of subjects out of school and unemployed could be identified through studies in hospital emergency

rooms, psychiatric hospitals, and drug abuse treatment programs.

Studies in the correctional system miss a large proportion of

these youth. Although approximately 70 percent of both samples

had been arrested at least once, approximately half of those arrested had been convicted.

The concentration of heavy drug users at such congregation sites

suggests research investigating sequences of use (Kandel and Faust

1975; Gould et al. 1977) and precursors (Halikas and Rimmer 1974;

Lettieri 1976) predictive of subjects at risk for adverse reactions

or progression to dangerous patterns of multiple drug use, for example, intravenous experimentation. Perhaps regular attendance

by adolescents at such sites itself may reflect high risk for adverse drug outcomes and other deviant behavior. The school and

employment histories of subjects are in marked contrast to those of

regular visitors to neighborhood locations previously studied

(Shick, Dorus, and Hughes 1978) and suggest interaction between

education and employment difficulties, drug using behavior, and

alienation from mainstream youth more typical of other areas. The

adverse outcomes implicit in all of this suqqest field studies to

investigate causes, correlates, and consequences of social

168
involvement in such settings.

Particular attention needs to be directed toward the composition

and characteristics of groups, their requirements for membership,

codes of loyalty and secrecy, status hierarchy, and territorial

hangouts. The activities, preferences, common understandings,

norms, and values need to be studied to increase our understanding

of their relationship to drug use. Studies of how these youth

chose to be certain types of teenagers, the labels they apply,

and the behavior expectations of each role -- the deviations and

the responses -- are part of our ongoing research. We need to

know how newcomers learn about such areas, and how they are socialized into the group. The range, patterns, and characteristics of

lifestyles in the community should be examined, and analysis should

include examination of the appeals of illegal sources of support

(or "hustles"), the socialization processes into such careers, and

the relationship between these hustles and drug use. Studies

should explore the popular folklore regarding specific drugs,

methods of administration and the effects on patterns of use. They

should describe how drug use is related to prestige -- or the loss

of it -- and how drug use reflects the values and expectations of

various groups, roles, and lifestyles.

These youth spend much of their time and activities with friends

and acquaintances. Studies which concentrate only on drug use

highlight drug centered activities to the exclusion of other behavior, often equally important in reinforcing or discouraging

certain facets of drug use. Comprehensive field studies should

place drug use in its broader social context by examining the

patterns of collective activities (what they do together) and how

much of their activities center around obtaining drugs and "getting

high." For example, what sorts of activities first require getting

high with drugs; when intoxicated, which activities are compatible

and which are avoided? How do individuals and groups arrive at the

decision to get high or to avoid taking drugs, and how is drug use

related to risk-taking, recreation, and the sear& for novelty or

constancy (Shick and Freedman 1975)?

Regular visitors to these sites were frequent users of a wide

variety of drugs, often intravenously, but considering their frequent use, adverse reactions tended to be minimal. In fact, most

adverse reactions were managed by the youth themselves and did not

involve hospital contact, suggesting that studies of the extent and

range of adverse reactions conducted at hospital treatment settings

or identified through DAWN data may be biased toward the most severe

reactions, include youth who are loners or least involved with drug

using peer groups, or who are relative novices to the drug using

scene.

Research into consequences and outcomes attempts to define a characteristic reaction, to understand a user's adaptation, and to

assess the cost to the individual and society, as well as to delineate any neurochemical or tissue basis for a reaction, and/or operative personal, social or historical factors. Only rarely does

169
research investigate such difficulties within the community, where

a (so far) unknown number of users experience adverse consequences,

yet define their difficulties in terms obviating -- in their minds

anyway -- medical intervention: they remain contained, tolerated,

or sheltered by their subculture.

These preliminary results suggest field studies investigating the

specifics of what youth term "adverse reactions." For example, how

do they define a "bad trip" or "overdose?" What do they mean when

they say thats someone on the street has a "drug problem?" Do they

apply the same or different criteria to themselves? Since so many

adverse reactions are managed without treatment, by the individual

himself or by his friends, what are the specifics of that management? How, in fact, do youth come to be treated at hospital emergency rooms; what are the selection factors? What drug problems

are the "ticket of admission" for psychiatric hospitalization?

How does a peer group decide that a reaction needs medical management?

The prevalence of intravenous experimentation among all age groups

in these samples suggests a relative lack of social norms discouraging intravenous use and that patterns of chronic intravenous

use my begin through acquaintances formed at such regional sites.

How does the spread of intravenous experimentation occur? Do older,

more experienced users initiate younger novices, or do friendship

groups of novices obtain drugs and injection equipment from older

users and try it for the first time among themselves? From a practical standpoint, it would seem that if a novice was determined to

experiment with intravenous drug use, the presence of more experienced user might decrease the chance of an adverse reaction.

S/he could impart the rituals and safety precautions born of experience without the novice's having to learn through trial and

error. On the other hand, the older user might more quickly teach

the novice to define the effects s/he experiences as pleasureful

and reinforce further trials and, perhaps, habitual use (Becker

1967). If initial experimentation occurs among same-age friendship

groups, how would peer pressure reinforce or discourage future

trials? What portion of the friendship group would engage in future

trials? The substance of the social norms about drug use and other

behavior, the criteria drug using youth use to designate individuals

with "drug problems," and the hierarchy of social roles in such

settings are questions to be explored in future research.

We recognize the tentative nature of our findings. Our studies have

focused on two regional (urban and suburban) congregation sites in

Chicago. The similarities and differences between geographical

and social organization of drug using groups and the patterns of

drug availability and use in other communities with different ethnic

and socioeconomic makeups should be investigated. Future comparative studies will define what segment of the total adolescent drug

using population we have observed -- whether only the heaviest users

hang out at such locations or whether infrequent users and nonusers

have similiar congregation sites. At these areas we were able to

obtain interview data on a sample only of the regular visitors.

170
Thus our findings do not necessarily reflect characteristics of

other groups less frequently present.

The alleged epidemic of phencyclidine use is as yet poorly defined. Epidemics of drug interest and panic have occurred before, and societies have sought to regulate attitudes on the consumption of new or familiar substances; for example, the gin epidemic of 18th century Britain, the opium problem in the United

States in the 1920's, the heroin epidemic among Chicago Negro

youths and the Japanese epidemic of amphetamine use following

World War II, and, of course, the "pot and acid" epidemic among

white, middle class youths in the late 1960's (Shick and Freedman

1975; Shick, Smith, and Meyers 1970; Musto 1973).

We most not forget the potential influence of drug education program, of premature publication of research results, and naive,

sensational reporting in the media. The public may have become

supersaturated with the notion of drug abuse, and further input

may serve only to reinforce interest in a deviant activity that,

in reality, only small numbers engage in with seriously incapacitating outcomes. The treatment response must be directed toward

those few, but what sort of treatment is effective remains a research issue. The prevention response has been hurriedly implemented without planning to research the needs of the receiver or

the effectiveness of the output (Shick and Freedman 1971). The

question of how and who should intervene needs careful planning

and study and has numerous ethical, social, and legal implications.

Presently, phencyclidine is classified as Schedule III under the

Controlled Substances Act of 1970. Interviews with fieldworkers

and subjects suggest that in chicago rescheduling certain pharmaceutically manufactured substances, for example, Tiunal, Seconal,

and Quaaludes, into Schedule II increased their cost, and initially

at least, decreased their illicit availability. In Illinois, all

Schedule II drugs require a triplicate prescription, and this may

have been equally important in reducing supply (from pharmacies and

pathological prescribers), a conclusion supported by field observations and informal interviews with users in the California area,

where, for example, Quaaludes, which do not require triplicate

prescriptions, appear to be more available (although similar in

cost) than in Chicago.

Such rescheduling (into Schedule I or II) in the case of phencyclidine, which is supplied predominantly from illicit manufacture,

will reduce supply less, if at all, my increase cost which is already substantial, and will have little effect on remission. It

my encourage substitution reactions of potentially more dangerous

drugs such as heroin.

Institution of tighter controls by National and State drug enforcement authorities, aimed at decreasing availability of drugs, ironically may have reinforced the establishment of an efficient illicit

distribution system for nonopiate drugs (as well as increased their

cost) and may have caused same users to substitute drugs, some of

171
which, for example PCP, potentially may be more harmful. deAlaroon

(1971) describes similar substitution reactions: the 19th century

"ether epidemic" in Central Europe following the restriction of

alcohol, the appearance of illegal "Chinese heroin" and the widespread intravenous barbiturate abuse in Britain after reducing the

legal prescribing of heroin was reduced in 1969. His study of

the effects in Britain of withdrawing injectable methedrine from

the retail pharmacies reported that although the use of that drug

declined, users transferred their preference to other drugs,and

after two years one-third were still injecting (de Alaroon 1972).

Lately, in the Chicago area, nonbarbiturate sedative-hypnotics

which do not require triplicate prescriptions have become increasingly available as alternatives to barbiturates and methaquaalone. Amphetamine availability also dwindled subsequent to

rescheduling, but large volumes of "uppers" resembling pharma

ceuticals, but containing ephedrine and caffeine, and Schedule III

and Schedule IV CNS stimulants replaced them.

Our research suggests that the nonopiate distribution system is

more stable than previously envisioned and occurs in public places

during warm weather, the residences of friends and dealers during

the winter months, and at certain urban sites active throuhout

the year (Shick and Wiebel 1978). In contrast to heroin addicts,

visitors' regularity of attendance at these sites has little to do

with physical dependence and seems to be determined more by the

fact that adolescents hang out with drug using peers for recreational purposes. The demand (and supply) for drugs, which can be

estimated from data on preference, prevalence, remission, and

frequency of use,and their cost,appears to be great. Although

the cost of these drugs is lower than for heroin, adolescents are

not sufficiently wealthy to put-chase large quantities and may visit

distribution sites more frequently than previously supposed.

Whether this is due to problems of availability and cost or whether,

as we suspect, it has more to do with the lifestyle and the influence of peer groups who supply drugs and initiate and reinforce

certain types of drug use and their accompanying attitudes, are

intriguing questions for field research studies.

172
ACKNOWLEDGMENTS

This research was supported by DHEW, National Institute on Drug

Abuse Grant D A 01083. We wish to thank Mr. W. Wayne Wiebel, M.A.,

Mr. Norman Altman, Mr. Bruce Shaw, Mr. James Allen, and Mr.Gregory

Shelton for their help in data collection and analysis.

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Becker, H.S. Sociological Work: Method and Substance. Chicago:

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Burns, R.S. and Lerner, S.E. Perspectives: acute phencyclidine

intoxication. In: Problems of Drug Dependence 1976. Washington:

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Burns, R.S., Lerner, S.E., Corrado, R., James, S.H., and Scholl,

S.H. Phencyclidine: states of acute intoxication and fatalities.

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Cheek, F., Newell, S., and Jaffee, M. Deceptions in the illicit

drug market. Science, 167:1276, 1970.

deAlaroon,R. Drug abuse as a communicable disease: the public

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Fauman, B., Baker, F., Coppleson, L.W., Rosen, P., and Segal, M.

B. Psychosis induced by phencyclidine. Journal of the American

College of Emergency Physicians, 4(3):223-225, 1975

Fauman, B., Aldinger, G., Fauman, M., and Rosen, P. Psychiatric

sequellae of phencyclidine abuse. Clinical Toxicology, 9(4):529-

538, 1976.

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Gould, L.C., Berberian, R.M., Kasl, S.V., Thompson, W.D., and

Kleber,H.D. Sequential patterns of multiple-drug use among high

school students. Arch Gen Psychiatry, 34:216-222, 1977.

Greene, M.H., Kozel, N.J.,-Hunt, L.G., and Appletree, R.L. An

Assessment of the Diffusion of Heroin Abuse to Medium-sized

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Habenstein, R.W., ed. Pathways to Data. Chicago: Aldine Publishing Company, 1970.

Halikas,J. and Rimmer,J. Predictors of multiple drug abuse.

Arch Gen Psychiatry, 31:414-421, 1974.

Heliston, C. 1976 drug analysis results. PharmChem Newsletter,

6(2):1-6, 1977.

Hughes, P.H. Behind the Wall of Respect: Community Experiments

in Heroin Addiction Control. Chicago: The University of Chicago

Press, 77.

Hughes, P.H. and Crawford, G.A. "A contagious disease model for

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Jaffe, J.H. The social structure of a heroin copping community.

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Hughes P.H., Schaps, E., and Sanders, C.R. A methodology for

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419, 1973.

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AUTHOR

J. Fred E. Shick, M.D., Research Associate (Assistant Professor),

Department of Psychiatry, University of Chicago, 950 E. 59th

Street, Chicago, Illinois 60637.

175
Chapter 8

Patterns of Phencyclidine Use

David B. Graeven. Ph.D.

INTRODUCTION

In recent years the use of phencyclidine (PCP) has been increasing. This increase has been accompanied by an evolution in conceptions about the motivation, patterns, and effects of phencyclidine use. These changing conceptions of PCP use have not

necessarily reflected actual changes in use of the drug. In some

cases they reflect the acquisition of new knowledge about the way

the drug has in fact been used for a considerable period of time.

This paper briefly examines some of the beliefs about PCP use and

presents the results of an exploratory study of PCP users.

CHANGING CONCEPTIONS OF PHENYCLIDINE USE

When PCP use began to increase one of the first beliefs was that

a person would not knowingly use the drug. Early sources of drug

information (STASH, 1975) stated that PCP was not a drug of choice

among young people. This information was found in drug information

publications as late as 1976.

One probable reason for the hesitation to acknowledge PCP as a

drug of choice was the drug's bad street reputation. This bad

reputation was based on reports from San Francisco in the late

1960's on the negative effects of the drug. Another reason for

the reluctance to acknowledge PCP as a drug of choice was the

fact that many samples sent in for analysis to drug laboratories

as THC or mescaline turned out to be PCP. The fact that PCP was

often misrepresented as some other drug led many to believe that

PCP was primarily sold that way. However, local reports from

various areas indicated that PCP was a drug of choice for many

young people during the early 1970's (Graeven 1977).

Once it was realized that there were PCP users who were aware of

what they were taking, the next issue was whether or not phencyclidine use would spread. It was generally believed that PCP

was a California drug and that it might be a fad limited to certain areas of that state. During the period from 1972 to 1976

176
PCP use had in fact spread to various parts of the country.

Reasons for the spread of PCP were that some users seemed to like

the effects, the drug was easy to make, and the dosage could be

regulated. Especially important for the spread of PCP was the

change in mode of administration from pill to smoking (Graeven

1977). It appeared that in order for PCP to diffuse and increase

in popularity as a drug of choice, less risky modes of administration such as smoking or snorting had to replace its use in pill

form.

Recent survey data reported by the National Institute on Drug

Abuse shows that PCP use has increased around the country (U.S.

Journal of Drug and Alcohol Dependence, 1978). There now seems

to be some agreement on the fact that many young people use PCP,

and for some proportion of the users it is their drug of choice.

Currently the predaninant conception about PCP use, as presented

in the mass media, is that PCP is an extremely dangerous drug.

With the advent of PCP as a media event there seems a remarkable

similarity to the drug information presented in the 1960's. At

that time, there was a good deal of negative publicity, horror

stories about users were published, and most often systematic

research to support the statements being made was lacking.

The picture of phencyclidine use as a primarily negative experience is due in part to the fact that the spectrum of use has not

been adequately examined. Most research reports have been based

on people having problems with PCP. Early research on most street

drugs, which is often based on persons found in treatment programs,

is likely to overstate the frequency of negative effects as a

result of using a drug, as well as overstating the importance of

a lack of personal adjustment as a factor leading to its use

(Graeven and Graeven, 1977). To present a valid picture of PCP

use it is important that research look at the broad range of users.

METHOD

To examine the spectrum of PCP use an exploratory study was conducted. The goals of the study were to examine patterns of use,

what people had heard about PCP, likes and dislikes about the

drug and its perceived effects. A short questionnaire was administered to a group of 89 persons who had used PCP. Snowball

sampling techniques were used, moving from known PCP users to

their friends and acquaintances who had also used.

The majority of the sample was black (78 percent), with nine percent Mexican-American and twelve percent white. The majority

came from the city of Oakland, California (68 percent), the

remainder from Hayward and Fresno. Seventy-four percent of the

sample was male and twenty-six percent was female. The median

age was 20 with a range from 15 to 33.

177
USE PATTERNS

Results on total amount of PCP use shown in table 1 indicate that

the largest group of users were those who used only once or twice

(29 percent). At the other extreme, nine percent of the users

had used more than one hundred times. Regarding frequency of

use, almost half of the respondents seldom used PCP, with nine

percent using it several times a day.

TABLE 1

PATTERNS OF PHENCYCLIDINE USE

(N=89)

Total Number of Times Used %

1 or 2 29

3 to 8 21

9 to 30 28

31 to 100 13

100 or more 9

Frequency of Use

Several times a day 9

3 to 5 times a week 14

l to 2 times a week 14

Couple times a month 15

Seldan 4 8

Quantity used

A few hits 36

1⁄2 joint 16

1 joint 26

2 joints 7

3 or more joints 15

All subjects reported that their most common mode of administration

was smoking PCP joints. Diverse patterns were found for the amount

usually used. As shown in Table 1, the modal amount used was a

few hits from a joint. These data on use patterns indicate that

for this population of users there was a large group of persons

who seldom used the drug,but for the remaining persom there was

a diversity in the total number of times used, frequency of use

and quantity of PCP ordinarily used.

Analysis of the patterns of use by age showed that the age group

19 to 21 had the highest use. Twenty-six percent of those in the

19 to 21 year old groupused five times or more week, compared to eight percent in the 18 and under group and nine percent

in the 22 to 30-year-old group. Comparing males and females,

males were somewhat more likely than females to have high use.

Twenty-three percent of the males used 31 times or more as com178
pared to nine percent of the females.

DRUG OF CHOICE

Subjects were asked to choose which drug they preferred: alcohol,

marihuana or phencyclidine. Eight percent preferred PCP, seventyseven percent preferred marihuana, and fourteen percent preferred

alcohol, Of those who used PCP frequently (3 or more times a

week), a third preferred it. Marihuana was preferred by 43 percent of the high PCP users, and the remaining 24 percent of the

high PCP users preferred alcohol. None of the subjects with lower

use patterns preferred PCP.

HEARD ABOUT PCP

Respondents were asked an open ended question on what they had

heard about PCP. Fifty-three percent had heard that people liked

PCP; one third had heard that PCP was physically bad for a person.

The main negative physical effect mentioned was that PCP could

kill brain cells. The third most frequent response was that

most people couldn't handle PCP (14 percent). Inability to handle

the effects of PCP was indicated by responses such as "people

would act crazy" or "people get into trouble on PCP."

Comparing patterns of use by what people had heard about PCP showed

that the more frequently PCP was used the more likely the respondent

reported that s/he had heard that people liked the drug. Forty

percent of the people who seldom used PCP had heard that people

liked it, as compared to 54 percent of those who used it a couple

of times a month and 75 percent of those used one or more

times a week.

LIKE MOST ABOUT PCP

In response to an open ended question on what was liked most about

PCP, the majority of the respondents (58 percent) said the high

they get when they use it. Twenty-nine percent said there was

nothing they liked about the drug, and twelve percent liked the

way they acted when they were on PCP. Comparing use patterns by

what they liked about the drug,the group with the lowest use

pattern,as would be expected, was most likely to mention that

there was nothing they liked about the drug.

DISLIKE MOST ABOUT PCP

In response to an open ended question on what they disliked about

the drug, nearly two-thirds (63 percent) of the respondents mentioned the lack of control of themselves when they weres on PCP,

e.g., "I can't control my body," or, "I can't control my thoughts."

About one-third (37 percent) stated that there was nothing they

disliked about the drug.

Those persons who used PCP most often were least likely to mention lack of control as a problem and most likely to say there

179
was nothing they disliked about the drug. Thirty-six percent of

those who used PCP three or more times a week mentioned lack of

control as what they disliked about the drug as compared to 73

percent of those who used the drug two or less times a week.

PERCEIVED EFFECTS OF PCP

Questions were also asked regarding whether subjects never, always, or sometimes had each of four experiences when they used

PCP: felt good, forgot their worries, liked to party, and had

mood changes. Field work suggested that PCP users varied in that

some persons liked to move around and dance while on a PCP (party),

while others didn't. The responses to these questions are shown

below in table 2. For each of the four experiences there was no

overwhelming agrees-tent on any one of the response categories.

Modal responses showed, however, that respondents were not likely

to forget worries or feel good about themselves while using PCP,

and were somewhat likely to party and have mood changes when

using.

TABLE 2

PERCEIVED EFFECTS OF PCP

(N=89)

Behavior % Never % Sometimes % Always

Forget worries 48 33 19

Feel good about self 38 37 25

Like to party 35 42 23

Mood changes 23 38 39

There was no relationship between patterns of PCP use and mood

changes, forgetting worries; and feeling good about oneself.

For 'partying," there was a slight relationship with the amount

of drug used. Thirty-six percent of those who used PCP three

times a week or more always partied on PCP as compared to 17

percent of those who used two or fewer times a week.

LACK OF CONTROL AND PERCEIVED EFFECTS

Comparing the perceptions of those who mentioned lack of control

as one of the adverse effects of PCP with the group that said they

had no problems with the drug revealed some interesting results.

While there were no differences between groups on forgetting

worries or mood changes, there were marked differences for "feeling good" and "partying." For those who disliked the lack of

control, only three percent always felt good when using PCP as

compared to forty-six percent of those who did not mention lack

of control. For partying, eight percent of the lack of control

group always partied when using PCP, as compared to forty-one

180
percent of those in the other group.

The difference found in the perceived effects of PCP for those

who did and did not dislike the lack of control, poins to an

interesting dimension of an individual's reaction to PCP use.

reaction to loss of control and whether or not a person experiences the loss of control seems to have consequences for how a

person behaves under the influence of PCP.

SUMMARY

Use of phencyclidine is a diverse phenomenon with wide variations

in both the amount taken and the frequency of use.There is a

large group of persons who have tried PCP once or twice and discontinued using. One of the key distinctions pointed out by this

exploratory study relates to the feelings of control persons have

over the effects of the drug.The PCP user who is not bothered

by the lack of control is more likely to feel good and party with

others when using and is more likely to have high use patterns.

Feelings of control over the effects of PCP indicate an important

individual difference in understanding reactions to PCP use and

further research should systematically examine this phenomenon.

There has been a discrepancy between our conceptions of PCP use

and the actual patterns of use found in the United States. It

appears that at this time most persons in the drug abuse field

are willing to accept the fact that PCP is a drug of choice among

young people and that some as yet unspecified proportion of users

is able to use PCP and avoid major problems. While there remains

much speculation about the motivation for use and the effects of

such use,it would appear that we are ready to engage in research

which systematically looks at the spectrum of users.

181
ACKNOWLEDGMENTS

I would like to thank Fredonia Honable, Beulah Brewster,and

James M. Washington for their assistance in the collection and

analysis of the data.

REFERENCES

Graeven, D.B. Phencyclidine (PCP): A local and national perspective. Addictive Diseases, 3:243-252, 1977.

Graeven, D. B., and Graeven, K.A. Treated and Untreated Addicts:

Factors Associated with Participation in Treatment and Cessation

of Heroin use. Paper presented at the National Drug Abuse Conference, San Francisco, California, May, 1977.

STASH, Student Association for the Study of Hallucinogens, Inc.

PCP (Phencyclidine): The New Delusinogen. Madison, Wisconsin:

STASH Press, 1975.

U. S. Journal of Drug and Alcohol Dependence, 2(2), February,

1978.

AUTHOR

David B. Graeven, Ph.D.

Department of Sociology

California State University Hayward

Hayward, California 94542

182
Chapter 9

The Psychiatric Aspects of

Chronic Phencyclidine Use:

A Study of Chronic PCP Users

Michael A. Fauman, M.D., Ph.D., and Beverly J. Fauman, M.D.

INTRODUCTION

Phencyclidine (PCP) first appeared on the “streets” as an abused

drug in 1967, two years after human clinical investigations of its

potent analgesic and anesthetic effects were discontinued because

of its severe behavioral side effects (Reed and Kane 1972). Since

that time illicit synthesis and abuse of PCP have increased under

the guise of various street names, such as TIC, TAC, THC, angel

dust, dust, dummy dust, rocket fuel, hog, sheets? crystal and

crystal joints (Fauman et al. 1976). Investigation of PCP’s

psychotomimetic effects were conducted in the early 1960’s,

coincident with early clinical trials of the drug (Davies and

Beech 1960; Bakker and Amini 1961: Luby et al. 1962). In the

early 1970’s the first reports of adverse medical and behavioral

side effects, including severe longterm psychotic episodes from

street PCP began to appear (Reed and Kane 1972; Stein 1973; Rainey

and Crowder 1974; Burns et al. 1975; Eastman and Cohen 1975; Fauman

et al. 1975; Luisada and Reddick 1975; Tong et al. 1975; Liden,

Lovejoy, and Costello 1975). Since that time abuse of PCP has

increased and has spread to all parts of the country. Several

recent papers have alerted physicians to the varied medical and

psychiatric presentations of PCP ingestion at low doses and in

cases of overdose (Fauman et al. 1976; Luisada and Brown 1976;

Bolter et al. 1976; Burns and Lerner 1976; Cohen 1977; Dupont 1977;

Aronow and Done 1978). Quantification of amounts of ingested

phencyclidine is often difficult because many street preparations

are mixtures of phencyclidine and other drugs, patients may come

to medical attention at varying times after using the drug, and

many medical centers do not have the necessary laboratory facilities

to test for phencyclidine (Lundberg, Gupta, and Montgomery 1976;

Aronow and Done 1978).

Recent concern has also been directed to the effects of chronic

abuse of phencyclidine (Burns and Lerner 1978). The presence of

chronic abuse implies that the phencyclidine experience is not

always as dangerous or undesirable as recent medical reports

have suggested. This paper reports the results of a pilot

183
psychiatric study of a sample of chronic phencyclidine abusers

whose length of use of this drug ranged from ten months to nine

years. Specifically, we have attempted to investigate the manner

of phencyclidine use, its psychological and interpersonal effects,

bad reactions from phencyclidine, and the sequelae of its abuse.

We have also tried to determine why its use is so widespread despite

its potentially dangerous side effects, the attitudes of users

toward PCP, and its effects on their lives. Finally, we hope to

point out the direction of further studies in this area, related

to the psychiatric and neuropsychological effects of chronic

phencyclidine abuse.

A STUDY OF CHRONIC PHENCYCLIDINE (PCP) USERS

Phencyclidine Study Population

Crossroads is a residential therapeutic community for the treatment of polydrug abusers between thirteen and twenty two years of

age.

1

It is operated by the Illinois Dangerous Drugs Rehabilitation

Systems (IDDRS), a private not for profit corporation. The residential program maintains a census of 35-40 clients. The census

at the time of the study was 8 women and 28 men. Thirty two of

the 36 clients had used phencyclidine in the past and 29 clients

(81.1 percent) had used phencyclidine for 10 months or longer

(average 3.6 years ± 1.8 years). Twenty five clients who were

chronic phencyclidine users consented to be interviewed.

Phencyclidine Study Questionnaire

The study questionnaire consisted of 73 questions about the user’s

family, schooling, psychiatric history, knowledge about phencyclidine, and use of phencyclidine. The study was explained to the

client and s/he was told that participation was totally voluntary.

Confidentiality was maintained by recording only the first name

and last initial on the first page of the eleven page questionnaire.

The pages were then nunber coded and separated for analysis. The

questions were administered to the phencyclidine user in a

45 minute interview with one of the senior authors.

PCP Users: Demographic Data, Personal and Family History

Tables 1 and 2 present demographic data and some personal and

family historical data for the 25 users in the study. The five

women reported considerably less average weekly spending money

than the men. Three of the five reported that their boyfriends

supplied them with phencyclidine so they did not need to buy the

drug. A substantial number of parents of PCP users were also

reported to use some form of drugs regularly. Seven PCP users

had fathers who were alcoholic and two of these seven also had

alcoholic mothers. Alcohol was the cause of death of one of these

mothers. Three other mothers and two other fathers routinely used

depressants, mainly diazepam. Two other mothers and one other

father routinely used pain medication. Two PCP users reported

that their mothers had been hospitalized for psychiatric problems

184
TABLE 1

PCP USERS: DEMOGRAPHIC DATA

REACE WEEKLY

SEX WHITE BLACK AGE YRS OF SCHOOL # OF SIBS SPENDING MONEY

MALE

FEMALE

AVERAGE

*Standard Deviation
TABLE 2

PCP USERS: DEMOGRAPHIC, PERSONAL AND FAMILY HISTORY

HISTORICAL INFORMATION

Parents separated or divorced

Mother used drugs*

Father used drugs*

User was only child

User was eldest child

Previous family psychiatric

problems

Previous user psychiatric

problems

Previous user suicide

attempt

Previous user OD from

any drug

Users who report that drugs

interfered with school

% OF USERS WHO REPORT

MALE FEMALE AVERAGE

25 20 24

30 40 32

40 60 44

5 20 8

40 40 40

30 80 40

40 40 40

20 40 24

35 40 36

60 60 60

Sample size: 20 Male, 5 Female

* Drugs include: Downers, Marihuana, Alcohol, Heroin, Pain

Medications

186
and one reported that a sister had been hospitalized for drug

problems. The remaining family psychiatric problems included

alcoholism, hyperactive siblings, marital problems and nonspecific

psychiatric problems. Ten phencyclidine users reported previous

psychiatric problems, often related to drug abuse. Nine users

reported drug overdoses and four reported more than one overdose.

Most users who attempted suicide did so by taking drug overdoses.

Others were quick to point out that their overdoses were not

conscious suicide attempts, but were instead accidents.

Many phencyclidine users reported that drugs interfered with their

schoolwork. Some were too “high” or “spacey” to be able to get up

in time for school or concentrate on their schoolwork. For others,

drug use, family and other interpersonal problems together led

them to leave school and often, their homes.

PCP Users: Drugs Used and Favorite Drugs

Table 3 presents the drugs used and favorite drugs of participants

in the study. Phencyclidine was reported as the favorite drug

for 56 percent of the users, because of its availability, low cost,

but mostly because of the effects they obtained from it. Eighty

eight percent (22) of the phencyclidine users had used LSD and

84 percent (21) had used it heavily, more than 24 times. All

88 percent reported that the experience obtained from LSD was

different from phencyclidine. Most felt that LSD has more of a

hallucinogenic effect, with colors and images, while phencyclidine

produced more of a "body high” with sensory distortions, but not

vivid visual hallucinations.

PCP Users’ Beliefs About the Dangers of PCP

Ninety six percent (24) of users had heard that phencyclidine is

a dangerous drug, and 88 percent (22) believed that it was

dangerous at the time of the study. Fifty two percent (13)

had heard this from friends, 32 percent (8) from drug counselors,

16 percent (4) from family, 24 percent (6) from reading, and

12 percent (3) decided phencyclidine was dangerous from personal

experience. Clients reported they had heard that phencyclidine

contained impurities, caused coma and death, killed "brain cells,”

makes you “rowdy” and “stupid,” causes brain damage and psychosis,

“burns you out,” causes cancer and liver damage, and can cause

convulsions. Many, if not most, of the phencyclidine users we

spoke with had heard and believed that phencyclidine was dangerous

before they entered the treatment program, but this apparently

did not stop them from using it for as long as nine years. Some

users reported that they could not stop using phencyclidine. One

20 year old user, who was asked to leave the program after six

weeks because of his behavior, immediately used phencyclidine

intravenously the day he left, even though he believed it was

dangerous. He was later readmitted to the program.

187
TABLE 3

PCP USERS: DRUGS USED AND FAVORITE DRUG(S)

DRUG USED % WHO USED DRUG

Uppers

(Stimulants)

Downers

(Depressants)

Marihuana

Alcohol

Glue

Cocaine

Phencyclidine

LSD, Mescaline

Heroin

Other Opiate

72

% WHO REPORTED DRUG AS*

THEIR FAVORITE DRUG

4

92 20

52 0

36 0

12 0

80 12

100 56

88 16

40 4

20 0

Sample size: 20 Male, 5 Female

*4 Male users reported 2 favorite drugs and 1 Male

user reported no favorite drug

188
Availability and Use of PCP

All of the users questioned stated that phencyclidine was easy

to obtain. Many laughed at the question and described going

into the parks or along the shores of Lake Michigan, and hearing

young dealers advertising their wares by yelling “Get your angel

dust, acid and coke here.” Another user described how student

dealers regularly used specific stalls in the school bathrooms to

sell phencyclidine and other drugs. Still others described

comparison shopping for phencyclidine on the street corner, asking

three dealers to show how much phencyclidine they would sell for

ten dollars. Most users agreed that the availability of phencyclidine was independent of the time of year.

