COCAINE: 1977

EDITORS: Robert C. Petersen, Ph.D.

Richard C. Stillman, M.D.

NIDA Research Monograph #13

May 1977

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EDITORIAL ADVISORY BOARD

Addiction Research Foundation

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College of Physicians and Surgeons

Columbia University, New York

Langley Porter Neuropsychiatric Institute

University of California

San Fransisco, California

William McGlothlln, Ph.D. Department of Psychology, UCLA

Los Angeles,California

Jack Mendelson, M.D.

Avram Goldstein, M.D.

Jerome Jaffe, M.D.

Reese T. Jones, M.D.

Alcohol and Drug Abuse Research Center

Harvard Medical School

McLean Hospital

Belmont, Massachusetts

Helen Nowlis, Ph.D. Office of Drug Education, DHEW

Washington, D.C.

Lee Robins, Ph.D. Washington University School of Medicine

St. Louis, Missouri

NIDA RESEARCH MONOGRAPH series

Robert DuPont, M.D. DIRECTOR, NIDA

William Pollin, M.D. DIRECTOR, DIVISION OF RESEARCH, NIDA

Robert C. Petersen, Ph.D. EDITOR-IN-CHIEF

Eunice L. Corfman, M.A. EDITOR

Rockwall Building 11400 Rockville Pike Rockville, Maryland, 20852
COCAINE: 1977
ACKNOWLEDGMENT

Support services for the development of this

monograph were provided by Koba Associates, Inc.

under NIDA Contract No. 271-76-3332.

Other publications on cocaine are available in the

NIDA Division of Research Research Issues series.

Numbers and titles are:

8 A COCAINE BIBLIOGRAPHY -- NONANNOTATED

15 COCAINE -- SUMMARIES OF PSYCHOSOCIAL RESEARCH

16 THE LIFESTYLES OF NINE AMERICAN COCAINE USERS

DHEW publication number (ADM) 77-471

Library of Congress catalog card number 77-77787

Publications in the NIDA Research Monograph series

are indexed in Index Medicus.
FOREWORD

Increasing chemical sophistication has brought a bewildering array

of drugs that produce feelings people like. Despite this increase

in the number of abusable psychoactive drugs, a few plant substances

have been the dominant psychochemical influence in many cultures

over millennia. One of these is the coca bush. Unlike tobacco,

marihuana, and opium, it has been geographically restricted --

primarily to the Andes mountains of South America, where its leaves

continue to be chewed by millions of Indians on a daily basis.

For most Americans, it comes as a surprise to realize that much

traditional drug use around the world has been and continues to be

work-related, rather than recreational. Contrary to expectations

based on modern pharmacology, this is true of such drugs as cannabis, opium, tobacco, and it is even more characteristic of the coca

leaf. In fact, the most compelling analogy to Andean coca chewing

is American coffee drinking as a work adjunct.

In most cultures over most of history, use of such substances as

coca, cannabis and opium has existed in a cultural context which

tended to moderate and restrict use.

During the last century, traditional patterns of drug use have been

increasingly, often profoundly, modified. The availability of the

concentrated psychoactive ingredients of traditional drug substances in purified form together with such new routes of administration as intravenous injection has markedly altered the drug

picture. Simultaneously with these pharmacological developments,

traditional cultures all over the world have been losing their

power. In addition, the numbers of people exposed to each psychoactive substance have grown dramatically.

Cocaine, the principal psychoactive ingredient of the coca plant,

has been a part of this trend. The purified drug was isolated a

little more than a hundred years ago. The leaves of the coca plant

are typically chewed or used for a tea in traditional settings of

use. By contrast, their psychoactive ingredients, from fifty to a

hundred times more concentrated, may be "snorted" (like snuff),

injected or smoked. The traditional customs that have governed coca

use in South America’s mountains are largely absent with respect to

cocaine.
Despite the spurt of scientific interest in cocaine when it was

first isolated and despite the drug’s limited medical use as a local

anesthetic, our knowledge of cocaine as a psychoactive substance is

modest. For most of the last half century, use was restricted to a

comparative few. The amount of research that was conducted using

modern pharmacological techniques was correspondingly small. Four

years ago, the awareness of increasing cocaine use and the realization of how little we know led the National Institute on Drug Abuse

to launch the present high priority cocaine research effort. About

a million dollars a year has been spent in the intervening period to

support 40 research projects exploring aspects of cocaine from the

chemistry of the substance to the characteristics of users.

This volume summarizes our current understanding of cocaine. One of

the most notable aspects of our knowledge is that so much is not yet

known. We are still, to a large extent, ignorant of the actual and

potential health hazards posed by this fascinating substance, even

though it was used by about two million Americans this past year.

Despite obvious knowledge limitations, we do know a few things that

are important: We know, for example, that cocaine can kill -- not

commonly but occasionally and perhaps not predictably. Despite the

street lore to the contrary, death sometimes occurs even when the

drug is snorted rather than injected. We also know that cocaine is

among the most powerfully reinforcing of all abused drugs. Although

not physically addictive in the sense that the opiates are, there is

good evidence that the desire to continue use when available is

remarkably strong. The relatively benign picture presented by

occasional use of small quantities might be markedly altered were

the single euphoric illicit dose now costing about $10 available at

the licit cost of about ten cents.

While the evidence accumulated thus far does not justify the claim

that the American public is now suffering greatly as a consequence

of cocaine use, it is evident that much more needs to be known

before any actions are taken that might result in a wider availability at lower cost.

In the tradition of the Marihuana and Health Reports, we at NIDA are

proud to publish our first major report describing what is known and

not known about cocaine and its implications for health. We hope

that this book will serve not only as a useful reference work for

clinicians and scientists interested in the area, but also that it

will become a useful document for those interested in applying

modern scientific knowledge to the serious social policy questions

associated with cocaine use in America today.

Robert L. DuPont, M.D.

Director

National Institute on Drug Abuse
CONTENTS

Foreword v

Robert L. DuPont, M.D.

Introduction

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

1

Cocaine: An Overview 5

Robert C. Petersen, Ph.D.

Chapter I History of Cocaine 1 7

Robert C. Petersen, Ph.D.

Chapter II Coca: The Plant and Its Use 3 5

Eleanor Carroll, M.A.

Chapter III Cocaine: The Material 4 7

Richard Hawks, Ph.D.

Chapter IV Behavioral Effects of Cocaine in Animals 63

James Woods, Ph.D.

Chapter V What are the Effects of Cocaine in Man? 9 7

Robert Byck, M.D. and Craig Van Dyke, M.D.

Chapter VI Cocaine: Recreational Use and Intoxication 119

Ronald K. Siegel, Ph.D.

Chapter VII Cocaine: Its Use for Central Nervous System Stimulation

Including Recreational and Medical Uses 137

Donald R. Wesson, M.D. and David E. Smith, M.D.

Chapter VIII The Forensic Toxicology of Cocaine

Bryan S. Finkle, Ph.D. and Kevin L. McCloskey, Ph.D.

153

Chapter IX Cocaine in Clinical Medicine 193

Paul G. Barash, M.D.

Chapter X Characteristics of Clients Admitted to Treatment for

Cocaine Abuse 201

Eduardo Siguel, Ph.D.

Author Index 211

Subject Index 215

List of Monographs 222

INTRODUCTION

The marked rise in interest in the use of illicit drugs in the past

decade has brought with it renewed interest in a drug with a long

and romantic history. As with other "recreational" drugs, cocaine

has elicited uncritical enthusiasm in some while others better acquainted with its earlier history have viewed it with alarm.

Cocaine today is perceived by many users as being a physically and

psychologically safe recreational drug. It is also an extremely

well liked drug. In one recent survey of 100 drug-using college

students (Stillman, pers. comn.), cocaine was the recreational drug

of choice of all but 2 of the 29 students who had tried it. From

their standpoint the only limitations on its use were its high cost

and lack of availability. Yet if cocaine becomes cheaper and more

readily available dosages will undoubtedly rise and the more unpleasant and dangerous aspects of the drug may become more apparent.

Although the data presented in this volume show that cocaine as

typically used in the United States at present poses only a limited

hazard, these same data also demonstrate that it can be physically

dangerous in ways that marihuana, for example, is not.

The present volume represents an attempt to summarize our admittedly limited knowledge of cocaine through a series of reports by

leading workers in the cocaine area. They range from animal

behaviorists conducting research at the preclinical level to clinicians contending with the problems of the street user. The emphasis

is on developing a picture of our current knowledge with special

attention to its limitations. The authors have not tried to gloss

over the areas of ignorance that exist nor to substitute unsubstantiated opinion for authoritative data. It is our belief that the

needs of all readers - from the interested layman to the practicing

clinician -- are better served by as objective an assessment as is

now possible rather than by more dogmatic assertions.

Although the present volume cannot be totally comprehensive, we

hope that it will serve as a useful "map" of the larger domain. To

that end a brief description of the contents of the various sections

may be helpful:

An overview of what is presently known about cocaine is

primarily intended to provide a non-technical review of

our present knowledge about the drug and to provide some

overall perspective.

1
The chapter on the history of coca and cocaine provides a

brief historical review which may be useful in placing

present use in a larger time perspective.

Ms. Eleanor Carroll, in her chapter on coca use and its

health implications, examines briefly what is known about

various aspects of the use of the plant material from which

cocaine is derived. While coca chewing is not part of the

U.S. drug scene, there has been considerable interest and

some confusion concerning the differing implications of

use of the plant material from that of the pure drug.

The chapter on the material itself by Dr. Richard Hawks

describes the chemistry of cocaine with particular attention to newer analytic methods for the detection of the

drug and its metabolites.

Dr. James Woods in his chapter on animal behavioral research summarizes the effects of cocaine on a wide range of

behavior and critically evaluates the evidence for and

against several proposed mechanisms of action of the drug.

Drs. Robert Byck and Craig Van Dyke provide a succinct

review of the known effects of cocaine in man. A meticulously constructed table of source material accompanies

their discussion and gives a clear indication of the

adequacy and limitations of the reports on which our

knowledge is based.

Dr. Ronald Siegel describes a detailed survey of a sample

of cocaine users providing a quantitative assessment of

the styles of use and reactions to the drug on the part of

some 85 users. He also describes a type of hallucinatory phenomenon reported by users which appears to be more

common than previously believed.

Drs. David Smith and Donald Wesson contribute their insights into street use of cocaine from the vantage point of

a "free clinic" in the Haight-Ashbury area of San Francisco, their association with the San Francisco Polydrug

Research Project and from their extensive clinical experience with drug users. They document their concern

that cocaine use may be significantly more hazardous than

marihuana use and that the psychological dangers of sustained heavier use are not to be dismissed lightly.

Drs. Bryan Finkle and Kevin McCloskey -- based on an

intensive study of cocaine-related deaths in the United

States and Canada -- analyze mortality connected with use.

2
While the number of deaths that were documented was small

(26 due to cocaine alone in a population of 63,000,000 over

a 5-year period), their findings suggest that cocaine use,

even by "snorting", can be occasionally and unpredictably

fatal.

Dr. Paul Barash in his chapter on current uses of cocaine

in clinical. medicine provides a review of the present

status of the drug as an anesthetic possessing some

uniquely desirable properties. He also describes hospital

treatment for cocaine overdoses.

Finally, in a brief chapter based on a nationwide Federal

drug abuse treatment monitoring system (CODAP), Dr.

Eduardo Siguel describes the characteristics of patients

seeking treatment for whom cocaine abuse is a prominent

feature.

A modest degree of overlap of content has been retained in sane of

the chapters in order to facilitate understanding should each be

read in isolation.

Although cocaine use and abuse has many broader implications related to the problems of social policy and drug abuse control, those

aspects seem more appropriately dealt with in a different context

from that of the health implications. Nevertheless, it is our hope

that this compendium will provide up-to-date information that contributes usefully to better informed discussion of the broader

social issues that cocaine use entails.

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

National Institute on Drug Abuse

3

COCAINE: AN OVERVIEW

Robert C. Petersen, Ph.D.

WHAT IS IT?

Cocaine is a naturally occurring stimulant drug which is extracted

from the leaves of the coca plant (Erythroxylon coca). The leaves

of this Western South American shrub have been chewed by Bolivian

and Peruvian Indians since antiquity for a variety of religious,

medicinal and work-related reasons (cf., Petersen, Chapter 1;

Carroll, Chapter 2, this volume). Allegedly, the chewing of coca

leaves has enabled the Indians to work under extremely arduous

conditions of high altitude and inadequate diet. This chewing of

the coca leaf which continues to the present day should not,

however, be confused with the use of the extracted drug, cocaine.

Coca leaves contain only about 1⁄2-1 percent cocaine; the cocaine

contained within them is released more slowly and the route of

administration is different (oral) from that of most cocaine use.

Because reports of native coca use had generated considerable

interest in Europe, efforts were made in the 19th century to isolate

the purified psychoactive ingredient in coca leaves. When success

in isolating cocaine was achieved in the 1880's, its potential value

as a tonic, its general stimulant properties, its possible value for

specific ailments and its local anesthetic properties were

explored. Its use as an anesthetic was particularly important

because it could be used in eye surgery for which no previous drug

had been suitable. A second desirable property of cocaine when used

as a local anesthetic was (and is) its ability to constrict blood

vessels and thus limit bleeding in the anesthetized area. This made

it especially valuable for surgery involving the nose and throat,

areas richly supplied with blood. Although many of cocaine's uses

as a therapeutic drug have been abandoned, its use as a local

anesthetic for specific medical purposes continues (cf. Barash,

Chapter 9).

Illicit cocaine is sold as a white translucent crystalline powder

frequently adulterated to about half its volume by a variety of

other ingredients. The most common adulterants are various sugars

(especially, lactose and glucose) and other local anesthetics

(lidocaine, procaine and tetracaine) with similar appearance and

taste to cocaine. The amphetamines, other drugs with stimulant

properties, are also sometimes used. Given the very high cost of

the drug, the temptation to adulterate at each level of sale is

great. The current street price (1977) may range from $60-$100 a

gram (about 1/30 of an ounce). The combination of the very high

price and the exotic properties attributed to it have contributed to

cocaine's street reputation as the status drug.

5
WHO USES COCAINE?

Determining the nature and extent of illicit drug use poses formidable problems. This is particularly true when assessing present

patterns and trends in cocaine use, which is thought to be used only

by certain segments of the population. Because the street drug is

typically adulterated to varying degrees, even self-reports of use

offered in good faith may be inadequate. The more naive experimenter may believe s/he is using cocaine when, in fact, s/he is

actually consuming an amphetamine or cocaine adulterated extensively by other substances.

While cocaine and coca extracts were widely used in patent medicine,

wines and soft drinks at the turn of the century, it is virtually

impossible to get any reliable estimates of who was using them and

in what quantities. And, aside from clinical reports, there are no

statistics indicating the number and kinds of adverse reactions

occurring among those users.

Figures dealing with Federal seizures of cocaine are of limited

value. The amounts confiscated are small compared to the total

imported and fluctuations in success in intercepting shipments can

result in substantial variations in quantities seized from year to

year which may not reflect levels of actual use.

Data from the several national interview surveys that have been

conducted in 1972, 1974 and 1975/76 have some value, but because

they are household surveys they are unlikely to include transient

street populations or to accurately reflect use in high status

professional, artistic or creative circles in which there are

anecdotal reports of widespread use. The honesty of respondents

will also determine the levels of use reported, and this candor may

vary from year to year. Despite these obvious limitations, the last

several years of uniformly collected nationwide data are still of

considerable interest. Among adults (those over 18) the percentage

reporting ever having tried cocaine'in all three surveys has been 3-

4 percent. The percentage of adults reporting having used in the

month preceding each of the surveys has been consistently just under

1 percent. The figures for youth -- those 12-17 -- have been

approximately the same as for adults. While there have been minor

fluctuations from year to year, the numbers involved are too small

to know whether the differences are real or simply variations to be

expected from sampling differences.

In the 18-25-year-old group, the peak age group for all illicit drug

use, nearly one in eight (13.4 percent) report having ever used

cocaine and of those who have, nearly one in six (2 percent of the

entire group) had done so in the month preceding the most recent

(1975/76) survey. Comparable figures for marihuana use in 1975/76

are much higher -- nearly four times as many young adults 18-25

(52.9 percent) have tried marihuana, almost half of those within the

past month.

6
A nationwide study of young men and drugs conducted in 1974 with a

random national sample of men between 20 and 30 provides additional

confirming evidence of use by young adults. Of this group 14

percent reported having ever used cocaine, half within the year

preceding the survey. At least in this sample it is also clear that

the likelihood of having used cocaine is much greater if one has

used other licit and illicit drugs (though not necessarily implying

a causal sense). Of those who had ever used cocaine, all had used

alcohol and marihuana and nearly all (96 percent) tobacco. More

than 7 out of 10 had also used sedatives, opiates (excluding

heroin), psychedelics or other stimulants. Almost two out of five

(38 percent) of those who had used cocaine had also tried heroin

(O'Donnell et al., 1976).

A nationwide study specifically aimed at high school seniors is of

interest because of their transitional status between adolescence

and adulthood. In this group, 9 percent of the 1975 senior class

reported having tried cocaine in 1975 and 9.8 percent in 1976 -- the

increase is too small to be certain it is not simply a result of

sampling variation. About 1 in 100 seniors in each of the 2 classes

reported having used cocaine 20 or more times. Most seniors

reported relatively conservative attitudes toward cocaine (and

other regular drug use) -- nearly 19 out of 20 disapproved of the

regular use of cocaine and more than 4 out of 5 disapproved of even

trying the substance (Johnston, 1976).