Phencyclidine was purchased in “dime” amounts or grams. A “dime”

cost ten dollars and contained an unspecified amount of drug,

usually arrived at by bargaining between user and dealer. A gram

of phencyclidine sold for approximately sixty dollars and contained

between 15 and 22 “dimes.” Users also referred to two, three, and

five cents worth of phencyclidine, meaning subdivisions of a “dime”

into amounts of PCP worth two, three, and five dollars.

Sixty eight percent (17) were introduced to phencyclidine by

friends and 16 percent (4) were started by dealers. Users reported

first hearing about phencyclidine at an average age of 13.4 (±1.6)

years and first using PCP at an average age of 14.2 (±1.5).

Fifty six percent (14) indicated that they used phencyclidine

continuously from the time they started until entering the treatment program. Others stopped when they moved out of the country,

could no longer afford PCP, were going with women who asked them

to stop, entered drug treatment programs, or became concerned

about the side effects. Sixty percent (15) of users felt that

phencyclidine was more special than other drugs, either because

of its availability and low price, or because of the effects it

produced. Finally, users estimated that 97 percent of their

friends used drugs, and 75 percent used phencyclidine.

Table 4 shows the frequency of phencyclidine use among the study

population. The first three columns in figure 4 report the user’s

estimate of the period of his/her heaviest use, including the

number of times per day, number of days per week PCP was used, and

the number of months this heavy use continued. The last column

reports the average total number of years of PCP use. The months

of heaviest use vary the most, with a range of 0.5 to 60 months

for men, and 2 to 12 months for women. Similar high estimates

of the frequency and duration of PCP use were obtained independent

of the senior authors by one of the staff nurses.

It is possible that the reporting of these high levels of PCP use,

as well as the frequent reporting of PCP as the drug of choice, was

influenced by the fact that our subjects knew we were interested

in PCP use. We asked about the use of one other drug, LSD, in

some detail. As mentioned earlier, 21 users reported they had

189
TABLE 4

PCP USERS: PERIOD OF HEAVIEST PCP USE AND TOTAL YEARS OF PCP USE

PERIOD OF

HEAVIEST USE OF PCP

DURATION IN TOTAL YEARS

TIMES/DAY DAYS/WEEK MONTHS OF PCP USE

MALE

n=19

FEMALE

n=5

AVERAGE

n=24

* Standard Deviation

¶ Range of Values
used LSD heavily. For the nine who gave more specific data about

their use of LSD, the average frequency was 3.2 (±2.8) times per

week, for an average of 18.6 (±16.0) months. The fact that they

reported a high incidence of LSD use suggests a different bias,

namely that our study sample probably consisted of heavy users

of multiple drugs.

PCP Users: Knowledge of Bad Reactions to PCP in Others

Eighty eight percent (22) of PCP users in the study reported

incidents of friends having bad reactions to phencyclidine.

One incident involved a friend who fell into the water and had to

be rescued because he couldn’t move or swim after taking phencyclidine. Two others reported incidents of friends becoming belligerent and starting fights, and four users reported bad reactions

in which friends could not move, or lost control of the car they

were driving, and hit other cars. Some became concerned that they

were going to die, while others feared that they would never

“come down.” Fifteen users had heard of or knew at least one

person who had a prolonged bad reaction to PCP, with some requiring

medical attention. Six of these were not specific about the

length or severity. Five reported the reaction lasting 3 to 5

days, two reported bad reactions lasting two weeks, and two

persisted for two months or more. Some prolonged "bad trips”

included psychotic delusion, severe paranoia and attempts at

self-mutilation.

The Phencyclidine Experience

The descriptions phencyclidine users gave of their first experience

using PCP varied considerably. One woman and 11 men described

the experience in very positive terms: fantastic, “mind blowing,"

an intense high, or a happy experience. Four women and six men

found the experience neutral or mildly unpleasant. One of these

reported he had taken an overdose on “five cents worth” of PCP

and became numb. A second fell into the water, thought he would

drown, and barely pulled himself out of the water before he

became unconscious for three hours. The third reported that he

started with a “dime” of PCP and then added more, until he

became stuporous for five days, periodically awakening with

hallucinations. A number of users described the experience as

one of feeling “light," as if they were walking on air or on

clouds. Others described feeling numb, pleasantly dissociated

from their bodies, unable to move, calm or “mellowed out,” as

if they had taken a tranquilizer, or feeling stimulated and

excited. A few had a feeling that everything was in slow motion.

One male user described feeling rowdy.

The usual phencyclidine experience varied considerably from user

to user, and was also distinctly different from the first

experience. None of the women and seven of the men reported

the usual PCP experience as being positive. They described

feeling high, calm, "mellow," or euphoric. Three women and eight

131
men found the experience to be unpleasant. They described

feeling numb, unable to understand people, paranoid, scared,

exhausted, moody, unable to move, and generally isolated from

the environment. Three men described feeling “rowdy” or violent.

The usual PCP experience was generally described as more dysphoric

than the first experience. Some users began to feel increasingly

moody or chronically numb and slowed. The same feelings which

were described positively for the first experience began to be

described in a negative sense as use continued.

Phencyclidine users were asked how their friends described the

user’s behavior when s/he was taking PCP. The female users were

described as “cool,” fairly normal, calm, or “spacey.” Eight

of the males were described as becoming irritable, rowdy, or

starting fights while taking phencyclidine. One reported that

he threw a 55 gallon aquarium off a stand and burned a car while

under the influence of PCP. Two others were described as acting

erratic, from being calm to attacking others for no reason.

Phencyclidine users were also asked to describe the behavior of

their friends when they used PCP. Friends were most commonly

described as acting “goofy" or like robots, not knowing what

they were doing or saying, bumping into objects, acting stupid,

and talking slowly with slurred speech. Nine users described

friends as acting rowdy, irritable, or picking fights on phencyclidine.

Fifty two percent (13) of users described their feeling immediately

before using PCP as scared, insecure, depressed, lonely, bored,

“uptight,” or misunderstood. Others described a need to be high

or the feeling of needing to “get away from things.” Forty four

percent (11) described feeling excited, eager, or “anticipating”

using PCP. After using PCP, some felt sad that they were right

back to the same problems they started with, while others felt

that they now had no worries. Many felt tired or worn out, and

some felt regret that they had used PCP again.

Table 5 shows information on the manner of use and experience of

phencyclidine. The predominant mode of use is “snorting,” inhaling

phencyclidine in powder form. Next most common is intravenous

injection of PCP, although only one user employed intravenous

injection as the sole method of use. Three subjects only snorted

PCP; the remaining users employed combinations of modes. Only

one reported usually taking PCP when alone. Others usually

took PCP with at least one additional person present.

Seventy six percent (19) of users reported having “bad trips” on

phencyclidine. The most commonly described severe symptoms

included numbness and loss of motor control, or paralysis,

confusion, sensory distortions and loss of consciousness. A few

reported cramps, nausea and emesis. Two users had auditory

hallucinations. two became violent, and two others became very

paranoid during the experience. Others described loss of

192
TABLE 5

PCP USERS: THE PCP EXPERIENCE

% OF USERS WHO REPORT

Method of PCP Use

Intravenous

Smoked

Snorted

Eaten

96

How Used

Alone

Another Person

Group

80

One Bad Trip

Continued to Use

PCP After Bad Trip

More than One

Bad Trip

Memory Loss During

PCP Use

Paranoia During

PCP Use

Need or Crave PCP

Physical Withdrawal

Difficulty with

Directions on PCP

Flashbacks

MALE FEMALE AVERAGE

50 80

50 60

95 100

45 60

56

52

48

50

65

70

75

40

60

80

48

68

68

76

70 80 72

55 48

90 92

60

75

25

20

100

40

40

0

0

0

56

68

20

50

35

40

28

193
judgement and memory which sometimes involved them in accidents.

One reported trying to cross a busy street, looking one way

and then the other for cars, but immediately forgetting what he

had seen when he turned his head. He finally decided to step

into the street and ran into a car. Only three users reported

being taken to a hospital during a "bad trip.” Two of these were

discharged within a day, and the third remained on a psychiatric

ward for two weeks. In the entire group of phencyclidine users,

this was the only report of a personal experience of a prolonged

psychotic reaction, including auditory and visual hallucinations

and violent behavior. Most users who had bad trips experienced

them alone, or waited them out with friends, rather than seek

medical attention. One woman reported that she would “check

my body out part by part” when she was experiencing the numbness

and paralysis of a bad trip. Generally, the experiences that

phencyclidine users reported for “bad trips” were similar to

some of the dysphoric sensations described during their usual

PCP experience, with the difference that the ‘bad trip” sensations

were far more intense and upsetting to them.

Despite the fact that 76 percent (19) of PCP users had one “bad

trip” and 48 percent (12) had more than one, 72 percent (19)

continued to use the drug. Six users reported that they needed

phencyclidine or liked it enough to continue. Five rationalized

the bad trip as being caused by circumstances, impure drug, too

much drug, or else felt that they had not had a bad enough “bad

trip” to deter them. Others reported that they used phencyclidine

again because it was freely available when no other drug could be

obtained.

Sixty eight percent (17) of PCP users stated that they felt a

need or craving for phencyclidine. Only 20 percent (5) reported

physical symptoms of withdrawal, describing these as nervousness,

upset stomach, “the shakes,” and “cold sweats.” One user stated

that PCP satisfied his craving for heroin. Another described

how his need for PCP caused him to carry some with him wherever

he went.

Many users reported a gradual change in their mood while using

PCP. Thirty two percent (8) indicated that their mood had

become more angry, irritable, or violent during the time they

were using phencyclidine regularly. Others reported becoming

more antisocial, depressed, lonely, or isolated from people.

Sixteen percent (4) felt that using phencyclidine had produced

positive changes in their personalities. They described feeling

more comfortable, socially easy going, hard working, and more

“masculine.” The majority of users felt that they had become more

selfish. Many reported losing their friends because of the changes

in their personalities.

We assessed cognitive functioning only superficially, by asking

users whether they had problems with memory, finding directions,

or making change (figure 5). Ninety two percent (23) indicated

substantial memory loss during the period of time they took PCP.

194
Thirty six percent (9) felt that their memory had improved

within two to three weeks after stopping phencyclidine, in the

treatment program. Forty percent (10) indicated difficulty

figuring out directions while on PCP. One user reported getting

lost three blocks from his home.

“Flashbacks” are usually described as the reappearance of a drug

effect when the drug has not recently been used. Twenty eight

percent (7) of PCP users experienced one or more flashbacks.

Sixteen percent (4) of these occurred when the individual smoked

marihuana after the PCP “high” had worn off. Finally, most users

reported the development of tolerance to PCP, requiring higher

doses to achieve a high. They usually started with two or three

“cents” worth of PCP, which made them quite high. Eventually, most

subjects were using one to two “dimes” at a time, and often up to

a gram of PCP in a day.

DISCUSSION

Chronic Phencyclidinc Abuse

Recent observations have indicated that the use of phencyclidine,

and more specifically, its role as drug of choice, has increased

markedly in the last year or two (DuPont 1977; Taylor 1978). Our

study corroborates these observations, finding an extremely high

prevalence of PCP use and choice of PCP as the preferred drug for

a sample of chronic polydrug users. Considering the frequency and

combined length of PCP use (a total of 105 years) in the study

sample, most users titrated or adjusted their consumption well

enough to prevent more than rare "bad trips.” Furthermore, since

our study indicates that relatively few “bad trips” are brought to

medical attention, estimates of PCP use based on hospital statistics

may be very low.

The initial and early experience with phencyclidine is usually

reported as a pleasurable or carefree “high” or numbness. The

experience is novel, short lived, and appears to provide an escape

from anxieties, depression, or external pressure. These early

experiences are almost always with low doses of the drug: two,

three, or five “cents.” Gradually, users become tolerant to the

effects of low doses of PCP, take larger amounts more frequently,

and begin to relate increasingly dysphoric experiences

on phencyclidine. The initial enjoyable sense of being “high,”

numb, isolated, and unable to move becomes more intense and sometimes distinctly unpleasant. Although some users continue to enjoy

their experiences with phencyclidine, for the most part the

comments become more critical of the drug. It was initially

difficult for us to understand why many of those we interviewed

continued to use PCP despite these unpleasant experiences. We now

believe that many users felt trapped by the drug. They remembered

their initial good experiences, and probably still had some

enjoyable “highs” during their period of chronic use. In addition,

the drug began to assume magical properties for some users, who

reported that they carried PCP with them almost like an amulet.

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Others couldn’t explain why they continued, except to say that

they needed to use it, or that it was cheap and available.

Nevertheless, it would be a mistake to claim that availability

was the major reason for the popularity of PCP. We feel that its

popularity is a combination of the effects it produces and its

availability, with the former perhaps the more significant.

Three types of adverse phencyclidine reactions were reported as

"bad trips.” Episodes of cramps, nausea, and emesis after taking

PCP may be due to impurities in the drug caused by incomplete

synthesis (Reed and Kane 1972). Prolonged psychotic reactions of

more than two weeks duration appear rare, and will be discussed

in more detail below. The majority of reported “bad trips,”

consisting of severe numbness, isolation, paralysis, confusion,

transient psychotic behavior, hallucinations, stupor or coma,

appear to be extreme examples of the dysphoric sensations

described for the usual PCP experience. We feel that these “bad

trips” are probably due to the periodic use of very high amounts

of phencyclidine, especially in individuals who are already using

large amounts. This would suggest a continuity between early

pleasurable “highs” with low doses of PCP, and later dysphoric

feelings with larger doses. In essence, phencyclidine produces

an organic brain disorder (Fauman and Fauman 1977; Fauman 1977).

In low doses, the organic brain disorder is mild and often

pleasurable. As users become tolerant to phencyclidine and use

larger doses, they may develop a chronic organic brain disorder

(Cohen 1977). Reports of chronic memory loss support this

conclusion. Periodic additional excessive amounts of phencyclidine

may produce toxic psychotic episodes or intense isolation and loss

of body control which is very frightening to users and often

stimulates fantasies of dying or remaining permanently dysphoric.

Such "bad trips” end as the phencyclidine is metabolized and

excreted. It is also possible that the interpersonal and

social circumstances contribute to the chemical effect of a large

dose of the drug to produce the "bad trip.”

This study also suggests that there may be significant personality

changes associated with chronic phencyclidine use. Many chronic

users reported the same increase in irritability, violence and

rowdiness that has been described for the phencyclidine-induced

psychosis (Luisada and Reddick 1975). Increased irritability

and belligerence is a common finding in patients with chronic

organic brain disorders (Fauman and Fauman 1977). Our study also

suggests that many phencyclidine users have difficulty tolerating

anxiety and depression or common stresses of daily life. They

use phencyclidine as a means of escaping from these feelings,

only to have them return after the “high” passes.

The Prolonged Phencyclidine Psychosis

Before we undertook this study, it was our impression that phencyclidine regularly caused prolonged psychotic reactions (Fauman et

al. 1975). These reactions typically are present as bizarre behavior,

with confusion and agitation: the patient may be mute and staring,

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and unresponsive to painful stimuli. There is usually a history

of a sleep disturbance if the patient presents some time after

the drug exposure, and evidence of cerebellar dysfunction,

including nystagmus, ataxia, and dysarthria, if the exposure

has been fairly recent. In some cases, the patient is also

violent or aggressive, particularly when s/he feels threatened.

In nearly all subjects there is a striking degree of fearfulness.

The patient may be diagnosed as schizophrenic if the history of

drug use has not been obtained. These symptoms persist for

several days to two weeks before beginning to remit, and may take

an additional four weeks to clear.

As an increasing number and range of reactions came to our

attention from our emergency department and in consultation

with other hospitals, most of which did not fit our description

of the psychosis we had seen initially, it began to appear that

the reactions were dose dependent. Eventually, as we learned

of the widespread availability and popularity of this drug,

we speculated that only a small number of people using the

drug were susceptible to the prolonged psychosis (Faunan et al.

1976). In our review of prolonged psychoses related to other

drugs, it appeared that this was also true for the severe

psychiatric morbidity that occurred rarely with cannabis, LSD,

and amphetamines. Most authors suggested that there was an

idiosyncratic propensity in those people who developed psychoses.

This corresponds with the data from early work with phencyclidine.

Normal volunteers experienced a brief psychotic reaction that

was dose related (Davies and Beech 1960; Bakker and Amini 1961),

but schizophrenics had prolonged exacerbations of illness

(Luby et al. 1962). Recent reports also support this, as Luisada

noted that one quarter of his series were readmitted with

recurrent psychotic illness, with no additional exposure to

phencyclidine, after an initial PCP-induced psychosis (Luisada

and Reddick 1975). He felt that these patients represented

a part of a continuum between normals and schizophrenics.

It is clear from our study that for some, phencyclidine use is not

merely recreational, weekend, or experimental, but has become a

regular and prolonged habit. With an accumulated total of 105

years of use in our study sample of 25 users, the appearance of

only one prolonged psychosis similar to those described by

Luisada and our previous observations suggests that PCP cannot

be the sole cause of the prolonged psychosis. It appears that

the prolonged phencyclidine psychosis may be the most dramatic

effect of the drug and the one most likely to come to medical

attention. Nonetheless, it is rare, and not the most devastating

effect of this drug.

The Direction of Future Investigation and Treatment

It should be realized that there are two distinct aspects of

phencyclidine abuse. The first is the special problem of the drug

phencyclidine, its use, and its dangerous sequelae. Equally

important is the type of personality problem which leads

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individuals to use drugs like phencyclidine. It is important

not to overlook the latter problem, because it is this one which

will remain long after phencyclidine has disappeared. Phencyclidine is popular because of the effect it produces as well as

its availability and low cost. Nevertheless, there are now,

and will be in the future, other drugs which have similar effects

and may well become as much of a problem as phencyclidine is at

present.

We feel that there are three major areas for future work related

to polydrug abuse, and specifically, phencyclidine abuse. First,

the behavioral and neuropsychiatric effects of chronic phencyclidine abuse must be studied and methods of treatment devised.

This expressly includes an assessment of the potential acute

and chronic organic brain disorder caused by phencyclidine. In

addition, the serious effects of phencyclidine should continue

to be publicized. Second, there should be more investigation

and attempts at treatment of the underlying personality problem

that leads to abuse of drugs like phencyclidine. Finally, there

should be an active monitoring of the polydrug abuse population

for early detection of new drugs with a potential for abuse.

Hospital emergency departments should be alerted to these drugs,

and methods of treatment for the side effects and over-dosage

developed and quickly disseminated to treatment centers.

FOOTNOTE

1. This study was conducted in December 1977 - January 1978, at

the Crossroads Youth Program, 7400 West 183rd Street, Tinley

Park, Illinois 60477.

ACKNOWLEDGMENTS

The authors would like to thank Peter J. Bokos, Executive

Director, Illinois Dangerous Drugs Rehabilitative Systems

(IDDRS); Michael Taylor, Director of Crossroads, and staff

members .Jane Early, R.N., and Pat Sohanski., R.N. , for their

generous assistance in the completion of this project.

REFERENCES

Aronow, R., and Done, A.K. Phencyclidine overdose: an emerging

concept of management, JACEP, 7:56-59, 1978.

Bakker, C.B., and Amini, F.B. Observations on the psychotomimetic

effects of Sernyl. Compr Psychiatry, 2:269-280, 1961.

Bolter, A., Heminger, A., Martin, G., and Fry, M. Cut-patient

clinical experience in a community drug abuse program with

phencyclidine abuse, Clin Toxicol, 9:593-600, 1976.

Burns, R.S., and Lerner, S.E. Management and treatment of acute

phencyclidine intoxications, In: Bourne, P.C., ed. Acute Drug

Abuse Emergencies. New York: Academic Press, 1976. pp. 297 305

198
Burns, R.S., and Lerner, S.E. The crystal people: chronic daily

users of phencyclidine. In preparation. 1978.

Burns, R.S., Lerner, S.E., Corrado, R., James, S.H., and Schnoll,

S.H. Phencyclidine -- states of acute intoxication and fatalities.

West J Med 123:345-349, 1975.

Cohen, S. Angel Dust. JAMA, 238:515-516, 1977.

Davies, B.M. , and Beech, H.R. The effect of 1-arylcyclohexylamine

(Semyl) on twelve normal volunteers. J Ment Sci, 106:912-924, 1960.

DuPont, R.L. Phencyclidine communication to emergency departments.

National Institute on Drug Abuse, 1977.

Eastman, J.W., and Cohen, S.N. Hypertensive crisis and death associated with phencyclidine poisoning. JAMA, 231:1270-1271, 1975.

Fauman, B.J., Aldinger, G., Fauman, M., and Rosen, P. Psychiatric

sequelae of phencyclidine abuse. Clin Toxicol, 9:529-538, 1976.

Fauman, B.J., Baker, F.B., Coppleson, L.W., Rosen, P., and Segal,

M.D. Psychosis induced by phencyclidine. JACEP, 4:223-225, 1975.

Fauman, M.A. A diagnostic system for organic brain disorders:

critique and suggestion. Psychiatric Quart, 49:173-186, 1977.

Fauman, M.A., and Fauman, B.J. The differential diagnosis of

organic based psychiatric disturbance in the emergency department.

JACEP, 6:315-323, 1977.

Liden, D.B., Lovejoy, F.H., and Costello, C.E. Phencyclidine. Nine

cases of poisoning. JAMA, 234:513-516, 1975.

Luby, E.D., Gottlieb, J.S., Cohen, B.D., Rosenbaum, G., and Domino,

E.F. Model psychoses and schizophrenia. Am J Psychiatry, 119:61-67,

1962.

Lundberg, G.D., Gupta, R.C., and Montgomery, S.H. Phencyclidine:

patterns seen in street drug analysis. Clin Toxicol, 9:503-511, 1976.

Luisada, P., and Brown, B.I. Clinical management of the phencyclidine

psychosis. Clin Toxicol, 9:539-545, 1976.

Luisada, P.V., and Reddick, C. An epidemic of drug induced

"schizophrenia." Paper presented at the 128th annual meeting of

the American Psychiatric Association, Anaheim, California, 1975.

Rainey, J.M., and Crowder, M.K. Prevalence of phencyclidine in

street drug preparations. N Engl J Med, 290:466-467, 1974.

Reed, A., and Kane, A.W. Phencyclidine (PCP): another illicit

psychedelic drug. J Psychedelic Drugs, 5:8-12, 1972.

199
Stein, J.I. Phencyclidine induced psychosis. The need to avoid

unnecessary sensory influx. Milit Med, 138:590-591, 1973.

Taylor, M. Personal communication.

Tong, T.G., Benowitz, N.L., Becker, C.E., Fomia, P.J., and

Boemer, U. Phencyclidine poisoning. JAMA, 234:512-513, 1975.

AUTHORS

Michael A. Fauman, M.D., Ph.D.

Assistant Professor, Department of Psychiatry

University of Chicago Hospitals and Clinics

950 East 59th Street

Chicago, Illinois 60637

Beverly J. Fauman, M.D.

Assistant Professor, Emergency Medicine

and Department of Psychiatry

University of Chicago Hospitals and Clinics

950 East 59th street

Chicago, Illinois 60637

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Chapter 10

Phenomenological Aspects of Phencyclidine

Abuse Among Ethnic Groups in Hawaii

Anthony J. Marsella, Ph.D., and Russell D. Hicks, M.D.

INTRODUCTION

The fact that phencyclidine, a drug originally developed in the

early 1950's by Parke, Davis and Company for use as a nonnarcotic

intravenous anesthetic agent , could emerge as a popular recreational and quasi-therapeutic drug among our nation's youth, raises

a number of interesting questions about the nature of the phenomenological experience associated with phencyclidine use. The

purpose of the present paper is to examine some of these questions

through a review of our clinical experiences with phencyclidine

users and to offer some speculations about the possible reasons

why young people begin and continue to use phencyclidine.

The Hawaii Job Corps

This discussion of phencyclidine is based on our experiences as

Director of Mental Health Services and Director of Medical Services for the Hawaii Job Corps, a Federally-funded residential

program to provide educational and vocational training for high

school dropouts between the ages of 16 and 21. It also provides

medical, psychological, and recreational services. The program

generally requires from 18 to 24 months to canplete. The Hawaii

Job corps in Honolulu has about 220 enrollees (55 females, 165

males) who reside in four dormitories. Because of disciplinary

and personal adjustment problems, the turnover is high. Nevertheless, the program completion rate runs around 40 percent.

The enrollees consist mainly of youth of mixed Hawaiian racial

ancestry ("locals") who cone from the rural areas of Oahu. The

second largest ethnocultural group represented consists of Micro

nesian youth. They are followed in number by Guamanians, Samoans,

Caucasians (mainly armed service dependents), Filipinos, and a

few Korean and Vietnamese immigrants. All of the enrollees are

from the lower sociceconomic class strata and many have personal

histories of delinquency and school maladjustment. Divorce, child

abuse, and parental rejection are present in many life histories.

Polydrug abuse and alcohol abuse occur in 80-90 percent of the

enrollees.

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Phencyclidine

Phencyclidine is a white crystalline solid. On the streets,

phencyclidine is called PCP, THC, or "Angel Dust." Burns

and Lerner (1976) provide an excellent overview of phencyclidine's pharmacological properties and clinical implications.

They note that it acts on the nervous system by either

stimulation or depression and that this variability in action

makes it difficult to classify.

Phencyclidine can be swallowed (generally in tablet form),

snorted (insufflated), or smoked (inhaled). Among the young

people we worked with, snorting and smoking are the preferred

routes of administration. When the drug is smoked, the

user spreads the phencyclidine over marihuana, parsley,

mint, or tea. This is called a "crystal joint." The time

course and active effects of phencyclidine vary as a function

of the concentration and the route of administration. The

users we have spoken with stated that the "hit" time ranges

from five to twenty minutes. Snorting results in a faster

action, and, in the opinion of some individuals, it produces

more side effects than smoking.

Phencyclidine is purchased by the "line." A "line" is about

3/4 of an inch long and 1/8 of an inch wide. This amount

sells for around $10 to $15 in Honolulu and is enough for

five users or "hits." The concentration of the phencyclidine

is determined by the number of visible crystals present among

the filler. The users indicated that phencyclidine is only

available from dealers periodically, but when available it

is very popular.

Who Uses Phencyclidine?

Because our experience with phencyclidine users is limited to

Job Corps enrollees, we clearly have no information regarding the

community distribution of phencyclidine use in Hawaii. However,

based on the comments of the Job Corps users, we are inclined to

conclude that the highest frequency of use is among preteen and

teen Hawaiian youth ("locals"). Everyone we spoke with indicated

that Micronesians and Guamanians prefer "hard liquor" and "grass"

rather than "T." They indicated that there is some use of "T"

among Samoans and Filipinos but that the highest use was clearly

among the "locals." Indeed, they noted that "T" was growing in

popularity among "local" kids and that they could not think of

any "local" friends who had not tried it. Although the Caucasian

youths use it, "T" does not seem to have much popularity among

them.

The high frequency of phencyclidine use among "locals" as opposed

to other groups raises some important questions about the reason

for this state of affairs. Our speculation is that among "locals"

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the use of all drugs is much higher and more flagrant. Thus, a

new drug like phencyclidine simply fits in with an already existing culture of users, and other ethno-cultural groups are often

excluded from these "local" drug-using groups. Indeed, some of

the other ethno-cultural groups look on the "locals" as being

crazy when it comes to taking drugs; the other groups describe

themselves as liking to drink a lot of booze and smoking a lot

of grass, but they do not see this as being really harmful, even

though they often consume entire bottles of liquor among a few

users.

In addition, it is our observation that the "locals" seen to have

the greatest ethno-cultural identity problems. The other groups

still use their native languages and follow many of their traditional customs. This is not true of the "locals" who are English

speaking and who are often unsure of their allegiance to Hawaiian

culture, although they describe themselves as Hawaiian. Their

identity is much too superficial to provide a perceptual framework for mediating life problems. The "local" youth are clearly the

most alienated and lacking in a sense of purpose and direction when

compared to other youth in the Job Corps.

Lastly, anger levels are extremely high among "locals" because of

their discontent with their social position. Unlike the Micronesians, Guamanians, and Samoans , the anger among the "locals" is

long term. "The Hawaiian people are getting shafted in their own

land" is a widely shared belief which seems to be constantly reinforced by family and media. Further, ability of the "locals"

to articulate their problems and to attribute them to their status

as Hawaiians provides a strong self-reinforcement of their anger.

The possible role of anger in phencyclidine abuse will be further

discussed in the next section of this paper.

WHY IS PHENCYCLIDINE ABUSED?

It is tempting to say that any drug with consciousness-altering

properties is likely to be abused by today's youth if it is available. However, this type of thinking is much too general to

account accurately for the preferences and patterns of drug abuse

which have developed. It may indeed be the case that each drug

has a unique pattern of situational and personality factors which

both encourage and maintain its abuse profile. In discussing the

reasons for phencyclidine abuse, we will comment on three topics:

(1) Situational, (2) Experiential, and (3) Psychosocial.

Situational Factors in Phencyclidine Abuse

Everyone with whom we have spoken told of being "turned on" to

phencyclidine by close friends who simply said, "Try it...it will

make you feel good!" Quite obviously, the social pressure to go

along with this soft sell amidst a group of friends is quite high.

To refuse is tantamount to saying you don't trust your friends or

that you are afraid. Both of these are higher risks than the

dangers associated with a new drug. Among young people with fragile or vulnerable self concepts, the pressure for acceptance

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simply outweighs the pressures of rational judgment regarding the

harmful sequelae. The group dynamics are critical in getting

started and in maintaining drug abuse with a substance like phencyclidine.

Phencyclidine use is not limited to a particular environment. It

is used indoors with mellow music and candlelight, and in noisy

settings with rock music and flashing lights. It is also used

outdoors at parks and beaches. Indeed, several people discussed

going swinming while on "T" and almost drowning. However, everyone indicated that the mood of the user is important in determining the reaction to the drug. You can get "spacey" or "mellow"

or you can just get "stoned." But, quite interestingly, everyone

said they always used "T" in a group rather than alone. This may

not be unusual, as many drugs are taken in group settings, but

it does deserve further study.

Experiential Aspects of Phencyclidine Abuse

A young "local" female with years of polydrug experience described phencyclidine as "the — [worst] snortin' drug you

can ever take!" Yet, when asked if she would take it

again she replied, "Sure...why not?" We have been continually

impressed with the almost total disregard for any of the medical

or legal consequences of drug abuse among many of the "Local"

youth in Hawaii. They simply say, "Man, who cares!" or just

smile and shrug their shoulders and say, Wan, ain't no big

thing!" Booze, grass, and "T" are mixed readily. We never heard

anyone, however, speak of mixing acid (LSD) or speed and "T". It

is also interesting that the users seem to categorize "T" as a

hard drug: many said it gives a "rough trip."

Efforts to understand the actual phenomenological experience associated with phencyclidine have always proved frustrating beCause the users tend to describe the experience in short phrases

like 'Wowie!," "Cloud nine!," "Far out!," or "Zap!" These phrases

are often accompanied by a throwing back of the head, a rolling of

the mouth in an almost reflexive manner.

Several individuals told us to "try it" to really understand what

it does because "you can't put it in words." "Being stoned is

something else!" We have speculated about whether the actual

subjectivity and privacy of the experience might in itself be rewarding. "You can't put it in words!" Here is something which

is truly yours, something which is unique and not subject to loss

through intellectual understanding. In a world of intruding influence, here is something that belongs to you. A few males and

females likened the "T" experience to that of "surfing all day"

when because of the repetitive excesses of sensory stimulation

and deprivation you come to lose your sense of self and become a

part of something more - the endless rhythm of waves.

On the other hand, if you take too much "T" you are really in for

it. It is much more than just "flipping out." One male described

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his experience under a high dose as being similar to "electric

man." His entire body was numb and paralyzed and he tingled all

over. He recalled praying to God and saying "Please don't let me

die." Yet in spite of the experience he took "T" again. It was

his fault, not the drug's. Another male said he felt like a

"zombie"; but he also used it again.

When used in smaller doses or concentrations, the youth described

the sensation of their body becoming "very light" or "floating,"

almost as if they were "walking on air." This is the pleasurable

sensation that they like and seek. One individual suggested it

was very similar to inhaling "laughing gas" in the dentist's

office. Another individual indicated that it made him see things.

He noted that on one occasion he thought he was body surfing and

extended himself on the rug as if he were riding the waves. Yet

another person said he liked seeing the "dragons" and "creatures"

when he was on "T."

Apparently, the "T" experience is also a function of how often you

take the drug. A male "local" who was experiencing visions and

was becoming quite afraid reported "talking with angels" and "seedead relatives." He also stated that he believed that he was

really "someone special" with unique "powers." At first, he denied

taking any drugs stronger than grass, and so we were inclined to

suspect that an incipient psychotic process was operating. However, when he was asked if he had been taking "Angel Dust," he

said that he was using it in "joints." He was asked to stop this

immediately and to refrain from using it any more. He agreed to

stop, and within. two weeks the hallucinations had disappeared

and he was no longer afraid.