Another measure that has sometimes proven useful in indicating

trends in drug use, especially as reflected in medical emergencies

resulting from such use, is the DAWN system (a Drug Abuse Warning

Network operated by the Federal government). DAWN receives reports

of drug related emergencies from 24 standard metropolitan

statistical areas, each of which transmits data from such facilities as crisis centers, emergency rooms and medical examiners.

Although the number of cocaine-related emergencies is presently too

small to provide a reliable indicator of cocaine use trends, the

most recently available figures are still of some interest. During

the one year period from May, 1975 to April, 1976, cocaine alone or

in combination with other drugs was mentioned in connection with

less than 1 percent of emergency roan episodes involving drug use

(958 of 118,311 drug mentions). In crisis centers (facilities

established to provide "walk in" or "phone in" help to those

experiencing personal crisis) 3.6 percent of the drug related

crises involved cocaine alone or in combination with other drugs

(1,802 of 49,633 drug mentions). In both emergency roan and crisis

center episodes involving cocaine, half involved cocaine alone, the

other half cocaine in caubination with other drugs. Thus, cocaine,

contrary to some beliefs, played a role in drug-related problems

although less commonly than other drugs. Unfortunately, there is no

way of knowing how the number involved in such emergencies compares

to the number using the drug during the period involved. It may

well be that present typical patterns of American use -- sporadic

use of relatively small quantities of the drug -- make cocaine

related emergencies less likely to occur than other drug-related

emergencies.

7
Overall, most evidence suggests that there is a trend toward

increasing use of cocaine, although the exact dimensions of the

increase are not known.

While a few other studies have been done of users (cf. Siegel,

Chapter 7, this volume), there is little detailed information about

typical patterns of use.

HOW IS IT USED?

Cocaine is most commonly inhaled or "snorted" through the nose. As

a result, the drug is deposited on the mucous linings of the nose

from which it is readily absorbed into the blood stream of the user.

Repeated use in this way often results in an irritation to the

nostrils and nasal mucous membranes. Symptoms may resemble those of

a common cold, i.e., congestion or a "runny nose."

In attempting to cope with these secondary symptoms of their cocaine

use, users often resort to a variety of "cold remedies" such as

nasal sprays to relieve their chronic nasal congestion. While their

has been no systematic study of this, some users have reported that

the chronic use of nasal sprays brings with it further difficulties -- the user may find he or she is unable to breathe comfortably through the nose without habitually using a spray to keep the

nasal passages open.

A less common route of administration for cocaine is intravenous

injection directly into the blood stream. The solution injected may

be cocaine alone or sometimes a combination of heroin and cocaine.

This alternative route of administration, of course, is more dangerous because of the hazards of hepatitis and other infections

transmitted by the use of non-sterile needles and syringes. Furthermore, it introduces unknown quantities of cocaine or cocaine

and heroin directly and suddenly into the blood stream, leaving body

organs wholly unprotected from the toxic effects of the drug.

Cocaine deaths from intravenous self-administration are more numerous than from snorting despite the greater prevalence of the latter

method (Cf., Finkle and McCloskey, Chapter 8 this volume).

WHY IS IT USED?

While it is difficult to give an altogether satisfactory

explanation of why people use any drug, we can talk about what they

say about their drug use. As other chapters in this volume

illustrate (Cf., Smith and Wesson, Chapter 6; Siegel, Chapter 7)

cocaine is ranked first among recreational drugs of choice by many

experienced users because it produces a euphoria, a sense of intense

stimulation and of psychic and physical well-being accompanied by

reduced fatigue. Users ranging from Sigmund Freud to William

8
Burroughs, have waxed lyrical over cocaine’s positive attributes;

occasionally these descriptions are tempered by descriptions of

more negative implications of heavier, prolonged use.

Unlike such drugs as LSD and heroin, which are frequently viewed as

leading to a greater orientation toward self and one’s internal

processes, cocaine is considered by users as a social drug -- one

which facilitates social interaction. It is also ranked high in

desirability because of its convenience of use, rapid onset of

action and its exotic qualities. At least part of its appeal is its

rarity, high price and use by celebrities, musicians and other folk

heroes. Users also believe that cocaine is relatively free from

markedly undesirable side effects and is generally safe. Its

reputation for safety may be overstated since it is based on low

doses taken relatively infrequently. Under conditions of heavier,

more frequent use, adverse consequences may be considerably more

common than generally believed.

It should be emphasized that with cocaine, as with other psychoactive drugs, the subjective effects of the drug are modified by the

circumstances under which the individual takes the drug; these

include the physical surroundings and the overall "atmosphere" of

those surroundings (both may be summarized as the "setting" of use).

A second equally important factor is the totality of the user’s

expectations molded by personality, previous drug experiences,

attitude, etc. (his or her "set"). In addition to set and setting a

variety of other properties of cocaine may be important, including

dose, route of drug administration, chronic vs. acute use and

possible interactive effects with other drugs used (including

alcohol and heroin). For example, if a normally somewhat apprehensive person takes cocaine among relative strangers, which may

contribute to a feeling of insecurity, it is likely that s/he will

react with more heightened anxiety and suspiciousness than with

close friends, in the relaxed circumstances of his/her own home.

WHAT ARE THE ACUTE AND CHRONIC EFFECTS OF COCAINE?

As the various authors of this monograph emphasize (especially Byck

and Van Dyke, Chapter 5 this volume), there has been a range of

effects attributed to cocaine. Some, which are individual and

subjective, can never be adequately confirmed simply because they

are idiosyncratic and atypical of most users. To the extent the

experience is shared with others, despite its subjectivity, it may

yield a common description either offered spontaneously or in

response to various rating scales. Other responses (e.g., blood

pressure, body temperature) can be objectively measured under carefully controlled conditions of the laboratory with known drug doses

and a specified schedule of drug administration. Some responses

which occur in other species as well as in humans -- the effects on

general activity or appetite are examples -- can be examined under

9
very tightly controlled conditions in which such variables as the

biological history of the organism is known and its learning history

can also be specified with precision. Others -- often among the

most fascinating effects of a drug -- may involve complex behavior

not easily measured. Distinguishing the drug’s effect from other

elements of expectation and the situation can be difficult -- the

effect of cocaine on sexuality is an example.

Other aspects of a drug, previously alluded to, which are important

include: length of drug use -- acute vs. chronic effects; the

dosage received -- the effects of a drug may be quite different at

low doses from those at higher doses, even opposite; and the route

of administration -- intravenous effects may differ from those of

snorted cocaine and both may be different from oral administration.

A final caveat should be stressed. Cocaine, like other drugs of

abuse, has both fascinated and repelled man throughout its history.

It is little wonder, then, that a bewildering array of "effects,"

which may have little to do with the pharmacological action of the

drug itself, have been attributed to it. Reassertion of often

repeated fictions does not, however, make them well verified facts.

Cur need for certainty is not necessarily matched by equally

adequate evidence to allay our doubts. Unfortunately, a lack of

adequate information is sometimes interpreted as indicating that a

drug is "safe" when it would be more accurate to admit that our

knowledge is simply inadequate to specify the parameters of risk.

Moreover, a substance which when used under conditions of relatively infrequent, low dosage may pose few hazards, may present quite a

different picture when widely available and regularly used in

larger amounts.

An important, verified effect when used medically is cocaine’s

local anesthetic action as well as its ability to constrict blood

vessels in the area to which it is applied. (Cf., Barash, Chapter 9

this volume) One consequence of this property when cocaine is used

illicitly and snorted repeatedly is a tendency to cause a chronic

inflammation of the nasal membranes, ulceration, local tissue death

and sloughing off of the injured tissue. While perforation of the

nasal septum (the wall dividing the two halves of the nose) is often

mentioned, it is noteworthy that in the United States, at least,

this consequence appears to be rare (Cf. Barash, Chapter 9; Smith &

Wesson, Chapter 6 this volume).

There is good evidence that cocaine in moderate doses (10-25 mg i.v.

and 100 mg intranasally) significantly increases both heart rate

and blood pressure. Increases following lower doses occurred more

rapidly when the drug was administered directly into the vein than

when snorted. Heart rate increased from about 30 to 50 percent

above normal non-drug levels. Increases in blood pressure when the

heart was in its contracting phase (systolic pressure) were oh the

order of 10-15 percent. (See Byck & Van Dyke, Chapter 5 this

volume).

10
In addition to the street reputation of the drug and historical

accounts, even under conditions of carefully controlled laboratory

administration, a sense of well-being -- euphoria -- subjectively

characterizes cocaine use. Interestingly enough, however, when the

drug was administered intravenously under laboratory conditions the

subjective effects were not easily distinguished from those of

amphetamines (synthetic stimulants having more prolonged activity).

A feeling of calmness and/or relaxation is described by most of the

subjects who have participated in controlled laboratory studies;

they also report diminished appetite. The observed and reported

effects of several laboratory studies are generally consistent with

anecdotal accounts based on street use. However, there is much

street lore and some clinical evidence emphasizing other effects

that have not been systematically verified by controlled experimentation.

Clinical reports dating back to the 1880's have described a range of

response to heavier, more prolonged use of cocaine. Early reports

by Freud and others also emphasized that there was wide individual

variation in the physiological and psychological responses to

cocaine. Von Fleischl (Cf. Petersen, Chapter 1 this volume), who

was encouraged to use cocaine by Freud to alleviate symptoms of

nerve pain, rapidly progressed to heavy, intravenous use (up to a

gram per day). With heavier use, Fleischl’s condition deteriorated

to the point of a chronic intoxication characterized by hallucinations of white snakes creeping over his skin and insects that had to

be dug out of his skin. A cocaine psychosis very similar to

paranoid schizophrenia has been described in the scientific literature. One common aspect of this disorder has been tactile hallucinations similar to those experienced by Fleischl. The hallucinations have been described as sufficiently real to the victim that

s/he frequently injures the skin in a futile attempt to remove the

offending parasites (Woods & Downs, 1973). Other paranoid delusions which have been reported as characteristic of chronic cocaine

intoxication include fears of imaginary police, beliefs one is

being watched, etc.

Apart from clinical description and case reports, however, there

have still been no systematic controlled studies to determine the

level and frequency of cocaine use which leads to serious, adverse

psychic effects such as those described. It is not known how common

such paranoid symptoms are at various levels of use, the degree to

which individual personality differences contribute to their development or whether they are a consequence of use if large enough

quantities are used over a sufficiently extended period. Because

present American use patterns are characterized by relatively infrequent use of small quantities of the drug, serious adverse

effects of use may be quite rare (Cf. Smith & Wesson, Chapter 5 this

volume) . In one recent study of recreational users (Siegel, Chapter

5) 85 regular users (1 gram per month or more) recruited by means of

newspaper ads were studied. None of these subjects were compulsive

users in the sense described in the earlier literature. Although

their self-reported experiences were generally positive (e.g., all

11
reported euphoria in connection with use), negative effects were

also indicated, such as restlessness, anxiety, hyperirritability

and for some (5 percent) paranoia. In this study, positive effects

were reported on all occasions of use with negative consequences

experienced in from 3-5 percent of them.

COCAINE MORTALITY

Unlike marihuana, there is little question that cocaine can cause

death as a direct effect of the pharmacological action of the drug.

By 1891 some 13 deaths had been attributed to the drug (Woods &

Downs, 1973) and in 1924, a report was published of 26 deaths

attributed to cocaine (Mayer, 1924). These deaths were results of

errors of medical administration when the drug was used therapeutically or as an anesthetic. They were virtually always rapid in

onset and characterized by respiratory depression and cardiovascular collapse. Because there has been little systematic study

of cocaine death in recent years aside from a few isolated case

studies, the National Institute on Drug Abuse recently commissioned

a study of cocaine-related deaths between 1971 and 1976 in 27 U.S.

and Canadian locations. (Cf., Finkle and McCloskey, Chapter 8 this

volume).

The geographical area covered by this study included nearly 30

percent of the population of the United States. The records of a

total of Ill deaths in which cocaine was in some way involved were

studied. While drugs were causative in 86 cases, only 26 involved

cocaine alone and of those 6 were suicides.

Another source of data on cocaine-related deaths is the Federal Drug

Abuse Warning Network (DAWN). During the one year period from May,

1975 through April, 1976, some 57 cocaine-related deaths were

reported to DAWN by the medical examiners of the 24 standard

metropolitan statistical areas monitored by the system. Of these, 6

of a total of 4,668 drug-related deaths reported involved cocaine

alone. These figures are roughly comparable to those in the more

intensive study discussed above. Both studies indicate that accidental deaths due to cocaine, while uncommon, do occur. This is in

contrast with the widespread street belief that cocaine is without

significant hazard. Moreover, the first of these studies found that

two deaths due to cocaine occurred in those who had "snorted" the

drug. This, too, is in some contrast to the widespread belief that

snorting is completely safe.

TREATMENT OF COCAINE ABUSE

Aside from some specific suggestions for the treatment of acute

anxiety, drug-induced depression and cocaine psychosis (cf., Smith

12
& Wesson, Chapter 6 this volume for treatment of medical toxicity

see Barash, Chapter 9), there has been little reported, systematic

information on the treatment of cocaine abuse. Because of the lack

of evidence for a physical dependence on the drug, it has been

suggested that using cocaine to "maintain" a patient in a manner

analogous to methadone maintenance of the heroin addict is inappropriate (Woods & Downs, 1973). Since many patients use both heroin

and cocaine simultaneously, physical addiction to the heroin involved may be the primary problem.

Reports based on CODAP (the Federal Client-Oriented Data Acquisition Process), a reporting system designed to monitor Federally

supported or assisted drug treatment programs, rarely indicate

cocaine as the primary drug of abuse (i.e., as the reason for seeking treatment). Only 1.2 percent of the 202,000 admissions in the

latest report (cf., Siguel Chapter 10 this volume) were for cocaine

abuse. An additional 5.5 percent of clients treated reported that

cocaine was a secondary or tertiary drug problem to other drugs of

abuse.

Although cocaine users apparently seek treatment rather infrequently, it is not known if this is the result of the limited

availability and high cost which, in turn, limits its use and

reduces the likelihood of more serious consequences.

FUTURE DIRECTIONS

As this and other monographs on cocaine illustrate, our present

knowledge of cocaine remains fragmentary. The areas of certainty,

when closely examined, are quite modest. Much of the anecdotally

based information about the drug has never been subjected to

systematic investigation.

While cocaine-containing coca, as well as the extracted drug are

alleged to enhance endurance and physical strength under conditions

of adversity, this has not been adequately explored. Aside from

Freud's early attempt to examine cocaine's effect on physical

strength in himself (Freud, 1885), there have been few experimental

studies of the effects of cocaine on physical performance and

endurance.

When we turn to the question of psychological effects (e.g., the

widely cited effect of cocaine on intellectual performance and

creativity), the "hard" evidence for such effects is non-existent.

While the drug has frequently been anecdotally linked with aggression and criminality, adequate evidence to assess cocaine's

possible impact in these areas is again lacking.

There is much controversy about cocaine's toxicity, especially its

psychotoxicity, and there is little adequate evidence to resolve

the uncertainty. As early as the late 19th century, there were

13
clinical reports that cocaine could cause paranoid thinking and

hallucinations resembling the alcoholicls delirium tremens.

Despite the numerous clinical reports and individual case histories

documenting this, little is known on the basis of controlled

experimentation of the extent to which such symptoms are related to

personality or the doses and patterns of use likely to precipitate

them.

Depression subsequent to extended use ("crashing") has been reported. Again, the correlates and patterns of use associated with this

symptom are inadequately specified.

Even the trends and patterns of typical use in the United States

remain a matter of speculation. The statistically low level of use

in the general population makes tracing trends in use difficult.

Although there are several converging lines of evidence suggesting

that use is increasing, the small numbers involved and the likelihood of variability from year to year make their interpretation

difficult. Thus it is hard to be certain whether the increased

attention cocaine is currently receiving reflects general patterns

of markedly increased use or renewed media interest because of the

prominence of some of cocaine’s users. Whatever the ultimate

realities or the imperfect relationship between interest in the

drug and actual levels of use, it is likely that use will increase

in response to the publicity of cocaine effects. This argues

persuasively for expanded research efforts in the following areas:

Incidence, prevalence and patterns of cocaine abuse;

Factors in popularity of the drug and the characteristics

of the cocaine "high."

The role of personality factors in determining who uses,

the patterns of use and the likelihood of adverse consequences;

The pharmacology of cocaine including the possible development of dependence;

Effects of cocaine on human performance;

Types of cocaine toxicity, the relation to dose and user

predisposition.

Robert C. Petersen, Ph.D.

Division of Research

Rational Institute on Drug Abuse

14
REFERENCES

Cocaine -- An Overview

Freud, S. A contribution to the knowledge of the effect of cocaine,

Vienna Medical Weekly, January, 1885. In Byck, R. (ed.),

Cocaine Papers: Sigmund Freud. New York, NY: Stonehill

Publishing Co., 1974.

Johnston, L.D. Monitoring the future: Continuing study of life

styles and values of youth. University of Michigan, Ann

Arbor, 1976. Personal comunication.

Mayer, E. The toxic effects following the use of local anesthetics.

Journal of the American Medical Association, 82: 876-885

(1924).

O'Donnell, J.A., Voss H.L., Clayton, R.R., Slatin, G.T. and Roan,

R.G.W. Young men and drugs -- A nationwide survey. Research

Monograph No. 5, National Institute on Drug Abuse, Rockville,

MD, 1976.

Woods, J.H. and Downs, D.A. The psychopharmacology of cocaine. In

Drug Use in America: Problem in Perspective, Appendix Volume

1: Patterns and Consequences of Drug Use, Washington, DC:

U.S. Government Printing Office, 1973, pp. 116-139.

15

Chapter I HISTORY OF COCAINE

Robert C. Petersen, Ph.D.