Although some of the young people we have worked with have beams

belligerent and antagonistic under phencyclidine, we know of one

case where violence occurred. This case was reported by a user

and involved a young "local" female who had been using "THC" for

"breakfast, lunch, and dinner" over a period of a week. The girl

dug out the cheeks of her little infant's face and then told her

mother, "Look what the devil did to my baby." A number of users

have talked of "T" users becoming "religious" after a while. HoWever, they were unable to explain why this happens. They simplY

said if you use "T" for a while you become a "Jesus freak" and

"get turned on to religion."

Most of the people we have spoken with stated that they preferred

to take "T" in quiet places where they could just "space out."

One individual said, "No feel like walkin', no like talkin', just

sit back and look." When talking does occur under phencyclidine,

it was described as being slow and drawn out. On higher "hits"

they reported having difficulty walking. One person reported

falling down and described it as a "slow motion" experience in

which each movement took a very long time.

None of the people with whan we have worked could be considered a

phencyclidine "freak," that is a person who chooses only phencycli205
dine when given a choice. Indeed, everyone agreed that they had

never encountered a "T freak" as they had encountered "acid heads"

or "speed freaks." People appear to use "T" when it is available.

It is just one of many drugs that can be used if you want to

"trip." Several people, however, said that "T" is better than

"booze" or "downers" if you want to trip out because it is faster

and stronger. They stated, "When you wanna git away, "T" is

good"; they noted that it "takes your mind off things and lets you

relax." In those circumstances, "T" is the preferred choice; they

start with grass and then snort a "hit" of "T."

In addition to the medical risks of a high dose, "T" users must

also cope with the side effects which accompany its use, even if

the dose is mall. Some people described the effects as being

similar to a hangover. They feel "wobbly" and "queasy" and have

headaches around the front of the head. Vomiting and dizziness

are also quite common. They all agreed that they were very tired

and wanted to sleep. One person said he felt "wasted" and "run

down." But, these are not very different from side effects associated with drinking too much, so they are considered worth the

risk.

Psychosocial Aspects of Phencyclidine Abuse

The medical aspects of phencyclidine intoxication will not be discussed here, since these have been very well presented in a number

of papers by Burns and Lerner (1976), Burns et al. (1975), Eastman

and Cohen (1975) and Linden, Lovejoy, arid Costello (1973). How

ever, there are several psychosocial aspects of phencyclidine

abuse which deserve comment. These include the role of chronic

feelings of anger and desperation, the role of agitated boredom,

and the results of conditioning deviant epistemic orientations.

1 . Chronic Anger and Desperation

Over the years, we have increasingly wondered about the effects

of the chronically high levels of anger and desperation found

among many of the Hawaiian youth with whom we have worked. We are

reminded of the effects which "low status" and "enduring frustration" have had on black Americans, the so-called "black rage." The

"local." people appear to be relatively helpless in altering their

own lives in the face of the continued onslaught of Western technology and values presently occurring in Hawaii. Their way of

life is demeaned. In the search for an escape from their feelings

of desperation, they see themselves as having few alternatives.

Freud, in his book Civilization and Its Discontents, wrote:

Life as we find it is too hard for us; it entails too

much pain, too many disappointments, impossible tasks.

We cannot do without palliative remedies....There are

perhaps three of these mans: powerful diversions of

interest...substitute gratifications...and intoxicating

substances.

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In the absence of diversions of interest and substitute gratifications, intoxicating substances have emerged as the most available

and effective mans for handling the annipresent tensions of anger

and desperation. Both of these require expression, release, or

catharsis. Assault and other forms of violence have already resulted in high rates of delinquency and crime among the "locals,"

and excessive drinking is also a major problem. To both of these

inadequate ways of coping must now be added the drug phencyclidine.

Here is an easy and quick way to relax, to remove the omnipresent

burdens of anger and desperation. Relief is just a snort away!

It's a magical release from life's pressures even though it only

lasts a short while. These points lead us to the role of boredom.

2 . Chronic Boredom

In a society which requires ever increasing levels of competence

and specialization to achieve recognition, success, and financial

reward, more and more individuals are finding that there is little

they can do. Many young people are simply retreating and withdrawing from societal demands rather than facing the challenge

of coping with life through the active pursuit of a skill or education. Indeed, it is quite obvious that our society simply asks

youth to wait their turn to make any meaningful input. Youth are

not given a chance to be adults. They must wait and learn. But,

when the learning experience offered by our schools is sometimes

so vacuous, there is only boredom.

Boredom is a problem which more and more young people are experiencing, and it is also one which is readily dissipated by a "hit

of T." There is little opportunity for our youth to feel important

and meaningful, and this problem is compounded for "local" youth

because of theirlowstatus and imprboble chances for altering

their poverty. Boredom, like any other aversive affective state,

requires relief: and in the absence of alternatives, "T" serves

the purpose quite well.

Yet, we are coming more and more to wonder whether the quick escape

promised by "T" is not exacting its toll. Here, we would speculate

that the deadening of experience or the alteration of conciousness

somehow produces a subsequent need for arousal. It is tempting to

believe that the nervous system requires periods of arousal and

periods of rest. An extended period of one leads to a need for

its opposite. Thus, we would speculate that, with continued

phencyclidine use, a cycle may be developed of increased agitation

and arousal when the drug is not in use. This could be experienced

as an undifferentiated emotional state of boredom. And so the

cycle of "stimulus reduction" and "stimulus seeking" continues.

Every "hit" of phencyclidine my require a subsequent period of

arousal or of undifferentiated alertness.

In the absence of a meaningful pursuit of some knowledge or skill,

agitated boredom emerges. If an incident should occur which might

be interpreted as hostile, the agitation simply comes to be interpreted as anger, and an acting out occurs even if it is unwarranted.

207
This cycle has yet another aspect which may ultimately prove to

be more dangerous. This latter aspect involves the conditioning

of deviant epistemic orientations.

3 . The Conditioning of Deviant Epistemic Orientations

There are some individuals who argue that the judicious use of

drugs should not cause alarm (e.g., Szasz 1972; Reinert 1974).

They claim that ethically we may not have a right to deprive

people of pleasure-giving drugs. Reinert (1974) stated:

What is our right to take away pleasure-giving drugs

from a person who through early deprivation, or current poverty, or lack of training, or lack of innate

capacity has little capability for pleasure in aesthetics, intellectural pursuits, or social intercourse?...

Are we morally justified in depriving an individual

whose life is without purpose, hope, and direction--

cramped, lonely, and bitter--of the chief pleasure of

which he is capable? (Reinert 1974, p. 56).

In the case of phencyclidine use among "local" youth in Hawaii,

Reinert's comments raise some interesting questions, especially

within the context of the social deprivation to which they are

ordinarily exposed. Yet, there is a risk which Reinert is ignoring, and this is the conditioning of deviant epistemic orientations which may ultimately make it impossible for an individual

ever to accomodate his life and thoughts to societal expectations

and demands.

In a previous paper (Marsella and Price-Williams, 1974), it was

argued that the continued use of consciousness-altering drugs

posed an ignored danger: the conditioning of deviant epistemic

orientations. An epistemic orientation involves certain conceptions of time, space, and cause-effect relationships. Through

the course of normal everyday life within a particular cultural

context, an epistemic orientation is created which is functionally

related to other cultural forms and practices. For example, in

our own society we have a shared notion of time, space, and causeeffect that n-takes it possible for us to function "normally."

The nervous system codes time, space, and cause-effect experiences

regardless of the consciousness level at which they are experienced. This means that even on a drug which alters consciousness,

the nervous system is still coding these epistemic dimensions:

The experiences of the "trip" are no less real to the

nervous system than those of everyday "normal" life.

The "trip" experiences are assimilated, coded, and

organized into existing cognitive and neurological

structures. Thus, over long periods....of use, the

person develops a new and conflicting epistemic organization that extends beyond the actual drug states....

(Marsella and Price-Williams 1974, p. 71).

208
In brief, with continued use of phencyclidine, the users may soon

find himself/herself experiencing reality according to levels of

consciousness which are in conflict with normative standards.

His/her sense of time, space, and cause-effect become deviant.

New standards of "normality" emerge which are not shared, thus

fostering deviancy and furthering the rejection cycle.

REFERENCES

Burns, E., and Lerner, S. Perspectives: Acute phencyclidine intoxication. Clin Toxicol, 1976, in press.

Burns, R., Lerner, S., Corrado, R., James, S., and Schnoll, S.

Phencyclidine: States of acute intoxication and fatalities.

West J Med, 123:345-349, 1975.

Eastman, J. and Cohen,S. Hypertensive crisis and death associated

with phencyclidine poisoning. JAMA, 231:1270-1271, 1975.

Linden, C., Lovejoy, F., and Costello, C. Phencyclidine (SernylanR)

poisoning. J Pediatr, 83:844-845, 1973.

Freud, S. Civilization and its discontents. London: Hogarth

Press, 1930.

Marsella, A.J., and Price-Williams, D. A note on epistemic organization and hallucinogens. Bull Menninger Clin, 38:70-72, 1974.

Reinert, R. Drugs and the discontents of civilization. Bull

Menniger Clin, 38:49-57, 1974.

Szasz, T. The ethics of addicition.

1972.

Harper's Magazine, 244:74-79,

AUTHOR

Anthony J. Marsella, Ph.D., Department of Psychology, University

of Hawaii, 2430 Campus Road, Honolulu, Hawaii 96822 and Russell

Hicks, M.D., School of Medicine, University of Hawaii, Honolulu,

Hawaii 96822.

209
Chapter 11

The Pharmacokinetics of Phencyclidine in

Overdosage and Its Treatment

Alan K. Done, M.D., Regine Aronow, M.D., and Joseph N. Miceli, Ph.D.

The unusually prolonged and vacillating clinical course of PCP

intoxication has been documented amply in other parts of this

publication and in citations included elsewhere (Done et al. 1977;

Aronow and Done 1978). Except for the demonstration of persistence

of urinary PCP excretion for at least several days in some cases

(refs. cited in Done et al. 1977) there had been no explanation

for that finding or the clinical course, and certainly no definition of the pharmacokinetic characteristics of PCP in overdosage,

until our recent studies (Done et al. 1977). This report supplements the earlier preliminary observations with extensive

additional observations which are soon to be published inconsiderably more detail.

SUBJECTS AND METHODS

Data presented here were obtained from seven patients whom we

treated for PCP overdosage; further clinical information about

them is presented by Aronow elsewhere in this publication. All

patients took unknown quantities of "street" PCP in various form,

and its identity and purity were established on the material itself and/or the gastric contents by gas chromatography/mass spectrometry as described elsewhere (Done et al. 1977). The procedures

for obtaining the blood, urine and gasttic fluid specimens were

also described previously. The present protocols varied somewhat

from the earlier ones and from patient to patient, particularly

in terms of the duration of urine or gastric fluid collections,

depending the aim of the particular study; however,continuous

urine and gastric contents ware collected quantitatively; and

blood specimens, insofar as possible, were obtained midway in

these collection periods. An exception is patient 1, who did not

have gastric suction because he presented before our studies had

indicated the importance of this procedure.

After our initial observations indicated the important influence

of urine pH on PCP excretion , some patients were given acidifying

agents in a manner described by Dr. Aronow (Aronow and Done 1978)

210
and in some individuals furosemide diuresis was instituted,usually

at time of peak acidification of the urine. All pH measurements

on urine and gastric fluid were made immediately using a pH meter

(Beckman model 3550), and in arterial blood with a conventional

clinical blood gas electrometer.

Specimens were frozen until analyzed for PCP concentrations by

Dr. Denis Lin of Battelle Columbus Laboratories using his gas

chromatographic/chemical ionization mass spectrometric method

(Lin et al. 1975). Measurements were confined to the free,unchanged compound.

RESULTS

Figure 1 shows (on the left) the time course of serum PCP concentrations and its relationship to PCP levels in urine and

gastric (G.I.) fluid. It can be seen that the gastric fluid [PCP]

FIGURE 1

[PCP] in serum, urine and gastric drainage

(left) and cumulative urinary and gastric secretions

of PCP (right) in a representative patient. In the

left half of the figure note that a log scale was used,

and urine and gastric (G.I.) concentrations were 10x

higher than shown (Done et al. 1977).

211
is very much higher than that in serum, and that the two curves

are strikingly parallel and have similar half life (T1⁄2) values.

The T1⁄2 varies considerably from patient to patient and, as will

be noted below, is strongly dependent upon whether or not there

is interruption of the gastroenteric recirculation of PCP; consequently, half life figures will be reserved until discussion

of this phenomenon. As will be discussed in considerable detail

later, the urine PCP concentration was strikingly dependent upon

the urine pH and so bore a variable relationship to the serum

level; however it also can be considerably in excess of the concentration in serum. That is to say that PCP is highly concentrated in an acid medium, which can cause it to achieve a tremendous gradient with plasma. The cumulative excretion data (the

right half of the figure) indicate that in some individuals the

elimination by way of gastric suction can, for a time at least,

substantially exceed that achievable through urinary excretion,

though this is highly variable from one patient to another.

That the pH effect on PCP concentration gradients is reflected in

in a similar effect on clearance is indicated by table 1. The

clearance figures are not identical with those presented by Dr.

TABLE 1

EFFECTS OF pH ON (PCP) PLASMA GRADIENI

AND PCP CLEARANCE, Mean ± SEM

(n)

pH:

(PCP)/(PCP)p

Gastric Urine

<2.5 >2.5 <5 5-6.5 >6.5

42±4.5 20±3.8 97±17.4 36±5.0 7±2.4

(42) (20) (19) (60) (32)

Clearance

ml/min)

53±11.2 21±5.0 86±15.0 44±6.6 10±2.4

(44) (15) (19) (59) (31)

Aronow because the data presented here include only those individuals who had exactly simultaneous collections of blood and the

other fluids under study; some of the clearance values presented

by her utilized interpolated serum level estimates when the curves

were sufficiently smooth that there was no sacrifice of accuracy.

Here it was desirable to compare simultaneous effects on the

gradient with serum concentration and the clearance. An interesting phenomenon with regard to gastric secretion of PCP is that

pH influence appears to be somewhat less striking than it is with

urine on the basis of extrapolation of the urine pH data. There

is ample precedent for such an observation provided by Brodie and

Hogben (1957), who found that most of the basic drugs studied

were incapable of being concentrated in the acid medium of the

stomach beyond maximum of about 40 times that in serum(about

the gradient that we see here), a phenomenon that in the dog was

found to be attributable to limitations on circulation of the drug

to the gastric mucosa. In other words, the nonionized fraction

of the drug was cleared with a single passage of blood through

the stomach's circulation and so the gradient of clearance was

212
limited by the bleed supply.

The present and our earlier observations (Done et al. 1977; Lin

et al. 1977) suggest that the effect of pH cm PCP distribution

is a truly tremendous me, probably due to an effect on ionization of this weak base thought to have pKa, of about 8.5. The

remainder of this discussion will be devoted principally to

further exploration of this conceptandits possible therapeutic

implications.

The relationship of pH to urinary excretion of PCP is variable

from one patient to another and possibly influenced by a number

of factors, butatleastin some the evidence supports a pure

ionization effect (Done et al. 1977). To the extent that we

are dealing with an ionization effect and ion trapping in more

acid, media one would expect pH influences on more than just the

products of excretion. Further,such effects should be interrelated and produce a somewhat predictable net result which might

have important clinical implications. While limited access to

the various other tissues, fluids, and compartments in the human

is an obvious obstacle to full explorations along these lines,

considerable can at least be surmised about some of the redistribution consequences. Table 2 shows some representative data

obtained from a patient at two points in time

TABLE 2

pH EFFECTS CN PCP DISTRIBUTION *

pH (PC) ,ng/ml pH

Serum 7.4 66 50 7.2

CSF 140 8

Urine 7.5 43 3997 5.0

Stomach 1.4 1395 1287 2.2

*patient 5, ammonium chloride

acidification

when spinal taps were performed because the clinical picture could

not exclude other intracranial pathology. One would expect acidification of plasma to result in considerable outflow of PCP from

the central nervous system, comparative trapping in the plasma,

and, to the extent that the urine becomes acidified in the process,

also a striking increase in excretion. Such can be seen here

where a drop of serum pH from 7.4 to 7.2, caused by ammonium

chloride administration, resulted in a decline in the cerebrospinal fluid PCP concentration from more than twice to less than

1/6 that in serum. During this time the serum level declined

only slightly, considerably less than would have been expected

from the tenfold increase in urine PCP concentration (and clearance),possibly because of shifts of nonionized drug to plasma

from less acidic compartments (such as the central nervous

system). In any event, these figures indicate the ability to

achieve desired shifts in PCP distribution and enhancement of

excretion through pH manipulations. Incidentally, these shifts

even within the body are associated with striking and immediate

213
improvement in the CNS effects. Also, if you remember that the

markedly enhanced urinary elimination of PCP can be accompanied

also by elimination of that amount in the stomach through the

simple expedient of gastric suctioning, it can readily be seen

that the net result is expected to include the substantial shortening and improvement of the overall course that we and others

have noted. Further,as is discussed by Aronow, induced diuresis

superimposed upon urine acidification substantially augments still

further the urinary excretion of PCP.

From the gastrointestinal standpoint, with the involvement of pH

in determining ionization of a weak base such as this, and its ion

trapping in the stomach, the expectation must be that there is

substantial gastroenteric recirculation of the drug. After it

leaves the acid of the stomach it would be expected to become

relatively less ionized in the more alkaline intestine and there

fore to be reabsorbed, and this would be fully expected to play

a role in determining the course, particularly the duration, of

PCP intoxication. When the time course of serum PCP is followed

it is found that discontinuance of previously constant gastric

suctioning is associated frequently with an immediate rise in

serum [PCP], its strikingsubseqent fluctuation, and a substantial slowing in the rate of disappearance from the circulation.

Table 3 compares serum [PCP] data obtained during and after discontinuance of constant gastric suctioning: the change of serum

concentration immediately

TABLE 3

before and after discontinuance of gastric suction is shown as a

daily rate or ke on the left; the "post absorptive" serum concentration half life measurements -- i.e., after serum concentrations,

either initially or upon discontinuance of gastric suctioning,

have begun to fall -- are shown on the right. Half life values

followed by a + are minimal ones because striking rises in serum

concentration (common after discontinuance of gastric suction)

were not included in the detemination; had they been, the apparent effect of gastrcenteric recirculation of PCP on serum

214
half life of the drug would have been even greater than shown.

It can be seen that in all patients the elimination rate immediately after cessation of gastric suctioning, compared with the

one immediately before,was slower or was apparently overridden

by increased absorption from the gastrointestinal tract so that

the level actually climbed.

In all but one case where the comparison could be made, the serum

concentrationhalf life of PCP was considerably longer without

gastric suctioning than with it. On the average, there was more

than a doubling, even if we ignore the striking rises that often

occurred long after discontinuance of suctioning. It should be

noted that the serum concentration T1⁄2 in untreated patients must

be assumed to be longer even than those shown here on the right

(table 3) not only for the reasons mentioned, but also because

all patients except 1 and 2 in this series were subjected to

therapeutic urine acidification. The natural serum concentration

T1⁄2 would appear to be over 3 days at the concentrations encountered

here.

DISCUSSION

The finding of an appreciable gastroenteric recirculation of PCP

helps to explain the prolonged course of intoxication from this

drug. This and the strikingeffects of pH on distribution in

various compartments, may well explain the notable vacillations

in the clinical course mentioned previously. These observations

also suggest a course of therapy that has been applied with the

dramatic success described by Aronow in this publication, and

in earlier reports by this group (Done et al. 1977; Aronow and

Done 1978).

The urinary excretion of trapped PCP is so striking that, as is

discussed by Aronow, the efficiency of peritoneal dialysis with

or without added albumin is dwarfed by the results that can be

obtained with highly acidified urines. Whether extracorporeal

hemodialysis would be more efficient and whether it could be

augmented by any safe and reasonable manipulations of the acidity

of the dialysis fluid remains to determined; this could be a very

important consideration in patients with renal insufficiency. We

have had no personal experience as yet with this particular problem,

but this possibility certainly deserves exploring and in the meantine the role of peritoneal dialysis and certainly that of gastric

suctioning would take on added potential importance in patients

having poor kidney function.

The gastric trapping of PCP has important forensic implications.

The drug is often smoked and occasionally is injected, but it

would be expected to appear in the stomach in large quantities

regardless of the routeofadministrationand such a finding

should not be interpreted as evidence of oral ingestion.

We are not aware of other basic weak electrolytes whose distributions are so profoundly affected by pH manipulations. However,

215
few bases (as contrasted with acids) have been so evaluated.

Hence, it is quite possible that ion trapping is mode of therapy

for poisoning with such compounds that has received inadquate

attention and deserves further exploration (Done 1976). We currently are actively exploring this possibility while also exploring

additional parameters of PCP pharmacokinetics that may provide

a basis for still more improvement in treatment.

The analytical method used in this study measures only unchanged

PCP, so the results are informative only with regard to the

parent drug. However, the hydroxylated derivatives known to be

pruduced by humans have not been demonstrated in the blood, apparently because they are converted to the glucuronides and excreted as rapidly as they are formed. All of the urinary metabolites are present as the glucuronides, and there is extensive

excretion of the free, unchanged drug. Thus, studies of the

partent compound alone probably suffice to define the toxicologically important kinetic parameters; however, studies of the

metabolites as well are required before this concept can be accepted without reservations. Such studies are currently underway in

this laboratory.

216
REFERENCES

Aronow, R., and Done, A. K. Phencyclidine overdose. Emerging

concepts of treatment. J Am Coll Emerg Phys, 7(2):56-59, 1978.

Brodie, B. B, and Hogben, A. M. Some physico-chemical factors

in drug action. J Pharm Pharmacol, 9:345-380, 1957.

Done, A.K. The toxic emergency. Setting traps for poisons.

Emerg Med, 8(8):196-199, 1976.

Done, A., Aronow, R., Miceli, J. N., and Lin, D. C. K. Pharmacokinetic observations in the treatment of phencyclidine poisoning. A preliminary report. In: Rumack, B. H. and Temple, A. R.,

eds. Management of the Poisoned Patient. Princeton: Science

Press, 1977. pp. 79-102.

Lin, D. C. K., Fentiman, A. F., Jr., Foltz, R. L., Fomey, R. D.,

and Sunshine, I. Quantification of phencyclidine in body fluids

by gas chromatography chemical ionization mass spectrometry and

identification of two metabolites. Biomed Mass Spectrometry,

2:206-214, 1975.

Lin, D. C. K., Foltz, R. L., Done, A. K., Aronow, R., Arcinue, E.,

and Miceli, J. N. Mass spectrometric analysis of phencyclidine

in body fluids of intoxicated patients. In: Deleenheer, A. P. ,

and Roncucci, R. R., eds. Quantitative Mass Spectrometry in Life

Sciences. Amsterdam: Elsevier, 1977. pp. 121-129.

AUTHORS

Alan K. Done, M.D.*, Regine Aronow, M.D.+, and Joseph N. Miceli,

Ph.D.* Departments of Pediatrics*+ & Pharmacology*, Wayne State

University; the Division of Clinical Pharmacology and Toxicology*+

and the Poison Control Center+, Children's Hospital of Michigan,

3901 Beaubien Blvd., Detroit, Michigan 48201

217
Chapter 12

Clinical Observations During Phencyclidine

Intoxication and Treatment Based on

Ion-Trapping

Regine Aronow, M.D., Joseph N. Miceli, Ph.D., and Alan K. Done, M.D.

Since technology to detect phencyclidine (PCP) in body fluids became

available to us, fifty cases of PCP overdose have been treated at the

Children’s Hospital of Michigan. The patients ranged in age from

nine months to almost twenty years. Preliminary observations in overdosed adolescent boys of the pharmacokinetics of the drug (Done et al.

1977) have led us to successfully treat a number of severely overdosed patients utilizing ion trapping by continuous gastric suctioning

and acidification of urine and/or blood with ammonium chloride (Aronow

and Done 1978). Although many of the children under eight years of

age presented after rapid onset of coma, only three seemed of sufficient severity to require urine acidification in addition to continuous gastric suctioning and supportive care. We have, however, no

quantitative data on young children. This report offers additional

data on seven patients above the age of thirteen years who are being

studied in detail and who are also discussed in Dr. Done’s paper in

this volume.

BACKGROUND

In the early 1970’s a number of small children with symptoms now

recognized as associated with phencyclidine overdose were seen at

the Children’s Hospital of Michigan, supposedly having ingested street

drugs, variously representedas THC, mescaline or LSD. Paper chromatography spot tests done elsewhere failed to reveal the presence of

narcotics, sedatives or tranquilizers commonly used in our area.

Beginning in December 1972, arrangements were made with a private

research laboratory to screen blood and urine samples on selected

patients for mescaline, LSD and PCP, the latter having been brought

to our attention by the Drug Enforcement Agency. By mid 1974 an

emergency service utilizing a GC-MS system became available (Horowitz

et al. 1976) and urine, gastric and blood samples have since been

submitted there for initial screening. Retrospectively, we learned

that although this system would identify large amounts of PCP, the

injection temperature used could destroy small amounts of PCP

(personal communication, Dr. Lin, 1978). Thus we may have missed

some cases.

218
All cases of PCP overdose referred to in this paper gave positive

evidence of PCP in body fluids by one of the methods mentioned above.

EPIDEMIOLOGY

Our experience with children younger than eight years of age (figure

1) shows an age distribution not unlike that of accidental poisoning

in general (National Clearinghouse Bulletin 1977), an indication of

the fact that the drug was commonly in their environments and subject

to being ingested by the children. Social service investigations

revealed someone may have purposefully administered the drug to two

of the children. All the cases had child abuse/neglect filed.

FIGURE 1

There were no cases recognized in the eight to thirteen year age

range.

Total patient data reveal an equal distribution between males, females,

blacks and Caucasians in the under eight years of age group, but a

disproportionate number of Caucasian males in the 13 to 20 year old

group (tables 1, 2).

219
TABLE 1

Patient Experience: Dec. 1972 - Feb. 1978

AGE (yrs.) SEX RACE

M-F B -C

<8 20 18 18 20

13-20 10 2 1 11

TABLE 2

Patient Experience: Dec. 1972 - Feb. 1978

AGE (yrs.) SEX by RACE

BF BM CF CM

<8 8 10 10 10

13-20 0 1 2 9

In the early calendar years included, there was a fifty percent

greater incidence of black children identified with PCP overdose than

of Caucasian children. This has reversed in the last year to sixtysix percent Caucasians (table 3).

TABLE 3

Patient experience (AGE vs RACE)

CALENDAR AGE

YEARS (yrs.) No. BLACK CAUCASIAN

1972(1 mo.)

1973 <8 10 8 2

1974

13-20 2 0 2

1975 <8 12 5 7

13-20 2 0 2

1976 <8 5 2 3

13-20 3 0 3

1977

1978 <8 11 3 8

(1 mo.)

13-20 5 1 4

220
Only rarely are adult PCP overdose cases seen at Detroit General

Hospital, the major inner city emergency service, which gives credence

to the race distribution. Most of the older Caucasian patients seen

at our hospital have come from communities other than Detroit.

SUBJECTS AND METHODS

The clinical courses of eight patients are given in summary form

in table 4. Patients 1, 2 and 3 were described previously with their

pharmacokinetic data (Done et al. 1977). The varying symptomatology

associated with PCP overdose has been described by many authors and

is tabulated and referenced in our previous publication (Aronow and

Done 1978).

Patient 4 was treated at another hospital with a representative of

our group in attendance from six hours to 36 hours after admission.

Quantitation of phencyclidine in his blood was done at a different

laboratory (Domino and Wilson 1977) than his gastric secretion and

urine. These were analyzed along with all specimens from the other

patients, as previously described (Done et al. 1977).

Patient 8 presented in an acute psychotic state after taking repeated doses of PCP over a Period of one to two weeks. Only limited

specimens were obtained and the patient’s clinical course was actually

biphasic. He showed dramatic improvement after twelve hours of iontrapping, with his personality becoming intact. All therapy was discontinued, only to have his psychosis resurface in 4 hours. Therapy

was again instituted, resulting in fluctuating improvement until 53

hours into therapy, when he regained normalcy. Modified therapy was

continued until discharge five days later. On the third day post

discharge the patient became agitated and paranoid, so he was rehospitalized and transferred to a psychiatric service. Unfortunately

no studies were done on his second admission.

Methods of collecting specimens and their treatment are described in

Dr. Done’s paper in this volume.

The lowest serum PCP levels collected within 2-3 hours of consistent

improvement of the patients’ sensorium are given in table 5. Although

the levels were taken at very diverse times in relation to estimated

time of PCP ingestion, there is a rather striking similarity in the

levels. It is not surprising that patient 5, with the longest period

of coma, had a lower serum level. This will be discussed in detail later.

TREATMENT

Principles for treatment of PCP overdose at varying levels have

recently been described (Aronow and Done 1978). In addition, careful

examination for coexisting injuries should be made, as these patients

are at high risk.

Patient 1 came to us late in his course and was given protective and

supportive care until obvious symptomatology disappeared. Patient 2

was in consistent coma with repeated convulsions and severe laryngospasm requiring tracheal intubation for five days. He was maintained

221
TABLE 4

PHENCYCLIDINE OVERDOSE

Patient Data
TABLE 4 (continued)
TABLE 5

PHENCYCLIDINE OVERDOSE

Lowest Serum Levels (ng/ml)

Related to State of Sensorium

Transferred

CHM Approx.

Time After Ingestion Coma Semicomotose

2.5 days

7 hours

? ?

125 95

Patient

1

2

3

4

5

6

7

8

24 hours 125 95

? (Another Hosp.) 114 68

9 days 71 63

31 hours 130 109

23 hours 132 61

Chronic Use

Disoriented

<42

25

25

?

23

24

22.4

– <1.83 –

224
on gastric drainage, initially to reduce aspiration hazard, and then

on a theoretical basis in hope of removing PCP if the tube advanced

to the duodenum. No consideration of the possibility of ion-trapping

in an acid medium was given at that time. Faced with the severity of

the patient’s symptoms, and a dearth of pharmacokinetic data on PCP,

peritoneal dialysis was undertaken in a heroic effort over 72 hours,

without obvious clinical improvement. Slowly, by the fourth day, coma

became semicoma, which changed to disorientation on the seventh day,

lasting for another week. The patient fully recovered.

Analysis of the data obtained from this patient’s blood and urine

samples revealed that PCP clearance seemed to be pH dependent (Done

et al. 1977; Lin et al. 1977).

Patients 3, 4, 5, 6 and 7 all presented with coma of varying durations.

The approach to their therapy was based on ion-trapping with variations in the dosage and route of ammonium chloride used. To attempt

to bring the urine pH to 5 or lower, the dose of ammonium chloride

delivered down the gastric tube was 75 to 125 mg/kg (Edelmann et al.

1967; Chan et al. 1974) every six hours. This was diluted in 2 ounces

of saline. If the patient vomited or had evidence of marked gastric

irritation, the dose was sometimes delivered in two small increments

one half hour apart. The gastric tube was then clamped for one to

two hours before continuous drainage was reestablished. Most

patients’ urines converted to a pH of 5 or lower after the second dose.

Concurrently, ascorbic acid, varying in dose from 500 mg to 2 gms,

was added to the intravenous fluids every six hours.

Particular attention must be paid to maintaining good urine flow

(2 mg/kg/hr) by adequate intravenous fluids and electrolytes,

especially potassium.

Once urine pH was at 5 or lower, furosemide (1/2 to 1 mg/kg) was administered. Often this was followed by a marked improvement in the

patients’ sensorium and symptoms. Repeat use of the diuretic was

dependent on the patient’s fluid balance as evidenced by the central

venous pressure, and could probably be repeated more often than was

done in these patients.

Patients 5 and 6 received ammonium chloride intravenously at a dosage

of 2.75 mg/kg as a 1 percent or 2 percent concentration in saline

(derived from Quadrate, a 21.4 percent solution of ammonium chloride)

purposefully to lower blood pH so as to create a gradient with spinal

fluid and hopefully clear the central nervous system and spinal fluid

of PCP more rapidly. Blood pH fell in patient 5 before urine pH

reached five, and the level of PCP in this patient’s spinal fluid

markedly decreased with concurrent clinical improvement.

Duration of gastric drainage was arbitrarily set at three to four

days but in some patients was discontinued earlier because of nasal

irritation and bleeding (patient 6), anxiety about gastric erosion

from the ammonium chloride solution, and patient discomfort as clearing of the sensorium occurred.

225
In patient 7 betazole hydrochloride (Histalog) was used once to

increase gastric secretions. There was no adverse effect reflected in

blood pressure; however, there was no dramatic change in sensoriun

following three hours of marked increase in volune and decrease in

pH of gastric secretions.