The purpose of this brief history of coca and its pure alkaloid

derivative, cocaine, is to place the present day scientific assessment of cocaine’s properties and possible health implications in

some cultural and historical perspective. The reader should recognize that cocaine, like other mind-altering drugs, has always

evoked emotions ranging from great optimism to fearful dread

regarding its societal implications. Even today, because fact and

myth about its use and properties are not always easily separated, a

concern about its hazards coexists with an optimism on the part of

others about its desirability for use as a recreational drug.

A history such as this can hope to do little more than convey some

of the highlights of the plant’s and drug’s background, barely

addressing the cultural and historical complexity of its origins

and earlier use. For the interested reader, recent interest in

cocaine has resulted is the publication of several more detailed

sources of information.

EARLY COCA USE

Although the history of the pure drug substance, cocaine, covers

little more than a hundred years, use of coca can be traced to

prehistoric times. While it is impossible to date precisely the

point at which chewing of the leaves of the coca plant, Erythroxylon

coca, began, the sixth century A.D. if not earlier is generally

agreed upon. Archeological evidence of this practice is found in

unearthed Indian mummies which had been buried with supplies of coca

leaves as well as in a variety of pottery portraying the characteristic cheek bulge of the coca chewer.

In contrast with later European and American consumption in the form

of an infusion of extract of the coca leaves, early (and presentday) use in South America involves chewing a wad of leaves along

with a quantity of a lime substance typically derived from the ashes

remaining after burning plants, shells or limestone. The exact

purpose of the lime is in some dispute; it may improve the flavor of

the leaves, potentiate the action, release the cocaine from the coca

leaves or it may simply promote salivation.

1

 Ashley, 1975; Byck, 1974; Mortimer, 1974; Grinspoon & Bakalar,

1976; Andrews & Solomon, 1975.

17
Because the wild species of the plant produces smaller leaves that

are regarded as inferior in flavor, cultivation of the plant took

place early in history. Although coca use antedated the Incan

civilization, it is most commonly associated with this empire which

became the dominant influence in what is now Peru, Bolivia, Ecuador

and Columbia during the 11th century. Whatever its earlier status,

coca use achieved great symbolic importance under Incan rule. The

plant was carefully cultivated on its own plantations, had central

religious significance and became identified with the politically

powerful as one of the prerogatives of rank.

Several Incan myths that account for its origins are reviewed by

Gagliano (1960) in his detailed social history of coca in Peru. In

one account, before coca was a shrub it was a beautiful woman who

was executed for adultery, cut in half and buried. Prom one part of

her remains, the coca plant grew and blossomed to be consumed, only

by men, in her memory.

A second myth describes coca as an herb created by the god, Inti.

Having instructed the moon mother, Mama Quilla, to plant coca in

humid valleys, he also ordered that only the descendants of the gods

were to eat of it. The drug was provided to mitigate the hunger and

thirst of the Incas, the descendants of the gods, so that they might

endure to meet earthly demands.

Less romantically, the use of coca may have become important in

Incan life as a result of their contact with coca chewing Indians

from the Eastern Andean slopes during the reign of the Inca Roca

(ca. 1250-1315 A.D.).

Since the drug was believed to be of divine origin even prior to the

Incas, its use was a privilege reserved for members of the highest

classes. By the end of the 15th century under the rule of Topa Inca

(ca. 1471-1493) coca plantations had become a state monopoly and

coca use was quite restricted. Indiscriminate chewing was viewed as

a sacrilege. Although use was originally confined to the members of

the ruling class, it was sometimes extended as a sign of special

merit to soldiers during military campaigns, workers engaged in

public works projects and others judged especially deserving.

Throughout the period of Incan rule and afterwards, coca had

religious significance. It was a magical offering to the gods for

such purposes as insuring safe passage through the Andes and good --

or restored -- health.

Learning the full range of coca’s uses by the Incas is hampered by

their lack of a written language. However, there is reason to

believe the drug may have been used as an analgesic in skull

trephining. In these early attempts at neurosurgery, openings were

cut in the skull presumably to permit evil spirits to escape from

their victims. Despite the crude procedures involved, there is

archeological evidence that the operation was sometimes a success

in that the victim survived.

18
With the decline of the Incan empire during the 15th century, many

of the rules and taboos concerning the use and cultivation of coca

became less restrictive. Coca growing, which had been a state

monopoly, now became a privilege granted to deserving followers of

the Incan emperor, Huayana Capes (ca. 1493-1527), concomitant with

the granting of noble status for their loyal service. By the time

of Francisco Pizarro's advance on Cuzco, which completed his conquest of Peru (1536)) coca had lost much of its earlier significance

and was no longer a symbol of exclusive political rank or of social

status.

The attitude of the Spanish conquerors toward coca was decidedly

mixed. On the one hand there was great opposition to it by some of

the missionaries (and some of the conquistadores as well) who saw in

it a symbol of persistent idolatry and a barrier to religious

conversion. At the same time it was recognized that the coca habit

was important to the health and motivation of the Andean Indian.

Phillip II of Spain in a crown law of 1569 declared the coca habit

essential to the well-being of Andean Indians while concurrently

urging the missionaries to end the idolatrous use of the plant.

The Spanish became increasingly aware that coca chewing was needed

to recruit the Indians to work in the mines and similar settings

where conditions were brutal, labor arduous and food limited. It

was inevitable therefore that coca cultivation, distribution and

use would be permitted -- and even encouraged -- as a tool for the

economic exploitation of a subjugated people.

Aside from the contribution of coca to the Indians' production in

the mines under arduous conditions, the Spaniards soon recognized

coca’s euphorogenic properties as well. Nicholas Monardes, writing

in 1569, described the Indian practice of chewing a mixture of

tobacco and coca leaves to make themselves drunk and to induce

"great contentment."

. . .(When the Indians wished to) make themselves

drunk and . . . out of judgment (they chewed a

mixture of tobacco and coca leaves which) . . . make

them go as they were out of their wittes . . .

-- from Joyful1 Newes out of the Newe Founde

Worlde (a 1596 translation of an essay which

appeared in 1569, Monardes, 1925)

During the 16th and 17th centuries there was also recognition of the

role of coca as an Indian folk remedy for such diverse medical

problems as stomach disorders, skin ulcerations, venereal diseases,

headache and muscular pains. Spanish physicians also began advocating its therapeutic use for skin disorders, colds, asthma,

rheumatism, laryngitis and toothaches.

In the 18th century Antonio Julian, a former Jesuit, urged the use

of coca by the laboring classes of Spain, believing that it would

improve both their health and productivity. He also felt its use

19
should be encouraged as the preferred stimulant drink in Spain, thus

reducing the economic drain resulting from the import of coffee and

tea. Moreover, he reasoned, should coca come to replace stimulant

drinks used elsewhere in Europe, this would be to the benefit of

Spain, which could then serve as a coca supplier for the remainder

of the continent.

While it has been suggested by some historians that the Spanish

colonialists in South America used coca as a conscious instrument

for suppressing the Andean Indians, such assertions seem questionable. It is doubtful that the Spanish were pharmacologically

sophisticated enough to recognize such a role for coca. Use was

extensive before the Spanish conquest, suggesting well entrenched

patterns needing little encouragement from the conquerors. There

were also abortive attempts by the Spanish to curb the use of coca

as an impediment to the religious conversion of the Indians. It is

possible that there was an increase in use following the fall of the

Incan Empire, but this may most readily be attributed to such

factors as a decline in food production, an increase in forced

labor, the profits involved in the exchange of coca for precious

metals and an increased desire to use the drug corresponding to

increased hardship following the conquest.

COCA IN EUROPE

When Pizarro returned from Peru to the Court of Spain it is likely

that he brought back coca. As Mortimer suggests, the plant's

obvious importance to the Incas, as evidenced by the gold replicas

found in their edifices, must surely have excited admiration and

comment (Mortimer, 1901; reprinted, 1974). But whatever the

informal status of coca's introduction into Europe, it was not

until two centuries later (in 1750) that the botanist Joseph de

Jussieu, then accompanying a scientific expedition to Peru, sent

specimens of the shrub to his brother Antoine in Paris for study.

These plants, which were preserved in the herbarium of the Museum of

Natural History, became the basis for much subsequent study.

Members of this expedition were aware of at least some of the

pharmacological properties of the plant. Captain Don Antonio

d'Ulloa wrote:

This herb is so nutritious and invigorating that

the Indians labor whole days without anything else,

and on the want of it they find a decay in their

strength (Mortimer, 1901; reprinted, 1974).

Despite the many contemporary accounts describing coca and even

advocating its substitution for tea and coffee by such figures as

Antonio Julian in the 18th century, it attracted little European

attention for over three centuries. The authenticity of its

attributed characteristics was even questioned.

20
How is the paradoxical lack of impact on Europe by this drug which

had been so glowingly described by so many travelers to South

America to be explained? Guttmacher writing in 1885 (Byck, 1974)

and Mortimer in 1901 offer a similar rationale: The pharmacologic

inertness of the poorly preserved leaves that were available early

in the drug’s European history. In addition to the probable

deterioration of the imported leaves during a long sea voyage,

growing it locally was difficult since the plant was ill suited to a

European climate (Guttmacher, 1885).

Several individuals played a role in the ultimate isolation and

extraction of cocaine as the principal psychoactive ingredient of

the coca plant. Mortimer traces the history as follows: As early

as 1850 a Dr. Weddell, following his personal experiences with coca

in the Andes, suggested that its stimulant properties might be the

result of having the same active ingredient as tea. Following an

analysis of coca leaves, a very bitter substance, soluble in

alcohol, but insoluble in ether, was found. Still later, in 1885,

Friedrich Gaedcke was able to separate an oily substance along with

a sublimate of small needlelike crystals from a distillate of the

dry residue of an aqueous coca extract. This substance he named

"Erythroxyline." Although several others contributed to the isolation of cocaine, ultimate success is usually attributed to Albert

Nieiuann of the University of Gottingen, who also characterized it

chemically and named it cocaine. William Lossen, also from

Gottingen, built on Niemann’s work and established cocaine’s formula in keeping with the then new chemical notation.

About the same time that Niemann was achieving his successful

isolation of cocaine, an Italian neurologist, Dr. Paolo Mantegazza,

made a significant contribution to the psychopharmacology of coca.

His lyrical observations of effects on a single subject, himself,

provide one of the more colorful descriptions of the drug’s subjective impact. He recounted in detail the physiological effects and,

especially, the "deeply joyful and intensely alive" feelings coca

engendered in him. Fart of his description is particularly communicative of the experience:

Some of the images I tried to describe in the first

part of my delirium were full of poetry. I sneered at

the poor mortals condemned to live in this valley of

tears while I, carried on the winds of two leaves of

coca, went flying through the spaces of 77,438

worlds, each more splendid than the one before.

An hour later I was sufficiently calm to write these

words in a steady hand: "God is unjust because he

made man incapable of sustaining the effect of coca

all life long. I would rather have a life span of ten

years with coca than one of 1000000 . . . (and here I

had inserted a line of zeros) centuries without

coca." (in Andrews & Solomon, 1975)

21
Mantegazza's early monograph based on his subjective and therapeutic impressions of coca, "On the Hygienic and Medicinal Virtues

of Coca" undoubtedly influenced a number of physicians and researchers, including Sigmund Freud. Cocaine initially inspired

Sigmund Freud’s uncritical endorsement, which bordered on the

lyrical, of both its therapeutic potential and contribution to

creativity. And in the process of touting cocaine’s virtues young

Freud nearly destroyed his career as a promising researcher.

Earlier in this century in the United States, dread of cocaine’s

putative powers to evoke superhuman aggression both fueled and was

fueled by rampant racist attitudes.

The obvious interest in coca and cocaine that was increasing in

Europe had its counterpart in the United States, where great

enthusiasm was developing for the therapeutic potential of this

promising new drug. By 1883, for example, the Index-Catalogue of

the Library of the U.S. Surgeon-General's Office listed well over 50

scientific papers concerned with the therapeutic potential of coca.

Two reports from the Therapeutic Gazette, (in Byck, 1974) an

American medical journal devoted primarily to new therapeutic

agents which advocated coca use in the treatment of the "opium

habit," were to prove especially influential on the work of a young

and ambitious Viennese physician -- Sigmund Freud.

FREUD AND COCAINE

Early in 1884 Freud was casting about for an area of research in

which he could both make a contribution and attain some success

permitting him to marry. He had become interested in coca and

cocaine from a variety of reports which had appeared in the literature including those from the Detroit Therapeutic Gazette. Another

report which especially impressed him was by a Bavarian army

surgeon, Dr. Theodor Aschenbrandt. Aschenbrandt had become interested in the effects of cocaine on humans while at the Wurzburg

Pharmacological Institute. Unfortunately, the unavailability of a

suitable subject population -- "strong and healthy people, exposed

to the greatest exertion, hunger, thirst and the like" -- precluded

this work. Later, while on maneuvers with a unit of the artillery,

Aschenbrandt seized the opportunity to treat soldiers suffering

primarily with exhaustion and diarrhea with cocaine. He found that

the stimulating effects of cocaine both on himself and these

patients permitted effective functioning despite physical adversity

(Aschenbrandt, 1883).

Freud ordered a supply of the new drug, determined to try it on

patients suffering from heart disease, "nervous exhaustion" and

morphine withdrawal. The latter intent was based both on the

favorable reports emanating from America and Freud’s concern over

the plight of a colleague, Ernst von Fleischl-Marxow. Fleischl,

whom Freud greatly admired, had become morphine-dependent as a

22
result of the use of the drug to treat nerve pain from the stump of

an amputated thumb. Upon receiving the drug, Freud tried it on

himself and was impressed with its effects both on his mood and his

capacity for work. He also offered the drug to von Fleischl whom he

later described in a letter (May 7, 1884) to his future wife, Martha

Bernays, as having clutched at the drug "like a drowning man"

(Jones, 1961).

By July of 1884, Freud’s famous paper, "On Coca," had appeared. In

it he briefly described the plant, its history and manner of use in

Peru citing several authorities who attested to its effects on the

Indians, enabling them to withstand great hardship without eating.

While mentioning in passing reports that coca's immoderate use was

reported to cause "physical and intellectual decadence" together

with weakness, emaciation and "moral depravity," he concluded, "but

all other observers affirm that the use of coca in moderation is

more likely to promote health than to impair it..." (in Byck, 1974).

In his highly acclaimed review of cocaine’s history up until that

time, Freud cited the work and observations of most of the leading

figures including Monardes, Julian, de Jussieu and Niemann. He

wrote approvingly of the observations of Paolo Mantegazza as "an

enthusiastic eulogist of coca" whose observations struck Freud as

essentially accurate. He also reported the drug’s effects in

warding off hunger, sleep, fatigue and "steeling one to intellectual effort" which he observed in himself and others.

In discussing therapeutic uses he cited the "promise of widespread

(therapeutic) recognition and use of coca preparations in North

America, while in Europe doctors scarcely know their name." This he

attributed to the "doubtful quality" of the preparations available

on the Continent, their high price and the initially unfavorable

(while in Freud’s opinion, unmerited) reports of adverse consequences of use. He went on to list the following therapeutic

uses:

a) as a stimulant;

b) for digestive disorders of the stomach;

c) in cachexia (wasting diseases);

d) in the treatment of alcohol and morphine addiction;

e) in treating asthma;

f) as an aphrodisiac; and

g) as a local anesthetic.

The last of these -- cocaine’s usefulness as a local anesthetic --

proved to be the only persistently medically useful property of the

drug. Ironically, it was with respect to this persistent use of

23
cocaine that whatever enduring fame Freud sought in his cocaine

research was to elude him.

Among Freud’s colleagues was a young ophthalmologist, Karl Koller.

His particular interest was in a possible local anesthetic for eye

Surgery. Such a substance was vital because in much of eye surgery

the patient’s cooperation is needed, precluding the use of general

anesthesia. Moreover, the’general anesthesia used at that time was

known to induce post-operative nausea and vomiting, the strain of

which could cause damage to the operated eye.

As Freud later related it, he was with a group of colleagues when an

intern passed by obviously in pain. Freud offered to help him,

explaining to the others that the drug cocaine with which he had

been working seemed to have impressive pain relieving qualities.

This may have jogged the thinking of Koller, who was in the group

and later read Freud’s paper. About three months later Koller

experimented with a cocaine solution and found it capable of

anesthetizing not only the eyes of experimental animals, but his own

as well.

Shortly thereafter, another ophthalmologist friend to whom Freud

had more directly suggested the possible use of cocaine as an ocular

analgesic and anesthetic, independently performed an experiment

somewhat similar to Koller’s. With Freud’s assistance, Leopold

Konigstein removed a dog’s eye using cocaine as the local anesthetic. His work was reported at a meeting at which Keller’s

research was also described. It was only later upon learning of

Keller’s "Preliminary Communication" the preceding month that

Konigstein was persuaded with some reluctance to acknowledge the

primacy of Karl Keller’s contribution (Bernfeld in Byck, 1974).

While others, such as Mantegazza, DeMarles, Moreno y Maiz and Von

Anrep, may have anticipated the potential of cocaine as a local

anesthetic in eye surgery, it was Karl Koller who is credited with

the decisive experimentation leading to this important medical use.

Freud apparently took the news well, at least initially, reporting

to his fiancee in a letter:

My second piece of news is pleasanter. A colleague

has found a striking application for coca in ophthalmology and communicated it to the Heidelberg Congress

where it caused great excitement. . .in any event it is

to the credit of coca, and my work retains its

reputation of having successfully recommended it to

the Viennese. (in Byck, 1974)

Whatever his ultimate lack of credit for a contribution Freud might

as easily have made, he and Koller had the satisfaction of assisting

when Konigstein operated on Freud’s father for glaucoma six months

24
later using the new anesthetic technique the three had helped

develop (Bernfeld in Byck, 1974).

Meanwhile, Fleischl, whom Freud greatly respected, was rapidly

transforming himself from the "first morphine addict in Europe to be

cured by cocaine" into "the first cocaine addict in Europe"

(Bernfeld in Byck, 1974). Whatever the accuracy of that description

(it is questionable whether cocaine can be described as "addictive"

in the same sense as opiates, for example), Fleischl, who had been

using increasing quantities of cocaine by injection, had undergone

serious psychological deterioration. He was troubled by paranoid

hallucinations very like those of the alcoholic with delirium

tremens. Other examples of cases of chronic intoxication were also

reported. They, too, were often characterized by hallucinations of

animals crawling on, under or digging into the skin.

Freud, who had hoped to achieve a reputation based on his work with

cocaine, found himself accused of irresponsibility and recklessness

three years after that work began. Erlenmeyer, an authority on

addiction, even charged Freud with unleashing "the third scourge of

humanity" (after alcohol and opiates) (Jones, 1961). In reply to

these charges, Freud indicated that he believed that cocaine was not

inherently addictive. He explained that for those already addicted

to morphine, their "weakened will power and need for stimulus" led

to the abuse of all stimulants. Whatever the ultimate reality, the

criticisms stung; he was later to describe that year as "(the least

successful and darkest year" of his life (Bernfeld in Byck, 1974).

Following the revelation that some people had become seriously

cocaine dependent, increasing anxiety about cocaine’s use naturally

set in. Among his other optimistic assertions, Freud had indicated

in his "Addenda to 'On Coca’" that, "For humans the toxic dose (of

cocaine) is very high, and there seems to be no lethal dose."

Contrary to this belief, one of Freud’s patients died from an

overdose prescribed by Freud. By 1891 some 200 reports of systemic

cocaine intoxication had appeared, including 13 deaths attributable

to the drug (Woods & Downs, 1973).

While the European enthusiasm regarding the therapeutic potential

of cocaine was being eroded by reports of adverse effects, interest

in America remained high. The work of William A. Hammond, a former

Surgeon General of the United States, is of particular interest not

only because Freud regarded it as significant enough to cite in his

last paper on cocaine, but also because his was among the earliest

attempts to determine a dose-response curve for cocaine. Hammond

reported favorably on the therapeutic use of the drug in overcoming

morphine addiction. He also commended it as a treatment for

"nervous prostration, and neurasthenia, general debility, etc." and

for treating mental depression (Byck, 1974). Interestingly enough,

in reporting on his own response to increasing doses of injected

cocaine, he spoke of having "lost consciousness of all my acts

within, I think, half an hour after administration of the dose" at

higher doses. He also admitted he "came very near taking a fatal

25
dose and I would not advise anybody to repeat the experiment."

Based on his own subjective experience and that of patients he had

treated, Dr. Hammond concluded that there was no such thing as a

cocaine habit; an individual could readily give up the drug of his

own volition (Hammond in Byck, 1974).

William Golden Mortimer, a New York physician, was the Editor of the

Pharmaceutical Journal and of the New York Journal of Medicine. A

man of impressively wide ranging interests, he published an extensive History of Coca in 1901 (reprinted 1974). This volume summarized the existing knowledge about coca and cocaine. While it

must be viewed as the product of an advocate more than a skeptic

(the book is dedicated to Angelo Mariani of Vin Mariani fame -- see

next page Patent Medicine Era), it is an impressively wide-ranging

book and a classic work on the subject. Its topics include not only

coca’s history, the botany of the plant, its products, chemistry,

physiological and therapeutic effects, but also its role in music

and in the singer’s voice production!

Mortimer (1901; reprinted, 1974) also has the distinction of being

among the first clinical investigators to systematically query his

colleagues on a large scale regarding the effects of a drug. In

18% he wrote to 5,000 fellow physicians principally teaching in the

medical schools of the day, inquiring about their "personal observations upon the uses of Coca." Almost 25 percent responded

(1,206). Mortimer’s tabulation of these responses provided a

systematic resume of the physiological action of the drug, its

therapeutic applications and its "food value," as reported by his

physician sample. The results were included as an appendix of his

book subtitled, "A Collective Investigation Upon the Physiological

Action and Therapeutic Application of Coca, Among Several Hundred

Physicians."

Perhaps the most significant American medical figure of the late

19th century to become involved with cocaine was the "father of

modern surgery," William Stewart Halsted. While Koller was demonstrating the use of cocaine as an ocular local anesthetic, Halsted

was developing a technique for using the drug as a "neural block."

By injecting cocaine into nerve centers, he was able to produce a

regional anesthesia of the area served’ by the chemically blocked

nerves. In 1884 he began publishing reports of his work, eventually

reporting on the results of 1,000 operations of many types using the

technique.

Unfortunately, there was one adverse consequence of this work. As a

result of his own experimental use, Halsted and several of his

assistants became heavily dependent on cocaine. Halsted’s habit in

particular became sufficiently disturbing to his friends that they

spirited him away on a ocean voyage to the Windward Islands in hope

of weaning him from his habit. This treatment failed, as did a

subsequent period of several months’ hospitalization. In a reversal of the usual sequence, Halsted apparently used morphine as a way

of "curing" his cocaine dependency. He continued to be morphine

dependent until his death in 1922 (Byck, 1974).

26
COCA, COCAINE AND THE PATENT MEDICINE ERA

The last two decades of the 19th century spawned both a serious

interest in coca and cocaine and a relatively uncritical promotion

and advocacy of cocaine-containing patent medicines and tonics. In

a relatively unrestricted age with modern pharmacology in its

infancy, there were few restraints governing the production and

sale of remedies containing a variety of what are now regarded as

abusable substances.

Given the enthusiasm that cocaine generated in scientists such as

Sigmund Freud, it is not surprising that it was actively promoted by

commercial interests. It must, of course, be remembered that the

prevailing standards did nothing to discourage such comercial

exploitation. Such international authorities as Dr. William

Martindale -- later president of the Pharmaceutical Society of

Great Britain -- were early advocates of the use of coca and cocaine

for a variety of specific medical problems as well as in tonics and

stimulant drinks. In a widely circulated book, he suggested

substituting an infusion of coca for coffee and tea as a means of

strengthening the nervous system (Martindale, 1886 in Ahdrews &

Solomon, 1975).

Manufacturers of patent medicines, tonics and soft drinks produced

a plethora of cocaine-containing products, ranging from ointments,

nose powders, suppositories, throat lozenges and sprays to wines

and coca cigarettes. They allegedly cured an equally wide range of

disorders, including alcoholism, asthma, colds, corns, eczema,

neuralgia, opiate addiction and venereal disease (Ashley, 1975).

Internationally, perhaps the most successful advocate and producer

of a coca-containing product was Angelo Mariani, a Corsican chemist

whose life’s work was the development and promotion of coca wine.

Of him the physician W. Golden Mortimer, a turn of the century coca

authority, was moved to say:

. . .the wonderful qualities of Coca remained locked as

a scientific mystery unsolvable by the multitude,

until it was finally released from its enchanting

spell as through some magic touch of a modern

Merlin." Mortimer, 1901; reprinted, 1974)

Allegedly, in 1863 Mariani, unlike some of his competitors, very

carefully experimented with a variety of coca leaves, choosing for

his purpose only those which combined the finest flavor with the

desired stimulant effect. Whatever his success in developing a

better tasting wine, he was clearly successful in its promotion. He

published some 13 volumes of testimonials by some of the greatest

luminaries of his day attesting to the value of his product. Among

27
these endorsers were two popes, reigning monarchs of a host of

countries, many physicians of prominence and such figures as

Anatole France, Henrik Ibsen, H. G. Wells, Jules Verne, Thomas A.

Edison and Auguste Rodin (The Mariani Album: 1884-1913; excerpted

in Andrews & Solomon, 1975).

Another coca-containing product ultimately destined to become

internationally famous was the soft drink, Coca Cola. Along with

many other cola drinks of the period (1886-1903), it used the

cocaine-containing extract of coca leaves together with other ingredients for flavoring. Originally advertised as a patent

medicine when introduced in 1886 -- "a valuable Brain tonic and cure

for all nervous affections – SICK HEADACHE, NEURALGIA, HYSTERIA,

MELANCHOLY, etc." -- it was later promoted simply as a soft drink.

By 1903, the manufacturer abandoned the use of cocaine-containing

syrup, resorting instead to a flavoring derived from decocainized

coca leaves (Musto, 1973).

An indication of the popularity of cocaine and cocaine-containing

products is given by Sir Arthur Conan Doyle's attribution of its use

to his famed literary character Sherlock Holmes, who used it as a

stimulant when bored by the lack of challenging cases.

THE END OF AN ERA

In view of the uncritical enthusiasm with which coca, cocaine and

their products were initially embraced by some physicians and

laymen, a reaction was probably inevitable. As with more recent

"wonder drugs," initial widespread acceptance was increasingly

tempered by the recognition that cocaine had undesirable side

effects and could pose a serious health hazard. While originally

considered relatively safe, it became apparent that cocaine created

dependence in susceptible individuals, and that toxic psychosis and

death could result from heavy injudicious use. Fleischl, who was

among the first to manifest symptoms of cocaine abuse like those of

alcoholic delirium tremens, was not the last; while deaths through

self-administration were rare, there was an increasing frequency of

deaths from medically administered overdoses and/or unusual susceptibility to the drug's effects. As Freud had observed earlier,

there were marked individual differences in response to varying

doses of the drug and this appeared to be true of its toxic effects

as well.

Another important factor in the restriction of cocaine use was a

reaction to the excesses of the patent medicine era. One has only

to peruse an early edition of a Sears, Roebuck catalog to realize

that patent medicines promised cures to diseases that have yet to be

conquered. . .and Sears was relatively conservative in its advertisements! (Sears, Roebuck and Company, 1902; reprinted 1969) It was

becoming clear that some degree of government control was necessary

to curtail the indiscriminate inclusion of opiates and cocaine in

over-the-counter medicines and tonics.

28
The beginning of the 20th century marked another important trend.

American medicine, characterized by relatively lenient professional

standards until that time, was coming of age. Prior to the 20th

century, a medical degree was easily obtained, even in the best

medical schools. While still in its infancy, the American Medical

Association became increasingly concerned with establishing and

maintaining higher standards of medical training and practice.

Pharmacists were also becoming more professional. While it has been

argued that physicians and pharmacists had an economic interest in

curbing patent medicine sales (Ashley, 1975), ethical concern over

the dangers of self-administration -- including the use of

dependency-producing proprietary medicines -- was also a factor.

"Muckraking" writers and journalists, bent on social reform,

included the patent medicine manufacturers in their targets, labeling them as irresponsible.

One of the reprehensible factors in curbing the use of cocaine and

of cocaine-containing preparations in the period from 1900 to 1920

was the spector raised by the mass media of cocaine-crazed blacks

committing heinous crimes. Even such "respectablen sources as the

Journal of the American Medical Association published accounts of

blacks becoming addicted to "a new form of vice" and indulging in a

"coke drunk" (The cocain (sic) habit, JAMA, 1900). Articles in the

popular press, including the New York Times were less restrained.

Thev reported that cocaine resulted in mass murders by "crazed

(black) cocaine takers" whose marksmanship was markedly improved by

the drug. It was also alleged that use of cocaine imparted

"temporary immunity to shock -- a resistance to the ‘knock down’

effects of fatal wounds." The drug was accused of being a "potent

incentive in driving the humbler negroes all over the country to

abnormal crimes (Williams, 1914 in Ashley, 1975). The same article

asserted that "Most attacks upon white women of the South...are the

direct result of coke-crazed negro brain." Whatever the incidence

of cocaine use among convicted felons -- and an examination of

objective evidence suggests there was little -- myths of this type

were potent in swaying public opinion.

State after state passed laws prohibiting or restricting the distribution of cocaine in some manner. By the time the Federal

Harrison Narcotics Act of 1914 was passed, 46 of the 48 states had

passed similar legislation. Obviously cocaine was viewed as a

greater threat than the opiates; only 29 states had laws regulating

the latter (Ashley, 1975)

In a detailed review of the legislative history of cocaine regulation, McLaughlin traced a trend started by many states which

required manufacturers, distributors, physicians and dentists to

keep records of their cocaine dispensing. These early laws typically made unauthorized possession of cocaine a misdemeanor. Under

these laws, patent medicine manufacturers were usually permitted to

include limited amounts of opiates or cocaine in their products

McLaughlin, 1973).

29
On the Federal level, legislative inroads were also being made into

the unrestricted use of cocaine. The Pure Food and Drug Act of 1906

had some impact on the marketing of proprietary remedies containing

cocaine by requiring that such ingredients be listed on the product

label. In practice this legal requirement was sometimes ignored,

since the penalties for non-compliance were modest, but it increased the likelihood that the wary consumer could avoid cocainecontaining products.

The Harrison Narcotics Act of 1914 was the first major Federal

legislation to significantly restrict the availability of coca and

cocaine and sounded the death knell for its inclusion in patent

medicines. The Act required registration with the Internal Revenue

Service of those involved in the importation, manufacture, distribution or dispensing of opium, coca or their derivatives and that

careful records of their transfers be kept. Use of cocaine in

proprietary medicines was specifically forbidden.

This act was important not only as a precedent, but also because it

invoked sufficiently strong penalties (fines of up to $2,000 and

prison sentences of up to five years for violators) to discourage

violation.

Subsequent legislation (in 1922) amended the Harrison Act to increase the penalties for violation (up to a $5,000 fine and 10 years

imprisonment) and to define (erroneously, from a pharmacological

standpoint) cocaine as a narcotic. Nevertheless, the pattern had

been set; henceforth, cocaine was legal only for restricted medical

uses.

Additional legislative amendments (in 1951 and 1956) to the

Harrison Act and to a companion piece of legislation, the Narcotic

Drugs Import and Export Act (which prohibited export of cocaine to

countries lacking import regulations)’ further increased penalties

and established increasingly severe mandatory minimum sentences for

violations.

Later state laws were based on the Uniform Narcotic Drug Act --

originally promulgated by the Commissioners on Uniform State Laws

in 1932 -- which, in turn, followed Federal precedent. This act was

adopted by almost all the states, with the exceptions of Pennsylvania and California (New Hampshire and Montana repealed their

versions in 1967).

Earlier legislation on the Federal level was replaced in 1970 by the

Comprehensive Drug Abuse Prevention and Control Act which categorized drugs in schedules according to their uses and potential for

abuse, required registration of those involved in the production

and distribution of controlled substances, and established import,

export and production limitations on these substances. A new model,

the Uniform Controlled Substances Act, was drafted by the

Commissioners on Uniform State Laws to replace the earlier Uniform

Narcotic Drug Act on the state level. Like the earlier act, it was

patterned after the Federal legislation.

30
In both the Federal and model state legislation, cocaine was placed

in Schedule II, the category for drugs with an acceptable medical

use, but with high potential for abuse. (Schedule I consists of

drugs with no recognized medical use, such as heroin; the other

schedules include drugs with progressively lower potential for

abuse.)

POST-REGULATORY COCAINE USE

With the passage of the various Federal and State laws making all

but restricted medical use of cocaine illegal, use patterns

markedly changed. Unfortunately, even before the introduction of

regulation, it was difficult to determine what proportion of the

population used the drug. Many used it inadvertently in patent

medicines. During one two-year period late in the patent medicine

era there was a five-fold increase in the amount of cocaine or coca

leaf imported. (In 1904, a cocaine yield of 4,125 pounds could be

obtained from the amount of cocaine and coca leaf imported. By 1906

the cocaine yield from the increased amount of coca leaf imported

had jumped to 21,000 pounds.) To what extent this increase represented an increased number of users, increased use by a relatively

constant number of users, or some combination, is unknown.

The combination of increasingly adverse publicity regarding the use

of cocaine and specific legislation making it illegal effectively

removed it from respectability. Widespread use by a broad spectrum

of society became use by a more "bohemian" set, such as jazz

musicians, actors, actresses and other members of the cultural

"avant garde." Use also continued among affluent drug dealers in

the ghetto.

As with other periods, it is difficult to describe with any precision the extent of cocaine use between the time of World War I and

its present re-emerging popularity. With the change in its legal

status, cocaine became quite expensive, making it affordable to

only an affluent minority. The drug’s prevalence among popular

musicians is indicated by the number of songs in which it figures

prominently. Perhaps the best known of these is the original lyric

from the Cole Porter musical of 1934, Anything Goes, for the song "I

Get a Kick Gut of You":

I get no kick from cocaine

I’m sure that if

I took even one sniff

It would bore me terrifically too

But I get a kick out of you.

31
Use in the movie colony in Hollywood is indicated by a number of

contemporary accounts although, again, the extent of such use is in

some doubt. It has been widely reported that during the Nazi period

in Germany, some of the prominent members of the party, including

Field Marshal Herman Goering, were users of cocaine (Ashley, 1975).

By the early 30's, the availability of amphetamines together with

the continued high cost of illicit cocaine reduced its popularity

even further. Although legal seizures of a drug are but imperfect

indicators of its use, it is noteworthy that only six pounds of

cocaine were seized by the Federal Bureau of Narcotics in 1960. By

1968 seizures by its successor agency had climbed to 63 pounds and

by 1971 to 436 pounds.

The combination of a new affluence and a greatly increased interest

in drug use in the late 1960's and early 1970's resulted in a

renascence of interest in cocaine as the status drug. Evidence for

this is provided by accounts of the drug use in the mass media, its

importance in such films as Easy Rider (released in 1969) and

Superfly (1972), a spate of books and articles dealing with cocaine,

and the re-emergence of cocaine-related songs.

By the 1970's a variety of local and national surveys (cf. Overview)

provided somewhat more data on the extent of cocaine use.

Robert C. Petersen, Ph.D.