Once the patients’ sensorium had cleared and the nasogastric tube had

been removed, ascorbic acid, two to eight grams in divided doses, was

given daily as well as several glasses of cranberry juice (excreted

as hippuric acid in the urine), to maintain an acid urine for at

least another week.

DISCUSSION

Ion-trapping to enhance PCP excretion has been employed successfully

in acute PCP overdosed patients, as evidenced by a lack of

convulsions or hypertensive episodes once treatment is underway,

relief of muscle hypertonicity, and steady improvement in sensoriun

until out of coma (even after 9 days of coma). With careful attention to good supportive care, there have been no complications of

therapy.

Cumulative data on these patients clearly show the influence of pH

on clearance of PCP (table 6). Although peritoneal dialysis can clear

some of the drug, it is the least efficient unless 5 percent albumin

is used. With only two samples on which to make a judgment, we would

reserve this treatment possibility for the patient with renal insufficiency.

Gastric suctioning may appear to be somewhat lower in efficiency

than it is, due to several factors. Patient 5 generally had lower

gastric clearance than other patients with her clinical severity,

perhaps because of the long time she was in coma before ion-trapping

was instituted, allowing for distribution of PCP into other body compartments. Also, from the pharmacokinetic data shown by Dr. Done

elsewhere in this volume, it is evident that even clamping the gastric tube following ammnonium chloride instillation adversely affects

the serum PCP level. We have also found that the pH of the ammonium

chloride solution used is in the range of 4.5 and raises the gastric

pH temporarily.

Histalog more than doubled the PCP clearance in the gastric secretion

but requires further evaluation before being used routinely as a

possible adjunctive approach, It may be especially helpful for patients with renal insufficiency. The observation that several of the

young children who presented in coma regained consciousness immediately following gastric lavage is further evidence of the importance

of the pool of PCP that may be in the gastric compartment.

Clearly the most dramatic increase in clearance occurs as urine pH

dips to 5 or lower and furosemide is given. This probably accounts

for the marked improvement that often occurs in the patients immediately following diuresis under these conditions.

226
TABLE 6

PCP CLEARANCE (ml/min)

(cumulative data on 7 patients)

Mean SEM

Urine, pH> 6.5

pH 5 - 6.5

+ furosemide

pH < 5

+ furosemide

Peritoneal dialysis

with 5% albumin

Gastric suction

after Histalog

7.0 ± 0.70

57.4 ± 6.57

(205.3) 

134.5 ±25.55

(299.3) 

2.4 ± 0.39

(4.1, 

4.5)

44.8 ± 8.40

(95.7) 

No. of Samples

34

128

3

44

7

11

2

61

3

278

Whether it is better to give furosemide when the urine pH is 5.5 or

to wait to get it down below 5 is not quite clear. Perhaps utilization of another diuretic agent would be more efficacious. These are

some of the refinements in the therapeutic approach that we have

under study.

There are other methods to acidify urine, but we have preferred to

use ammonium chloride. It is contraindicated, however, in anyone

with liver disease. Three of the children under eight years of age

have received one or two doses, as a gastric bolus, with successful

acidification of urine to pH 5 or lower. Although we did not find

evidence of hyperosmolarity in the patients given ammonium chloride

intravenously, this treatment must be used cautiously in small children

as they are exceedingly sensitive to hyperosmolar states.

Although all but one of the patients were considered acute overdoses,

there was reason to believe at least three were regular members of

the drug culture. No doubt chronic use of PCP can result in storage

of the drug in various compartments in the body and influence the

course of an acute overdose. This may account for certain variations

in data seen among patients. The cursory application of our

emerging concept of treatment (Aronow and Done 1978) to one patient

with a history of chronic use resulted in at least an initial improvement. This has led us to undertake further studies of such cases.

ACKNOWLEDGMENTS

The authors wish to acknowledge the invaluable contributions of Dr.

Annette Kelly of Henry Ford Hospital, Dr. Lynn Van Wagnen, Dr. Larry

Fleischmann, Dr. Edgardo Arcinue, Dr. Ashok Samaik, David Ryan and

the personnel of the Intensive Care Unit, Children’s Hospital of

Michigan.

227
REFERENCES

Aronow, R., and Done, A.K.

of treatment.

Phencyclidine overdose: Emerging concept:

J Am Coll Emerg Phys, 7(2):56-59, 1978.

Chan, J.C.M., Ma, R.S., Malekzadeh, M.H., Hurley, J.K. and Chaimovitz

C. Renal response to acute ammonium chloride acidosis in subjects

with single kidney. J Urol, 111:315-320, 1974,

Domino, E.F., and Wilson, A.E. Effects of urine acidification on

plasma and urine phencyclidinc levels in overdosage. Clin Pharm

Therap, 22:421-424, 1977.

Done, A.K., Aronow, R., Miceli, J.N., and Lin, D.C.K. Pharmacokinetic observations in the treatment of phencyclidine poisoning: A

preliminary report. In: Rumack, B.H., and Temple, A.R., eds.

Management of the Poisoned Patient. Princeton: Science Press,

1977. pp. 79-102

Edelmann, Jr., C.M., Boichis, H., Soriano, J.R., and Stark, H. The

renal response of children to acute ammonium chloride acidosis.

Pediat Res, 1:452-460, 1967.

Horwitz, J.P., Hills, E.B., Andrzejewski, D., Brukwinski, W., Penkala,

J., and Albert, S. Adjunct hospital emergency toxicology service.

JAMA, 235:1708-1712, 1976.

Lin, D.C.K., Foltz, R.L., Done, A.K., Aronow, R., Arcinue, E., and

Miceli, J.N. Mass spectrometric analysis of phencyclidine in body

fluids of intoxicated patients. In: DeLeenheer, A.P. and Roncucci,

R.R., eds. Quantitative Mass Spectrometry in Life Sciences.

Amsterdam: Elsevier, 1977. pp. 121-129

National Clearinghouse for Poison Control Centers Bulletin, Tabulations of 1975 case reports. Feb., 1977.

AUTHORS

Regine Aronow, M.D.,+ Joseph N. Miceli, Ph.D.* and Alan K. Done, M.D.*

Departments of Pediatrics*+ Pharmacology*, Wayne State University;

the Division of Clinical Pharmacology and Toxicology*+ and the Poison

Control Center+, Children's Hospital of Michigan, 3901 Beaubien Blvd.,

Detroit, Michigan 48201

228
Chapter 13

The Diagnosis and Treatment of the

PCP Abuse Syndrome

David E. Smith, M.D., Donald R. Wesson, M.D., Millicent E. Buxton,

Richard Seymour, M.A., and Honey M. Kramer

INTRODUCTION

Our first exposure to PCP occurred during the summer of 1967 in

the Haight-Ashbury District of San Francisco in which the drug

was first introduced as the "PeaCe Pill" during a rock concert.

We saw that day between twenty-five and thirty acute PCP toxic reactions. In some respects, these reactions were like the bad LSD

trips we were used to treating, but in other respects quite different, with greater physical toxicity and paranoid thinking. We

had samples of the "PeaCe Pill" analyzed through a local Bay Area

toxicology laboratory and found that the psychoactive drug was PCP.

The "PeaCe Pill" was not well received by the majority of individuals in Haight-Ashbury at that time, although PCP became the

drug of choice for a small number of users who continued to use

it on a chronic basis. For them most part, PCP was a drug of deception, usually marketed as "THC" or as one of the psychedelics

which were more in demand. Within the past five years, however,

PCP has become increasingly visible as a primary drug of abuse

under a variety of street names, including "hog," "krystal," and

"angel's dust." The drug is illicitly manufactured and taken in

a variety of ways: orally, intranasally, and by intramuscular or

intravenous injection. This paper provides the clinician who

treats PCP problem with a conceptual framework for the diagnosis

and treatment of the PCP abuse syndrome. Certainly not everybody

who uses PCP develops toxic consequences, but we have seen a

variety of short term and long term adverse reactions and have

found that many clinicians have difficulty in both the diagnosis

and treatment of PCP-induced problems. (Our work is based primarily on the following clinical experience: 1) the Haight-Ashbury

Free Medical Clinic Drug Detoxification and Aftercare Program;

2) our Emergency Medical Service at rock concerts; 3) Patient

consultation through our Physician Training and Consultation

gram, in which we receive telephone calls and individual requests

from physicians treating people who have PCP abuse problems; 4)

Outreach Training and Clinical Work: 5) Inpatient treatment of

PCP abusers at Gladman Psychiatric Hospital: 6) our collective

229
private practices; 7) work and patient consultation with other

community based treatment agencies; and 8) fellow clinical investigators. Our information is based on our clinical experience

and review of literature. There are many more questions than

there are answers, and the clinical staging presented later in

this paper is designed primarily for the clinician, not the PCP

researcher. As the PCP abuse problem has increased, clinicians

all over the country are faced with management of various stages

of PCP abuse with relatively little help on diagnosis and treatment.

The effects observed when PCP is ingested result from a complex

interaction among pharmacological, physical, and sociocultural

variables, and the pre-PCP psychological makeup of the individual.

In the natural setting, of course, these variables cannot be isolated. In designing the diagnostic and treatment plan, one is

confronted with their simultaneous interaction.

Our clinical findings show four behavioral phases of the PCP abuse syndrome, which may appear as successive stages.

Stage I. Acute PCP toxicity: These reactions are a direct result

of PCP intoxication. Their onset may be minutes to hours following PCP ingestion.

Stage II. PCP toxic psychosis: This stage is apparently not related to toxic blood levels of PCP and does not inevitably follow

stage I.

Stage III. PCP-precipitated psychotic episodes: In some individuals, PCP may precipitate a psychotic reaction lasting a month or

more which clinically appears much like schizophrenia.

Stage IV. PCP-induced depression: PCP can produce a depressive

reaction in some individuals. This may follow any of the previous

stages and last from one day to several months.

Each stage is shown in outline in table I and will be described

in more detail, followed by case histories illustrating salient

clinical features.

DISCUSSION AND CASE HISTORIES

STAGE I. ACUTE PCP TOXICITY

In acute PCP toxicity there are four "C's": combativeness, catatonia, convulsions and coma. These effects are dose-related.

Combativeness and catatonia are frequently observed together at

the lower dosages, while convulsions and coma are related to higher

dosage effects. During this stage, one also sees hypertensive

crisis sufficiently severe to be fatal, although such crises are

relatively rare in our experience. Illusions can dominate:

space walking, the detachment of sounds, objects changing in

size, shape, and distance. Visual illusions rather than true

230
TABLE 1

DIAGNOSIS AND TREATMENT OF THE PCP ABUSE SYNDROME
hallucinations are common, but occasionally auditory hallucinations occur. If the dose of PCP is high enough, the patient may

have many grand mal seizures and coma which require hospitalization and supportive care to stabilize and maintain the respiratory and cardiovascular function. With proper management, most

patients who go into a PCP-induced coma survive, although the

period of coma may be quite prolonged. Our experience indicates

that the usual duration of acute PCP toxicity is 0 to 72 hours.

Lab results indicate that blood is almost always positive and

urine is positive. A large number of people clear after stage

I, PCP acute toxicity; some go into stage II, PCP toxic psychosis.

Case 1

At a rock concert in the San Francisco Bay Area, six adolescents

who had previously experimented with a variety of psychoactive

drugs, including PCP, ingested an unknown quantity of PCP in

tablet form. Although they had experience with PCP, they had been

primarily smoking it in a form of "krystal joints," and this was

their first exposure to the tablet form of PCP. All six became

acutely intoxicated; one, a 17-year-old white male high school

senior, became comatose. Friends took him to the emergency room

of a local hospital after observing the young man for a couple

of hours and becoming concerned over his extreme muscular rigidity

and shallow respirations. He was hospitalized and maintained on

a respirator for over three days. With this supportive management

he recovered fully, but there was a period of cerebral dysfunction

with poor memory and depression lasting for over a week following

the acute PCP toxicity. This case example also demonstrates that

a patient can go from stage I acute PCP toxicity to stage IV,

cerebral dysfunction and depression, without going through stage

II and stage III psychotic phases.

Treatment of Stage I

Acute PCP toxicity patients can be divided into two groups: those

who are comatose, and those who are acutely intoxicated but conscious.

A. Comatose Patients

As in the management of any coma patient, the first level of consideration is stabilization of the ventilation and cardiovascular

systems, and protecting the individual from inflicting bodily harm.

Secondly, consideration should be given to the elimination of the

offending agent.

1 . Stabilization of medical signs and psychiatric signs and

symptoms.

a. Cardiovascular System

Treatment of the hypertension with Hyperstat has been recommended

(Eastman and Cohen 1975).

232
b. Convulsions

Convulsions may occur and are not necessarily limited to one or

two. Therefore, treatment is recommended with intravenous diazepam

(ValiumR) given over a period of two minutes following the seizure.

c. Respiratory Depression

Respiratory depression with pure PCP is unusual except in very

high dosages. However, respiratory depression may be marked when

combined with alcohol, other sedative hypnotics, or opiates. If

the patient is sufficiently depressed, respiratory assistance on

a respirator is necessary.

B. Conscious Patients

Patients in acute toxicity may also present as psychiatric emergencies with symptoms of paranoia, agitation, thought disorder,

negativism, hostility, and grossly altered body image. Assaultive

and antisocial behavior often results in the individual's coming

to the attention of treatment personnel. In the management of

such individuals, Luisada and Brown (1976) have delineated the

immediate goals of treatment as: 1) prevention of injury to

the patient or others; 2) assurance of continuing treatment; 3)

reduction of stimuli; 4) amelioration of the psychosis: and 5)

the reduction of agitation. The reduction of external stimulation

through the use of seclusion or a "quiet room" is of prime importance. Clinicians disagree as to the most appropriate pharmacological intervention. Luisada and Brown (1976) recommend chlorpromazine (Thorazine), although we generally prefer diazepam

(Valium) for symptomatic or behavioral control. Haloperidol

(Haldol) has also been used (Showalter and Thornton 1977).

C. Elimination of PCP from the body

Although many clinicians prefer conservative supportive management,

Aronow, Miceli, and Done (this volume) have successfully utilized

continuous gastric suction, acidification of the urine, and a

potent diuretic such as furosemide (Lasix) to enhance elimination

of the PCP. Their technique and rationale for use are described in

detail in other papers in this volume. PCP is recycled through

the enterohepatic circulation, and introducing a slurry of activated charcoal into the intestine may decrease reabsorption of

PCP from the small intestine. This should not be used instead of

gastric suction in a comatose patient; however, 100 ml of activated

charcoal slurry should be inserted into the stomach just before

the nasogastric tube is removed, or may be given orally to a noncomatose patient.

STAGE II. PCP TOXIC PSYCHOSIS

After the acute PCP toxicity phase has passed, some individuals

develop a prolonged toxic psychosis. Our experience has been

233
that incidence of the PCP toxic psychosis is highest among chronic

abusers. In trying to detemine prognostic indicators to why

certain patients will become psychotic, we have looked at different clinical variables, but found chronic abuse to be the major

factor. In this stage, one finds impaired judgment and paranoid

delusions with agitation and both auditory and visual hallucinations. The individual can be self-destructive or destructive to

others. Hallucinations and flattened affect are characteristic.

The usual duration is 24 hours to 7 days or more. Lab results

indicate blood negative and urine positive for PCP. The amount

of PCP excreted in the urine is highly dependent upon urinary

acidity, and an attempt to collect the urine under conditions of

urinary acidification with ammonium chloride or ascorbic acid

(vitamin C) should be made.

Case 2

A 38-year-old black male with no previous history of drug abuse

or psychiatric problem acquired some new marihuana which was

described to him as "superweed." He had regularly smoked marihuana for over twenty years and described no adverse consequences

of any sort with its use. He began smoking this new "superweed"

and found himself (according to his girlfriend) beaming paranoid,

delusional, and uncharacteristically hostile. After approximately

two weeks of daily smoking of the "superweed" he felt that there

might be some correlation between this new drug and his symptoms

and stopped smoking the drug for a day. He found no symptom

relief; after that, he actually increased the dosage, as he felt

it might help him feel better and recover from the symptoms which

he felt were unrelated to the drug use. Shortly after, he became

quite assaultive, cut off the head of his dog, and assaulted a

stranger on the street with a razor. His girlfriend, who had

read in the newspaper of the bizarre behavior PCP can produce,

brought him to the Haight-Ashbury Free Medical Clinic where he

was examined. The material was analyzed and found to be marihuana laced with a significant quantity of PCP. The toxicity of

PCP was explained to both the patient and his girlfriend. Both

decided on an abrupt cessation of the drug. Following a brief

period of hospitalization in which antipsychotic medication was

administered, the patient was discharged and refused further

hospitalization or medication, but remained in supportive counseling. After approximately two weeks the psychotic symptomatology

faded, but the patient still complained of impaired thinking,

difficulty in believing that the delusions that he perceived during his PCP intoxication were unreal, and prolonged depression.

Weekly supportive counseling without medication gradually resolved

these symptoms in approximately twelve weeks.

Treatment of Stage II

Most clinicians recommend the use of non-phenothiazine tranquilizers such as haloperidol (Haldol). Some clinicians use sedative

hypnotic medication. There is no sound research basis for the use

of either of these medications; nor in our experience, is there

234
any indication that these medications shorten the course of acute

PCP toxic psychosis. It does appear, however, that they make the

patient more manageable in a ward, which is probably the major

reason that these medications are used. In those clinical cases

that we have seen where patients have received either no medication, sedative hypnotic medication, or antipsychotic medication,

these variables do not appear to change the total length of time

the individual is psychotic, but they do modify the characteristic

symptoms.

STAGE III. PCP-PRECIPITATED PSYCHOTIC EPISODE

Early investigators reported on the tendency of PCP to exaggerate

signs and symptoms in schizophrenic patients (Luby et al. 1959,

and Domino 1964). Many other studies have described the PCPinduced psychosis. Luisada and Brown (1976) have described individuals who were not previously schizophrenic, who became so

following ingestion of PCP, and who periodically have return of

symptoms, although of less intense nature than when the PCP was

first used. To what extent it is possible to have a prolonged

psychosis in an individual who is not predisposed to schizophrenia

is not known. Certain individuals, mostly with psychotic or

prepsychotic personalities, tend to develop a PCP-precipitated

psychotic episode that mimics schizophrenia. This may occur after

a single dose administration of PCP. This is not a result of

chronic PCP abuse producing a toxic psychosis, but rather a PCPprecipitated adverse reaction to an underlying psychological

condition. The characteristics of the episode are of the schizoaffective type with paranoid features and a waxing and waning

thought disorder, A majority of the cases that we have seen in

stage III have had psychotic or prepsychotic personalities, and

we believe that this is the major prognostic indicator. However,

we have seen a few cases that have had a prolonged PCP-precipitated

psychotic episode after single dose administration, with no unequivocal history of preexisting psychosis. Our time range is 7

days to 30 days or more, with patients moving from the PCP toxic

psychosis into the PCP-precipitated psychotic episode. Lab results indicate blood negative, urine negative. Most investigators

recommend the use of chlorpromazine (Thorazine) in dosages comparable to those used in schizophrenia and remark that the paranoia

appears to yield at a slower rate (Luisada et al. 1976). The need

for long term antipsychotic drug maintenance for the individual

with PCP-precipitated psychotic episodes makes it important to

differentiate the PCP-induced toxic psychosis from the PCP-precipitated psychosis. It is also important to emphasize that individuals with schizophrenia can go into a prolonged psychotic phase

after a single dose of PCP. This is demonstrated by the following

case:

Case 3

A 26-year-old white female with a long history of psychiatric disturbance, including hospitalization for psychosis, but no history

of alcohol or drug abuse, was at a party and shared a joint of

235
"angel dust," a drug with which she had no previous experience.

After smoking approximately half of the joint, she started becoming quite paranoid and delusional, and developed both auditory

and visual hallucinations. After remaining at home with her

parents for two days, she was taken to a San Francisco psychiatric

hospital where she was admitted. The material she smoked was

analyzed and found to contain PCP. At the time of hospitalization, both her blood and urine were negative for PCP. She remained psychotic for over two weeks, but the thought disorder

gradually faded, giving way to a substantial depression. Her

psychosis was treated with haloperidol (Haldol).

Treatment of Stage III

A. Immediate goals of treatment are the same as those described

for acute PCP toxicity, including prevention of injury and

reduction of stimuli.

During the PCP-related psychotic break, it appears that the drug

precipitates an underlying thought disorder, rather than producing a direct toxic psychosis, which we define as a major break

with reality secondary to an intoxicant. In general, many clinicians use a non-phenothiazine major traquilizer, such as haloperidol (Haldol), for the PCP toxic psychosis because of the

concern over the additive effect between PCP arid chlorpromazine

(Thorazine). However, there is no controlled research in humans

to support this. Domino and Luby (1972) have described animal

research which shows some additive effect of chlorpromazine

(Thorazine) and PCP. In PCP-precipitated psychosis, however,

experienced clinicians (Luisada and Reddick 1975) recommend residential seclusion with frequent observation and high doses of

antipsychotic phenothiazine medication, such as chlorpromazine

(Thorazine) given daily, starting with 400 mg a day in divided

doses and increased as necessary by 200 mg a day to an average

daily dose of 1600 mg per day. Clinical experience in the San

Francisco Bay Area has varied between the use of sedative hypnotic

medication such as diazepam (Valium) and low doses of haloperidol

(Haldol) and has avoided the high doses of chlorpromazine (Thorazine) as described by Luisada and Reddick (1978). All clinicians

treating stage III, however, agree that the PCP-induced psychotic

reaction can be quite prolonged and should be managed on an inpatient basis.

STAGE IV. PCP-INDUCED DEPRESSION

PCP-induced depressionis a very frequent condition that many

clinicians miss, particularly when it comes after a stage III PCPprecipitated psychotic reaction. The clinician is so relieved

when the psychosis is over that s/he discharges the patient with

relatively little followup and without realizing that in this depression the individual has high suicide liability or may use

other types of drugs to alleviate the depression. A paradox with

PCP is that it does give an energizing, numbing, consciousnessaltering effect which the patient perceives as antidepressant.

236
Clinically, it appears that many of these patients have prolonged

cerebral dysfunction, as well as depression. The complaints of

memory impairment subside as the depression clears. The patients

who we have treated have indicated that they feel less depressed

as they think their "brain damage" is clearing. It becomes very

difficult to figure out whether depression clears as the cerebral

dysfunction itself clears or as their concern over the cerebral

dysfunction waves. In addition, some of the symptoms may be the

result of the depression rather than the cause. PCP-induced depression can last from one day to several months, and can follow

any of the preceding stages. That is to say, the patient can be

in PCP acute toxicity and clear with no problem, or go into stage

II PCP toxic psychosis, or into stage III PCP-precipitated psychotic espisode, and then have prolonged PCP-induced depression.

Or, the patient can wake up from a PCP acute toxic reaction and

go right into the prolonged depression. Laboratory results will

show blood and urine both negative for PCP.

Case 4

A 19-year-old white female came to the Haight-Ashbury Free Medical

Clinic after a PCP overdose. She described a long history of

agitated depression and suicidal ideation from which she found

she gained relief when she "snorted" two lines of PCP containing

approximately 20 mg each day. She indicated that drugs such as

amphetamines actually made the depression worse because they increased the agitation. Conversely, when she took PCP, the alteration in consciousness and energizing effect gave her relief

from the depression. When she stopped the PCP, however, she

found the depression became worse than it was prior to use of the

drug. She indicated that she had no intention of stopping prior

to this me overdose episode. She expressed amazement about the

overdose because she indicated that she had not snorted a higher

dose on the day she became comatose.

This case illustrates a number of principles, including motivation

for usage in individuals who are self-medicating their depression.

In addition, it demonstrates that chronic abusers can have overdose episodes even if the dosage of the drug is not increased,

and it suggests clinically that this may be the result of accumulation of the drug in both brain and fatty tissues of the body.

Also, there is a high incidence of secondary drug abuse following

this stage IV PCP-induced depression. Many individuals turn to

other drugs, including alcohol, stimulants such as amphetamines

or cocaine, or even heroin to deal with the PCP-induced depression.

This is illustrated by the following case:

Case 5

A 34-year-old white male used PCP by the intranasal route on a

daily basis for three years. He developed a grandiose religious

delusion in which he described himself as the "Prince of Peace"

and thought he was "Jesus Christ." He was using PCP with a number

of other friends, who also felt he was "Jesus." Following an

237
adverse PCP reaction and confrontation with another individual

using PCP, this religious delusion was shattered and he became

extremely depressed. In an attempt to self-medicate this depression, he began snorting and finally injecting heroin and eventually

became dependent on heroin. He also used large quantities of cocaine. As a consequence of antisocial activities undertaken in

order to acquire the drug, he was arrested and served time in

jail. He is how drug-free and involved in treatment in a nonmedical outpatient program stressing a chemical-free philosophy.

He denies that he had any history of depression prior to his prolonged period of PCP abuse, or any history of religious delusion.

He feels that the depression and religious delusions were a direct

result of his daily and prolonged abuse of PCP.

Treatment of Stage IV

We have not had notable success in treating PCP-induced depression

with the tricyclic antidepressants amitriptyline (Elavil) and

imipramine (Tofranil). Certainly, the PCP depression can result in return to PCP usage, or to a suicidal attempt for individuals who are self-medicating a preexisting depression with PCP.

If treatment is initiated with antidepressants, full therapeutic

dosages should be given 100 to 250 mg/day). Many of these patients

take medication erratically, and the usual precautions used with

patients on tricyclic antidepressants should be observed. We

certainly prefer inpatient treatment. If antidepressants are

prescribed on an outpatient basis, not more than two or three

days' dosages should be dispensed at once. The patient should

be cautioned about possible interaction of tricyclic antidepressants with PCP, alcohol, and other drugs, and advised to discontinue the tricyclic antidepressants if PCP usage is resumed.

The underlying basis of a PCP-induced depression is unknown, and

no controlled clinical procedures are available to guide the

clinician.

SUMMARY AND QUESTIONS FOR FUTURE RESEARCH

PCP abuse may present in a variety of ways to the clinician.

Treatment strategies may be conceptualized in terms of four

stages, each having specific types of treatment intervention:

acute PCP toxicity: PCP toxic psychosis; PCP-precipitated psychosis; and PCP-induced depression. Clinical treatment of the

severe overdose in coma is best understood and defined by clinical

protocol. The treatment of other stages is still primarily dictated by clinical intuition; disagreement exists among experienced

clinicians as to what constitutes the most appropriate treatment.

For the clinician responsible for treating PCP abuse, a number of

Clinically important questions remain unanswered. For example:

1 . Does chronic PCP use produce long-lasting, perhaps permanent,

brain damage? Is the association observed by clinicians spurious in that most PCP users have used a variety of other drugs?

Are the effects thought to be long term actually secondary to

238
2.

3 .

4.

chronic intoxication?

Does PCP ingestion produce long-lasting psychological disorganization in individuals who are not schizophrenic? If so,

how can these effects be characterized and distinguished from

schizophrenia?

Are the antipsychotics useful in shortening the duration or

intensity of PCP acute toxicity, the PCP toxic psychosis,

or the PCP-precipitated psychosis? Should patients who manifest prolonged psychoses following PCP ingestion be diagnosed

or treated differently than schizophrenics?

Is the PCP-induced depression observed in PCP users actually

induced by the drug? If so, what is the underlying biochemical

mechanism, and should the antidepressants be used in treatment

of the depression?

The answers to these and other clinically relevant questions can

be resolved by careful clinical research. In view of the current

differing opinions as treatment, double blind random treatment

assignment studies should be undertaken. Practically, the barriers

to definitive research include the difficulty in establishing informed consent to participate in a study while the patient is

acutely psychotic and the difficulties inherent funding such

research. Until answers are available, prudent clinical treatment

must proceed according to clinical intuition. We believe the

concept of distinct clinical stages is a step toward rational

treatment.

239
REFERENCES

Domino, E.F., and Luby, E.D. Abnormal mental states inluced by

PCP as a model. In: Cole, J.O., ed. Psychopathology and Psychopharmacology. Baltimore: John Hopkins, 1972. pp. 37-50.

Domino, E.F. Neurobiology of phencyclidine (Sernyl). A Drug

Neurobiology, 6:303-347, 1964.

Eastman, J.W., and Cohen, S.N. Hypertensive crises and death

associated with. JAMA, 1270-1271, 1975.

Luby, E.D., Cohen, B.D., Hosenbaum, G. et al. Study of a new

schizophrenomimetic drug Sernyl. Arch Neurology and Psych, 81:

363-369, 1959.

Luisada, P.V., Brown, B.L. Clinical management of phencyclidine.

Clinical Toxicology, 9:539-545, 1976.

Luisada, P.V., and Reddick, C. An epidemic of drug induced

"schizophrenia". Presented at the 128th annual meeting of the

American Psychiatric Association, Anaheim, CA., May 5, 1975.

Showalter, C.V., and Thornton, W.E. Clinical pharmacology of

phencyclidine toxicity. Am J Psych, 134(11):1234-1238, 1977.

AUTHORS

David E. Smith, M.D.

Associate Clinical Professor of Toxicology

University of California

Director, Haight-Ashbury Free Medical Clinic

409 Clayton Street

San Francisco, California 94117

Donald R. Wesson, M.D.

Assistant Clinical Professor

University of California Medical School

Department of Psychiatry, San Francisco

2999 Regent Street, Suite 501

Berkeley, California

Millicent E. Buxton, Information Coordinator;

Richard B. Seymour, M.A., Administrator; and

Honey M. Kramer, Administrative Assistant

Haight-Ashbury Training and Education Project

409 Clayton Street

San Franciso, California 94117

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Chapter 14

The Phencyclidine Psychosis:

Phenomenology and Treatment

Paul V. Luisada, M.D.

INTRODUCTION

Washington, D.C. has been a major center for phencyclidine (PCP)

production and abuse since the early 1970's. This phenomenon,

however, did not reach the awareness of the public or of most

mental health professionals until mid-1977.

Phencyclidine's propensity for reactivating schizophrenic psychoses also remained buried in the literature on model psychoses

from the early 1960's. Finally, the fact that phencyclidine can

produce long-term treatment-resistant schizophreniform psychoses

in subjects who have had no prior psychiatric histories was not

known until 1974. This paper concerns itself with the diagnosis

and clinical management of the phencyclidine psychosis.

During the fall of 1973, the admission rate for what appeared to

be unusually long, severe, and treatment-resistant initial schizophrenic psychoses suddenly tripled at the Area D Community Mental

Health Center in Washington, D.C. (Luisada and Reddick 1975).

These patients had all smoked a drug called "Angel Dust" before

becoming psychotic. Unlike the vast majority of toxic psychoses,

however, these episodes often required two weeks of aggressive

inpatient treatment before resolution began. In addition, violently agressive behavior was characteristic of the onset, and the

presenting picture was at first indistinguishable from a florid

schizophrenic episode.

The first case to catch our attention was unusual in several ways

and presented a diagnostic dilemma: An 18-year-old high school

senior was admitted after becoming violently psychotic at home

without any prodromal signs. He presented with the primary and

secondary signs of a florid schizophrenic psychosis. Escalating

doses of major tranquillizers and intensive staff involvement

failed to influence his illness during the first two weeks in the

hospital. In fact, contact with staff appeared to aggravate his

symptoms. His ambivalence and paranoia made him unpredictable

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and posed a constant threat of violence. He assumed bizarre

autistic postures, demonstrated a formal thought disorder, and

voiced the delusions that his mother was dead and that he had

a "knot" in his head.

The diagnosis was complicated by several factors: his mother

denied a family history of schizophrenia or the presence of prodromal signs and symptoms in the patient. A toxic psychosis

seemed improbable on the basis of lack of history or physical

stigmata, the absence of a clouded sensorium, the persistence of

the psychosis, and the presence of all four primary signs of

schizophrenia.

When the patient's personality was dramatically reconstituted to

its premorbid level in the third and fourth weeks of hospitalization, however, he reported smoking a drug called "angel dust"

just prior to admission.

Similar admissions rose from a trickle to a flood, peaking in

February 1974 at the rate of one third of the first inpatient

admissions. The epidemic ended even more suddenly, with no more

than three cases each during April, May, and June. This decline

followed by several weeks a police raid on local PCP laboratory.

Another epidemic began toward the end of 1974, and for some periods

of 1975 and 1976 PCP psychosis became our leading cause of inpatient psychiatric admissions, surpassing both schizophrenia and

alcoholism. By the beginning of 1976, the Drug Enforcement Administration was calling the Washington Metropolitan Area the PCP

capital of the country. However, despite a proliferation of

local laboratories (and an increase in raids on these laboratories),

admissions to our center for PCP psychosis began a slow but steady

decline. At the same time, experienced drug users presenting for

treatment of other drug abuse problem began referring to PCP as

a drug to avoid "because it makes people crazy." Meanwhile, the

suburbs began experiencing noticeable increases in the incidence

of PCP psychoses.