Division of Research

Rational Institute on Drug Abuse

32
REFERENCES

History of Cocaine

Andrews, G. and Solomon, D. (eds.) The Coca Leaf and Cocaine

Papers. New York, NY: Harcourt Brace Jovanovich, 1975.

Aschenbrandt, T. Die Physiologische Wirkung und Bedeutung des

Cocain auf den Mehschlichen Organisms. Deutsche Medizinische Wochenschrift, 50:730-732 (1883), reprinted in Byck, R.

(ed.), Cocaine Papers: Sigmund Freud. New York, NY: Stonehill Publishing Co., 1974.

Ashley, R. Cocaine: Its History, Uses and Effects. New York, NY:

St. Martin's Press, 1975.

Bentley, W.H. Erythroxylon coca in the opium and alcohol habits.

In Byck, R. (ed.), Cocaine Papers: Sigmund Freud. New York,

NY: Stonehill Publishing Co., 1974, pp. 15-19.

Bernfeld, S. Freud's studies on cocaine. In Byck, R. (ed.),

Cocaine Papers: Sigmund Freud. New York, NY: Stonehill

Publishing Co., 1974, pp. 321-352.

Byck, R. (ed.) Cocaine Papers: Sigmund Freud. New York, NY:

Stonehill Publishing Co., 1974.

The cocain (sic) habit. Journal of the American Medical Association, 34:1637 (1900).

Gagliano, J. A social history of coca in Peru. Unpublished

doctoral dissertation, Georgetown University, Washington, DC,

1960.

Grinspoon, L. and Bakalar, J.B. Cocaine: A Drug and Its Social

Evolution. New York, NY: Basic Books, 1976.

Guttmacher, H. New medications and therapeutic techniques. Concerning the different cocaine preparations and their effect.

In Byck, R. (ed.), Cocaine Papers: Sigmund Freud. New York,

NY: Stonehill Publishing Co., 1974, pp.120-125.

Hammond, W.A. Coca: Its preparations and their therapeutical

qualities with some remarks on the so-called "cocaine habit."

In Byck, R. (ed.), Cocaine Papers: Sigmund Freud. New York,

NY: Stonehill Publishing Co., 1974, pp. 177-193.

Jones, E. The Life and Work of Sigmund Freud. Volume I. New York,

NY: Basic Books, 1961.

Mantegazza, P. On the hygienic and medicinal virtues of coca. In

Andrews, G. and Solomon, D. (eds.), The Coca Leaf and Cocaine

Papers. New York, NY: Harcourt Brace Jovanovich, 1975, pp.

38-42.

33
Martindale, W. Coca, cocaine and its salts. In Andrews, G. and

Solomon, D. (eds.), The Coca Leaf and Cocaine Papers. New

York, NY: Harcourt Brace Jovanovich, 1975, pp. 43-49.

McLaughlin, G.T. Cocaine: The history and regulation of a dangerous drug. Cornell Law Review, 58:537-573 (1973).

Monardes, N. Joyful1 Newes out of the Newe Founde Worlde. Translated into English by J. Frampton. New York, NY: Alfred

Knopf, 1925.

Mortimer, W.G. History of Coca The Divine Plant of the Incas.

1901, reprinted, San Francisco, CA: And/Or Press, 1974.

Musto, D. The American Disease--Origins of Narcotic Control. New

Haven, CT: Yale University Press, 1973.

Sears, Roebuck and Company. The 1902 Edition of the Sears Roebuck

Catalogue (Facsimile). New York, NY: Bounty Books, 1969.

Williams, E.H. Negro cocaine "fiends" are a new southern menace.

In Ashley, R., Cocaine: Its History, Uses and Effects. New

York, NY: St. Martin's Press, 1975.

Woods, J.H. and Downs, D.A. The psychopharmacology of cocaine. In

Drug Use in America: Problem in Perspective. Appendix Volume

1: Patterns and Consequences of Drug Use. Washington, DC:

U.S. Government Printing Office, 1973, pp. 116-139.

34
Chapter II

COCA: THE PLANT AND ITS USE

Eleanor Carroll, M.A.

COCA AND HEALTH

Extent of Use -- Past and Present

At the time of the Inca, use of coca was confined, according to many

historians, to the royal family, and to certain favored others --

for example, courtiers, court orators, and members of the army

during battles. It is impossible to say how much coca was produced

or consumed during this time, but there is abundant evidence from

many sources, that it was considered to be an extremely important,

even precious crop.

Contemporary observers, at the time of the Conquest, commented on

the gold representations of the coca plant in the special gardens of

the Inca in Cuzco. From the same Inca period (AD 800-1000) come

numerous examples of small spoons or spatulas for extracting the

lime added to coca leaves) made of bronze, silver or gold, with

miniature figures of men or animals on the handles. Even before the

time of the Inca the quality of the grave goods from various

archaeological sites attest to the supreme value placed on coca by

higher classes of society. The Moche period (AD 200-700) has

yielded up valuable figured gold bags for coca leaves, and containers for lime made of precious metals come from the coastal Tiahuanaco period (AD 800-1000).

The Spanish conquerors made an early, and unsuccessful attempt to

eliminate the use of coca, because of its prominence in native

religious ceremonies. They soon became not only reconciled to its

use but even exploiters of the plant. Use was no longer confined to

the nobility; as soon as the stimulating effects of coca on work

production were recognized, hacienda owners took full advantage of

the fact and put more and more land into the production of coca.

Sixteenth Century chroniclers report that many Spaniards became

extremely wealthy simply from the yields of their coca plantations.

To meet the need of more land for coca production, the Spaniards

extended their subjugation efforts even to primitive forest Indians

who had not succumbed to Inca domination. Even the Church, which

had initially been so opposed to coca production and use, saw its

economic value, and initiated and maintained coca plantations of

its own.

35
It was also, shortly after the time of the Conquest that the custom

of giving workers coca as part of their wage began. This custom

persists to this day, both on the part of major employers (for

example mining companies and major hacienda owners) and on the part

of small farmers who have assembled a group of their neighbors for

cooperative farming activities.

At the time of the Inca, production of coca had spread as far north

as the Isthmus of Panama and the Caribbean, and as far south as

Chile. During the latter half of the 19th century, when the use of

cocaine for various therapeutic purposes had come to be recognized,

production of coca was introduced into Java, Ceylon and even the

island of Jamaica.

Today, most of the coca which is legally produced comes from Peru

and Bolivia, although there is still extensive illegal cultivation

and use in Colombia, parts of Argentina, Brazil and some parts of

Ecuador. Concern about illegal channeling into the production of

cocaine is centered in Peru, Colombia, Bolivia and Ecuador. Neither

Peru nor Bolivia has ever outlawed the production of coca, although

in Peru efforts have been made to confine its production to certain

departments. In Bolivia the abolition of large estates after the

Bolivian agricultural reform of 1953 led to a temporary reduction in

coca production because of neglect of the estates during the

transition and because the government forbade the planting of new

coca fields. However, the agricultural workers who had become

independent ignored the government decree and extended the area of

cultivation in order to keep up with increasing demand.

According to figures submitted by the Peruvian Government to the

United Nations Fund for Drug Abuse Control in December, 1975,

production of coca is authorized in 11 of the 24 Peruvian Departments. These departments are Amazones, La Libertad, Cajamarca, San

Martin, Ancash, Junin, Cuzco, Puno, Ayacucho, Apurimac and

Arequipa. Approximately 17,500 authorized growers of coca are

distributed over 16,000 hectares of territory. These growers

produce almost 10,000,000 kilos of coca annually. About 57 percent

of production comes from the Department of Cuzco. The government

estimates that about 6,000,000 kilos of coca are consumed locally by

approximately 900,000 persons.

In Peru, as well as Bolivia, the primary coca producing and consuming countries, comparatively little is known about the ways coca

is ingested or its distribution of use across racial, ethnic, social

class and occupational categories. The bulk of Indian users

continue to employ coca as a masticatory, while most of the mestizo

and criollo users ingest coca in the form of a tea, as either a

refreshing beverage or as a treatment for a variety of ailments.

For a long time, the conventional wisdom asserted that coca chewing

was confined to Andean Quechua-speaking Indians, and that Indians

living in a tropical environment did not use it. There is now

increasing evidence that even lowland Indians chew coca. In

addition, of course, an unknown amount of coca is used by the

Indians in teas, or for poultices, etc. Current findings indicate

that mestizo farmers in the Peruvian coastal areas below Arequipa

36
chew coca, as do truck drivers, fishermen, and stevedores in various

parts of the country. In Cuzco, coca is chewed by some mestizo and

criollo intellectuals and artists. Coca tea is dispensed in many

tourist hotels in Cuzco to help guests cope with the difficulties of

altitude sickness ("soroche"). Coca is currently being packaged in

tea bags in Lima and simply marked as "refreshing tea."

Bolivia is another principal producer of coca. For a while, during

the latter part of the 19th century, when cocaine was extensively

used in various therapeutic preparations, the coca leaf of Bolivia

was prized above that of Peru because of the higher cocaine alkaloid

content.

There are no exact figures on the overall amount of coca being

produced in Bolivia nor on the number of acres under cultivation,

according to Bolivia’s December, 1975 statement to the United

Nations Fund for Drug Abuse Control. Coca production is legal in

all department of Bolivia, but most of the production is confined to

the subtropical, humid valleys of the Yungas (north of La Paz), to

Chapara in the Department of Cochabamba, and to Yepecani in Santa

Cruz.

According to estimates produced for the U.S. Embassy in Bolivia in

1975, more than half of the native population of about 5 million are

coca consumers -- in other words at least 2-3 million persons.

About 7,000 metric tons are consumed legally within the country each

year, and at least 2,000 metric tons are exported legally each year.

The actual number of consumers of coca in Bolivia is a matter of

more than purely academic interest, since the Bolivian Government

is on record as having no intention of doing away with the

indigenous consumption of coca. However, it is firmly committed,

with the aid of United States agricultural experts, to reducing the

overall coca production to levels consonant with traditional use

and to experimenting with substitute crops to determine the potential contribution of these crops to the overall economic well-being

of the country.

There is almost no material in the literature about the process of

socialization into the use of coca, particularly in the case of

children. We do not know at exactly what age a child is socialized

into the use of coca; whether male and female children are socialized at the same, or different, ages, in the same ways; or, indeed,

whether and how many females use coca at all. The differential use

of coca by the sexes varies not only from one country to another,

but even from one region to another within the same country.

It is safe to assume that there is postponement of the use of coca

as a masticatory until adolescence or later, a time which will

correspond to the assumption of adult role and occupational responsibilities. Among the variety of uses to which coca, in various

forms, is put, certainly one of the preeminent is its use as a work

adjunct (as a stimulant) and this fact would dictate that full use

would coincide with the beginning of mature work patterns.

37
Not enough work has been done so far on the crucial distinctions

between the varying types of role allocations and role responsibilities, and the amount of coca which might be consumed in carrying

out one’s duties. It is especially necessary to break down any

occupational role into the component parts tied to specific functions, and to determine -- both from observation and from interviews

with users themselves -- what they consider the appropriate amounts

of coca to be used by members of both sexes, by persons with varying

degrees of responsibility and so on. Similarly, it is also

necessary to ask such questions as what kinds of coca are to be used

and how the respondent chooses the leaves he/she is going to buy.

some initial efforts have been made to account for the differences

in the way volume is conceived and measured by the Indian population

and by official investigators.

In any consideration of drug use (whether natural or synthetic) it

is essential that the fullest possible description be given both of

the material and of the method of ingestion. It is not necessary to

go into a botanical description of the coca shrub and of its many

species (estimated to be about 250) here. About 24 of these 250 are

known to grow in Peru. The two domesticated species most widely

cultivated in Peru are Erythoxylon coca and Erythoxylon novogranatense var truxillense, usually called Truxillo coca. Huanaco

coca, from Bolivia, was preferred by 19th century manufacturers of

cocaine-based products because it is much richer in cocaine alkaloids.

It is interesting to note, however, that from the 18th century

onward, travelers have commented on the fact that the Indians, given

a choice of leaves for chewing, always rejected those leaves with

the heaviest concentration of the cocaine alkaloid, since those

leaves have a bitter taste. They much preferred leaves which are

richer in aromatic alkaloids. Unfortunately, some modern studies

do not distinguish between the various types of coca, and almost all

research to date has concentrated solely on the cocaine alkaloid;

the other 13 known alkaloids in the leaf have been neglected almost

completely.

Martin (1975) has noted that the process of masticating coca --

termed "chaccarn or "acullicar" in Peru and Bolivia -- is essentially the same now as it was in the time of the Incas. The Indian

carries the coca leaves (in a woven sack) with him carefully

choosing several leaves to chew until they form a sort of quid (the

acullico), which is held between the mouth and gums. Then an

alkaline mixture is inserted into the wad of leaves. This alkaline

mixture -- known as, "llipta," "tocra," or "mambe" --varies from one

region to another, depending on the materials available. It can be

made up of quick lime, ashes obtained from burning the stalks of the

quinoa plant, or bark from certain trees. This alkaline mixture is

carried in a separate container, quite frequently a gourd ("ishcupuru" in Peru; "poporo" in Colunbia), an ancient method represented

in the grave goods at pre-Incan burial sites. The present day

Indians usually use a moistened stick to dip into the alkaline

mixture and moisten the coca quid with it; in earlier times, these

38
spatulas were themselves often made of precious materials and

extensively decorated. Great care must be exercised to prevent this

caustic material from touching the lips or gums, as some novices

have learned to their sorrow. Apparently this alkaline mixture

facilitates the release of the active alkaloid principles of the

coca. The leaves and alkaline mixture is kept in the mouth, and the

juice trickles into the stomach. Although the term masticate is

used to describe the process, it is not strictly accurate to say

that the Indians chew the leaves. It might be added that this

admixture of a lime substance to a plant drug is not confined solely

to the use of coca -- it is also the practice of many betel nut

chewers.

There are some variations on this method of preparing and using coca

leaves. Some small Indian groups in Colombia (in the areas bordering on Brazil), as well as some Brazilian Amazonian Indians, do not

use the leaves until they have been pounded into a fine powder. The

ashes of burned alkaline substances are then added to this powder

before putting it into one’s mouth.

The supposedly noxious effects of coca chewing attributed to it by

some observers, have succeeded in giving the coca leaf a reputation

only slightly less abhorrent than that of cocaine. However, even

cocaine does not produce withdrawal symptoms similar to those

produced by narcotics. Coca leaves were employed by the Indians for

over 2,000 years prior to cocaine’s discovery without any notable

toxic effects. The reports of overindulgence in coca leaves are few

and far between in the literature. No clinical disease is directly

attributable to coca chewing; even the withdrawal syndrome is

relatively mild. Indians of the Sierra, when drafted into military

service, where use of coca is forbidden, give it up without any

noticeable ill effects.

In the last several decades, an increasing number of authors have

asserted that a variety of pathological defects can be attributed to

coca chewing, including hyponutrition, ocular disturbance, enlarged

thyroid glands and lymph nodes; yet, for each of these assertions,

an equally well-trained observer has claimed just the opposite.

From the standpoint of health, we lack research which will fit the

coca shrub into the overall folk pharmacopoeia of the country. (It

is estimated that in Bolivia alone there are more than 5,000

different plants, each with its assigned role in the folk medicine

of the country.) We need an investigation of medical folklore --

the reasons assigned to various kinds of illnesses, and the way in

which the Spanish notions of hot and cold (in relationship to both

the origin and the treatment of various ailments) have been tied

into the pre-Conquest beliefs of the Indian populations. Further,

there have been no studies, in either Peru or Boliva which examine

the beliefs and attitudes toward coca and coca chewers of a crosssection of the populations of these countries.

Coca is only one of the many indigenous psychoactive drugs presently

used by large portions of the population in various Latin American

countries, particularly Mexico, Ecuador, Peru and Brazil. Although

use of such drugs is most characteristic of the rural, primarily

39
Indian, sections of the countries, use is spreading to the more

urbanized areas. This extension of use is due in great part to the

fact that many of these drugs (for example, ayahuasca and San Pedro

cactus) are used by native curers (curanderos) in their healing

ceremonies. Curanderos are patronized in the towns not only by

Indians, but by mestizos (i.e. those of mixed Indian-Spanish

origins) as well.

There are tremendous difficulties attendant upon the initiation of

research in this area, beginning with the choice of sample and

control subjects to be studied. If the study is to be undertaken in

the high Andes region, traditionally the area of greatest coca

consumption, it may be difficult to find control subjects who are

not users. Extreme poverty, malnutrition, and inadequate health

care are characteristics of the inhospitable ecological regions

where these heavy coca chewers live. These conditions make it

difficult to factor out the possible causal effects of coca chewing

on poor physical health. Further, most ethnographic evidence

indicates that coca chewing increases with age, so this is another

confounding factor. Possibly the most difficult correlative factor

to control for is alcohol use. Heavy users of coca also tend to be

heavy users of alcohol (usually an indigenous type of beverage,

fermented rather than distilled). Alcohol, as well as coca, is

consumed at major and minor fiestas. There is, indeed, some slight

indication that as Indians become acculturated to the meztizo way of

life, particularly in cities, that they may increasingly turn to

alcohol as a substitute, rather than as a supplement to coca use.

COCA AS A THERAPEUTIC

Coca is one of the most important, if not the most important of all

drugs in the folk pharmacopeia of the Altipano. The Indians use

the term "mamita kukita" (little mother coca) to describe the coca

plant, and this sobriquet gives eloquent expression to the

essentially protective and comforting role they assign to the drug.

The role, of course, has many facets.

The most widely publicized function of the drug is its energizing

capacity; that is, its ability to reduce muscular exhaustion and

alleviate hunger and thirst. The Incas recognized this quality, and

distributed coca leaves to their "chasquis" (relay messengers) as

well as to soldiers.

The Incas believed that coca could stimulate mental as well as

physical activity, and the "varavecsw (court orators), who served

as the repositories of Incan history in the absence of written

records, were among the privileged few allowed to chew coca. Some

present day Peruvian commentators, however, not only completely

reject the idea of coca as a spur to mental production, but go so

far as to say that it impedes cerebral activity.

from the 16th century onward, foreigners have commented extensively

on the incredible ability of the Peruvian Indians of the Sierra to

40
travel along narrow mountain paths while bearing heavy burdens,

sustained only by an occasional "acullico," or chew of coca. These

Indians are even accustomed to measuring the length of a journey by

the hours that one chew of coca will sustain them -- a period of

time called the "cocada" (about 45 minutes).

Coca is equally important to the routine work of the Indians either

on the farm or in the mines. The Spanish conquerors recognized the

stimulating quality of the drug soon after the Conquest and, devil

or not, they began to employ it extensively and brutally. They

sometimes forced the Indians to work unbelievably long hours -- up

to 48 hours at one stretch -- without any food or rest. Work in the

Potosi mines of Bolivia was so terrible that many Indians committed

suicide when told they were being sent to work there.

An insightful article about the miners and their lives underground

by June Nash (1972), an anthropologist, explains that coca is used

not only as an energizer, but also as an important ingredient in

religious and magic rituals. According to the article, coca use is

inextricably intertwined in the daily lives of these Aymara

Indians.

The miners believe that a pre-Christian ogre "Huari," lives in the

hills where the mines are located, and he is venerated in the form

of the devil, or Tio. They are convinced that Huari alone knows the

location of rich veins of ore and that he will lead persons who

sacrifice to him to those veins. Not only can the Tio reveal, or

withhold, the knowledge of rich veins; he can also cause accidents

to those who fail to placate him with proper offerings.

Miners make images of the Tio (the features may differ, but the body

is always made of ore) and place them in niches cut into the walls

of the mine, where the miners rest. Hands, face, arms and legs are

shaped of clay from the walls of the mine, and the main feature of

the figure is always an enormous mouth into which offerings are

placed. Coca remains are placed there; his hands grasp bottles of

alcohol and his nose is burnt black by lighted cigarettes. Every

Friday the workers make a ceremonial offering, a "ch’alla," to the

Tio, composed of coca, cigarettes and alcohol. Here, too, the

beneficial effects of coca are also recognized because the miners

say that coca is a gift of the Pachamama (a deity who precedes the

Incas) to help them in their work.

In the rituals of the ch’alla and the even more elaborate "k’araku"

(involving the sacrifice of llamas in addition to the offerings of

coca and "chicha") after deaths caused by mine accidents, Tie’s

power to destroy is transformed into the socially useful function of

increasing mineral yield, giving at least some peace of mind to the

miners.

Coca is very important to the Indian farmer who also practices

special rituals involving the use of coca for the specific tasks of

farming (e.g., sowing, weeding, harvesting, house building). The

Indians almost universally regard coca as a food, although this does

not mean that they choose to subsist exclusively on coca, as has

sometimes been alleged.

41
Some modern observers have condemned the use of coca, alleging that

it simply anesthetizes the feelings of hunger without contributing

in any way to nutrition. In fact, some of these observers attribute

malnutrition to the use of coca. Other observers, however, point

out that chemical analysis of coca leaves has shown that they are

relatively rich in vitamins, particularly vitamin B1, riboflavin

and vitamin C. Approximately 2 ounces of coca leaves (an average

daily amount) contains almost the minimum daily vitamin requirement, an important point, they have argued, in view of the great

shortage of fruits and vegetables (particularly fresh vegetables)

in the Sierra. Many Indian farmers in the Altiplano subsist today,

as they have for centuries, on a diet consisting primarily of

varieties of dried and frozen potatoes, very small amounts of dried

meat (something like jerky), and roasted maize and barley.

Some 19th century observers stated that coca assisted in the

assimilation of other foods, by increasing the flow of saliva and

gastric secretions and giving strength to the muscles of the gastrointestinal tract. Whatever the validity of this observation, it is

noteworthy that even today, throughout a great part of South

America, an infusion of coca leaves is regarded as a sovereign

remedy for indigestion and stomach complaints. A decoction of the

leaves, drunk regularly, allegedly guards against bowel laxity,

while a powder of the leaves, drunk with salt and egg white, is used

in the treatment of ulcers.

Coca continues to be used to relieve the pain of rheumatism and

external sores. In the 16th century, indigenous practitioners

employed coca to reduce the swelling of wounds and to strengthen

broken bones. It is widely believed that coca served as a local

anesthetic in skull trephining in pre-Conquest times. Coca seeds

employed in vapors are used to stem nose bleeds, while powdered coca

taken in tea’ with sugar is used for asthma. One 19th century

scientist pointed out that Bolivian Indians, employed in collecting cinchona bark in the forests of Bolivia, were inclined to rely

more heavily on coca for the treatment of malaria than on the

malaria-specific antidote, quinine-containing cinchona bark.

Coca is also employed by the Indians not only to prevent but also to

treat disease of the teeth and gums -- an effect attested to by many

European observers. Masticated coca leaves are used as a poultice

for the treatment of sore eyes. For headache, in addition to the

tea made of an infusion of coca leaves, a poultice of chewed leaves

is placed on the patient’s forehead. Coca ia also used to ease

uterine contractions in childbirth.

Coca is esteemed by the Indians as an aphrodisiac, and is reputed to

insure longevity with unimpaired sexual powers. Nineteenth century

observers commented on the incredible longevity of some Ecuadorean

Indians, with life spans stretching up to 100 years or more.

One aspect of health in relation to coca which has rarely been

mentioned is psychic. health; that is, what is the contribution of

coca to the psychic well-being of the Andean populations? Coca is

used to diagnose disease, to divine the future, to placate irate

42
spirits; in other words, to give an individual some sense of control

in a hostile and threatening world. Only now are the importance of

studies which would delineate the role of coca in the maintenance of

mental health beginning to be appreciated, and there have been some

small beginnings in this area.

During the latter part of the 19th century, U.S. physicians experimented widely with many coca preparations, as they had with cannabis

preparations. Coca was used in the treatment of a variety of

ailments, including neurasthenia (nervous exhaustion), depression,

nervous disorders, stomach disorders and throat infections. Then,

all coca preparations fell under a cloud, not only because of the

growing reluctance to depend on herbal remedies, but also because

coca was increasingly identified with cocaine and that substance’s

toxic effects.

The history of coca is, in many ways, strikingly similar to that of

cannabis. Although, of course, the provenance of the shrub

Erythoxylon coca is more circumscribed than that of cannabis, and

coca history -- so far as is known at the present time --is of much

shorter duration, coca is, in many ways, a multi-purpose drug as is

cannabis. It is a plant deemed by its indigenous users to be of

divine origin because of its miraculous properties, which is the way

cannabis was regarded both in India and China. It is a plant which

has been used, and continues to be used, in religious rituals, just

as cannabis is in many parts of India and Pakistan; it is a basic

ingredient in fiestas, as cannabis was, for example, in celebrations of the harvest in Poland, Hungary and parts of Russia well

into this century. It is the basic ingredient in the folk pharmacopeia -- a sort of all-purpose drug -- similar to the role of

cannabis in India, parts of Pakistan and Jamiaca, to name but a few

countries. Coca has always been employed as an energizer, as a work

adjunct, as a motivator for undertaking and continuing arduous

types of jobs, which is, indeed, the way ganja is used today in

Jamaica, bhang in India and cannabis among some Brazilian Indians.

Coca also resembles cannabis in the variety of methods of ingestion

which can be employed in its use, with the sole exception of

smoking. Coca is ordinarily used as a masticatory, and the user

keeps coca leaves, along with "llipta," in his mouth. However, in

some parts of Colombia, for example, the coca leaves and the

ingredients of the llipta are ground together into a very fine

powder, and it is the powder which is placed in the mouth. In some

parts of Brazil, coca is mixed with "cassava," (a bread), which is

strongly reminiscent of cannabis’ traditional use for food preparation in, to cite only one example, Nepal. In several parts of the

world, coca is used externally in the form of poultices, as is

cannabis for example, to treat aching teeth.

Less is known about the chemical properties of coca than about

cannabis. Of the 14 alkaloids known to be contained in the plant,

almost all the research to date has concentrated only on the cocaine

alkaloid, despite the fact that as early as the late 19th century,

there were calls to investigate the alkaloid cuskohygrine.

43
There are other ways, of course, in which coca and cannabis resemble

each other, as there are ways in which coca resembles other widely

used indigenous drugs. For example, coca still serves as a medium

of exchange, as does opium in many parts of the Golden Triangle; it

is like khat, from Yemen, in that it is always a part of celebrations; it is like peyote from Mexico in that it is still widely

used as a method of divination. from the standpoint of the Indians

who use it, it is not accident that the coca plant has been given a

divine origin and attributes, since it is used for so many

purposes -- therapeutic, religious, recreational, occupational,

and economic.

Eleanor Carroll, M.A.

Division of Research

Rational Institute on Drug Abuse

44
REFERENCES

Coca: The Plant and Its Use

Grinspoon, L. and Bakalar, J.B. Cocaine, A Drug and Its Social

Evolution. New York, NY: Basic Books, Inc., 1976.

Gutierrez-Noriega, C. and Zapata Ortiz, V. Estudios sobre la Coca y

la Cocaina en el Peru. Lima, Ministero de Education Publica,

1947.

Hanna, J.M. Coca Leaf Use in Southern Peru: Some Biosocial

Aspects. American Anthropoligist, 76:281-296 (1974).

Martin, R.T. The role of coca in the history, religion and medicine

of South American Indians. Economic Botany, 24, (1970). In

Andrews, G. and Solomon, D. (eds), The Coca Leaf and Cocaine

Papers. New York, NY: Harcourt Brace Jovanovich, 1975.

Metzger, D. Personal communications. (5 ROl DAO1257. Quechua Use

of Erythoxylon Coca in Southern Peru).

Murphy, H.B.M., Rios, O. and Negrete, J.C. The Effects of

Abstinence and Retraining on the Chewer of Coca Leaf.

Bulletin on Narcotics 21(2):41-47 (1969).

Nash, J. Devils, Witches and sudden death. Natural History,

71(3):52-60 (1972).

45

Chapter III COCAINE: THE MATERIAL

Richard Hawks, Ph.D.

Cocaine and its companion alkaloids are found in the leaves of the

shrub Erythroxylon coca, a plant whose principal habitat is western

South America. Trace amounts of the alkaloid have been isolated

from other species of ‘the Erythroxylon genus (Willaman & Schubert,

1961), but the major source is the E. Coca species, principally

found in Bolivia and Peru.

The cocaine alkaloid itself makes up about 0.5-1.0 percent of the

dry weight of the plant material (DeJong, 1974; Aynilian et al.,

1974). Several other related alkaloids are also present in the coca

leaf and may contribute to the leaf’s pharmacological properties

(Martin, 1975). These constituents apparently do determine the

quality of the leaf for the chewing consumer. Leaf choice is made

on the basis of smell and taste, but these factors do not correlate

with the actual cocaine concentration in the leaves (Martin, 1975;

Mortimer, 1901, reprinted 1974). Plants cultivated for harvest are

kept pruned to a height of 3-6 feet, convenient for picking. The

elliptical leaves, which vary from 1 to 4 inches in length, can be

harvested several times a year since the plant is an evergreen.

Although estimates vary significantly, it seems that approximately

one-half of the harvest is consumed by inhabitants of coca growing

countries. The role coca plays in the life and health of these

users is a matter of some controversy Martin, 1975; Mortimer, 1901,

reprinted 1974; Burchard, 1975). The rest of the crop is exported

to the United States and Europe for the production of cocaine for

pharmaceutical use. In Peru a portion of the harvest is used in

legally sanctioned laboratories to produce cocaine for export but

no legitimate laboratories for cocaine production exist in Bolivia.

Only one company in the U.S. is licensed to import coca leaves.

This company produces all the pharmaceutical cocaine used in the

U.S. (approximately 410 kg in 1976 Streit et al., 1976) while at the

same time producing the "decocainized" resin extract from the leaf

which is used in the production of Coca Cola(R). This extension

process, instituted in 1910, removes all detectable amounts of

cocaine from the leaf. Prior to 1910, cocaine-based cola drinks

were both popular and readily available in this country and in

Europe.

A portion of the coca harvest is diverted to illicit laboratories in

producing countries for the preparation of cocaine for illegal

47
exportation. The production process in these labs involves: 1)

extraction of the total base from the leaf material with a solvent

(often kerosene); 2) portioning the alkaloids into an aqueous acid

solution with subsequent solvent extraction to remove non-alkaloid

impurities; and, finally 3) neutralization of the acidic solution

to allow extraction and isolation of the partially purified

cocaine. The final stages of purification involve one or two

recrystallizations of the hydrochloride salt form of cocaine. If

the purity of the salt is good (90-100 percent), the crystals will

appear as fine white flakes having a powdery consistency. Some

illicit laboratories use less sophisticated extraction processes

which usually involve only the crude crystallization of the initial

extract without extraction of non-alkaloid impurities. These processes yield material of 70-85 percent purity.

STRUCTURE ELUCIDATION AND SYNTHESIS

Due to great academic interest in its stimulant properties, cocaine

was one of the most intensively studied natural products of the late

19th century. The first extraction of cocaine is generally credited

to Gaedcke in 1855 who distilled a portion of a residue from an

aqueous extraction of coca leaves. from this distillation,

crystals formed, mixed with an oily residue. These crystals were

given the name "Erythroxyline" after the family of which coca is a

species.

Coca leaves eventually came into the hands of professor V. Wohler of

Gottingen for analysis (Mortimer, 1901, reprinted, 1974). Professor Wohler, who is often referred to as the father of synthetic

organic chemistry, had synthesized urea, the first synthesis of a

compound of biological origin. The leaves were turned over to his

assistant, Dr. Albert Niemann, who proceeded to extract and purify

a crystalline compound, which was named cocaine (Wohler, 1862).

The first structural studies involved the acid hydrolysis of

cocaine, from which benzoic acid, methanol and a basic compound were

isolated (Mortimer, 1901, reprinted, 1974). This result indicated

that cocaine must contain a carbomethoxy and benzolyloxy group.

Other studies showed cocaine to be a monomethyl tertiary base, due

to its action with methyl iodine (Einhorn, 1888) and cyanogen bromide (Braun & Muller, 1918) (see Figure 3-1). The basic compound

resulting from the hydrolysis of cocaine was isolated in salt form

and given the name "ecgonine" a word derived from the Greek word

meaning "son" or "descendant" (Mortimer, 1901, reprinted, 1974).

Ecgonine (2 in Figure 3-1) was later shown to yield tropinone when

subjected to chemical oxidation (Willstatter & Muller, 1898), thus

providing the link between a known organic compound, tropinone (3),

and cocaine (1) itself. By considering the sequence of chemical

degradation steps between cocaine (1) and tropinone (3), the

chemical structure of cocaine was secured. The proposed structure

of cocaine resulting from these studies was confirmed in 1923 by

total synthesis (Willstatter et al., 1923). By the application of a

48
FIGURE 3-1
four-step chemical synthesis, Wilstatter crystallized a pure

material which was chemically identical to naturally occurring

cocaine. The synthetic approach used by Willstatter in 1923 is

still the preferred method of cocaine synthesis today, with only

minor modification (Archer & Hawks, 1976).

The stereochemical nature of the molecule, that is, the orientation

of its substituent groups in three-dimensional space and the

stereochemical characteristics of the molecule which enables a

solution of cocaine to rotate plane polarized light remained undetermined until the mid 1950s. This latter ability is shared by

nearly all molecules of biological origin and the source of this

ability is a particular structural characteristic of the individual

molecule. This stereochemical determination was made by the

chemical degradation of cocaine through specific reactions to yield

a compound of known structure and stereochemistry. However simple

this process now sounds, the feat was not achieved until 1955

(Hardeggar & Ott, 1955) after much work by a number of skillful

investigators. These studies determined that cocaine had the

stereochemical characteristics depicted in Figure 3-2. Thus,

cocaine was established as 3S-benzoyloxy-2R-methoxycarbonyl tropane. (The symbols R and S refer to accepted designations of

absolute stereochemistry.) For a detailed account of the chemistry

involved in this investigation, the reader is referred to several

reviews of the subject (Archer & Hawks, 1976; Fodor, 1970).

METABOLIC PATHWAYS OF COCAINE

Cocaine is rapidly metabolized in animals to yield benzoylecgonine

(4 in Figure 3-1) and ecgonine (2) as the principal products along

with the several other metabolites listed in Figure 3-2.

These metabolic products are inactive when administered to animals

with the exception of norcocaine (5) which is reported to be equipotent to cocaine (Hawks et al., 1974; Misra et al., 1975). The

absence of activity of these metabolites may be due to the fact that

they are very polar, a characteristic which causes them to be

eliminated rapidly by excretion and to be relatively ineffective in

crossing the blood/brain barrier, which is critical to eliciting a

central nervous system effect. In vitro experiments have shown that

these metabolites show little activity in influencing the concentration of catechol neurotransmitters at nerve endings (Hawks et

al., 1974). The catechol neurotransmitters make up the biological

system in animals which is thought to be involved in the regulation

of mental processes affected by drugs such as cocaine. Roth cocaine

and norcocaine show significant activity on this system. It has

been reported, however, that the metabolites norbenzoylecgonine (6)

and to a lesser extent benzoylecgonine (4), show pharmacological

activity in rats after intracisternal injection (Misra et al.,

1975). Since the material was administered directly to the brain,

there was no need to cross the blood/brain barrier.