PCP presently remains the major drug of abuse in the Washington

Metropolitan Area. This situation prevails despite a recent wave

of local media publicity about its adverse effects.

DEFINITION

The PCP psychosis may be defined as a schizophreniform psychosis

which occurs in some individuals after phencyclidine use and

which persists for more than a day. The psychosis may last for

days or weeks despite abstinence, and it characteristically becomes more severe during the first few days of its course.

The PCP psychosis is characterized by the appearance of the cardinal signs of schizophrenia and unpredictable aggressive or withdrawn behavior. Characteristically, there is autistic and delusional thinking, commonly including global paranoia, delusions

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of superhuman strength and invulnerability, as well as delusions

of persecution and grandiosity. A formal thought disorder, with

loosening of associations, blocking and auditory hallucinations

can be demonstrated. Affect is generally blunted, with periods

of suspiciousness often alternating with extreme anger or terror.

Patients are ambivalent and unpredictable even toward their close

friends and relatives.

Behavior is extremely unpredictable. These patients may be reluctantly cooperative one minute and violently assaultive the

next. Some carry lethal weapons to protect themselves from

their imagined persecutors. Bystanders have often been furiously,

unexpectedly, and unremittingly attacked without provocation, because the psychosis may include both extreme global paranoia and

delusions of superhuman strength.

REVIEW

PCP was originally developed in the 1940's by Parke, Davis & Co.

as an intravenous general anesthetic under the trade name "Sernyl."

Animal trials demonstrated very high levels of general anesthesia

(Chen et al. 1959). Lower doses produced a cataleptic state, and

still lower doses a tranquilized state during which fingers could

be inserted in wild animals' mouths with impunity (Davies and

Beech 1960). PCP was later used to tranquilize wild animals for

handling (Domino 1964), and it is still available for veterinary

use (Reed and Kane 1972).

Initial trials with humans were undertaken with the expectation

that PCP would have great promise for surgical anesthesia. As

an anesthetic, it fulfilled all expectations until the patients

woke up: one-sixth of the original group were severely psychotic,

but only for several hours. Their behavior was described as extremely agitated and bizarre, with echolalia and logorrhea as

prominent symptoms (Greifenstein et al. 1958). Significantly,

this psychotic reaction was most common in young or middle aged

males (Johnstone 1960).

Because of these severe postoperative reactions, the focus of investigation of PCP in humans shifted from its possible use as an

anesthetic to its utility for producing model psychoses. The drug

was given to "normal volunteers" whose psychoses were documented

in an eruption of papers which lasted until 1965, when ParkeDavis withdrew PCP from experimental use in humans (Reed and Kane

1972).

The major finding of these studies was that PCP had no equal in

its ability to produce brief psychoses nearly indistinguishable

from schizophrenia (Rosenbaum et al. 1959). Generally, the psychoses began immediately after infusion of the drug (Davies and

Beech 1960), lasted about two hours, and were characterized by

changes in body-image, thought disorders, estrangement, autism,

and occasional catatonia (Luby et al 1959). Subjects reported

feeling numb, had great difficulty differentiating between

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themselves and their surroundings, and complained afterward of

feeling extremely isolated and apathetic (Bakker and Amini 1961).

Of particular interest was the observation that these volunteers

often became violently paranoid while acutely psychotic.

Other workers who compared PCP is mescaline and LSD commented on

the ego-alien quality of the psychoses (Dan et al. 1961). Preoccupation with death and fear of death was common while under

the influence of the drug, and it had an impressive ability to

loosen up these subjects! unconscious conflicts.

Although these studies agreed that PCP can produce schizophrenia

on demand in "normal volunteers," the psychoses were limited to

a maximum of several hours. By contrast, when Luby gave PCP to

four hospitalized chronic schizophrenics, the results were much

more severe (Luby et al. 1959). "It was as though in these patients, the acute phase of their illness had been reinstated."

They became nearly unmanageable in an inpatient setting, not for

several hours, but for six weeks. Other observers noted that

PCP's effects on schizophrenics are exactly the opposite of LSD's,

since schizophrenics are considerably more resistant than "normals"

to that drug.

The literature on PCP in humans therefore describes two related

but distinct psychotic effects:

A schizophrenic syndrome lasting several hours in "normals."

An extreme exacerbation of their psychoses lasting up to 6

weeks in chronic schizophrenics.

The psychoses we have seen seem to fall between these categories.

Although our patients had not been hospitalized before, lacked

prior psychiatric histories, and were living in the community,

their psychoses were longer and more severe than those described

in "normal volunteers," but shorter than those described in

schizophrenics: yet they seemed to resolve without sequelae.

METHOD

To describe the clinical aspects of this syndrome more precisely,

we selected for study a group of PCP users in the following way:

We screened the 200 inpatient admissions to a single catchment

admission ward in the CMHC between July 1973 and June 1974, which

approximated the epidemic's time-frame. The records of all patients who were psychotic on admission or had a history of drug

use were examined for an explicit history of exclusive PCP use

during the two months before admission. After applying these

selection criteria, we were left with 11 men.

These selection criteria resulted in the exclusion of about twothirds of PCP-related admissions. These exclusions were all on

the basis of multiple drug-use, and were made in order to limit

the drug effects to those of PCP as much as possible. The

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following observations were assembled from the patients' charts,

nursing notes, ward logs, and shift reports.

CLINICAL COURSE

The course of the treated psychosis was found to consist of three

distinguishable phases of approximately equal length over the

course of an average two-week hospitalization: The initial phase

is characterized by the violent, psychotic behavior described

earlier, and this persists for an average of five days. During

the second phase, behavior is more controlled, but patients remain

restless and unpredictable for approximately five more days. The

final phase lasts about four days and is characterized by rapid

personality reintegration and rapid disappearance of thought disorders and paranoia.

The majority of patients presenting with this entity were in their

late teens to mid-twenties, and the majority have been males.

most did not reach treatment until hours or days after the onset

of the psychosos, and did so during its initial phase. Chief complaints ranged from mute posturing to "attacking everyone in

sight." The majority of these patients were brought to treatment

after their aggressive behavior exceded the limits tolerated by

family, friends and police. Those few patients who presented

themselves voluntarily were generally treatable on the outpatient

basis, and were neither as violent, as agitated, nor as psychotic

as those described here.

Where admission histories were obtained from these patients, they

generally included several days of confusion, paranoid ideation,

insomnia, and intermittent restlessness. However, a history of

phencyclidine use was not reliably obtainable on admission, and

some of the patients were initially misdiagnosed as schizophrenic.

Family numbers generally describe the pre-admission period as

characterized by continuous insomnia, tension, hyperactivity,

and intermittent, unexpected aggressive behavior, bizarre paranoid

delusions, ideas of reference, delusions of being controlled by

others, and grandiosity, but no fixed or systematized delusional

system.

Apart from the characteristic history of acute onset, and an irregularly obtained history of using PCP in its current street

guises, the majority of these patients lacked prior psychiatric

histories and tended to be more independent of their families

than schizophrenics. Most were doing reasonably well in high

school, college, or work, although some did have poorer social

adjustments prior to the onset of their psychoses.

Other patients we have seen had prior admissions for schizophrenia

but experienced sudden psychotic reactivations after experimenting with PCP. As a rule, these psychoses involved significantly

more violent and unpredictable behavior than the initial schizophrenic psychoses.

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CLINICAL MANAGEMENT

Phencyclidine psychosis in the initial phase constitutes a psychiatric emergency; hence, its early, acurate diagnosis is of

great importance. These patients are an immediate danger to

others merely on the basis of their misperceptions, paranoia and

hostility; and this threat is compounded by their confusion,

tendency toward violence, and the extreme unpredictability of

their behavior. They also constitute a danger to themselves not

only on the basis of impaired judgment and inability to care for

themselves, but also because their violent, threatening behavior

may provoke lethal countermeasure by those around them. Burns

has reported a case of PCP intoxication in which the patient was

shot and killed by police after not heeding their warnings. One

of our patients was hospitalized involuntarily on the basis of

"attacking everyone in sight," including the investigating police

officer, after a car accident.

Patients in the initial stages of the PCP psychosis almost invariably require inpatient psychiatric treatment. Furthermore,

these patients are poor candidates for voluntary treatment, first

because their paranoia makes them unlikely to sign on admission,

and second because their restlessness, ambivalence, confusion,

and unpredictability at this stage of the psychosis lead to a

high percentage of premature discharges against medical advice.

A factor which further militates against successfully continuing

treatment on a voluntary basis is admission under pressure from

family or friends. These patients often demand to leave as soon

as their relatives and friends return home. In our experience,

they cannot be dissuaded on the basis of rational discussion

during this phase of their illness. In one instance, a newly

admitted patient insisted on "fighting my way out" despite the

presence of sixteen male nursing staff, some of whom were injured

in the process of restraining him.

As discussed above, patients in the initial stage of the PCP

psychosis are dangerous, ambivalent, unpredictable, psychotic

and agitated. The immediate goals of treatment are therefore:

(1) Prevention of injury to the patient or others

(2) Assurance of continuing treatment

(3) Reduction of stimuli

(4) Amelioration of the psychosis

(5) Reduction of agitation

Treatment which meets the first three of these goals included

prompt inpatient hospitalization, preferably on an involuntary

Isolation in a bare, locked seclusion room with frequent

but unobtrusive observation is the treatment of choice. Seclusion

not only safegards other patients and staff but also calms the

patient through the reduction of stimuli which he can misperceive

as threatening. This applies particularly to the sight of other

people.

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Chlorpromazine is the only antipsychotic agent which meets the

last two goals: amelioration of the psychosis and sedation. Our

experience indicates that the use of nonsedating antipsychotic

agents prolongs the time these patients require seclusion, delays

improvement of the insomnia, and makes them more difficult for

staff to manage at mealtimes. Although the use of sedatives such

as diazepam and chlordiazepoxide has been suggested for the management of acute phencyclidine intoxication, the dual treatment

goals of ameliorating the psychosis and reducing agitation make

the use of a single drug which meets both goals (chlorpromazine)

more attractive than the combination of a nonsedating antipsychotic

agent and a sedative.

Some authors have noted that chlorpromazine has not been shown

to antagonize the behavioral effects of PCP, and even enhances

some of then (Balster and Chait 1976). These conclusions, however, are based upon observations of animals intoxicated with

PCP who were given chlorpromazine. There is some doubt as to

whether these conclusions apply to the PCP psychosis as seen in

humans. First, behavioral changes persisting for days or weeks

after PCP intoxication have been reported only in humans. Thus

there is no animal model for the PCP psychosis. Second, the

experiments were performed chiefly on monkeys, and PCP's effects

on monkeys is tranquilization, not the psychotic agitation seen

in humans. Finally, chlorpromazine enhances the depressant

effect of PCP on these animals. Our experience has been that

chlorpromazine also acts as a depressant in our patients, and

that it antagonizes the persistent excited behavior seen in humans

with the PCP psychosis.

Once the possibility of anticholinergic drug intoxication has been

ruled out, the daily dose of chlorpromazine is increased by 200

to 400 milligrams per day from a starting dose of 400 milligrams

per day in divided doses. On the average, a daily dose of 1600

milligrams per day has been reached by the end of the initial

phase of the psychosis.

Behavior in seclusion during the initial phase is characterized

by continuing global paranoia, insomnia, anorexia, intermittent

agitation, and strong reactions to such stimuli as the presence

of staff during meal times. Patients may throw food about the

rooms or smear it on the walls. They are extremely suspicious of

food and oral medication, and may vacillate at length before reluctantly accepting it. It is helpful if the same staff members

bring the patient's food and medication from day to day.

This slow response to the most aggressive treatment is characteristic of the phencyclidine psychosis and sets it apart from paranoid schizophrenia, in which equally agitated patients respond

much more rapidly. Indeed, the sense of lack of progress engendered by this slow treatment response was a factor leading to our

first investigation of these psychoses.

The transition from the initial to the mixed phase is characterized

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by several gradual changes which become prominent around the fifth

day of treatment: Although restless, the patient is no longer

hyperactive: he is less threatened by or overtly hostile to the

presence of others in the seclusion room. He is cooperative to

the extent of following simple concrete suggestions, and accepts

medication without suspicious vacillation. He can agree to seclude himself if he becomes upset.

Thus, although he is confused, still demonstrates a thought disorder, hallucinations, blocking, and paranoid ideation, he is

relatively calm and reasonable a good portion of the time and can

accept some degree of responsibility for and control of his behavior.

Despite these signs of progress, there are still intermittent

periods of gross paranoia, agitation, terror, and hyperactivity

alternating with quiet paranoid watchfulness. Affect remains

quite constricted, and inappropriate demands which are not met

immediately may explode in an unexpected flurry of violence.

Thus, patients in the second (mixed) phase are psychotic, paranoid,

unpredictable and intermittently dangerous, although they are no

longer as sensitive to stimuli.

The goals of treatment in this stage are:

(1) Prevention of injury

(2) Amelioration of the psychosis

(3) Reduction of paranoia

The first goal may be met by close and continuous monitoring of

behavior and a flexible seclusion policy aimed at helping the

patient voluntarily to seek seclusion at the first signs that he

is losing control. Operationally, a patient who sits near other

patients shows stability, whereas a patient who isolates himself

in a comer with his back to the wall, watching others suspiciously, requires further isolation.

Clinical judgmemt will indicate whether further increases in

chlorpromazine dosage, or switching to an equipotent dose of a

nonsedating antipsychotic agent is indicated. Reestablishment of

sleep pattern may be aided by switching the entire dose to bedtime. Participation in group and milieu therapy is helpful in

restoring the patient's confidence in his perceptions and in establishing rapport.

The third phase begins, on an average, during the tenth day of

hospitalization, and is characterized by rapid reintegration of

the premorbid personality and the development of insight into the

events leading to the hospitalization. There is often some amnesia

for the early events of the psychosis, but a history of the use

of phencyclidine prior to its onset is usually obtained during

this period. Patients may be converted to voluntary status during

this stage, and the groundwork for outpatient followup laid.

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Outpatient followup is helpful as patients are tapered off medication. In this connection, it is interesting to note that despite

repeated warnings against further phencyclidine use, a large proportion of our patients use it at least one more time and return

for treatment of a second psychotic episode. Most of these patients explained using the drug again on the basis of "feeling

good" and wanting to see if they could "handle it."

Less encouraging is our finding that about one fourth of the

patients originally treated for phencyclidine psychoses return

within a year with schizophrenic psychoses in the absence of

drug use. By contrast, these later episodes have lacked the

characteristic violence of the phencyclidine-induced ones, and

they have been much more quickly responsive to antipsychotic

drugs; yet they have also left behind typical schizophrenic personality changes. Those patients who had experienced the longer

phencyclidine psychoses were generally the same ones who returned

later with schizophrenic ones.

Epidemics of drug abuse are nothing new in the United States.

The past two decades have seen epidemics of heroin, LSD and

several other drugs, while alcoholism has been endemic for centuries. Our experience with several epidemics of PCP psychosis,

however, shows that widespread use of PCP in a community produces

manifestations which are not only different, but also more dangerous in some ways.

As noted earlier, our epidemic of PCP psychoses did not initially

seem related to drug abuse at all. Our community was experiencing

what appeared to be an epidemic of schizophrenia. This was unusual only because the rate of new cases of schizophrenia in a

given population does not fluctuate widely and because our community mental health center admits only patients who live in a

specific part of the city. Even with our present hindsight, we

cannot be certain about the exact time when patients with PCP

psychoses began appearing at the doors of our center. Until we

learned that those psychoses were drug-induced, these patients

were diagnosed and treated as schizophrenic.

Our experience indicates that although PCP abuse is spreading

to other parts of the country, its incidence, and particularly

that of the PCP psychosis, tends to be under-reported for a

number of reasons:

(1) The incidence of overdose, which is a common indicator of

drug abuse patterns in a community, tends to be lower for

PCP than the incidence of psychoses in areas where the drug

is smoked rather than taken internally.

(2) As we have noted, the presenting symptoms of the PCP psychosis

arc often indistinguishable from schizophrenia. This is compounded by the amnesia induced by PCP. Where it is possible

to perform admission interviews on these patients, they usually do not recall taking the drug. Unless family or friends

243
are aware of the patient's drug use, no history is obtained

and routine laboratory screens for drugs do not detect PCP.

Consequently, these patients are reported as cases of schizophrenia, a label which may follow them for the rest of their

lives.

(3) As Burns and others have reported (Burns et al. 1975), some

PCP intoxications and psychoses result in violent or accidental deaths. In the absence of a routine toxicologic

test for PCP, medical examiners may report such deaths as

accidents rather than as the consequences of drug use.

The only signs that PCP abuse is prevalent in a community may be

police seizures of the drug, an increase in violent and accidental

deaths, and an increase in the number of new cases of "schizophrenia" admitted to mental hospitals. Unless public awareness

of the dangers of PCP is raised, these statistics may never come

together.

Another dimension of the PCP problem is the connection between

the PCP psychosis and schizophrenia. The connection between

schizophrenia and phencyclidine psychosis appears to go well beyond the phenomenological similarities. As reported by Luby, one

of phencyclidine's unique qualities is not only to mimic schizophrenia, but also to reactivate schizophrenic psychoses. The

treatment of phencyclidine psychoses outlined in this paper is

also quite similar to that for extremely agitated schizophrenics.

Furthermore, our experience indicates that people whose sensitivity

to phencyclidine has been demonstrated by the development of a

psychosis will develop another psychosis upon reexposure to the

drug. Finally, there are some patients who have first experienced

phencyclidine psychoses and later have developed schizophrenia.

The PCP psychoses seen in our patients approached those reported

in chronic schizophrenics in terms of severity and duration: they

were far more severe than those reported in 'normals" in term of

both parameters. Yet none of the patients in our initial study

had experienced prior schizophrenic psychoses, and most had been

leading lives which demonstrated a fairly high level of social

integration.

One interpretation of this apparent paradox might be that our

patients literally do fall between the two groups reported in the

literature in some way: Those PCP users in the catchment area

with psychoses as brief as the ones experienced by "normal volunteers" would have improved before becoming inpatients and consequently would not have been admitted. All the hospitalized chronic

schizophrenics in the catchment area were already on the CMHC's

inpatient units and were therefore not exposed to the drug.

Our results support this interpretation, since they show a variation in the time required for recovery in our eleven patients

which nearly spans the extremes reported in the literature. The

patient with the briefest stay went through the three phases

250
described earlier in about three days. The longest-hospitalized

patient required about four weeks, and those in between tended to

be evenly distributed. Furthermore, those patients who later returned and were rediagnosed as schizophrenics were at the upper

end of the distribution in terms of the duration and severity of

their psychoses. Thus, our study patients might represent that

part of the population of the catchment area which is significantly

more sensitive to PCP than "normals" but not so sensitive as

chronic schizophrenics.

These findings suggest several further conclusions: First, they

support those studies cited earlier which linked schizophrenia

and sensitivity to PCP. Second, they suggest that sensitivity to

the drug varies with the individual. Third, they suggest that

this sensitivity, rather than being extreme for schizophrenics and

mild for "normals," covers a wide sprectrum, with chronic schizophrenics at one extreme, and "normals" at the other: the patients

studied here would therefore be distributed in between. Our

"schizophrenia epidemic" might therefore be interpreted as evidence

that the distinction between having or not having schizophrenia is

not clearcut; perhaps it implies that in a large population, a

graded continuum of "schizophrenia" exists between those who are

most "schizophrenic" and those who are least so.

Thus, our experience with phencyclidine psychoses not only supports

earlier finds that schizophrenics are highly sensitive to the

drug, but also suggests the existence of an individual sensitivity

to the drug, a sensitivity which is related to schizophrenia in

some way. The widespread use of phencyclidine in our catchment

area might even be viewed as a crude "screening test" for

"schizophrenicity." The ease with which phencyclidine may be

synthesized in large quantities on a clandestine bases raises the

possibility that this "screening test" may soon spread elsewhere.

Finally, because PCP was so well-studied in its days as a promising anesthetic, we can offer some other more speculative correlations: Domino's research on monkeys with chronically implanted

electrodes found that PCP had two major central effects which

correlated with behavior: an enhancement of neocortical activity,

and a nearly complete suppression of evoked potentials in the

amygdala (Domino 1964). Delgado (1971) has found that electrical

stimulation of this part of the limbic system in monkeys inhibits

rage and enhances placidity. The studies suggest that an explanation for the high incidence of violent and aggressive behavior

observed in our patients might include PCP's suppressant activity

on the amygdala.

Domino's work also suggests a neurophysiological mechanism which

might account for the persistence of our patients' psychoses long

after the drug was presumably metabolized: He found that PCP

selectively enhances the sensitivity of adrenergic and serotonergic

neurons to their neurotransmitters, and that this enhancement

persists long after the drug has been fully metabolized (Domino

1964). This explanation also supports recent studies implicating

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adrenergic and serotoninergic components of the limbic system in

the mechanism of schizophrenia.

If there is a solution to the problem of PCP abuse, that solution

is prevention. Practitioners must be alerted to the fact that

PCP is not just another hallucinogen, to be warned about in the

same breath as LSD. The public must be alerted to the fact that

PCP is far more dangerous to some individuals than the other

abused drugs. Medical examiners should consider toxicologic

analysis for PCP in all deaths resulting from drowings, falls

from high places, apparently avoidable accidents, and from attempts

to contain violently assaultive subjects. Psychiatric facilities

should investigate any sudden local increases in the incidence

of schizophrenia, and should routinely include PCP psychosis in

the differential diagnosis of all apparent schizophrenics in

whom the illness is of acute onset and characterized by violent

behavior, whether or not a history of drug abuse is obtained.

Policemen should be alerted to the unique dangers of dealing with

those individuals who have violent paranoid reactions to the

drug. And. finally, schizophrenic patients who have any leanings

towards drug experimentation should be warned that they are unusually sensitive to the adverse effects of PCP.

Further research is needed to determine whether there are more

effective treatment methods for the PCP psychosis than what has

been presented here. Research is also needed to document further

PCP's adverse effects, and the Drug Enforcement Administration

might consider whether this drug warrants reclassification under

Schedule I.

PCP use is spreading rapidly because of ignorance of its unpredictable adverse effects among potential users, and because of the

ease with which the drug is illicitly manufactured. It is important to increase awareness of PCP and its effects, as we might

well anticipate a nationwide epidemic, an epidemic which, as far

as we know, may exist even now.

REFERENCES

Bakker, C.B., and Amini, F.B. Observations on the psychotominetic

effects of Sernyl. Compr Psychi, 2:269-280, 1961.

Balster, R. and Chait, L. The behavioral pharmacology of phencyclidine. Clin Tox, 9:513-528, 1976.

Ban, T.A., Lohrenz, J.J., and Lehamann, H.E. Observations on

the action of Semyl--a new psychotropic drug. Can Psychiatr

J, 6:150-156, 1961.

Burns, R., Lerner, S., and Corrado, R. Phencyclidine - states of

acute intoxication and fatalities. West J Med, 123:345, 1975.

Chen, G., Ensor, C.R., Russell, D., and Bohner, B. The pharmacology of 1-(1-phenylcyclohexyl) piperidine HCL. J Pharm and

Exp Ther, 127:241-250, 1959.

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Davies, B.M. and Beech, H.R. The effect of 1-arylcyclohexylamine

(Sernyl) on twelve normal volunteers. J Mental Sci, 106:912-924,

1960.

Delgado, J.M. Physical Control of the Mind: Toward a psychocivilized Society. Scranton, PA.: Harper and Row, 1971.

Domino, E.F. Neurobiology of phencyclidine (Sernyl), a drug with

an unusual spectrum of pharmacological activity. Int Rev Neurobiol,

6:303-347, 1964.

Greifenstein, F.E., Devault, M., Yoshitake, J., and Gajewski, J.E.

A study of 1-Arylcyclohexylamine for anaesthesia. Anaesthes and

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Johnstone, M. The use of Sernyl in clinical anaesthesia. Der

Anaesthesist, 9:114-114, 1960

Luby, E.E., Cohen, B.D., Rosenbaum, G., Gottlieb, J.E., and Kelley,

R. Study of a new schizophrenomimetic drug--Sernyl. AMA Arch

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Luisada, P. The PCP psychosis: A hidden epidemic. Presented

at the VI World Congress of Psychiatry, Honolulu, HI., August

29, 1977.

Luisada, P. and Brown, B.I. Clinical Management of the phencyclidine psychosis. Clin Toxicology, 9:539-545, 1976.

Luisada, P. and Reddic, C. An epidemic of drug-induced "schizophrenia." Presented at the 128th annual meeting of the American

Psychiatric Association, Anaheim, CA., May 5, 1957.

Reed, A. and Kane, A.W. Phencyclidine (PCP): Another illicit

psychedelic drug. J Psychedelic Drugs, 5:8-12, 1972.

Rosenbaum, G., Cohen, B.D., Luby, E., Gottlieb, J, and Yelen, D.

Comparison of Sernyl with other drugs.

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Arch Gen Psychiat, 1:651-

The Washington Post, January 21, 1974.

The Washington Post, December 20, 1975.

AUTHOR

Paul V. Luisada, M.D.

Deputy Medical Director

Area D Community Mental Health Center

National Institute of Mental Health

Saint Elizabeths Hospital

Washington, D.C. 20032

253
Chapter 15

Long Term Treatment of

Adolescent PCP Abusers

Gerald G. DeAngelis, Ph.D., and Elliott Goldstein, M.A.

INTRODUCTION

The population described in this publication are residents in a

licensed, social rehabilitation facility, known as Pride House.

This 70 bed facility specializes in the treatment of adolescents

with mental health and substance abuse problems. Males and females between the ages of 14 and 22 years are accepted into the

program The mean age for the past two years has consistently

approximated 16.5 years.

Over the years Pride House has developed a reputation for offering services to "difficult to treat" adolescents. Basic problems

presented by these adolescents are as follows:

 Psychiatric illness such as depression, anxiety,

character disorders, suicidal ideation, and

schizophrenia.

Substance abuse: approximately 95 percent of the

client population are polydrug abusers who have

ingested many substances ranging from marihuana to

PCP and heroin. Some of these drugs have been ingested on a regular basis.

Criminal offenses including grand theft auto,

possession and dealing of drugs, pimping, prostituition, burglary, assault, running away, et

cetera.

Most clients are referred to Pride House through the Probation

and Social Welfare offices of Los Angeles County by a placement

order from the courts. Clients are also referred from the majority of surrounding counties. In addition, there are a number of

private referrals from hospitals, practicing psychiatrists, and

psychologists in the area, as well as from local families. Most

of these clients have had social-psychological profiles done by

the referring institution's psychologist or psychiatrist. These

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profiles reveal that the majority come from broken homes. Approximately 78 percent of the total population come from single parent

families: 45 percent come from divorced families; in the other

33 percent a parent was lost through death. The remaining 22 percent of the clients come from intact families.

Approximately 29 percent of the total population have been involved

in aberrant family sexual behavior, primarily in the form of incest.

This incestuous behavior is far more prevalent among the females

than the males. Approximately 60 percent of females who have entered the program during the last six months report involvement in

incestuous relationships with either parents, grandparents, or

other members of the immediate family. To date, we have validated

23 percent of these reported incidents. The process of validation

is ongoing and will continue for some time. Verification is difficult for clients who have left the program.

The majority of adolescents served by this program have been physically or emotionally battered and would qualify as "battered"

children. Most are emotionally and educationally handicapped and

have little opportunity to experience normal maturation and growth.

TREATMENT: GENERAL PROGRAM SUMMARY

Treatment of drug abusers in the context of an adolescent rehabilitation center has been specifically defined at Pride House. An

initial prospect interview is done with each client. After this

pre-intake interview is canpleted, the client's suitability for

the program is evaluated. If the client is deemed suitable for

Pride House, a lengthy diagnostic intake process is initiated.

During the initial interview, a detailed personal, psychiatric,

drug, family and social history is taken. An initial treatment plan

is then formulated from these intake profiles. The treatment plan

discusses existing relationships between the presenting symptoms and

underlying psychopathology, and choice of drugs and the extent of

drug use. This is especially important when the staff feels the

client has chosen drugs as the major palliative of internal and/or

external emotional conflicts. A basic assumption is that most

adolescents coming to us are troubled and have chosen the use of

drugs as the major vehicle to resolve these conflicts.

Substance abuse is seldom discussed during the course of therapy.

In fact, the discussion of drug abuse during the therapeutic process is generally proscribed as antitherapeutic and distracting.

This parallels our approach in working with all special problem

areas. For instance, with homosexual clients the discussion of

sexual activity is usually proscribed except in specific therapy

sessions dealing with the sexuality of the client (Wellisch, De

Angelis, and Paternite 1978). Our research has shown that youngsters will usually use their major behavior problem as the discussion focus in order to prevent the therapist from dealing with

the underlying issues causal to their abnormal behavior.

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Long term treatment includes a regimen of individual and group

therapy, as well as family therapy. There is an educational program at Pride House which includes remedial mathematics, reading,

tutoring and study for the California Proficiency and GED examinations. Pride House provides a complete and intense recreational

program for the male population. Currently, the recreation program

for females is not as sophisticated. The average number of hours

of therapy per client each month is 36. Furthermore, 6.5 recreational sessions per resident per month are provided. In addition,

40-60 hours of teaching and tutoring activities per resident per

month are available, excluding study time. On the whole, the milieu

is totally supportive with little, if any, classical confrontation

used. Generally, therapeutic approaches include Gestalt, Transactional Analysis, psychotherapy, and other supportive, humanistic,

therapeutic regimes.

METHODOLGY

Initial investigation into the use of PCP in clients who entered

Pride House during the last 6 months (from September 1977 through

February 1978) identified approximately 50 percent of the population as either chronic or occasional PCP users. Chronic users were

defined as those using at least 3-4 times a week and occasional

users were identified as those using PCP once a week or less. This

definition may seem arbitrary considering the powerful effects of

PCP. However, our definition is similar to chronic PCP use as described by Fauman and Fauman (1978) who report use ranging from

2.5-5.8 days per week. This paper will report the results of our

work with these PCP users/abusers.

Prospect and intake evaluation forms for 87 clients were analyzed

in order to identify all PCP users in a 6-month cohort. Forty-five

(45) clients representing 52 percent of the study cohort were

identified as users of PCP. Clinical records of these 45 individuals were further analyzed to ascertain behavioral, familial, sexual,

psychological, and other characteristics. The data collection form

used is shown as appendix I.

After the data were collected, the information was sent to the

Health Care Delivery Service Evaluation Research Unit. There, the

data were validated and tallied, tabulated and analyzed as percentage differences. Results are provided in tables 1 through 7 and are

discussed below.

RESULTS

Table 1 compares the demographic variables for (1) the occasional

PCP user, (2) the chronic PCP user, and (3) the general Pride House

population. In terms of sex, approximately fifty-eight percent

(58.4 percent) of the general population are males as compared to

78.3 percent and 31.8 percent of the occasional and chronic PCP

users, respectively. Females represent the majority of chronic PCP

abusers (68.2 percent) while they are a minority of the general

population (41.6 percent).

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Only slight racial differences are seen a percentages of

Caucasian, black and Hispanic chronic and occasional PCP users.

However, there are greater percentages of Caucasians in the two

groups of PCP users thah in the general Pride House population.

Eighty-seven percent of the occasional users and 81.8 percent of

the chronic users are Caucasians, as compared to 64.7 percent of

the general population who were Caucasians.

Racial differences for degree of PCP use proved to be statistically

insignificant (X2 = 0.28; d.f. = 2; .90 < p < .80). However, the

observed sex difference in PCP use proved to be statistically significant (X2 = 9.82: d.f. = 1; p < .01). Females represented a

greater proportion than males of the chronic PCP users. Mean age

is approximately the same for the two PCP users groups and the

general population. Only slight variations are observed in the

age ranges for the three groups.

Table 2 describes frequency of PCP use for the sample. The largest

proportion of occasional users ingested PCP once per week. Usage

ranging from twice to several times month accounted for 34.8 percent of the occasional users. Approximately nine percent of the

occasional users ingested PCP only once per month.

The majority of chronic users (61.9 percent) ingested PCP on a daily

basis. About thirty-eight percent used PCP three to four times per

week.

Equally significant is the extremely high daily use of drugs other

than PCP in both groups. Approximately 86 percent and 91 percent

of both the occasional and chronic use groups, respectively, ingested a variety of drugs on a daily basis. Therefore, it is safe

to assume that both groups are chronic drug abusers, with one group

supplementing its other daily drug usewithheavy PCP usage.

While occasional and chronic users show about the same percentages

displaying depressive symptomatologies (table 3), they differ quite

drastically in other clinically observed behaviors. Comparisons in

terms of anxiety show that 44.8 percent of the occasional users

exhibited anxiety symptoms as compared to only 7.7 percent of the

chronic users. On the other hand, 30.7 percent of the chronic

users were described as having character disorders as compared to

3.4 percent of the occasional users. Interestingly, while clinical

management of chronic PCP users is similar to that of schizophrenic

adolescents, neither the occasional nor the chronic users were

diagnosed as being schizophrenic. Accurate diagnosis of this illness is even more difficult in a drug abusing population. In the

past, Pride House has treated adolescents who have been diagnosed

as schizophrenic. None of the present cohort displayed symptoms

or behaviors which would result in such a diagnosis.