50
FIGURE 3-2
The mechanism by which cocaine causes its central nervous system

effects is not clear. The implication of the two experiments

mentioned above seem to be that there is more involved than simply

cocaine's effect on the neurotransmitter system. A more complicated mechanism is necessary to explain why norbenzoylecgonine

has no effect on the concentration of neurotransmitters at nerve

junctions in in vitro experiments, but elicits a pharmacological

effect when administered directly to the brain of the animal. More

research in this area is indicated.

STREET PREPARATIONS

Cocaine illicitly prepared in South America for export to the United

States street market is for the most part relatively pure -- and

usually prepared as the hydrochloride salt. The purity generally

ranges from 80-95 percent. The substance usually appears as a

translucent crystalline material ("flake") or as small, somewhat

transparent chunks ("rock"). These forms are the most desirable to

the street purchaser, but are rare since the material is usually

adulterated for economic reasons as it passes through the chains of

middlemen. Typically, cocaine is purchased in one or two kilogram

quantities (although larger shipments are frequent) in Bolivia,

Peru or Colombia by users/dealers. Upon arrival in this country, it

is divided into lots of several ounces each and sold quickly. These

ounces are then cut into lots of single ounces or multigram sizes

before resale. Eventually, the quantities are reduced to single

grams or to "spoons." "Spoons" are in the half-gram category and

are so-called because of the often used method of measuring the

material by the quarter teaspoon. Since each division into smaller

portions for further resale lends a tempting opportunity to either

add an adulterant or, in the case of the smaller doses, to weigh

short, it would be a rare case if material which started at 90

percent purity ended up at that level. For this reason the user who

can afford to buy the larger quantity gets the purer product (Lee,

1976).

Street cocaine is adulterated with a variety of substances. The

most common ones are mannitol, lactose and glucose. These

substances are all of the carbohydrate family and are relatively

innocuous. Mannitol, which crystallizes in a form similar to

cocaine, is useful as an adulterant when cocaine is to be dissolved

and recrystallized. lactose and glucose are common sugars which

cause no adverse effects. Among the other compounds sometimes used

as active substitutes for cocaine are lidocaine, procaine and

tetracaine. These are local anesthetics which have an appearance,

taste and local anesthetic effect similar to cocaine. They may be

added to or, in some cases, substituted entirely for cocaine. The

effects of these compounds on the central nervous system are

different from cocaine and allergic reaction to them is not

uncommon. Street cocaine is also sometimes sold mixed with heroin.

It can probably be assumed that such a mixture is sold as the

mixture rather than as a subterfuge.

52
Caffeine and the amphetamines have also been used as stimulant

adulterants in street cocaine, particularly where the original

material has been so diluted that its lack of stimulant activity

makes it unsalable. Occasionally quinine is used in the cut due to

its availability and, perhaps, to the dealer’s experience in using

it to adulterate heroin. Allergic reactions to quinine can lead to

pulmonary edema and death in some individuals; in fact, quinine has

been implicated as a possible factor in heroin "sudden death

syndrome" (Fodor, 1960, 1970).

ANALYTICAL METHODOLOGY

Various methods for analyzing cocaine and its metabolites have been

developed for forensic or research applications. Less rigorous

methods have even been devised for analyzing street samples by the

illicit user (Lee, 1976).

In forensic chemistry, post-mortem samples are analyzed to determine if cocaine can be implicated in death. Law enforcement

organizations employ assays to determine the content of street

samples confiscated during drug-related arrests. Other forensic

applications include urine screening methods, which are used to

detect drug use in methadone maintenance programs and in various

"drug free" treatment programs. Analytic methods used in postmortem assays are often qualitative or semi-quantitative. A

qualitative assay provides information oh the presence of the drug,

but does not actually indicate the amount of the drug in the sample

being tested. In some cases this information is sufficient for the

post-mortem test. However, in many situations it is useful to knew

the actual quantity of cocaine (or metabolite) present in the sample

of blood or urine to determine, for example, the time of ingestion

of the drug or whether cocaine could be considered the principal

cause of death (e.g., where it is determined that other drugs are

also present in the body). In cases of confiscation of illicit

cocaine, quantitative analysis of the sample might indicate the

extent to which it has been cut with adulterants and whether a given

sample (due to its quantitative composition) matches other samples

in the same geographic area, perhaps indicating that they came from

a common source. For purposes for which urinalysis is done, it is

sufficient to determine the presence of cocaine; quantitative

assays are usually unnecessary.

In research, a quantitative assay is usually used, since most

research involves the determination of a time course of drug action

in the body making it necessary to determine an accurate concentration of the drug at each sample (blood, urine, etc.) collection

time.

Basic differences, therefore, exist between the forensic requirements for an assay and research needs. Even if a quantitative assay

is used for both purposes, there will be cost and time constraints

on the forensic assay, not necessarily factors in an assay used by

53
researchers. A description of four types of analytical methodology

follows. The choice of which analysis to use depends oh such

factors as cost per sample, the number of samples to be analyzed in

a given period of time, the limits of sensitivity and specificity

required in the assay and, in some cases, the scientific sophistication required of the person actually performing the assay.

Thin Layer Chromatography (TLC)

Thin layer chranatography (TLC) is the most widely used method for

the qualitative-analysis of cocaine. This method employs the use of

plates made of glass, metal or plastic which are coated with an

absorbent substance -- usually silica gel or alumina. The drug

sample in a very small amount of solvent is spotted on the bottom of

the plate and the plate is then placed upright in a closed container

with a shallow layer of solvent on the bottom. As the solvent moves

up the plate due to the action of the absorbent, the drug is carried

along because of its solubility in the solvent. A second factor

impedes this progress, however: The drug also has atendency to be

absorbed by the material on the plate. This competition between the

drugs tendency to be absorbed by the plate and its tendency to move

with the solvent provides the essence of chranatography. Due to

structural differences among molecules, drugs will respond

differently to this competition between solvent and absorbent with

the net effect that the various drugs will appear at different

distances from the bottom of the plate by the time the solvent

reaches the top. Since each drug has its characteristic distance, a

qualitative assay is provided. TLC methods for detecting cocaine

and its metabolites differ in the solvents employed and the

reagents used for spraying the plate after solvent development,

which reveal the spots where the drug is located.

Thin-layer chranatography (TLC) requires a minimal investment in

equipment and supplies. Correspondingly, it is also the least

sensitive technique, being capable of detecting, usually 5-10 μg of

compound which is in the samples applied to the plate, although

sensitivity to 0.5 μg has been reported for behzoylecgonine

(Wallace et al., 1975). TLC is also the least specific in that more

compounds can potentially interfere with the analysis. Interference results when some other material in the sample has a

coincidental migration characteristic on the plate, thus producing

a spot in the same vicinity as cocaine’s (or a metabolite’s). TLC

is relatively rapid because several samples can be applied to the

same plate and run simultaneously.

1Misra et al., 1973, 1975; Bastos et al., 1974; Meola & Brown, 1975;

Valanju et al., 1973; Wallace et al., 1975.

54
Gas Liquid Chromatography (GLC)

Another method for analyzing cocaine and its metabolites is gasliquid chromatography (GLC). This method is theoretically similar

to that of TLC. In this method, the absorbent phase analogous to

the coating on the TLC plate occurs in a long tube of glass or

metal. The tube is usually 2-4 mm internal diameter and 4-6 feet in

length and is referred to as the chromatographic "co1umn." The

absorbent material is actually a high boiling point viscous liquid

coated on an inert solid support. Rather than a liquid phase like

the solvent in TLC, GLC employs a gas. The drug is applied to the

end of the column which is enclosed in an oven. An inert gas is

passed through the column continuously. The drug, again, has the

tendency to equilibrate between the phase coated on the solid

support and the hot gas phase in which it is soluble. A detection

device, which is located at the end of the tube, measures material

passing through it, recording the results on a strip chart. ( A

peak appears on the chart when a compound makes contact with the

detector.) Since different molecules equilibrate between the two

phases to a different extent, a means of characterization is

provided by measuring the time it takes for a given drug to get

through the tube. GLC provides the added potential for quantitative

analysis as well as qualitative analysis since the height of the

peak is proportional to the amount of material passing through the

detector. It is employed both in forensic chemistry 1 and in

research2.

Gas chromatography requires the purchase of an instrument costing

several thousand dollars and requiring more sophistication of the

operator. It is slower than TLC since samples have to be run

individually and the usual time for each compound to pass through

the column (tube) is on the order of several minutes. However, it

is more specific than TLC and considerably more sensitive, depending on the type of detector employed. Another advantage is its

versatility in that it can be applied to many types of drugs and can

be used both qualitatively and quantitatively.

The EMIT(R) System

The EMIT(R) (Bastos et al, 1974) system is another approach used by

many forensic laboratories for the analysis of cocaine. It is

generally employed as a qualitative assay system for determining

the presence of the major cocaine metabolite, benzoylecgonine, in

biological specimens. The extent to which this reaction occurs is

mediated by an immunological reaction involving a competition

1Blake et al., 1974; Hammer et al., 1974; Koontz et al., 1973;

Moore, 1974.

2As discussed in Jatlow & Bailey, 1975; Javaid et al., 1975; Wallace

et al., 1976.

55
between benzoylecgonine in the sample to be analyzed and the assay

reagent material. Therefore, if a large amount of drug (benzoylecgonine) is present in the unknown sample, the reaction monitored

will achieve a maximum response; but if little or no benzoylecgonine

is present, inhibition of the reaction will be maximized. By

calibrating the system with known amounts of benzoylecgonine, a

means of predicting the presence of the metabolite is provided by

the extent to which the measurable reaction is inhibited.

EMIT(R) assays require the purchase of a comercial system which

costs several thousand dollars as well as the purchase of reagent

materials from the commercial source on a per assay basis. In terms

of cost per sample it is the second least expensive technique to

TLC. Samples have to be run individually but each takes less than

two minutes. The sensitivity is on the order of 1 μg/ml of urine

and is relatively specific for the cocaine metabolite. To be more

specific, a sample giving a positive response will often be subjected to a subsequent confirmatory analysis by gas-chramtography.

EMIT(R) requires relatively little training of its operators.

Gas chromatography - Mass Spectrometry (GC-MS)

Another method of cocaine analysis used by researchers is that of

gas chrauatography-mass spectrometry (Archer & Hawks, 1976; Hawks,

1974). In this technique a gas chromatograph discussed above is

connected to a mass spectrometer which acts as the detector. The

mass spectrometer is an instrument capable of detecting very small

amounts of material caning through the column of the GC and

specifically detecting those compounds of a specific molecular

weight, thus providing a means of excluding many compounds which

might interfere with the assay. This technique is too cmbersome

and expensive to be used in most situations other than research

projects.

The technique of gas chranatography-mass spectrometry is the most

expensive, specific and sensitive of the methods mentioned. The

initial investment will usually exceed $60,000 and the sophistication required of the operator is significantly higher than for

the other techniques. This technique is, therefore, generally

employed for research purposes only.

A Comment on Methods

At the present time, the technique of gas chromatography is probably

the most generally useful for both forensic and research purposes,

considering its cost and versatility. The analytical situation

with cocaine is changing rapidly, however, with the advent of more

sensitive techniques for TLC, better detectors for GLC and, particularly, new advances with high performance liquid chromatography, which will have considerable application to the analysis

of cocaine metabolites.

56
Cocaine has a high clearance rate in vitro. It is metabolized and

excreted rapidly from the kidney. When cocaine is added to blood

plasma outside the body, (in vitro), it manifests a half-life (the

time for its concentration to decrease by half) of approximately

0.5-1.0 hour. This is reportedly due to pseudocholinesterase

activity in the plasma (and is reported to be inhibited by the

addition of a fluoride ion) (Jatlow et al., 1976). Since this halflife is comparable to that of cocaine's in vivo half-life (Hawks,

unpublished), it is possible that the majority of cocaine's in vivo

metabolism occurs in the blood rather than in the liver. These

considerations have implications to forensic scientists who may be

analyzing samples taken from a corpse which is several hours old.

It is important to consider in these situations that the cocaine

present may be only a small part of that which was present at the

time of death. This rapid enzymatic breakdown of cocaine in blood

complicates the investigation of post-mortem cases, particularly in

determining whether cocaine itself was the principal factor in the

death. This ability to hydrolyze also makes quantitative analysis

of cocaine more difficult in the work-up stages of the analysis.

Care must be exercised in the design and execution of extraction and

chromatographic steps in the work-up in order to minimize loss of

cocaine.

SUMMARY

Coca and cocaine have been subjects of fascination to historians,

anthropologists and chemists for many years. The use of coca has

had a great influence on many South American cultures as far back as

recorded history. It was one of the first of the "natural" organic

compounds to be chemically investigated. It seems that these

various interests in cocaine and coca waned somewhat during the

first two-thirds of the 20th century, perhaps due to restrictions on

its use which came about in the early 1900's.

At the present, however, this interest has revived and the number of

chemical, anthropological and pharmacological studies of cocaine

has mushroomed. Analytical chemical techniques for cocaine still

have much room for improvement in the areas of sensitivity and

simplicity. At present much information remains to be gathered

concerning the use of coca by populations of South America. The

biomedical considerations underlying the habitual and cultural use

of the coca leaf is an area of research which will require extremely

sensitive assays.

Much is still not known about cocaine use in this country -- its

toxicity during chronic use, its basic mode of action after

different types of administration, and the basic ethnography of

use. In all of these areas of study, cocaine's chemistry plays an

essential role. Analytical techniques are needed for studying

plasma and tissue levels in humans and animals under many

conditions. Fast and reliable qualitative analyses are necessary

for forensic purposes. Sufficient historical evidence exists to

57
warrant an examination of the volatile constituents of the coca leaf

using modern techniques for new biologically active compounds.

Even though much new information about coca and cocaine has appeared

in recent years, the dearth of basic knowledge concerning the plant

and the chemical leaves much room for investigation.

Richard Hawks, Ph.D.

Division of Research

National Institute on Drug Abuse

58
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Archer, S. and Hawks, R.L. The chemistry of cocaine and its

derivatives. In Mule, S.J. (ed.) Cocaine: Chemical, Biological, Social, and Treatment Aspects. Cleveland, OH: CRC

Press, 1977, pp. 13-32.

Aynilian, G.H., Duke, J.A., Genter, W.A. and Farnsworth, N.R.

Cocaine content of Erythroxylon species. Journal of Pharmaceutical Sciences, 63:1938 (1974).

Bastos, M.L., Jukofsky, D. and Mule, S.J. Routine identification of

cocaine metabolites in human urine. Journal of Chromatography, 89:335-342 (1974).

Blake, J.W., Ray, R.S., Noonan, J.S. and Murdick, P.W. Rapid,

sensitive gas-liquid chromatographic screening procedure for

cocaine. Analytical Chemistry, 46:288 (1974).

Braun, J. and Muller, E. Umwandlung des cocains in neue, physiologisch wirdsame substanzen. Deutsche Chemische Gesellschaft, Berlin, 51:235 (1918).

Brecher, E.M. and the Editors of Consumer Reports. Licit and

Illicit Drugs. The Consumers Union Report on Narcotics,

Stimulants, Depressants, Inhalants, Hallucinogens, and Marijuana -- including Caffeine, Nicotine and Alcohol. Boston,

MA: Little, Brown & Co., 1972.

Burchard, R.E. Coca chewing: A new prospective. In Rubin, V.

(ed.) Cannabis and Culture. The Hague: Mouton & Co., 1975,

p. 463.

Byck, R. Personal comunication.

DeJong, A.W.K. The alkaloids of coca. Recueil des Travaux Chimiques des Pays-Bas, 25:233, 1938 (1974).

Einhorn, A. Weitere uhtersuchungen uber das cocain. Deutsche

Chemische Gesellschaft, 21:3029 (1888).

Fodor, G. The tropane alkaloids. In Manske, R.H.F. (ed.) The

Alkaloids, Volume 6. New York, NY: Academic Press, 1960,

pp. 145-177.

Fodor, G. Tropanealkaloids. In Pelletier, S.W. (ed.), Chemistry

of the Alkaloids. New York, NY: Van Nostrand Reinhold, 1970,

pp. 431-467.

Gaedcke, F. Uber das Erythroxylin, dargestellt aus den blattern des

in Sudamerika cultiverten strauches erythroxylon coca lam.

Archiv der Pharmacie, 132:141-150 (1855).

59
Hammer, R.H., Templeton, J.L. and Panzik, H.L. Definitive GLC

method for the identification of cocaine. Journal of Pharmaceutical Sciences, 63:1963 (1974).

Hardegger, E. and Ott, H. Konfiguration des Cocains und Derivate

der Ecgoninsaure. Helvetica Chimica Acta, 38:312 (1955).

Hawks, R.L. Gas chromatographic mass spectrometry in drug screening by immunoassay. In Mule, S.J., Sunshine, I., Braude, M.

and Willette, R.E. (eds.), Immunoassays for Drugs Subject to

Abuse. Cleveland, OH: CRC Press, 1974, pp. 73-85.

Hawks, R.L., Kopin, I.J., Colburn, R.W. and Thoa, N.B. Norcocaine:

A pharmacologically active metabolite of cocaine found in

brain. Life Sciences, 15:2189-2195 (1974).

Jatlow, P., Barash, P.G., Van Dyke, C. and Byck, R. Impaired

hydrolysis of cocaine in plasma from succinylcholine sensitive individuals. Clinical Research, 23(3):255A (1976).

Jatlow, P.I. and Bailey, D.N. Gas chromatographic measurement of

cocaine in plasma using a nitrogen detector. Clinical Chemistry, 21:946 (1975).

Javaid, J.L., Dekirmenjian, H., Brunngraber, E.G. and Davis, J.M.

Quantitative determination of cocaine and its metabolites

benzoylecgonine and ecgonine by gas-liquid chromatography.

Journal of Chromatography, 110:141 (1975).