In other work with this population, we have uncovered relatively

large numbers of cases wherein clients have been sexually molested

or violated (incest). Approximately 32 percent of chronic PCP

users report sexual molestation and/or incest. In the occasional

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FREQUENCY OF USE
TABLE 3

PSYCHIATRIC DIAGNOSES
PCP use group this was universally absent. Chi square (x2) was

calculated and the differences between the two groups were found

to be significant (X2 = 8.67; d.f. = 1; p < .01).

We investigated the behavior of PCP abusers within the treatment

milieu. This was important in light of the common belief that PCP

abusers are hostile and disruptive. Table 4 verifies this belief

to some extent. Surprisingly, the occasional users of PCP acted

out in an angry or belligerent manner far more often than the

chronic users. Sexual acting out was much more prevalent for the

chronic PCP user (30.8 percent) than for the occasional PCP users

(12 percent). Hostility was displayed at about the same level in

both groups, but the chronic users reported themselves as delusional, while occasional users did not (X2 = 7.46; d.f. = 3; < .10

p < .05).

Table 5 shows that chronic PCP users were more likely to commit

rule infractions based on sexual conduct(49.9 percent) than occasional PCP users (39.0 percent). On the other hand, occasional

PCP users were more likely to commit drug-taking infractions (73.7

percent) or violent acts (12.9 percent) than chronic users. Chronic

users violated drug rules 68.2 percent of the time and commited

acts of violence only 4.5 percent of the time. It should be noted

that violent behavior is defined as extreme verbal abuse as well as

such activities as destruction of property and vandalism. No violent acts against persons have been recorded in either group.

For both occasional and chronic users, drug-taking is the most

frequently occuring rule infraction. Acts of violence are the

least frequently occurring infraction.

Table 6 verifies the data presented in the previous table. When

all rule infractions are totalled it can be seen that drug-taking

predominates in both the occasional and chronic use groups. Sexual

misbehavior is the second most frequent rule infraction, and violent behavior is the least frequent.

We also investigated length of stay or program retention rate of

chronic, occasional and non PCP-using residents. Table 7 demonstrates that chronic PCP abusers remain in the program longer,on

the average, than the other groups. No statistically significant

difference was found when length of stay for occasional users was

compared to chronic users. On the other hand, statistical significance was achieved when length of stay of all PCP users was compared

to an equal nunber of non PCP users (t = 2.29; d.f. - 74; p < .05).

T-tests were computed after excluding members of both comparison

groups whose length of stay was far beyond the standard deviations

(n = 39 PCP users; n = 37 non PCP users). Nevertheless, it should

be noted when all data for length of stay were included in

the computations, the computed t-value was 1.98.

DISCUSSION

It is difficult to compare our results with published reports of

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TABLE 4

TYPE OF BEHAVIOR DISPLAYED
TABLE 5

FREQUENCY OF ABERRANT BEHAVIORS
TABLE 6

OCCURRENCE OF PROGRAM RULE INFRACTIONS
TABLE 7

LENGTH OF STAY COMPARISON

(a) t-tests between all PCP vs. non PCP users done initially included extremes of stay. Corrected

t-tests were performed eliminating 3 lower end 2,3,3,6,13,13 and 2 upper end 225,226,276,316 lengths

of stay for each group. Both ends far exceeded standard deviations and high end represents lengths

of stay longer than present study period. When all of these days are included the t-test was as

follows: t=98; d.f.=84; 0.10<p<0.05; a t of 1.99 would have been significant at the 0.05 level.
PCP use. Most of the previous studies used "ever used" and "never

used" categories, whereas we chose "occasional" and "chronic" use

categories. Lerner and Burns (1978) and Fauman and Fauman (1978)

reported that males constituted the majority of their samples

(68.7 percent and 80.0 percent respectively). In our study this is

true only of the occasional user. Chronic use was much more prevalent for females.

In terms of race, the Faumans report the highest use for blacks.

Lerner found that Caucasians predominated in his work. Our findings parallel Lerner's, since Caucasians predominate in our population. This my be due to our treatment program's physical location

in a suburb of Los Angeles that is predominantly Caucasian. Most

referrals to our program over the last four years have been Caucasian youth. No significant age differences exist between the

population we have studied and those studied by Lerner and Burns

and the Faumans.

Approximately fifty-two percent (51.7 percent) of our entire sample

cohort (87) reported use of PCP. The Faumans report 66.6 percent

of the treatment population which they studied used PCP, while

Lerner and Burns report 31.8 percent use in their study. Our

similarity to the Faumans' results may be due to similar residential

treatment program milieus, whereas Lerner and Burns'data are taken

from DAWN and the National Youth Polydrug study.

Approximately forty-nine percent (48.8 percent) of out study cohort

who used PCP were classified as chronic users. Lerner and Burns

(1978) reported 35.6 percent of PCP users in their study had used

PCP with the same frequency.

Both the chronic and occasional users reported high usage of drugs

other than PCP. This is not surprising when the following are considered: (1) These clients are in a social rehabilitation program

known to treat all types of drug abuse, and (2) polydrug combination with the increased psychopathology observed in the polydrug

abuser (Bienvenuto and Bourne 1975; Raynes, Patch, and Cohen 1975)

my help to explain the high percentage of reported anxiety, depression and character disorders found in our study population.

These clients may be ingesting drugs in an effort to reduce the

psychic and emtional distress which they are experiencing.

Of foremost importance is that we have diagnosed little or no

schizophrenia in this population. Perhaps this is due to our

unwillingness to label a child as schizophrenic simply because his

or her behavior does hot fit the norm. This may account for the

little difficulty we have had in working with PCP-abusing youth.

A significantly larger proportion of chronic PCP abusers in our

sample report sexual molestation and/or incest. We have had no

explanation for this other than to offer the possibility that. PCP

provides a drug-induced respite from the emotional pain and anger

suffered by most of our adolescent clients who have had these experiences. Perhaps PCP intoxication controls this rage at some

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stage of the intoxication. It may be that as the drug effects

diminish, the suppressed anger may surface in the form of overt

hostility, belligerence and verbal abuse which we witness. The

long term acting out observed with clients in residential treatment settings may represent an extended and necessary catharsis

which offers an excellent opportunity for therapeutic intervention.

Although differences were seen in the types of behavior displayed

by PCP users, statistical differences were not achieved when the

groups were compared. Both groups act out; the type of acting out

may be influenced by drug states or therapeutic milieu. We have

no way to determine this at the present time.

The fact that chronic PCP abusers stay in treatment longer than

non PCP or occasional PCP users, is probably the most important

practical finding of this study. If one assumes that chronic users

are more in need of treatment than other types of drug users,then

length of stay is an important therapeutic variable, since therapeutic intervention takes time to have effect. Whether or not

chronic abusers stay longer because they are more troubled and

realize they need help, or whether our therapeutic interventions

are effective with this group is difficult to detemine. Perhaps

it is safe to say that were our therapeutic endeavors not effective,

the more troubled PCP abusers would leave. The increased length

of stay may indicate that whatever conflict resolutions were provided by PCP use are provided by the treatment staff. This

will be discussed in more detail below.

TREATMENT CONSIDERATIONS

Occasional users of PCP having no history of long term effects are

treated similarly to all other clients in the program admitted for

substance abuse treatment. In effect, staff and client expectations

are the same for the occasional PCP abuser as for the general population. With the exepction noted below, all clients participate

in all normal therapeutic activities, taking responsibility in the

program, attend school, et cetera. Therapeutic responses are dictated by the client's present behavior, combined with our knowledge

and understanding of the child's family and personal history. The

client's abuse of PCP at one point in his/her life is considered

fairly irrelevant within the context of the milieu.

As shown in tables 1, 3, 4, 5, and 6, clinical differences exist

in psychiatric diagnoses, acting out behaviors and program rule

infractions. These differences do not necessarily mean that clinical interventions in the PCP-using group need be dramatically different than those in non PCP-using groups of adolescents which we

treat. Anxiety and depression, commonly seen in our general population, are treated similarly to the same states seen in PCP abusers.

Program clinicians target their efforts at the behavior and symptoms

rather than on a substance(PCP)which may or may not be the cause

of these reactions. As shown in table 4, occasional users are often

angry and/or belligerent. Clinically this is handled as is any

angry confrontation with a client. However, in the PCP population

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staff is more aware of the frequency of an angry reaction and is

prepared for this response. It is important that staff anticipate

these angry outbursts in order to take control and demonstrate an

understanding of the situation.

Both the occasional and chronic PCP users have little difficulty

integrating into the general population and responding to treatment. As mentioned, PCP users stay in treatment longer than nonusers. (Certain clinical differences are observed between chronic

PCP users, occasional users, and the general population. The

treatment of chronic PCP abusers coming into Pride House with histories of adverse drug reactions is somewhat different from the

treatment of the general population. In many ways, treament simulates our work with schizophrenic and other very troubled youngsters.

Basically, PCP abusers who enter the program and are past the

acute intoxication phase are treated as follows:

Minimal confrontation or hostility-provoking behavior cm the part of staff or other clients is

the rule.

Particular care is taken to provide PCP users a

non-threatening environment in which they can

begin to feel comfortable.

Minimal involvemnt in specific therapeutic intervention is expected immediately.

Many PCP users display flattened affect, depression, agitation,

hostility and belligerence. They are usually unable to cope with

the demands and expectations of a structured, intensive therapy

regimen. With these clients, staff expectations are drastically

lower. This means that the PCP abuser is not expected to participate extensively in either group or individual therapy, school or

recreation programs. It is understood that he/she may be belligerent and refractory to treatment. Hostility, agitation, and depression, as well as memory loss and motor impairment are considered part of the pathology to be treated, rather than major

impeding problem. A program of support and reinforcement is

provided both within the milieu and in therapy.

Drug therapy, either with the administration of tricyclic antidepressants or tricyclic and other antipsychotic agents is minimal.

Use of these agents has not been shown to be effective and caution

has been urged in their application in treating PCP abusing clients

(Varippa 1977).

Certain acting out behavior is tolerated in these clients, more so

than in clients having no history of PCP abuse. Generally, acting

out behavior takes the form of extreme verbal abuse. We assume

that these outbursts of anger and hostility will occur and we work

with them, rather than prohibit the behavior and thereby exacerbate

the situation.

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Finally, another aspect of dealing with PCP abusers is a remedial

education and tutoring program. It is therapeutic to help a

young client understand that any existing memory loss and/or motor

impairment is most likely a drug related event and will usually

reverse itself over a period of time. At this point, careful

tutoring and handling by the education staff are very important.

In this way, the client is actually engaged in a therapeutic process (school), yet not expected to do "therapy." Individual attention provided by the educational tutors, coupled with the educational testing and the learning diagnostician's work, give the

client a sense that he/she will soon be able to function normally.

ACKNOWLEDGMENTS

The authors would like to thank V.Tokita and D.Marple for their

technical assistance.

REFERENCES

Bienvenuto, J., and Bourne, P. The Federal Polydrug Abuse Project:

Initial Report. Journal of Psychedelic Drugs, VII (2), 1975.

Fauman, M.A. and Fauman, B.J. The Psychiatric Aspects of Chronic

Phencyclidine (PCP) Use: A Study of Chronic Phencyclidine Users.

Paper presented at the NIDA Conference on Phencyclidine, Asilomar,

California, February 27-28, 1978.

Lerner, S.E. and Burns, R.S. Phencyclidine Use Among Youth. Paper

presented at NIDA Conference on Phencyclidine, Asilomar, California,

February 27-28, 1978.

Raynes, A.E., Patch, V.D. and Cohen, M. Canparison of opiate and

polydrug abusers in treatment. Journal of Psychedelic Drugs,

VII (2), 1975.

Varipapa, B.J. PCP treatment. Clinical Toxicology, 10 (3), 1977.

Wellisch, D., De Angelis, G.G., and Paternite, C. Therapy of

homosexual adolescent drug abusers in a residential setting: A

controlled study. In Press, 1978.

AUTHORS

Gerald G. De Angelis, Ph.D., and Elliot Goldstein, M.A., Health

Care Delivery Service, Inc., 11340 West Olympic Boulevard,

Los Angeles, California, 90064.

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APPENDIX I
APPENDIX I (continued)
Chapter 16

Phencyclidine, Criminal Behavior, and the

Defense of Diminished Capacity

Ronald K. Siegel, Ph.D.

“The cause of the world-wide consumption of hashish, opium, wine,

and tobacco,” wrote Leo Tolstoy (1890), “lies not in the taste,

nor in any pleasure, recreation, or mirth they afford, but

simply in man’s need to hide from himself the demands of conscience.” Tolstoy argued that men “stupefy” themselves with drugs

that make them commit actions contrary to conscience. He cited

robbery, rape, and murder as examples.

Modern courtrooms in the United States are becoming increasingly

plagued by examples of such drug related acts, acts which would

have surely outraged Tolstoy’s 19th Century moralism and supported his notion that man is an “animal being.” The magical elixir

which is usually credited with this transformation of man from

a “spiritual being” to an “animal being” is phencyclidine (PCP).

Perhaps more than any other drug, with the exception of alcohol,

PCP is becoming increasingly conspicuous in both criminal behavior and in the criminal defense of diminished capacity. Diminished capacity itself is a “defense in which criminal culpability is gauged upon various mental states. If the defense is

proven, it can reduce the degree of the crime or even result in

an acquittal” (Schwab 1976).

A young man smokes some PCP and proceeds to rob a gas station

at gunpoint. A juvenile smokes PCP and rapes his baby sister.

A witness to a fatal stabbing is admittedly intoxicated with PCP

but claims to remember clearly all the events. A witness to

another murder claims to be intoxicated with PCP and amnesic

for most of that time. A police officer encounters a young man

who may have ingested an analog of PCP. The man, naked and unarmed, reportedly becomes combative and assaultive and is shot

to death by the officer. Two lovers are smoking PCP alone in

their bedroom. Within a few minutes one is bleeding to death

from a knife wound which may or may not have been self-inflicted.

A middle-aged woman takes some cocaine which has been adulterated

with PCP and tries to rob a bank armed only with a broom which

she manipulates as if it were a gun. In these and many similar

cases the law enforcement and judicial systems are turning more

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and more to expert witnesses in order to help clarify the effects

of PCP on behavior. The process is rapidly defining a new field:

forensic psychopharmacology. Forensic psychopharmacology can be

considered the application of the study of drugs and behavior to

legal issues. The present chapter attempts to discuss aspects

of PCP-induced behavior which can be applied to legal issues.

DRUGS AS SCAPEGOATS AND THE ORIGINS OF DIMINISHED CAPACITY

Psychopharmacology is essentially the study of drugs and behavior.

The underlying lay assumption is that drugs inevitably affect

behavior. A corollary is that abnormalities in behavior often

may be blamed on drugs. In his critique of the drug abuse field,

psychiatrist Thomas Szasz (1974) noted that this assumption has

led to the persecution (and prosecution) of drugs, drug users,

and drug dealers throughout history. Indeed, even in their linguistic roots drugs have been associated with scapegoats. The

pharmakos in ancient Greece was the human who was sacrificed as

a scapegoat in primitive ceremonies. Later, when human sacrifice was abandoned in Greece, the term pharmakoi came to mean

“human medicine” and was applied to poisons and drugs. The

classic association of drug-induced altered states of consciousness

and diminished capacity was most dramatically portrayed throughout the tragedies of fifth century Greek playwrights. The association of drugs with scapegoats has been with us ever since those

times.

In Euripides’ The Bacchae, Agave, the bacchante queen, kills her

son, Pentheus,in an altered state which was probably a combination of alcohol intoxication and religious hysteria (Emboden 1977). Agave believes she has killed a lion as a scapegoat,

and the murder itself is perhaps one of the most gruesome in

the annals of psychopharmacology, rivaling even the TateLaBianca murders of the present century:

But she was foaming at the mouth, and her crazed eyes

rolling with frenzy. She was mad, stark mad,

possessed by Bacchus. Ignoring his cries of pity,

she seized his left arm at the wrist; then, planting

her foot upon his chest, she pulled, wrenching away

the arm at the shoulder--not by her own strength,

for the god had put inhuman power in her hands.

Ino, meanwhile, on the other side, was scratching off

his flesh. Then Autonoë and the whole horde

of Bacchae swarmed upon him. Shouts everywhere,

he screamed with what little breath was left,

they shrieking in triumph. One tore off an arm,

another a foot still warm in its shoe. His ribs

were clawed clean of flesh and every hand

was smeared with blood as they played ball with scraps

of Pentheus’ body (Euripides, p.204).

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Emerging from that intoxicated state, Agave realizes that what

she has killed is not a lion but her son. Agave confused the

reality in which she confronted a lion with the reality in

which she confronted her son. Crucial to an understanding of

the lay are the Greek concepts of sophia (meaning wisdom,

skill , expertise) and amathia (meaning uncontrolled violence).

Specifically, sophia implies a firm awareness of one’s own

actions, judgements, and morals. Conversely, amathia means an

uncontrollable ignorance of one’s actions and capacities,

someone prone to violence, harshness, and brutality. In its

essence, Euripides’ play tries the case on the merits of diminished capacity (amathia) versus premeditation and intent

(sophia). A modern day defense attorney might argue that Agave

was diminished in capacity as a result of both the alcohol and

religious intoxication. A prosecutor might successfully argue

(and win a first degree murder conviction) that the killing was

motivated, since Pentheus bitterly opposed Agave’s involvement

in Dionysian rites and Agave knew it all along. However, the

jury at the time--the Greek chorus in the play--finds Pentheus

guilty of amathia because he want only and violently refused to

accept the necessity of the Dionysian rites (wine, dance, and

religious ecstasy), thus committing an immoral act against a

god Accordingly, Agave is declared sophia in supporting the

sacrificial rites. While the judge, Dionysus himself (who

could be challenged in a modern courtroom for obvious prejudice),

finds the murder justified, he banishes Agave from the city

forever. The verdict of the play is probably the equivalent of

voluntary manslaughter with absence of malice due to diminished

capacity. Thus concluded history’s first diminished capacity

trial.

INTOXICATION AND BEHAVIOR

The case discussed above is important in emphasizing the numerous

variables that can influence drug-induced intoxication and behavior. Although the definition of the word intoxication (which

comes from the Latin intoxicatio, meaning poisoning or inebriation) is far from precise, one that is generally accepted in

pharmacology and medicine is “the abnormal state induced by a

chemical agent....excitement or exhilaration beyond self-control.”

Pollack (1976) defines such intoxication for legal purposes as:

a temporary state of mental impairment due to drugs

or alcohol in which the alcohol or drug influence

creates a mental impairment that makes the person unable to form the specific intent for the crime charged

against him, although the defendant committed an illegal

act at the time.... Intoxication is thus a clinical

condition that is defined by clinical signs and symptoms, ranging from mild, moderate, to severe, with

coma and eventual death (p. 258).

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This clinical condition can be modified by a wide variety of

variables, including both drug variables and user variables.

Among the important drug variables are: preparation and purity,

dose, route of administration, rate of ingestion of the drug,

rate of absorption, site of action, rate of metabolism, rate

of elimination, mechanism of action? and others. Among the

important user variables are: individual variability, age, sex,

weight, general state of health, medical history, drug history,

behavioral history, presence of other psychoactive agents

(prescription and nonprescription drugs), personality, psychological set (attitudes, expectations, etc.), setting (physical

environment and psychological state of others present), and

others. The more specific this information is, the more precise

can be the description of drug induced behaviors and the

stronger can be the opinion of the expert witness in court.

While a full understanding of these interactions is presently

restricted by limited knowledge about phencyclidine, the presence

of such a myriad of variables should temper a desire to simplify

behavior with labels such as sophia, amathia, “diminished capacity," “criminal responsibility,” “legal insanity,” “mental

incompetency ,” “unconscious ,” “psychotic ," “loaded,” “dusted,”

“toasted,” “stoned,” “wasted,” or even “high.”

PHENCYCLIDINE AND BEHAVIOR

The nature of phencyclidine-induced effects on behavior are discussed in several sections elsewhere in this volume. The nature

and phenomenology of phencyclidine intoxication are also described

more fully in another chapter (see “Phencyclidine and Ketamine

Intoxication: A Study of Pour Populations of Recreational Users,"

by Siegel, this volume). Only those behaviors which are characteristic of intoxication for purposes of diminished capacity

defenses or for purposes of understanding criminal behavior are

discussed here.

While phencyclidine remains medically classified as an anesthetic

agent, it is well known that intoxication with the drug can be

marked by excitatory, sedative, hallucinatory, catatonic, and

even seizure behaviors. These apparently paradoxical reactions

have prompted numerous investigators to re-examine the effects

of phencyclidine on the brain and behavior. In an important

series of preclinical studies with animals, Winters and his coworkers (e.g., Winters et al. 1967) have demonstrated that there

is a progression of effects following increasing doses and these

differ considerably from the modes of action of most anesthetics

but compare more closely with most hallucinogens. like LSD. This

progression forms a continuum ranging from an awake state, to

a hyperactive aroused state, to a state of inappropriate movements, to a state of unresponsive behavior, to generalized seizures, and to death. In animal studies with cats these states

are marked by changes in both behavior and electroencephalograms

(EEGS). The progression is described in the following way:

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The initial effects of administration of phencyclidine consisted of cortical desynchronization and development of hippocampal theta waves.

After 5 to 6 minutes, intermittent and then continuous hypersynchronous bursts appeared accompanied by inappropriate movements of the

head. Within 15 minutes an increase of amplitude and a decrease of frequency of the hypersynchrony, separated by short periods of desynchronization, were observed. At this time the

animal (cat) was crouched, unresponsive to

stimulations, had a fixed gaze, pupillary

dilation, salivation and increased muscle tone.

Desynchronization became more prominent and

finally a generalized high frequency high voltage seizure pattern appeared which was accompanied initially by limb twitching, then generalized convulsions (Winters et al., 1967, p. 75) .

In man, there are four basic types of behavioral responses to

these excitatory states of the central nervous system. Initially the user becomes excited in terms of motor activity and

this is usually accompanied by mood elevation. Secondly, as

excitation increases, the mood becomes euphoric but the motor

behavior becomes ataxic. Thirdly, further excitation produces

bizarre and inappropriate motor movements coupled with subjective reports of hallucinatory intoxication. Fourthly, a state

of epileptoid activity is reached which is marked by myocionic

jerks and generalized seizures. At this point the user may

appear cataleptic and subsequently report amnesia for the

experiences.

Typically, when PCP is smoked, the onset of symptoms appear within 2 to 5 minutes (Burns and Lerner 1976). These authors also

report that a peak, plateau, or “high” period ensues for 15 to

30 minutes followed by a “loaded” period of 4 to 6 hours. Recovery time to normal behavior may take from 24 to 72 hours or

longer. Indeed, some cases may require as long as 15 days for

behavior to become alert, oriented and normal. During such intoxications, PCP can be detected in blood or urine but detected

levels are not necessarily associated with specific behavioral

states (Reynolds 1976). Burns and Lerner (1976) and Siegel

(this volume) offer numerous clinical features of both the acute

confusional state or delirium (low to moderate doses) and the

state of stupor or coma (high doses). Some of these features

are discussed in the sections which follow.

CLINICAL ENCOUNTERS WITH INTOXICATED INDIVIDUALS

Typically, the vital signs of the PCP-intoxicated person would

indicate normal or slightly increased respiratory rate, increased blood pressure, increased pulse, and normal or slightly increased temperature. In terms of the motor system, the gait

276
may be grossly ataxic and the person may be unable to stand or

walk properly, perhaps due to increased muscle tone and rigidity.

The body movements may appear restless, repetitive, and often

facial grimacing is observed. High doses can produce “purposeless movements,” muscle tremors and twitching, and generalized

motor seizures which are unpredictable in frequency or duration.

Other features include: repeated episodes of vomiting (produced by the central action of the drug); increased salivation,

tearing, and perspiration; and increased discharge of mucus

from the nose, mouth, and throat.

With low doses or during early stages of high dose intoxication,

the person would initially appear responsive, awake, and capable of responding to simple yes/no questions. Speech, however,

is commonly slurred (dysarthria). As intoxication progresses

through the continuum of excitation, verbal responses to yes/no

questions may be replaced by simple nodding or facial gestures.

This usually results from increased slurring which progresses to

stuttering and extreme difficulty in speaking properly. The

user may simply “give up” trying to verbalize, but this does

not necessarily imply attentional dysfunction. Indeed, sensation is heightened at this point, and the user may have increased

sensitivity to visual and auditory stimuli. Conversely, some

individuals may appear more talkative and communicative, but

this is rare. Individuals are usually disoriented in both time

and space and consequently may appear confused and even fearful,

especially if environmental stimuli are overly intrusive or

intense.

However, in deprived environments, such as dark and quiet rooms,

these clinical features may be absent. Since the brain is in a

state of hyperexcitability, it is not surprising to find that the

user will be unable to sleep or rest during acute intoxication.

The eyes remain open in low dose conditions (“stare” appearance)

and sometimes the upper eyelids droop due to the sympathetic

innervation induced by PCP. High doses may cause the eyes to

close but the user is still clinically awake, although s/he may

not respond to stimuli. Examination of the eyes may reveal

additional findings. Low doses have been characterized by an

inability to fixate, and the eyes may appear to gaze independently at different points. Attempts to control and fixate the

vision may result in involuntary, abrupt, and rapid movements

or jerks of both eyes. High doses simply exaggerate these symptoms which have been described as “roving eye movements” and

“doll’s eye movements.” In both high and low dose intoxications,

intermittent horizontal and vertical nystagmus as well as a decreased or absent corneal reflex have been noted.

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POLICE ENCOUNTERS WITH INTOXICATED INDIVIDUALS

When encountering PCP-intoxicated individuals, law enforcement

officials frequently observe some of these characteristic

clinical features. Specifically, speech is usually described

as slurred, the gait is unsteady, and the eyes glassy, staring,

or blank. Consider the followed edited excerpts from the reports of arresting officers:

Subject’s speech was slurred and at times subject

was unable to talk. Subject’s reactions were very

slow. In officer’s opinion the subject was under

the influence of a drug.

He was oblivious to all of the occurrences around

him, and walked about in a dazed condition. It was

the arresting officer’s opinion that the minor was

under the influence of a hallucinogenic drug,

possibly that of PCP.

Suspect looked in officer’s direction and immediately

tensed up. He stopped and his anns went stiff. As

officer exited his vehicle and approached suspect,

officer noted his breathing to be extremely heavy.

The suspect’s eyes bulged and he began to lick his

lips as he looked about numerous directions.

Of course, such observations alone, while helpful to the forensic

psychopharmacologist, may not indicate intoxication per se.

Indeed, arresting officers are frequently misinformed as to the

nature of drug-behavior interactions, and there is admittedly

a paucity of police knowledge concerning PCP use itself (Overend

1977). One police officer told the author that “the smell of a

minty breath” was characteristic of his encounters with PCP users.

While PCP is frequently smoked on mint leaves, without observation of other clinical features of intoxication, smell alone is

insufficient to warrant the presumption of PCP use. Other

police officers are beginning to attribute any bizarre behavior,

even some motor vehicle violations, to PCP intoxication.

Reynolds (1976) reports that in nine such cases, seven suspects

failed field sobriety tests, while the remaining two individuals

were judged incapable of even attempting tests.

Police encounters with PCP-intoxicated individuals are frequently associated with violent, assaultive, combative, suicidal, and

even homicidal behaviors, In most such cases, the intoxicated

individual is hyperexcitable, hypersensitive, disoriented, and

confused. Therefore, violent and aggressive reactions can be

triggered in these individuals by common police practices including: interrogation, detainment, physical contact, restraining holds, handcuffing, and general arrest procedures. Even

seemingly mild stimuli, such as shining a flashlight in a suspect’s eyes, may trigger aggressive behavior. Aggression induced by PCP may take the form of fear, flight, or fight reac278
tions. The nature of the reaction can be influenced by the

police officer’s own behavior and approach to the individual.

Mild verbal behaviors and minimal physical contact are usually

indicated (see “Clinical Management of the Phencyclidine Psychosis;’ by Luisada and Brown 1976). Nonetheless, violent encounters occur frequently. Consider the following edited excerpt from an arresting officer’s report:

The suspect vehicle driver exited the vehicle and

attempted to flee. He stopped abruptly and stared

at the arresting officers who were approaching on

foot. Suspect ignored the arresting officers’ demands to lay on the ground. Arresting officers

forced him to the ground and attempted to handcuff

him. Suspect displayed a phenomenal strength and said

absolutely nothing. Sgt. C. and Officer R. assisted

the arresting officers in subduing the suspect,

which took approximately 1 1/2 to 2 minutes. During

that time, the suspect was struck several times on

the right elbow and arm in attempt to force same behind him for handcuffing. Such striking had no effect

at all on the suspect’s resistance. Officer R.

finally used a carotid choke hold to render the suspect unconscious.

Not all aggression is emitted by the intoxicated individuals.

Unaccustomed to the often bizarre and inappropriate behavior of

phencyclidine users, police officers occasionally react with cons iderable force. Arrest techniques for suspects involve an “escalation process” of control. Techniques range from "no contact”

with a cooperating suspect to “deadly force” for use in situations of life-endangering attack. Under certain circumstances

where the suspect becomes violent, unconsciousness-rendering

holds are considered necessary. These holds include the "bar

arm” hold (forearm across the front neck) and the “carotid

hold” (pressure on carotid artery). Durning the process of escalating force, the police officer depends, to some extent, on

the reactions of suspects to force or pain (threatened or actual)

in order to gauge appropriate levels of force. The PCP intoxicated suspect is often analgesic, feels no pain, and thus deprives the officer of much of the deterrent value of his force.

In addition, unconsciousness-rendering holds on PCP-intoxicated

individuals may complicate the respiratory difficulties seen in

cases of toxic overdose. Contact force with police batons or

other weapons runs the risk of provoking hyperexcitability and

even triggering psychomotor seizures. Probably the best procedures are those that employ manual restraint by several (3-4)

officers. Officers and users alike would be well advised to

note those final words in Leary, Metzner, and Alpert’s (1964)

guide to handling hallucinogenic emergencies: “Remain calm, remember the teachings” (p. 159) . Otherwise, the escalation process may run its full and tragic course. Consider the following account from the Los Angeles Times (Overend 1977):

279
While the controversy continued over the fatal

shooting of a 35-year-old biochemist by a Los

Angeles policeman, the county coroner’s office confirmed earlier this month what narcotics officers

had suspected since the morning of Aug. 4. It was

then that (the victim), described by friends and

relatives as a “nonviolent and peaceful man,” was

shot to death while allegedly resisting arrest

after being spotted at 5:30 a.m., naked and trying

to climb a street sign near his Laboratory. The

coroner’s report that traces of a drug similar to

PCP, also known as angel dust, had been found in

(the victim’s) blood did not resolve the issue of

whether the policeman was justified in shooting

(6 times at close range) the unarmed man. It remained for the legal system to determine that (p.2).

STATEMENTS OF INTOXICATED INDIVIDUALS

When the legal system tries to determine the role of PCP in

cases such as the one discussed above, statements made by the

intoxicated individuals, either to arresting officers or witnesses, can be as helpful as the clinical observations themselves. Even when intoxicated individuals make no statements,

subsequent examination and interviewing by a skilled forensic

psychopharmacologist may probe for and elicit information regarding the specific phenomenology of PCP intoxication (see

Siegel, this volume) . However, owing to the possibility of confabulation, post-hoc statements must be accepted with extreme

caution. While such statements are hearsay and cannot be admitted in court, they do add to the weight of the examining

expert’s opinion. Several types of statements seem characteristic of PCP intoxication, but by themselves are insufficient

proof of such intoxication. The following edited statements are

typical of those made to police or witnesses:

I was smoking Dust. I had two hits. That was bad

stuff. (Statement later denied by suspect).

I was smoking Dust and got really whacked out.

Like I was driving in a dream, felt funny at times.

We were laughing a lot, riding the bumps and

floating. I remember hitting another car, someone telling me to get out of the car, and waking

up at the police station.

I thought I had been shot by the police at the

party and I started running and fell to the ground.

Then I was attacked by black widow spiders. They

were over everyone and all over me. It was like a

dream.

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Everything was loud, real loud. Lights were very

bright. It was a trip. I don’t remember a lot.

I got sick of it and threw up.

She tried to jump out the window through the glass.

I pulled her back once. She was Busted. She

said she can fly.

I couldn’t walk. I don’t know where I am. I don’t

remember anything.

It was like tying myself in knots. I couldn’t

communicate. I got mad, screamed, cried. They

were all afraid of me.

I was feeling out of my body and liked it. It’s

all right.

It could have been a dream. To be honest, I don’t

know if I was physically up there (indicating

scene of crime) or spiritually there.

I felt spaced, things were for real but distorted.

Things were moving, patterns overlaying things and

people, patterns projected onto people.

My hands won’t fit in there (indicating handcuffs).

They’re all swollen and big. Too big.

You guys (indicating officers) seemed so far away.

Miles away. I thought I had plenty of time. What

a trip. Wow!

THOUGHTS OF INTOXICATED INDIVIDUALS

Even when overt verbal statements or other motor behaviors are

absent, the PCP- intoxicated individual may engage in a wide

variety of cognitive processes. An appreciation of these inner

subjective thoughts and mental images will enable a better

understanding of PCP-induced behaviors and possible criminal

actions. Such knowledge also may help in both predicting and

controlling behavior when encountering intoxicated individuals.

Two stages of intoxication can be distinguished: the acute

stage and the psychotic stage. The acute stage results from

recreational patterns of intoxication which are discussed elsewhere (Siegel, this volume). The psychotic stage may occur from

acute usage, but it more often represents high dose or chronic

administration, and the psychosis may not be manifested until

several hours or even days later. Only data from acutely intoxicated individuals are discussed here and such individuals

may differ substantially from those seen in the psychotic

stage by other authors (e.g., Fauman et al. 1976; Luisada and

Brown 1976) .

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Traditionally, psychologists consider cognitive processes to include perception, learning, and thinking, since they all deal,

to some extent, with the problem of knowledge (including the

knowledge of right and wrong). Perception can be defined as

the process by which an individual receives or extracts certain

information about the environment, Learning is defined as the

process by which this information is acquired through experience

and becomes part of the individual’s storage of facts (memory).

Thus, the results of learning facilitate the further extraction

of information, since the stored facts become models against

which cues are judged. The most complex of these cognitive processes, namely, thinking, is an activity that is inferred to be

going on when an individual is engaged in solving problems,

which also involves the use of models. Thinking is also inferred to be going on when an individual simply “scans” his own

memories or perceptions. Hallucinogenic drugs such as PCP can

cause these thoughts to be elaborated into fantasies, dreams,

and hallucinations.

Thoughts of PCP-intoxicated subjects are usually short, confused,

wandering, rapidly changing, and unvolitional in nature. The

intoxicated individual experiences waves of such thoughts interrupted by waves of blank (amnesic) periods. The rapidly

accelerated thinking itself, coupled with the drug-induced hyperexcitability and euphoria, can lead to the clinical condition

called “flight of ideas” or “mania.”

The most common thoughts during intoxication concern changes in

body image. Each individual normally develops techniques for

integrating the feelings and experiences emanating from his/her

body. This is referred to as body image, body concept,

or body scheme. ‘The PCP-intoxicated individual has difficulty

in experiencing and organizing his/her body as a perceptual object. Individuals become so unaware of their bodies that they

often feel free of them and have the sensation of floating out

of them. They often float back and forth into and out of their

bodies. When they do perceive their bodies, their thoughts contain exaggerated and elaborated views such as inflated limbs,

changes in head size, difficulty in estimating size of body

parts, difficulty in estimating distance between body parts, and

a general tendency to overestimate body size and height. While

such subjective reactions have not been confirmed experimentally,

they are similar to those findings reported for the hallucinogen LSD (Fisher 1970).

Frequently, the intoxicated individual considers himself/herself

endowed with unique and superior abilities (both bodily abilities

and mental abilities) as a result of the thought changes. In

the extreme cases, this state can be manifested as paranoia,

whereby the subject tries to account for these thought disturbances with persecutory or grandiose delusions.

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THINKING ABOUT DEATH

Intense hallucinogenic experiences, including PCP experiences,

can be regarded as journeys to new states of consciousness

(Lear-y, Metzner, and Alpert 1964). The characteristic features

are “the transcendence of verbal concepts, of space-time dimensions, and of the ego or identity” (p. 11). The journey has

been described as one resembling psychological death and many

similarities between hallucinogenic experiences and those of

dying patients have been noted (Grof and Halifax 1977). There

are also considerable similarities between PCP intoxications

and death experiences.

Domino and Luby (1972) describe a salient feature of PCP intoxication as reduced verbal productivity, the appearance of calm

in the subjects, and reported experiences of sheer “nothingness.”

One subject reported lying in a meadow and that “this meadow was

a place that he has often considered he would like to be buried

in. The theme of death ran through most of his retrospective

account of the episode. Possibly the experience of combined cutoff of interoceptive and exteroceptive cues is close to one’s

conception of what death must be like” (p.42).

Other common deathlike experiences in PCP intoxications include

ineffability of the experience and difficulty in verbal behavior;

feelings of peace and quiet; disturbances in space and time perception; out-of-body phenomena (including ecstatic feelings of

timelessness, weightlessness, peace, serenity, and tranquility);

no perception of smells, odors, temperature, or kinaesthesia;

fear; and confusion. Naturally, this can lead to a concern with

death and deathlike thoughts for the PCP-intoxicated individual.

This state of preoccupation with death has been termed meditatio

mortis.

It is well known that survivors of near death situations developed, as a result of such experiences, new concepts about death.

Many of these individuals lost their fear of death and developed positive attitudes toward it. Indeed, it is this observation

that forms the basis for much of the recent psychotherapy with

hallucinogenic compounds for terminal patients. However, it

must be emphasized that these positive changes in attitudes

about death are not associated with a desire for death or with

suicidal tendencies. Nonetheless, it may be speculated that in

the acutely intoxicated PCP user, such attitudes may function

to remove or reduce fear in situations which risk extreme bodily

harm or death.

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AGGRESSION AND CRIMINAL BEHAVIOR

A variety of factors contribute to the development of aggression

and criminal tendencies. Many of these can be understood in

terms of social psychological concepts: frustrations creating

an emotional arousal predisposing to aggressive behavior; aggressiveness habits also predisposing to such behavior; external

cues evoking the hostile actions; and, disinhibition of socially disapproved responses (Berkowitz 1962).

PCP intoxication can produce frustration by interfering with a

person’s ongoing goal-directed activity, arousing anger, and

thus leading to aggressive reactions if suitable aggression cues

(stimuli associated with the frustrater) are present. Even if

such cues are not present in reality but simply inferred by

the user to be present due to hallucinations and/or thought

disorders (e.g., paranoia state), the individual may display

relatively uncontrolled, intense emotional responses. These

intense reactions to real or imagined frustrations predispose

him/her to extremely hostile behavior. However, the predisposition to aggression is not manifested necessarily by aggressive

behavior per se, and this depends on individual personality,

social, and cultural factors. Nonetheless, given the presence

of the hostility-evoking cues as found in police encounters or

in criminal activities where resistance is encountered (as in

robbery or rape), violent aggressive behaviors are more likely

to be elicited from the user.

Chronic use of PCP may induce a poor judgement syndrome which

could be a factor in nonviolent criminal acts such as perjury

and theft. The hypersexuality sometimes reported during some

psychotic stages of PCP intoxication may influence motivation

involved in assault and rape situations. Conversely, one could

speculate that crime related to continuous use of drugs (e.g.,

theft to support the drug habit) would be infrequent among PCP

users owing to the drug’s low price and availability. In

addition, like most hallucinogens, PCP does not appear to be

used in escalating doses indicative of addiction.

PCP intoxication also can produce panic reactions in the sense

that the individual becomes frightened due to the overwhelmingly

intense hallucinogenic effects. Changes in body image, perceptual distortions, and mental confusion can catapult the naive

user into a state where s/he feels and fears loss of ego and

identity, loss of contact with reality, and even permanent mental

dysfunction. Consequently, panic ensues, and deviant behavior,

including aggression, can occur. It is probable that assaultive

behavior, when it does occur during PCP intoxication, takes

place for many individuals at this time. This is similar to the

occurrence of aggressive behaviors during intoxication with other

hallucinogens: "Aggressive outbursts do occur during the panic

reaction of psychedelic intoxication, especially if the reaction

includes paranoid components” (Tinklenberg 1973, p.265).

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The PCP-intoxicated user’s orientation toward the immediate present and disregard for long range consequences of his/her behavior would make it difficult for him/her to premeditate criminal

acts. But the tendency to react strongly to sensory stimuli in

the immediate environment, the inclination to refer everything

to oneself that often develops into paranoia, and the need to

do something due to intense psychomotor stimulation can all produce an aggression-prone individual. Once again it must be

emphasized that emotionally stable people under the influence

of low doses of PCP probably will not act in a way very different from their normal behavior. To the extent that this is true,

case histories and statistics regarding PCP-related crime,

aggression, and violence should thoroughly investigate the user’s

prior conduct and social psychological history.

THE DIMINISHED CAPACITY DEFENSE

Forensic psychopharmacologists and psychiatrists are frequently

called upon as expert witnesses in cases involving PCP and

diminished capacity. The expert will frequently evaluate several sources of data regarding the defendant’s possible state of

intoxication at the time of the alleged offense. These sources

include: chemical and laboratory reports and studies, field

sobriety tests, observations made by arresting officers, arrest

reports, investigative reports, statements of witnesses, medical

and psychiatric histories, and allied materials. According to

Pollack (1976), the expert “must be able to assess, integrate,

and evaluate all of these data on the question of whether the

defendant at the time of the alleged act was intoxicated; and

if he was, whether his mental functions of significance for

forming the specific intent for the crime were substantially

impaired” (p. 257) . Thus, the threshold for simply being intoxicated or under the influence of a drug such as PCP is significantly lower than that defining intoxication for purposes of

diminished capacity. The former requires minimal evidence of

impairment while the latter requires a substantial degree of

mental impairment. In an effort to gather as much information

as possible, experts will frequently employ additional data such

as physical medical examination of the defendant soon after the

alleged offense, EEG examinations, in-depth interviewing and

testing of defendants and witnesses regarding the specific

phenomenology of the intoxication, among other methods. All

such materials can be used as collateral and supporting data.

Since there is no statutory presumption identifying PCP intoxication for diminished capacity (in contrast to the statutory

presumption of being under the influence of alcohol with blood

alcohol levels of .10 percent), the expert witness can only

offer considered opinion. In court, when accepted according to

the rules of evidence, psychopharmacologic or psychiatric expert

opinion carries weight as “opinion evidence” and is not accepted

as “scientific fact.” The ultimate legal question will be decided by the trier of fact, namely, the judge or jury.

285
Since PCP intoxication can resemble closely some forms of schizophrenia, superficially it would appear to be an ideal candidate

for defenses of diminished capacity. PCP intoxication can show

all the essential ingredients for such a defense: altered consciousness wherein the defendant’s attention, awareness, and

ability to respond meaningfully to the environment and situation

are disturbed; mental confusion regarding the meaning of the act

or its consequences; involuntary behavior which might prevent

optional courses of action; and interference with goal-directed

behavior so as to prevent organizing and directing physical

movements. Thus, PCP can diminish the capacity to form

or to harbor criminal intent. It does so by interfering

with the mental functions which are essential to the mental

process of forming intent for an act.

Diminished capacity defenses are extremely difficult to prove

and are generally far less successful than the insanity defense,

which is probably successful in about 66 percent of the insanity

trials. Even when the diminished capacity defense is successful,

the outcome may not result in the adequate treatment of the defendant for the drug abuse and mental health problems signified by such

extreme PCP use. Whereas the defendant who is found legally insane

is usually diverted to a state mental health system for evaluation,

disposition, and treatment, the defendant who ‘is successful in

a diminished capacity defense is usually committed to prison for

punishment.

OVERVIEW AND SPECULATIONS

Euripides presented us with the notion that drugs work in some

magical way. The figure of Dionysus was clearly that of sorcerer and his magic was to be found in wine. The social importance

of Dionysian intoxication and ecstasy was that it permitted

temporary impairment of reason for the folly and madness of

criminal behavior. Ever since those ancient times, drugs, and

especially alcohol, have been used as scapegoats for the argument of diminished capacity in criminal acts. The mechanisms

of action for such effects are neither magical nor predictable.

They are not magical because they reflect characteristic states

of behavior induced by the pharmacological properties of drugs

on the central nervous system. They are not predictable because

of a wide range of interactions with nondrug variables, including

set and setting.

Phencyclidine is not a magical drug. It does not magically produce violent, assaultive, or criminal behavior. When the psychopharmacology of the drug is fully appreciated, we can begin to

understand that the criminal behavior associated with its use is a

result of interactions between the drug and the user. At that

time the magical notions will begin to disappear from courtroom

trials of diminished capacity which often turn into trials of

the drugs themselves as good or evil.

286
Such a future state of enhanced knowledge about drugs has already

been envisioned by science fiction writer H.H. Hollis (1972) in

his short story "Stoned Counsel.” In that fictitious world of

the future, hallucinogenic drugs have become a routine part of

the legal process as both defense attorneys and prosecutors have

had personal experiences with drugs which enhance their understanding and sympathy for the defendants. Even some present day

PCP users have coined the term “Pig Killer” for the drug in

order to connote that if ingested by police it would kill their

ideas about the drug turning people into “beasts.” While such

personal use is unnecessary and certainly ill-advised with drugs

such as PCP, a full understanding of phencyclidine will undoubtedly reveal it to be simply a hallucinogenic drug with certain

chemical properties and behavioral possibilities.

ACKNOWLEDGMENTS

The author thanks Dr. Murray E. Jarvik for numerous helpful services

in the research and preparation of this study. The author is

indebted to Ada Hirschman for superlative research assistance.

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1, pp. 242-299.

Tolstoy, L. (1890). Why Do Men Stupefy Themselves? Translated by

A. Maude. Hankins, New York: Strength Books 1975.

Winters, W.D., Mori, K., Spooner, C.E., and Bauer, R.O. The

neurophysiology of anesthesia. Anesthesiology, 28:65-80, 1967.

AUTHOR

Ronald K. Siegel, Ph.D.

Department of Psychiatry and Biobehavioral Sciences

School of Medicine

University of California, Los Angeles

Los Angeles, California 90024

Mailing Address:

Ronald K. Siegel, Ph.D.

Psychopharmacology Unit

Research Trailer 350

Brentwood VA Hospital

Los Angeles, California 90073

288
Chapter 17

Control of Drug Self-Administration:

The Role of Aversive Consequences

Nancy K. Mello, Ph.D.

Despite a continuing search for commonalities across the

various forms of substance abuse, it has been difficult to

identify factors which apply equally to the abuse of opiates,

alcohol, stimulants and hallucinogens. The traditional focus

on specific syndromes associated with the abuse of certain

drugs, e.g., alcoholism and heroin addiction, has tended to militate against appreciation of similarities between drugs. Moreover, known differences in the pharmacological and behavioral

consequences of alcohol, heroin, cocaine and phencyclidine intoxication would appear to argue against the notion that any

meaningful similarities could be found.

Re-examination of the behavioral consequences of drug use and

abuse suggest that one pervasive factor has often been overlooked. Many drugs of abuse have now been shown to have

aversive consequences during intoxication. These data have

led to the hypothesis that “aversive” consequences may be an

important factor in the control of many forms of drug abuse

(Mello 1977). Recent findings relevant to this hypothesis will

be examined in the remainder of this review. One basic

assumption is that drug self-administration behavior is controlled or maintained by its consequences. Therefore, any

consistent consequence which transcends drug specific effects

may be a common factor which contributes to the maintenance of

substance abuse.

EFFECTS OF DRUGS IN NAIVE USERS

In thinking about the way in which drugs come to control

behavior leading to their self-administration, it is instruct-’

ive to review some reported effects of acute drug use by naive

users. It would be convenient if the initial drug experience

was so overwhelmingly positive that repeated drug use would be

almost inevitable. Yet the reported effects of acute doses of

opiates, barbiturates, alcohol and nicotine summarized in

Table 1 do not appear to be especially appealing. These drugs

each produce a variety of somatic and emotional effects that

would seem disadvantageous to the user. Yet, despite these

“aversive” consequences of initial drug use, many individuals

persist in self-administration of these same drugs to the point

of abuse and addiction.

289
TABLE 1

SOME REPORTED ACUTE EFFECTS OF DRUGS IN NAIVE USERS*

*From Mello, Stimulus Self-administration: Some implications for

the prediction of drug abuse liability. In: Thompson and Unna, eds.

Predicting Dependence Liability of Stimulant and Depressant Drugs.

© 1977 University Park Press, Baltimore. Reprinted with permission.

Adapted from Jaffe 1975, Mello and Mendelson 1976, Russell 1976.

It has often been observed that alcohol addicts tend to have

a clear recollection of their “first drink” (Kuehnle,

Anderson, and Chandler 1974). However, clinical impressions

suggest that the first drink was not memorable because of its

relaxing, euphorigenic, tension-reducing, or self-actualizing

effects for the drinker (Kuehnle, Anderson, and Chandler 1974;

Catanzaro 1968). It is more likely that the future alcoholic

drank to the point of intoxication with associated despondency,

nausea and vomiting.

The process by which an initial aversive drug experience becomes

translated into a repetitive drug use pattern is not understood.

It could be postulated that with the development of drug tolerance, these seemingly unpleasant somatic and emotional effects

290
undergo a transition to a more positive state, i.e., euphoria,

relaxation, tranquility. Alternatively, it could be postulated

that the initial dysphoria, nausea, and vomiting is an integral

part of the reinforcing properties of subsequent drug abuse.

It is now evident that drug abuse is maintained despite the

recurrence of these seemingly aversive consequences.

EFFECTS OF DRUGS IN CHRONIC USERS

It is generally acknowledged that the long-term effects of

chronic substance abuse are adverse and may compromise health

and employability as well as disrupting family and social

relationships. However, the immediate consequences of drug

use are usually believed to be sufficiently positive to outweigh these long-term effects. If in fact, abused drugs consistently produced relaxation, euphoria, relief from anxiety,

tranquility and serenity, then chronic drug use and abuse

might be more understandable. However, common expectancies

about drug related pleasures have not been confirmed in

clinical studies of addicts during intoxication. Direct observations of intoxicated individuals are often discordant

with retrospective self-reports of drug effects obtained

during a period of sobriety. This discrepancy is particularly

troublesome since most of our information about the effects of

abused drugs is based on retrospective reports of users during

sobriety.

It now appears that increases in dysphoria, anxiety, and agitation frequently accompany chronic intoxication, both with

alcohol (Mello and Mendelson 1978) and with heroin (Mirin

et al. 1976; Meyer and Mirin 1978). These findings challenge

the traditional view of the behavioral effects of these drugs,

and are one basis for the idea that “aversive” consequences

are important in the maintenance of drug self-administration

behavior. Clinical research has shown that the behavioral

effects of drugs are far more complex than concepts related

to hedonism would suggest.

Behavioral Effects of Alcohol Intoxication

Many of the consequences of alcohol intoxication are similar

for the naive or social drinker, and for the alcohol addict.

The major determinant of the behavioral effects of alcohol

appears to be the dose of alcohol consumed, relative to the

experience and behavioral tolerance of the drinker. A list

of some of the subjective states that alcohol is believed to

improve or enhance, and findings from clinical studies of

intoxicated individuals appears in Table 2.

291
Low doses of alcohol, sufficient to produce a blood alcohol

level of between 30 and 50 mg/100 ml often produce the anticipated pleasurable consequences. However, social drinkers

report increased depression, dysphoria and anxiety after an

acute high dose of alcohol (6 to 8 ounces) (Williams 1966;

Warren and Raynes 1972).

Alcohol addicts often ingest between 26 and 32 ounces of distilled spirits per day (or the equivalent in beer or wine)

(Mello and Mendelson 1978). Since the alcoholic is tolerant

to alcohol, considerably higher doses of alcohol may be

required to produce significant changes across a range of

subjective experiences and interpersonal reactivity. However,

clinical studies from many laboratories, employing a variety

of techniques agree that chronic intoxication, sufficient to

maintain blood alcohol levels between 150 and 300 mg/100 ml,

is associated with increased depression, agitation, anxiety,

and belligerence in the drinker (Mello and Mendelson 1978).

Severe chronic alcohol intoxication may also be associated

with illusions and hallucinatory experiences during drinking

as well as during alcohol withdrawal (Wolin and Mello 1973).

TABLE 2

OBSERVED EFFECTS OF ALCOHOL INTOXICATION*

*Adapted from Mello and Mendelson 1978.

292
It is not clear why the discrepancies between the expected and

the observed effects of chronic alcohol intoxication are not

more generally recognized and why they appear to have so little

effect on the behavior of the alcohol addict. It has been

found that alcohol addicts, interviewed before, during, and

after an episode of alcohol intoxication tend to recall predrinking expectancies about the experience even if these are

completely at variance with the actual effects of alcohol

intoxication (McGuire et al. 1966). Alternatively, it may be

that these “aversive” consequences, similar to the “first

drink” experience summarized in Table 1, are an important

aspect of the reinforcement for drinking.

Behavioral Effects of Heroin Intoxication

Retrospective reports of the effects of heroin intoxication by

heroin addicts emphasize euphoria and serenity. As Jaffe (1975)

has described it:

Narcotics do more than produce indifference to pain.

They also suppress those drives that motivate an

individual to appease hunger, seek sexual gratification and respond to provocation with anger. In

short, they seem to produce a state of total drive

satiation. Nothing needs to be done because all

things are as they should be. For certain types

of personalities, but clearly not for all, such

a state is extremely pleasant (Jaffe 1975, p. 284).

Clinical observations of heroin addicts during a period of

opiate intoxication are at variance with these reports.

Chronic opiate use appears to be accompanied by an increase

in dysphoria, irritability, hypochondriasis, psychopathology,

belligerence, negativism and motor retardation (Wikler 1952;

Haertzen and Hooks 1969; Mirin et al. 1976; Meyer and Mirin

1978). These dysphoric consequences of chronic heroin intoxication appear to be directly related to heroin use rather

than to situational or social factors. Heroin addicts,

maintained on the long-acting opiate antagonist, naltrexone,

during the same period of residence on a clinical research

ward did not develop dysphoria, anxiety, or belligerence comparable to that shown by heroin users (Mirin et al. 1976;

Meyer and Mirin 1978).

It could be argued that a brief and transient positive mood

change which is purportedly associated with the induction of

alcohol and heroin intoxication is sufficient to maintain drug

self-administration behavior (Mirin et al. 1976; Davis 1971).

In the case of alcohol intoxication, these initial changes

293
during the induction of intoxication have been difficult to

characterize either in terms of subjective quality or temporal duration (Davis 1971). In the case of heroin addiction,

the intensity of the positive feelings associated with the rush

appears to be attenuated as tolerance develops during the course

of chronic heroin use (Meyer and Mirin 1978).

Comparisons with Phencyclidine

Clinical reports of the consequences of phencyclidine selfadministration appear to be a further extension of the “aversive”

end of the drug effect continuum. Acute effects of dose-related

illusions, dissociation, perceptual disturbance, and depersonalization, which may culminate in convulsions and coma would be

difficult to categorize as “positive” effects according to the

usual criteria. Yet even the development of toxic psychosis

does not appear to be an effective deterrent to repeated use.

However, re-evaluation of the consequences of alcohol and opiate

intoxication suggests that phencyclidine abuse may differ only

in the intensity of aversive effects.

ANIMAL MODELS OF “AVERSIVE” STIMULUS SELF-ADMINISTRATION

Although it is tempting to dismiss these clinical data as

optimistic expectancies failed, the quest for aversive stimulation is not restricted to man. There is evidence that

seemingly aversive consequences will also maintain self-administration behavior in animals under certain conditions. Two

examples of aversive stimulus self-administration will be

described.

Narcotic Antagonist Self-Administration

Narcotic antagonists induce withdrawal signs in opiate

dependent monkeys. A summary of some typical withdrawal signs

appears in Table 3. It is evident that the somatic consequences

of opiate withdrawal resemble some consequences of acute intoxication in naive drug users shown in Table 1. It is not surprising that opiate-dependent monkeys will work to escape and

to avoid the infusion of narcotic antagonists (Downs and

Woods 1975; Hoffmeister and Wuttke 1973). However, it has also

been found that under certain conditions morphine dependent

monkeys will work to produce injections of narcotic antagonists.

294
TABLE 3

SOME SIGNS OF OPIATE WITHDRAWAL IN OPIATE-DEPENDENT RHESUS MONKEYS*

Autonomic and Gastrointestinal

Signs Motor Activity Signs

Vomiting

Retching

Coughing

Tachypnea

Dyspnea

Salivation

Sweating

Tearing

Miosis

Erection Masturbation

Loose stools

Tremors

Rigidity in extremities

Spasticity

Shivering

Piloerection

Holding of abdomen

Gross Behavioral Changes

Yawning and grimacing

Restlessness

Screaming (provoked and unprovoked)

Attacking [provoked and unprovoked)

*Adapted from Villarreal and Karbowski 1974.

Goldberg and co-workers (1972) were the first to observe selfadministration of the narcotic antagonist nalorphine by opiatedependent monkeys. During studies in which either saline or

nalorphine was substituted for morphine injections during a 7.5

hour session, it was found that responding that was followed by

nalorphine injections was maintained at a higher rate than

responding that was followed by saline injections. The distribution of responses within successive 2.5 hour segments of the

7.5 hour saline and nalorphine substitution sessions is shown

in Figure 1. It is apparent that nalorphine maintained responding. Monkeys continued to self-administer nalorphine despite

severe withdrawal signs which included vomiting? coughing,

salivation, tremors, and irritability. Responding for nalorphine did not extinguish during the substitution sessions.

295
FIGURE 1

Distribution of responses within the

last three saline substitution sessions and nalorphine-substitution sessions (100 mcg/kg injection),

compared to the distribution of morphine-maintained

responses at comparable times on control days.

Abscissa: successive 2.5-hour segments of 7.5-hour

saline or nalorphine substitution sessions; Ordinate:

cummulative number of responses during successive 2.5-

hour segments. Each point represents the mean of

results of three sessions with two monkeys. From:

Goldberg, S.R., Hoffmeister, F., Schlichting, U.U.:

Morphine antagonists : Modification of behavioral

effects by morphine dependence. In: J.M. Singh,

L. Miller and H. Lal eds. Drug Addiction I.

Experimental Pharmacology, pp. 31-48. ©1972, Symposia

Specialists, P.O. Box 610397,

Reprinted with

Miami, Florida 33161.

permission of the publisher.

These data indicate that under certain conditions, response

produced nalorphine injections can maintain responding in monkeys

which are physiologically dependent upon morphine. Goldberg and

co-workers concluded that these findings illustrate that the

experimental history of the organism, and the behavioral schedule

under which a stimulus event is presented, rather than the type of

event may determine the effect that an event may have upon

behavior (Goldberg, Hoffmeister, and Schlichting 1972).

296
These findings have recently been confirmed and extended by

Woods and co-workers (Woods, Downs, and Carney 1975). It was

found that under certain conditions, morphine dependent monkeys

will work to produce the same injection of a narcotic antagonist,

naloxone, that they previously worked to avoid. Cumulative

records of narcotic antagonist self-administration by a morphine

dependent monkey is shown in Figure 2. Each response on an

operant manipulandum advances the stepping pen of the cumulative

recorder approximately one-quarter of a millimeter and consequently, cumulative records provide a direct analog of

response rate. The top row of figure 2 show cumulative

records of responding on a second-order schedule of reinforcement (FR 10 (FR30:S). Every 30 responses produced a secondary

reinforcing stimulus (i.e., a 1.5 second flash of light),

previously associated with drug infusion and every three

hundred responses produced an injection of naloxone (0.002

mg/kg). Antagonist injections were followed by a one-minute

time out and a light signal. The downward deflection on the

event marker indicates the delivery of each successive

naloxone injection.

It is clear that naloxone, rather than any associated stimuli

maintained responding since removal of naloxone resulted in

extinction of response behavior. The second row of Figure 2

shows the effect of disconnecting the naloxone infusion pump

when the secondary reinforcing stimuli, i.e., the light signal,

the time-out, etc., remain unchanged. The monkey worked briefly,

then stopped responding when no naloxone infusion was delivered.

The third row of Figure 2 illustrates the reinstatement of

naloxone maintained responding during the first session after

the naloxone pump was reconnected. The reinforcement schedule

requirement was reduced from 300 to 150 responses for each

naloxone injection. Under these conditions, morphine dependent monkeys could earn approximately 10 naloxone injections

over the course of an hour. It is apparent that the monkey

resumed and maintained responding for naloxone injections.

ELECTRIC SHOCK SELF-ADMINISTRATION

The aversive properties of electric shock stimuli have been

amply documented. However, it has also been found that the

same electric shock event that can maintain escape and

avoidance behavior, may under certain conditions, be selfadministered by the same monkey. Identification of this

phenomena, called response-produced shock, developed from

the initial observations of Kelleher and co-workers that

during a pre-shock stimulus, responding increased and if

the terminal shock was removed, responding decreased

(Kelleher, Riddle, and Cook 1963). Response produced shock

297
FIGURE 2

Cumulative records of responding maintained

by naloxone in a morphine-dependent monkey. The upper

record shows the eighth session of responding when

every completed FR 30 unit produced a 1.5~sec flash

of the house light and every tenth completed FR 30

unit produced an injection of naloxone (0.002 mg/kg

per injection) plus a 1-min time-out accompanied by

house light illumination. The center record shows

performance in the third session with the naloxone

infusion pump disconnected. All other aspects of

the procedure were as described above. The lower

record shows reinstatement of naloxone-maintained

responding in the first session with the naloxone

pump reconnected. In this and subsequent sessions,

the schedule value was reduced to FR 5 (FR 30).

Injections of naloxone or saline are indicated by

downward deflections of the center event pen.

Each session was terminated after 10 injections

or about 1 hour. From Woods, J.H., Downs, D.A.,

and Carney, J. 1975. Behavioral functions of

narcotic antagonists: Response drug contingencies.

Reprinted with permission of the publisher, from

FEDERATION PROCEEDINGS 34(9): 1777-1784, 1975.

298
has now been observed in many laboratories, across several

species, and has been shown to be a reliable and persistent

phenomena (Byrd 1969; Eubanks et al. 1975; Kelleher and Morse

1968; McKearney 1968, 1969, 1972; Morse and Kelleher 1970;

Morse, McKearney, and Kelleher 1977; Morse, Mead, and

Kelleher 1967; Stretch, Orloff, and Dalrymple 1968; Stretch,

Orloff, and Gerber 1970). Under certain conditions monkeys

will continue to self-administer electric shock for months

and even for years.

An illustration of behavior maintained by the delivery of

electric shock is shown in Figure 3 (Morse and Kelleher 1970).

Cumulative response records of the operant performance of a

single monkey are shown under two different conditions;

shock termination and shock production. The top row of

Figure 3 shows behavior on a schedule of shock termination

(FI 5 min) in which the first response after five minutes

have elapsed terminates a 7 ma electric shock which is presented

every five minutes. Cumulative responses of the same monkey on

a schedule of shock production are shown in the second row of

Figure 3. Instead of terminating a shock presented every five

minutes, the monkey self-administers a shock of 1 ma every five

minutes, If a response did not produce shock within five

seconds after elapse of the five minute fixed interval, a 7 ma

shock was presented automatically. It is obvious that the rate

of responding was higher when responses produce shock than when

responses terminate shock.

Another example of response-produced electric shock is shown

in Figure 4 which compares the effects of non-contingent and

response produced shock on operant behavior (Morse and

Kelleher 1970). In the cumulative record shown at the top of

Figure 4, a monkey with a particular behavioral history

received 5 ma shocks every two minutes, independent of his

response behavior, Each shock was followed by a brief timeout period. In the lower portion of Figure 4, a shock of the

same intensity (5 ma) was scheduled to occur after the first

response after an interval of two minutes had elapsed (an FI

2 min schedule), Shock presentation was followed by a brief

time-out. Response behavior was maintained by electric shock

presentation. The rate of responding increased and the pattern

of responding was more positively accelerated on a shock

presentation schedule than when shocks were not contingent on

responding. These findings that an animal will work to selfadminister a seemingly noxious electric shock, indeed the same

electric shock he previously worked to avoid, or to escape

from is eloquent testimony to the capacity of “aversive”

events to control behavior leading to their self-administration.

Morse, McKearney, and Kelleher (1977) have reviewed data on the

control of behavior by noxious stimuli and discussed the

generality of this phenomenon.

299
FIGURE 3

Performance under an FI 5 min schedule

of termination of electric shock and an FI 5 min

schedule of presentation of electric shock (Monkey

S-28). A: Short diagonal strokes in the event

record (bottom) indicate successive electric

shock presentations (7 ma); diagonal strokes

on the cumulative record (top) indicate the

termination of shock. B: Strokes on the cumulative record indicate 1 ma electric shock presentations. If a response did not produce shock

within 5 seconds after 5 minutes had elapsed, a

7 ma shock was presented automatically. When

responses produced shock, rates of responding

became higher and patterns of positively accelerated responding became more marked. From Morse,

W.H., and Kelleher, R.T., 1970. Schedules as

fundamental determinants of behavior. In: W. N.

Schoenfeld, ed. The Theory of Reinforcement

Schedules. pp. 139-185. Appleton-Century-Crofts,

New York. © 1970. Reproduced by permission of

Prentice-Hall, Inc., Englewood Cliffs, New Jersey.

300
FIGURE 4

Comparison of performances under schedules

of response-independent and response-dependent 5-ma

electric shocks (Monkey S-13). Short diagonal strokes

on the cumulative records indicate presentation of

electric shock; a time-out period, in which the

paper did not moue, followed each shock. The

recording pen reset to the baseline whenever 275

responses had accumulated. A: Performance under the

schedules of response-independent shock. B: Performance wader FI 2-min schedule of response produced

shock after eight sessions. The rate of responding

increased, and the pattern of responding was more

clearly positively accelerated with response-produced

shocks. From Morse, W.H., and Kelleher, R.T., 1970.

Schedules as fundamental determinants of behavior. In:

W. N. Schoenfeld (ed.) . The Theory of Reinforcement

Schedules, pp. 139-185. Appleton-Century-Crofts,

New York. © 1970. Reprinted by permission of

Prentice-Hall, Inc., Englewood Cliffs, New, Jersey.

301
The parallels between these data on response-produced shock

and narcotic antagonist self-administration in primates, and

the aversive consequences of drug self-administration in

humans are provocative. Although the control of drug selfadministration by aversive consequences has not been shown

unequivocally in man with the degree of precision that it

has been shown in primate models, the inference that aversive

consequences are one part of the reinforcement complex that

maintains human drug self-administration behavior is compelling.

IMPLICATIONS AND CONCLUSIONS

These clinical and experimental data challenge common sense

assumptions about what constitutes a “positive” and an

“aversive” event, and what types of events will be reinforcing. In the language of the experimental analysis of

behavior, reinforcement is any event that maintains

behavior, i.e., a reinforcer is a consequence of behavior

that increases the probability of the recurrence of that

behavior (Skinner 1938, 1953). Although behavioral

scientists are usually careful to distinguish between

reinforcement and reward, the terms reinforcing, rewarding,

and euphorigenic are often used interchangeably to describe

the consequences of drug abuse and by inference to explain

its recurrence and persistence. The notion of “reward” has

a compelling face validity that does not invite critical

examination. One advantage of the term reinforcement is that

it does not imply anything about the nature of the reinforcing events, but rather describes a functional relationship between events and behavior.

The defining characteristics of reinforcements and punishers

are how they change behavior. The same stimulus may have

either reinforcing or punishing effects, depending upon the

condition under which it is presented. According to this

empirical formulation, shown schematically in Table 4, if

the presentation or removal of the stimulus event increases

the behavior leading to that consequence, it can be defined

as a reinforcer. If the presentation or removal of the

stimulus event decreases the behavior leading to that consequence, it can be defined as a punisher (Morse and

Kelleher 1977).

302
TABLE 4

BEHAVIORAL EFFECT *

EVENT

INCREASE BEHAVIOR DECREASE BEHAVIOR

PRESENT

STIMULUS REINFORCEMENT PUNISHMENT

REMOVE

STIMULUS REINFORCEMENT PUNISHMENT

*From Mello, Stimulus self-administration: Some implications for

the prediction of drug abuse liability. In: Thompson and Unna, eds.

Predicting Dependence Liability of Stimulant and Depressant Drugs.

© 1977 University Park Press, Baltimore. Reprinted with permission.

Defining stimulus events in terms of their behavioral effects,

rather than in terms of an apriori assumption about the

alleged properties of the stimulus event and conclusions

about its consequences, represents a radical departure from

our usual ways of thinking. However, a definition of reinforcement and punishment in terms of behavioral effects, can

account for data on response-produced shock and antagonist

self-administration as well as the persistence of drug selfadministration which results in aversive consequences during

intoxication.

Electric shock and antagonist self-administration data indicate

that it is not the inherent properties of the event, per se, but

the way in which the event is scheduled that determines the subsequent effect on behavior (Morse, McKearney and Kelleher 1977).

The reinforcing or punishing properties of stimulus events are

dependent upon a variety of factors including the behavioral

history of the organism, the schedule of presentation of that

event, and the ongoing behavior at the time. Clearly, it is

impossible to assume an invariant effect of any particular

Stimulus event. We have seen that under certain conditions of

behavioral history and schedule controls, substances that were

so noxious that animals would work to avoid them, undergo a

transition from punishing to reinforcing stimuli as a

function of the schedule of presentation.

Since consequences which appear to be aversive do maintain

behavior leading to their self-administration, more careful

attention to the role of “aversive” consequences in human

drug self-administration seems indicated. Traditional concepts

303
that drug abuse is maintained primarily as a function of

rewarding or euphorigenic consequences are not consistent

with the clinical data. Reward related concepts appear

too limited to account for clinically observed consequences

of many forms of drug abuse including phencyclidine selfadministration.

Stimulus Self-Administration ?

Beyond the issue that both seemingly “aversive” and “positive”

consequences contribute to the maintenance of drug self-administration, there are many other apparent paradoxes which remain

unaccounted for. One example is polydrug use which often

involves the simultaneous and sequential use of several drugs

with different pharmacological properties and presumably different effects, e.g. stimulants and depressants; opiate analgesics

and stimulants. Phencyclidine may be used concurrently with

other drugs, e.g. alcohol, barbiturates, marihuana, each of

which has different pharmacological effects and presumably

modulates the effect of phencyclidine in different ways.

Twenty-five years ago, Wikler and Rasor (1953) wrote that one

reason for using drugs advanced by some opiate addicts is to

“get off the normal”. The nature of the positive effects of

drugs described by addicts varies considerably in different

types of drug addiction (Wikler and Rasor 1953). Anecdotal

accounts of voracious polydrug use, and extreme drug effects

produced by agents such as phencyclidine, suggest that the

users goal is to achieve a rapid change in state. The

direction of the change, up or down, may be of secondary

importance. Accumulating clinical evidence of aversive consequences during intoxication also lends credence to a state

change hypothesis. An extreme example is the repeated intravenous injection of phencyclidine to the point of unconsciousness (Fauman and Fauman 1978).

To the extent that stimulus change affected by drug use may be

more important than any inherently positive or negative characteristics of that stimulus, it may be useful to consider

drug self-administration within a more general framework of

stimulus self-administration (Mello 1977). Central to the

idea that stimulus self-administration is important in the

maintenance of drug self-administration is the notion that

the stimulus properties of drugs, rather than the specific

qualities of the stimuli, may be important determinants of

this behavior. State change may be the subjective response

to the drug induced stimulus, whatever that stimulus may be.

Perhaps, under some conditions, in individuals with a

certain behavioral history, drug self-administration

304
has less to do with the pharmacological properties of the

compound, or with its anticipated effects, than with its

properties as a definite stimulus event that results in a

change in subjective state. This hypothesis implies that

any drug which has definite stimulus properties, i.e.,

behavioral effects for the user, is a drug which has abuse

potential.

ACKNOWLEDGMENTS

Preparation of this review was supported by grants DA 01676

and DA 4RG010 from the National Institute of Drug Abuse, ADAMHA.

Portions of this paper have been adapted from "Stimulus SelfAdministration: Some Implications for the Prediction of Drug

Abuse Liability" by N.K. Mello, 1977.

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Hoffmeister, F., and Wuttke, W. Negative reinforcing properties of morphine antagonists in naive rhesus monkeys,

Psychopharmacologia (Berl.) 33: 247-258, 1973.

Jaffe, J.H. Drug addiction and drug abuse. In: Goodman, L.S.,

and Gilman, A., eds. The Pharmacological Basis of Therapeutics.

Fifth Edition. New York: Macmillan Publishing Co., Inc., 1975,

pp. 284-324.

Kelleher, R.T., and Morse, W.H. Schedules using noxious stimuli.

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shocks. J. Exp. Anal. Behav. 11: 819-838, 1968.

Kelleher, R.T., Riddle, W.C., and Cook, L. Persistent behavior

maintained by unavoidable shocks. J. Exp. Anal. Behav. 6: 507-

517, 1963.

Kuehnle, J.C., Anderson, W.H., and Chandler, E. Report on first

drinking experience in addictive and nonaddictive drinkers.

Arch. Gen. Psychiat. 31: 521-523, 1974.

McGuire, M.T., Mendelson, J.H., and Stein, S. Comparative psychosocial studies of alcoholic and non-alcoholic subjects undergoing

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AUTHOR

Nancy K. Mello, Ph.D.

Associate Professor

Alcohol and Drug Abuse Research Center

Harvard Medical School

The McLean Hospital

Belmont, Massachusetts 02178

308
Conference Participants

Regine Aronow, M.D.

Director, Poison Control Center

Children’s Hospital of Michigan

Department of Pediatrics

Wayne State University

3901 Beaubien Boulevard

Detroit, Michigan 48201

Robert L. Balster, Ph.D.

Assistant Professor

Department of Pharmacology

Medical College of Virginia

Box 726

Richmond, Virginia 23298

R. Stanley Burns, M.D.

Lerner, Burns, Linder and

Associates

350 Parnassus Ave., Suite 304A

San Francisco, California 94117

Sidney Cohen, M.D,

Professor of Psychiatry

University of California

13020 Sky Valley Road

Bel Air, California 90049

Gerald G. DeAngelis, Ph.D.

President, Health Care Delivery

Service, Inc.

11340 W. Olympic Blvd., Suite 185

Los Angeles, California 90064

Edward F. Domino, M.D.

Professor of Pharmacology

University of Michigan

M-6414 Sci Med 1

Ann Arbor, Michigan 48109

and Lafayette Clinic

Detroit, Michigan 48207

Alan K. Done, M.D.

Professor of Pediatrics and

Pharmacology

Director, Division of Clinical

Pharmacology and Toxicology

Children’s Hospital of Michigan

3901 Beaubien Boulevard

Detroit, Michigan 48201

Beverly J. Fauman, M.D.

Assistant Professor

Emergency Medicine and Department

of Psychiatry

Box 448

University of Chicago Hospital

and Clinics

950 East 59th Street

Chicago, Illinois 60637

Michael Fauman, M.D., Ph.D.

Assistant Professor

Department of Psychiatry

University of Chicago Hospital

and Clinics

Box 411

950 East 59th Street

Chicago, Illinois 60637

David B. Graeven, Ph.D.

Associate Professor

Department of Sociology

California State University at

Hayward

Hayward, California 94542

Russell D. Hicks, M.D.

Assistant Professor of Medicine

John A. Buns School of Medicine

University of Hawaii

Honolulu, Hawaii 96822

309
Kenneth M. Johnson, Ph.D.

Assistant Professor

Department of Pharmacology and

Toxicology

Univ. of Texas, Medical Branch

Galveston, Texas 77550

Steven Lerner, M.S.

Lerner, Burns, Linder and

Associates

350 Parnassus Ave. , Suite 304A

San Francisco, California 94117

Walter Ling, M.D.

Chief, Drug Dependence Treatment

Program

Veterans Administration Hospital

16111 Plummer Street

Sepulveda, California 91343

Paul V. Luisada, M.D.

Deputy Medical Director

Area D Community Mental Health

Center

St. Elizabeth’s Hospital, NIMH

Washington, D.C. 20032

Anthony Marsella, Ph.D.

Associate Professor

Department of Psychology

University of Hawaii

Honolulu, Hawaii 96822

Nancy K. Mello, Ph.D.

Associate Professor

Alcohol and Drug Abuse Research

Center

Harvard Medical School

The McLean Hospital

Belmont, Massachusetts 02178

J. Fred E. Shick, M.D.

Research Associate

(Assistant Professor)

Department of Psychiatry

University of Chicago

5737 Drexel Avenue

Chicago, Illinois 60637

Alexander T. Shulgin, Ph.D.

Consultant

1483 Shulgin Road

LaFayette, California 94549

Ronald K. Siegel, Ph.D.

Brentwood Veterans Administration

Hospital 530/151D

Research Trailer 350

Los Angeles, California 90073

David E. Smith, M.D.

President, Youth Projects Medical

Director

Haight-Ashbury Free Medical Clinic

1698 Haight Street

San Francisco, California 94117

Donald R. Wesson, M.D.

Department of Psychiatry

University of California Medical

School

Private office at:

2999 Regent Street! Suite 501

Berkeley, California 94705

Richard Wyatt, M.D.

Director, Division of Special

Mental Health Research

Chief of Laboratory of Clinical

Psychopharmacology

William A. White Building

St. Elizabeth’s Hospital, NIMH

Washington, D.C. 20032

NIDA STAFF

National Institute on Drug Abuse

5600 Fishers Lane

Rockville, Maryland 20857

Dorynne Czechowicz, M.D.

Special Assistant to Director

for Medical Affairs

Division of Community Assistance

Robert C. Petersen, Ph.D.

(Conference Moderator)

Assistant Director for Program

Integration and Coordination

Division of Research

Richard C. Stillman, M.D.

(Conference Moderator)

Staff Psychiatrist

Clinical/Behavioral Branch

Division of Research

310
monograph series

While limited supplies last, single copies of the monographs may be

obtained free of charge from the National Clearinghouse for Drug

Abuse Information (NCDAI). Please contact NCDAI also for

information about availability of coming issues and other

publications of the National Institute on Drug Abuse relevant to

drug abuse research.

Additional copies may be purchased from the U.S. Government Printing

Office (GPO) and/or the National Technical Information Service

(NTIS) as indicated. NTIS prices are for paper copy. Microfiche

copies, at $4.50, are also available from NTIS. Prices from either

source are subject to change.

Addresses are:

NCDAI

National Clearinghouse for Drug Abuse Information

Room 1OA-43

5600 Fishers Lane

Rockville, Maryland 20857

GPO NTIS

Superintendent of Documents National Technical Information

U.S. Government Printing Office Service

Washington, D.C. 20402 U.S. Department of Commerce

Springfield, Virginia 22161

1 FINDINGS OF DRUG ABUSE RESEARCH. Not available from NCDAI.

Vol. 1: GPO out of stock NTIS PB #272 867/AS $32.50

Vol. 2: GPO out of stock NTIS PB #272 868/AS $29.50

2 OPERATIONAL DEFINITIONS IN SOCIO-BEHAVIORAL DRUG USE RESEARCH

1975. Jack Elinson, Ph.D., and David Nurco. Ph.D., eds. Not

available from NCDAI.

GPO out of stock NTIS PB #246 338/AS $16

3 AMINERGIC HYPOTHESES OF BEHAVIOR: REALITY OR CLICHE? Bruce J.

Bernard, Ph.D., ed. Not available from NCDAI.

GPO Stock #017-024-00486-3 $6.50 NTIS PB #246 687/AS $16

311
4 NARCOTIC ANTAGONISTS: THE SEARCH FOR LONG-ACTING PREPARATIONS.

Robert Willette, Ph.D., ed.

GPO out of stock NTIS PB #247 096/AS $8.50

5 YOUNG MEN AND DRUGS: A NATIONWIDE SURVEY. John A. O'Donnell,

Ph.D., et al. Not available from NCDAI.

GPO Stock #017-024-00511-8 $6.50 NTIS PB #247 446/AS $16

6 EFFECTS OF LABELING THE "DRUG ABUSER": AN INQUIRY. Jay R.

Williams, Ph.D. Not available from NCDAI.

GPO Stock #017-024-00512-6 $4.75 NTIS PB #249 092/AS $8.50

7 CANNABINOID ASSAYS IN HUMANS. Robert Willette, Ph.D., ed.

GPO Stock #017-024-00510-O $6.00 NTIS PB #251 905/AS $14.50

8 Rx: 3x/WEEK LAAM - ALTERNATIVE TO METHADONE. Jack Blaine, M.D.,

and Pierre Renault, M.D., eds.

Not available from GPO NTIS PB #253 763/AS $14.50

9 NARCOTIC ANTAGONISTS: NALTREXONE PROGRESS REPORT. Demetrios

Julius, M.D., and Pierre Renault, M.D., eds. Not available from

NCDAI.

GPO Stock #017-024-00521-5 $7.00 NTIS PB #255 833/AS $17.50

10 EPIDEMIOLOGY OF DRUG ABUSE: CURRENT ISSUES. Louise G. Richards,

Ph.D., and Louise B. Blevens, eds. Not available from NCDAI.

GPO Stock #017-024-00571-1 $6.50 NTIS PB #266 691/AS $22

11 DRUGS AND DRIVING. Robert Wlllette, Ph.D., ed. Not available

from NCDAI.

GPO Stock #017-024-00576-2 $5.50 NTIS PB #269 602/AS $16

12 PSYCHODYNAMICS OF DRUG DEPENDENCE. Jack D. Blaine, M.D., and

Demetrios A. Julius, M.D., eds. Not available from NCDAI.

GPO Stock #017-024-00642-4 $5.50 NTIS PB #276 084/AS $17.50

13 COCAINE: 1977. Robert C. Petersen, Ph.D., and Richard C.

Stillman, M.D., eds. Not available from NCDAI.

GPO Stock #017-024-00592-4 $6.00 NTIS PB #269 175/AS $19

14 MARIHUANA RESEARCH FINDINGS: 1976. Robert C. Petersen, Ph.D..

ed. Not available from NCDAI.

GPO out of stock NTIS PB #271 279/AS $22

15 REVIEW OF INHALANTS: EUPHORIA TO DYSFUNCTION. Charles Wm.

Sharp, Ph.D., and Mary Lee Brehm, Ph.D., eds.

GPO Stock #017-024-00650-5 $7.50 NTIS PB #27S 798/AS $28

16 THE EPIDEMIOLOGY OF HEROIN AND OTHER NARCOTICS. Joan Dunne

Rlttenhouse, Ph.D., ed. Not available from NCDAI.

GPO Stock #017-024-00690-4 $6.50 NTIS PB #276 357/AS $20.50

312
17 RESEARCH ON SMOKING BEHAVIOR. Murray E. Jarvik, M.D., Ph.D.,

et al., eds. Includes epidemiology, etiology, consequences of

use, and approaches to behavioral change. From a NIDA-supported

UCLA conference.

GPO Stock #017-024-00694-7 $7.50 NTIS PB #276 353/AS $29.50

18 BEHAVIORAL TOLERANCE: RESEARCH AND TREATMENT IMPLICATIONS.

Norman A. Krasnegor, Ph.D., ed. Theoretical and empirical studies

of nonpharmacologic factors in development of drug tolerance.

GPO Stock #017-024-00699-8 $5.50 NTIS PB #276 337/AS $16

19 THE INTERNATIONAL CHALLENGE OF DRUG ABUSE. Robert C. Petersen,

Ph.D., ed. Papers from the VI World Congress of Psychiatry.

GPO Stock #017-024-00822-2 $7.50 NTIS PB #293 807/AS $28

20 SELF-ADMINISTRATION OF ABUSED SUBSTANCES: METHODS FOR STUDY.

Norman A. Krasnegor, Ph.D., ed. Techniques used to study basic

processes underlying abuse of drugs, ethanol, food, and tobacco.

GPO Stock #017-024-00794-3 $6.50 NTIS PB #288 471/AS $22

21 PHENCYCLIDINE (PCP) ABUSE: AN APPRAISAL. Robert C. Petersen,

Ph.D., and Richard C. Stillman, M.D., eds. for clinicians and

researchers, assessing the problem of PCP abuse.

GPO Stock #017-024-00785-4 $7.00 NTIS PB #288 472/AS $25

22 QUASAR: QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS OF

ANALGESICS, NARCOTIC ANTAGONISTS, AND HALLUCINOGENS. Gene

Barnett. Ph.D.; Milan Trsic, Ph.D.; and Robert Willette, Ph.D.;

eds. Not available from NCDAI.

GPO Stock #017-024-00786-2 $8.00 NTIS PB #292 265/AS $35.50

23 CIGARETTE SMOKING AS A DEPENDENCE PROCESS. Norman A.

Krasnegor, Ph.D., ed. Discusses factors involved in the onset,

maintenance, and cessation of the cigarette smoking habit.

Includes an agenda for future research.

GPO Stock #017-024-00895-8 $6.00 NTIS PB #297 721/AS $19

24 SYNTHETIC ESTIMATES FOR SMALL AREAS: STATISTICAL WORKSHOP

PAPERS AND DISCUSSION. Jos. Steinberg, ed. Papers from a workshop on statistical approaches that yield needed estimates of

data for States and local areas. Not available from NCDAI.

GPO Stock #017-024-00911-3 $8.00 NTIS PB #299 009/AS $23.50

25 BEHAVIORAL ANALYSIS AND TREATMENT OF SUBSTANCE ABUSE. Norman

A. Krasnegor, Ph.D., ed. Papers on commonallties and

implications for treatment of dependency on drugs, ethanol, food,

and tobacco.

GPO Stock #017-024-00939-3 $5.00 NTIS PB #80-112428 $22

26 THE BEHAVIORAL ASPECTS OF SMOKING. Norman A. Krasnegor, Ph.D.,

ed. Reprint of the behavioral section of the 1979 Report of the

Surgeon General on Smoking and Health; introduction by editor.

GPO out of stock NTIS PB #80-118755 $17.50

313
27 PROBLEMS OF DRUG DEPENDENCE, 1979: PROCEEDINGS OF THE 41ST

ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS OF DRUG DEPENDENCE, INC. L.S. Harris, Ph.D., ed. Not available from NCDAI.

GPO Stock #O17-024-00981-4 $9.00 NTIS PB #80-175482 $37

28 NARCOTIC ANTAGONISTS: NALTREXONE PHARMACOCHEMISTRY AND

SUSTAINED-RELEASE PREPARATIONS. Robert Willette, Ph.D., and

Gene Barnett, Ph.D., eds. Papers report research on sustainedrelease and long-acting devices for use with the narcotic antagonist naltrexone. Not available from NCDAI.

GPO Stock #017-024-01081-2 $7.00 NTIS PB #81-238875 $23.50

29 DRUG ABUSE DEATHS IN NINE CITIES: A SURVEY REPORT. Louis A.

Gottschalk. M.D., et al. Not available from NCDAI.

GPO Stock #O17-024-00982-2 $6.50 NTIS PB #80-178882 $17.50

30 THEORIES ON DRUG ABUSE: SELECTED CONTEMPORARY PERSPECTIVES.

Dan J. Lettieri, Ph.D.; Mollie Sayers; and Helen Wallenstein

Pearson, eds. Volume presents summaries of major contemporary

theories of drug abuse by each of 43 leading theorists.

GPO Stock #017-024-00997-1 $10.00 Not available from NTIS

31 MARIJUANA RESEARCH FINDINGS: 1980. Robert C. Petersen, Ph.D.,

ed. The text of the 8th Marijuana and Health report to Congress

and the background scientific papers on which it was based.

GPO out of stock NTIS PB #80-215171 $20.50

32 GC/MS ASSAYS FOR ABUSED DRUGS IN BODY FLUIDS. Rodger L. Foltz,

Ph.D.; Allison F. Fentiman. Jr., Ph.D.; and Ruth 6. Foltz. A

collection of methods for quantitative analysis of several

important drugs of abuse by gas chromatography- mass spectrometry.

GPO Stock #017-024-01015-4 $6.00 NTIS PB #81-133746 $19

33 BENZOOIAZEPINES: A REVIEW OF RESEARCH RESULTS, 1980. Stephen

I. Szara, M.D., D.Sc., and Jacqueline P. Ludford. M.S., eds.

A RAUS (Research Analysis and Utilization System) Review Report

on the abuse liability of the benzodiazepine "tranquilizers."

GPO Stock #017-024-01108-8 $5.00 NTIS PB #82-139106 $13

34 PROBLEMS OF DRUG DEPENDENCE, 1980: PROCEEDINGS OF THE 42ND

ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS OF DRUG

DEPENDENCE, INC. Louis S. Harris, Ph.D., ed. Not available from

NCDAI.

GPO Stock #017-024-01061-8 $8.00 NTIS PB #81-194847 $34

35 DEMOGRAPHIC TRENDS AND DRUG ABUSE, 1980-1995. Louise G.

Richards, Ph.D., ed. Estimates of probable extent and nature of

nonmedical drug use, 1980-1995, based on age structure and other

characteristics of U.S. population.

GPO Stock #017-024-01087-1 $4.50. NTIS PB #82-103417 $13

314
36 NEW APPROACHES TO TREATMENT OF CHRONIC PAIN: A REVIEW OF MULTIDISCIPLINARY PAIN CLINICS AND PAIN CENTERS. Lorenz K.Y. Ng. M.D..

ed. Discussions by active practitioners in the treatment of pain.

GPO Stock #017-024-01082-1 $5.50. NTIS PB #81-240913 $19

37 BEHAVIORAL PHARMACOLOGY OF HUMAN DRUG DEPENDENCE. Travis

Thompson, Ph.D., and Chris E. Johanson, Ph.D., eds. Presents a

growing body of data, systematically derived, on the behavioral

mechanisms involved in use and abuse of drugs.

GPO Stock #017-024-01109-6 $6.50 NTIS PB #82-136961 $25

38 DRUG ABUSE AND THE AMERICAN ADOLESCENT. Dan J. Lettieri,

Ph.D., and Jacqueline P. Ludford, M.S., eds. A RAUS Review

Report, emphasizing use of marijuana: epidemiology, sociodemographic and personality factors, family and peer influence,

delinquency, and biomedical consequences.

GPO Stock #017-024-01107-O $4.50 NTIS PB #82-148198 $14.50

39 YOUNG MEN AND DRUGS IN MANHATTAN: A CAUSAL ANALYSIS.

Richard R. Clayton, Ph.D., and Harwin L. Voss, Ph.D. Examines

the etiology and natural history of drug use, with special focus

on heroin. Includes a Lifetime Drug Use Index.

GPO Stock #017-024-01097-9 $5.50 NTIS PB #82-147372 $19

40 ADOLESCENT MARIJUANA ABUSERS AND THEIR FAMILIES. Herbert

Hendin, M.D., Ann Pollinger, Ph.D.. Richard Ulman, Ph.D., and

Arthur Carr, Ph.D. A psychodynamic study of adolescents

involved in heavy marijuana use, to determine what interaction between family and adolescent gives rise to drug abuse.

GPO Stock #017-024-01098-7 $4.50 NTIS PB #82-133117 $13

41 PROBLEMS OF DRUG DEPENDENCE, 1981: PROCEEDINGS OF THE 43RD

ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS OF DRUG

DEPENDENCE, INC. Louis S. Harris, Ph.D., ed. Not available from

NCDAI.

Not available from GPO NTIS PB #82-190760 $41.50

42 THE ANALYSIS OF CANNABINOIDS IN BIOLOGICAL FLUIDS. Richard L.

Hawks, Ph.D., ed. Varied approaches to sensitive, reliable, and

accessible quantitative assays for the chemical constitutents of

marijuana, for researchers. Not available from NCDAI.

GPO Stock #017-024-01151-7 $5 NTIS PB #83-136044 $16

43 PROBLEMS OF DRUG DEPENDENCE, 1982: PROCEEDINGS OF THE 44TH

ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS OF DRUG

DEPENDENCE, INC. Louis S. Harris, Ph.D.. ed. Not available from

NCDAI.

GPO Stock #017-024-01162-2 $8.50 NTIS PB #83-252-692/AS $40

315
44 MARIJUANA EFFECTS ON THE ENDOCRINE AND REPRODUCTIVE SYSTEMS.

Monique C. Braude, Ph.D., and Jacqueline P. Ludford. M.S., eds.

A RAUS Review Report of animal studies and preclinical and

clinical studies of effects of cannabinoids on human endocrine

and reproductive functions.

GPO Stock #017-024-01202-5 $4. NTIS PB #85-150563/AS $14.50

45 CONTEMPORARY RESEARCH IN PAIN AND ANALGESIA, 1983. Roger M.

Brown, Ph.D.; Theodore M. Pinkert, M.D., J.D.; and Jacqueline P.

Ludford, M.S., eds. A RAUS Review Report on the anatomy,

physiology, and neurochemistry of pain and its management.

GPO Stock #017-024-01191-6 $2.75 NTIS PB #84-184670/AS $11.50

46 BEHAVIORAL INTERVENTION TECHNIQUES IN DRUG ABUSE TREATMENT,

John Grabowski, Ph.D.; Maxine L. Stitzer, Ph.D., and Jack E.

Henningfield, Ph.D., eds. Reports on behavioral contingency

management procedures used in research/treatment environments.

GPO Stock #017-024-01192-4 $4.25 NTIS PB #84-184688/AS $16

47 PREVENTING ADOLESCENT DRUG ABUSE: INTERVENTION STRATEGIES.

Thomas J. Glynn, Ph.D.; Carl G. Leukefeld, D.S.W.; and

Jacqueline P. Ludford. M.S., eds. A RAUS Review Report on a

variety of approaches to prevention of adolescent drug abuse, how

they can be applied, their chances for success, and needed future

research.

GPO Stock #017-024-01180-1 $5.50 NTIS PB #85-159663/AS $22

48 MEASUREMENT IN THE ANALYSIS AND TREATMENT OF SMOKING

BEHAVIOR. John Grabowski, Ph.D., and Catherine S. Bell, M.S.,

eds. Based upon a meeting cosponsored by NIDA and the National

Cancer Institute to delineate necessary and sufficient measures

for analysis of smoking behavior in research and treatment

ettings.

GPO Stock #017-024-01181-9 $4.50 NTIS PB 84-145-184 $14.50

49 PROBLEMS OF DRUG DEPENDENCE, 1983: PROCEEDINGS OF THE 45TH

ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS OF DRUG

DEPENDENCE, INC. Louis S. Harris, Ph.D., ed. A collection of

papers which together record a year's advances in drug abuse

research; also includes reports on tests of new compounds for

efficacy and dependence liability.

GPO Stock #017-024-01198-3 $12 NTIS PB 85-159663/AS $22

50 COCAINE: PHARMACOLOGY, EFFECTS, AND TREATMENT OF ABUSE. John

Grabowski. Ph.D., ed. Content ranges from an introductory

overview through neuropharmacology, pharmacology, animal and

human behavioral pharmacology, patterns of use in the natural

environment of cocaine users, treatment, through commentary on

societal perceptions of use.

GPO Stock #017-020-01214-9 $4 NTIS PB 85-150381/AS $14.50

316
51 DRUG ABUSE TREATMENT EVALUATION: STRATEGIES, PROGRESS, AND

PROSPECTS. Frank M. Tims, Ph.D., ed. A state-of-the-art review

of drug abuse treatment evaluation, identifying research needs,

promising approaches, and emerging issues.

GPO Stock #017-020-01218-1 $4.50 NTIS PB 85-150365/AS $17.50

52 TESTING DRUGS FOR PHYSICAL DEPENDENCE POTENTIAL AND ABUSE

LIABILITY. Joseph V. Brady, Ph.D., and Scott E. Lukas, Ph.D.,

eds. Describes animal and human test procedures for assessing

dependence potential and abuse liability of opioids, stimulants,

depressants, hallucinogens, cannabinoids, and dissociative

anesthetics.

GPO Stock #017-024-0204-1 $4.25 NTIS PB 85-150373/AS $16

54 MECHANISMS OF TOLERANCE AND DEPENDENCE. Charles Wm. Sharp,

Ph.D., ed. Review of basic knowledge concerning the mechanism of

action of opiates and other drugs in producing tolerance and/or

dependence.

GPO Stock #017-024-01213-1 $8.50 NTIS PB No. to be assigned.

55 PROBLEMS OF DRUG DEPENDENCE, 1984. PROCEEDINGS OF THE 46TH

ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS OF DRUG

DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

IN PRESS OR PREPARATION

53 PHARMACOLOGICAL ADJUNCTS IN SMOKING CESSATION.

John Grabowski. Ph.D., ed.

56 ETIOLOGY OF DRUG ABUSE: IMPLICATIONS FOR PREVENTION. Coryl

LaRue Jones, Ph.D., and Robert J. Battjes, D.S.W., eds.

57 SELF-REPORT METHODS OF ESTIMATING DRUG USE: MEETING CURRENT

CHALLENGES TO VALIDITY. Beatrice A. Rouse, Ph.D., Nicholas J.

Kozel, M.S., and Louise G. Richards, Ph.D., eds.

58 PROGRESS IN THE DEVELOPMENT OF COST-EFFECTIVE TREATMENT FOR

DRUG ABUSERS. Rebecca S. Ashery, D.S.W.. ed.

59 CURRENT RESEARCH ON THE CONSEQUENCES OF MATERNAL DRUG ABUSE.

Theodore M. Pinkert, M.D., J.D., ed.

60 PRENATAL DRUG EXPOSURE: KINETICS AND DYNAMICS. C. Nora

Chiang, Ph.D., and Charles C. Lee, Ph.D., eds.

317
DHHS Publication No. (ADM) 85-728

Printed 1978 Reprinted 1979, 1984, 1985