Koontz, S., Besemer, D., Mockey, N. and Phillips, R. Detection of

benzoylecgonine (cocaine metabolite) in urine by gas chromatography. Journal of Chromatography, 85:75 (1973).

Lee, D. Cocaine Consumer's Handbook. Berkeley, CA: And/Or Press,

1976.

Lossen, W. Uber das Cocain. Justus Liebigs Annalen der Chemie,

133:351 (1865).

Martin, R.T. The role of coca in history, religion and medicine.

In Andrews, G. and Solomon, D. (eds.), The Coca Leaf and

Cocaine Papers. New York, NY: Harcourt Brace Jovanovich,

1975.

Meola, J.M. and Brown, H.H. Detection of benzoylecgonine (metabolite of cocaine) in urine; drug abuse screening by thin-layer

chrauatography. Clinical Chemistry, 21:945 (1975).

Misra, A.L., Nayak, P.K., Block, R. and Mule, S.J. Estimation and

disposition of (

3H)-benzoylecgonine and the pharmacological

activity of some cocaine metabolites. Journal of Pharmacy

and Pharmacology, 27:784-786 (1975).

60
Misra, A.L., Pontani, R.B. and Mule, S.J. Separation of cocaine,

some of its metabolites and cogeners on glass fiber sheets.

Journal of Chromatography, 81:167 (1973).

Moore, J.M. Gas chromatographic detection of ecgonine and benzoylecgonine in cocaine. Journal of Chromatography, 101:215

(1974).

Mortimer, W.G. History of Coca The Divine Plant of the Incas.

1901, reprinted, San Francisco, CA: And/Or Press, 1974.

Mule, S.J. (ed.) Cocaine: Chemical, Biological, Social, and

Treatment Aspects. Cleveland, OH: CRC Press, 1977.

Streit, F., Nicolich, M.J. and Backenheimer, M.S. Purchase of

Predictions of Schedule II Drugs under the Controlled Substances Act of 1970. Rockville, MD: National Institute on

Drug Abuse, 1976.

Valanju, N.N., Baden, M.M., Valanju, S.M., Bulligan, D. and Verma,

S.K. Detection of biotransformed cocaine in urine from drug

abusers. Journal of Chromatography, 81:170 (1973).

Wallace, J.E., Hamilton, H.E., King, D.E., Bason, D.J., Schwertner,

H.A. and Harris, S.C. Gas-liquid chromatographic determination of cocaine and benzoylecgonine in urine. Analytical

Chemistry, 48(1):34-38 (1976).

Wallace, J.E., Hamilton, H.E., Schwertner, H. and King, D.E. Thinlayer chromatographic analysis of cocaine and benzoylecgonine

in urine. Journal of Chranatography, 114:433 (1975).

Willaman, J.J. and Schubert, B.G. Alkaloid bearing plants and their

contained alkaloids. Technical Bulletin No. 4234. Washington, DC: Agricultural Research Service, U.S. Department of

Agriculture, 1961.

Willstatter, R. and Muller, W. Uber die Constitution des Ecgonins.

Deutsche Chemische Gesellschaft (Berlin), 31:2655 (1898).

Willstatter, R., Wolfes, 0. and Mader, H. Syntheses des Naturlichen

Cocaines. Justus Liebigs Annalen der Chemie, 434:111 (1923).

Wohler, V. Fortsetzung der Untersuchungen uber die Coca und das

Cocain. Justus Liebigs Annalen der Chemie, 121:372 (1862).

61

Chapter IV BEHAVIORAL EFFECTS OF

COCAINE IN ANIMALS

James Woods, Ph.D.

The inclusion of a paper on the behavioral effects of cocaine in

animals in a set of papers that deals primarily with cocaine's

effects in man may seem peculiar at the outset. Yet, there are a

variety of reasons for covering this subject. Often we are faced

with such complex problems concerning the behavioral effects of

cocaine in man and it is more straightforward to approach the

problems by involving animals. Often we will want to examine

questions associated with cocaine self-administration, but the

ethical issues associated with human experimentation may dictate

severe restrictions, if not total prohibition. Animals, however,

can provide much useful information about cocaine self-administration. Further, we often face the problem of the need for control

of behavioral history as it influences drug effect. Such histories

can be better controlled using animals in laboratory settings e.g.,

where the amount and kind of drugs previously taken can be specified.

This paper is intended to be a review of experimental work on the

effects of cocaine on the behavior of non-human animals. It is not

intended to be a critical review of this literature, but rather a

rapid way of providing the interested reader with a general awareness of what has been done in this area.

Early descriptions of the behavioral effects of cocaine in a variety

of animal species (e.g., Tatum & Seevers, 1929) established some of

the general reactions to cocaine that occur in animals and may also

occur in man. Later descriptions of the effects of cocaine included

changes in conditioned behavior as well as elaborations of descriptions of the drug's actions on unconditioned behaviors. Still

later, animals were shown to self-administer cocaine, showing

another parallel to man's behavior with respect to cocaine (e.g.,

Deneau et al., 1969) These are some of the effects of cocaine in

animals that may resemble its effects in man and which will be

described in greater detail in this chapter.

To introduce the effects of cocaine on behavior, a brief outline of

the effects of cocaine on a variety of physiological systems is

provided. These occur in concert with behavioral effects and while

the reader should be mindful of their occurrence, physiological

effects will not be mentioned subsequently.

63
In rodents or primates, the physiological effects of the smallest

doses of cocaine that can be reliably measured are pupil dilation,

heart rate and respiratory rate increases. Blood pressure increases at slightly higher doses. At still larger doses, body temperature increases significantly; in addition, the previously described

effects are exacerbated. Electrical activity of the brain is

characterized by patterns of activity of an aroused state; still

larger doses may lead to grand mal convulsions. At the stage of

imminent death, the physical signs may be a mixture of stimulation

of the central nervous system, respiratory depression and cardiovascular collapse. Death may be due primarily to either cardiovascular collapse or respiratory depression, or a complex joint

action of these effects. (For a more detailed discussion, see Woods

& Downs, 1973.)

Many of the effects of cocaine depend to an important extent on

environmental factors that exaggerate or diminish the physiological

and behavioral effects of cocaine. Even the lethal dose of cocaine

may be modified ‘by the environment in which the animal is placed.

Cocaine will produce a greater proportion of deaths in mice if they

are grouped together rather than if they are isolated. Likewise, if

mice are given electric shocks after having been administered

cocaine, many more will die even though the electric shock alone is

not strong enough to induce lethal effects (La1 & Chessick, 1965).

Still other factors (e.g., environmental temperature and exercise)

may decrease the dose of cocaine necessary to produce death. It is

thought that these effects may be exerted through the exaggerated

hyperpyrexia induced by these environmental manipulations (Peterson

& Bardinge, 1967).

There are a variety of other determinants of cocaine’s actions on

behavior. The magnitude and quality of every effect of cocaine will

critically depend on the dose of cocaine and the route of administration. Species differences in effect are marked; a dose of

cocaine that would produce a modest increase in locomotion in a

mouse would kill a rhesus monkey. It is difficult to appreciate the

importance of these differential effects until one has a sample of

them.

Cocaine may alter behavior in a variety of ways; it may change both

unconditioned and conditioned behaviors. We shall first examine

the varieties of behavior that are changedby cocaine in situations

that do not explicitly depend on prior experience. Cocaine alters

the gross behavioral activity of animals: it induces specific kinds

of behaviors and it alters certain reflexive responses to aversive

stimuli. In addition, a number of experiments have examined the

biological systems utilized for the mediation of these effects.

LOCOMOTOR ACTIVITY: The amount of locomotor activity an animal

engages in may be measured by the rate at which it interrupts a beam

of light that crosses an enclosed space occupied by the animal. For

example, a mouse may be placed in an enclosed circular chamber with

64
an 18-inch diameter; the chamber is divided by two perpendicular

light beams. The mouse may, in its normal meanderings, interrupt a

beam of light at a rate of 300 times per hour. Cocaine will

increase the number of interruptions five-fold at its maximal doses

(30-56 mg/kg , intraperitoneal); lower, and higher doses produce

smaller increases or none at all (Dews, 1953; Villarreal et al.,

1973). Similar results have been reported by other investigators in

the mouse (e.g., Costa et al., 1972; van Rossum & Simons, 1969).

Locomotor activity increases have also been obtained in rats (e.g.,

Fog, 1969; Wilson & Holbrook, 1974; Post & Rose, 1976) and the dog

(Tatum & Seevers, 1929). In the latter species, 3 mg/kg induces a

small increase in activity, an increase in reaction to slight

environmental changes (apprehension) and quick head movements. The

rhesus monkey reacts at this dose of cocaine with restlessness,

heightened activity, and an increased sensitivity ‘to environmental

change (e.g., Tatum & Seevers, 1929; Wilson et al., 1976).

STEREOTYPY: At very large doses in rats (250-600 mg/kg, subcutaneous), cocaine induces a form of invariant repetition of

responses, e.g., grooming a portion of the body. This stereotyped

behavior, which occurs to the exclusion of normal variations in

behavior, emerges slowly with high doses and may continue for more

than a day (Fog, 1969). Similar activities have been observed in a

variety of animal species, including man, with amphetamines and

other related drugs (Randrup & Munkvad, 1967). The occurrence of

these behaviors, at doses usually larger than those required to

produce increases in general activity, has been observed in cats

(Wallach & Gershon, 1971), in dogs (Tatum & Seevers, 1929; Hatch &

Fischer, 1972; Hatch, 1973) and in monkeys (Tatum & Seevers, 1929;

Wilson et al., 1976).

AGGRESSION: Cocaine changes aggressive behavior in the situations

and species in which it has been studied (Hutchinson & Emley, in

press ) . Reflexive fighting can be produced by the delivery of

electric shock to pairs of members of the same species, providing

they are housed in chambers in which the chance for bodily contact

is relatively high and there is no opportunity for escape from the

shock. Aggression may also be indicated by biting attacks toward

inanimate, soft objects when shocks are administered or when positive reinforcement is terminated; in addition, these biting

responses may be reinforced by delivering a reinforcing stimulus

when the biting response has occurred, or the biting response may be

reinforced by postponement of electric shock (e.g., Hutchinson,

1973). In each of these situations, some aspect of aggression is

investigated and the relation of cocaine to aggression may be

established.

In the squirrel monkey, cocaine at intermediate doses (0.1 to 1.0

mg/kg, subcutaneous) increases responding that is elicited by electric shock. It increases biting responses maintained by avoidance

of electric shock over a similar dose range; it produces only a very

modest increase in biting responses that are reinforced by food. At

higher doses, cocaine reduces responding in each of these situations (Hutchinson & Emley, in press).

65
Pigeons have been studied in situations in which a hungry bird

attacks a restrained bird or a stuffed model if food delivery to the

"free" bird is momentarily terminated. In another behavioral

situation similar to those described above with the squirrel

monkey, biting responses are obtained from mice when they are

shocked. With both these animals, cocaine reduced aggressive

responses (Hutchinson & Emley, in press). It is clear that aggressive behaviors may be increased or decreased by cocaine depending

upon conditions under which they are studied. Cocaine does not

appear to induce an enhanced aggressiveness at doses that do not

affect a variety of other behaviors (e.g., behaviors controlled by

food reinforcement as discussed in a subsequent section). In the

studies noted above, cocaine does not by itself induce aggression;

however, when aggression has been elicited by environmental events,

cocaine may increase or decrease this aggression.

INTERACTIONS WITH OTHER DRUGS: In attempts to understand more fully

the biological mechanisms for some of the direct behavioral effects

of cocaine, a number of studies have investigated the ability of

other drugs to alter cocaine’s effects. Frequently, these drugs

alter the activity of putative neurotransmitters. Through studies

of this kind, it is hoped that those of cocaine’s effects which are

accomplished through changes in neurotransmission will be better

understood. In most of the experiments that have been done on this

topic, locomotor activity in rats or mice has been modified by

cocaine administration. For example, van Rossum et al. (1962) and

Smith (1963) showed that cocaine-induced increases in activity were

less in mice pretreated with reserpine. Reserpine reduces the brain

content of three neurotransmitters in the mouse: norepinephrine,

dopamine and serotonin. Villarreal et al. (1973) showed that alphamethyl-para-tyrosine, a drug which depletes the brain of norepinephrine and dopamine, had no effect upon cocaine-induced increases

in locomotion. Drugs that prolong the actions of dopamine,

norepinephrine and serotonin by a variety of mechanisms have not had

uniform effects upon cocaine-induced hyperactivity. Smith (1964)

found that iproniazid, a drug which slows the metabolism of the

transmitters noted above, did not alter the response of mice to a

variety of doses of cocaine; other drugs, which have actions similar

to those of iproniazid, increased cocaine’s locomotor effects

(Christie & Crow, 1973; Scheel-Kruger, 1972). Atropine, a drug

which blocks some of the central and peripheral actions of the

neurotransmitter, acetylcholine, potentiates cocaine’s effects on

locomotor activity (Galambos et al., 1967).

There are a vast number of centrally acting drugs that may modify

cocaine’s actions in a way that may be relatively obscure at the

cellular level of description; it is surprising that a larger number

of experiments have not been done on the topic. There is an

interesting report of the potentiation of toxic actions of cocaine

by phenytoin in dogs (Hatch & Fischer, 1972; Hatch, 1973). Blumberg

and Ikeda (1975a; 1975b) have reported that morphine in large doses

will reduce cocaine hyperactivity, and naltrexone, a narcotic

antagonist, did not alter the locomotor stimulation produced by

cocaine in mice or rats.

66
Taken together, these data suggest that cocaine’s locomotor stimulant effect may be altered by a variety of drugs but the experiments

have not pointed to a single neurochemical mechanism even for

cocaine’s locomotor stimulant effect in rodents.

BEHAVIORAL ACTIONS OF COCAINE METABOLITES: It is generally believed that cocaine acts directly to bring about its effects; in other

words, it need not be converted metabolically to some other active

compound in order to achieve its action in the body. However, in a

variety of species it is de-esterified and N-demethylated, although

as Nayak et al. (1976) point out, its metabolism is not well

characterized in any species other than the rat. The N-demethylation product, norcocaine, has been identified in both the monkey

brain (Hawks et al., 1974) and rat brain (Misra et al., 1974a)

following the administration of cocaine. Hawks et al. (1974)

demonstrated that norcocaine is equipotent with cocaine in blocking

the uptake of norepinephrine in rat brain synaptosomes, and norcocaine has been shown to have convulsant actions similar to cocaine

in the rat (Misra et al., 1975). Apart from this report, there is

as yet very little characterization of norcocaine’s actions on

behavior. Cocaine may also be hydrolyzed at the ester in the 2

position (see Hawks, Chapter 3, this volume) to form benzoylecgonine or, at the equivalent position, to form benzoylnorecgonine from norcocaine. Both have been identified as urinary

metabolites of cocaine in the rat (Nayak et al., 1976). Neither of

these compounds has locomotor stimulant activity in rats even in

very high doses by systemic administration (Misra et al., 1975).

Probably due to their polar characteristics, they achieve only

relatively small concentrations in brain tissue. By injection into

cerebral spinal fluid, however, both compounds have strong stimulant characteristics that appear to be qualitatively different from

cocaine or norcocaine (Misra et al., 1975). However, if either of

the compounds is formed in the brain in significant concentrations,

it may play a role in the behavioral effects of cocaine.

Benzoylecgonine may be further hydrolyzed to form ecgonine. Due to

its polar nature, it is thought to be relatively unimportant in the

behavioral effects of cocaine. Misra et al. (1974b) reported a

sensitive technique for its identification; apparently it is not

further metabolized in the rat. Thus, while a number of metabolites of cocaine have been identified, it is not clear as yet

whether any of these metabolites are involved in the behavioral

effects of cocaine.

Just as the variety of metabolites of cocaine must be studied

further for their contribution to the behavioral pharmacology of

cocaine, the study of structural relatives should yield important

insights into the mechanisms of cocaine’s actions. Spealman et al.

(1976) have recently reported that elimination of the ester link

between the phenyl and tropane portions of the cocaine molecule

prolongs its action but does not change the qualitative effects on

operant behavior in squirrel monkeys. There are also stereoisomers

and epimers of cocaine whose effects on behavior need to be examined

in considerable detail.

67
CHANCES IN COCAINE’S DIRECT EFFECTS WITH CHRONIC ADMINISTRATION:

Some of the effects of cocaine have been shown to decrease or

increase following repeated administration. These changes, regardless of their direction, should not be viewed as changes in the

character of the drug; rather, they are changes in the dose required

to bring about the same cocaine effect.

Tolerance to cocaine’s action is inferred when the dose required to

bring about an effect is increased, or when there is a shift to the

right in the dose-effect relation for cocaine. In examining

increases in heart and respiratory rates of rhesus monkeys administered 4 mg/kg of intravenous cocaine during a three-day period,

Matsuzaki et al. (1976) demonstrated a reduction in the increases by

the second and third day. Likewise, the dose required to induce

changes in the electroencephalographic record, predictive of convulsions, is increased following the initial administration of the

drug. It appears that the reduced effect is obtained very quickly,

i.e., within 3-5 administrations of cocaine. This reduced sensitivity is not lost with a 2-3 day interruption of drug administration, but recovery does occur following 30-40 days of abstinence

(see Figure 4, Matsuzaki et al., 1976). It is not likely that

similar reduced effects are encountered with behavioral endpoints

with the rhesus monkey since they have not been noted in the

behavioral literature; however, the effect described is an initial

drug administration effect and may reflect the novelty of the first

experience with cocaine. Protocols that are designed to detect

novelty effects must be applied to this phenomenon for further

elucidation.

Woolverton et al. (in press) described an experiment which suggests

that the behavioral context of cocaine’s administration may be

important to the prediction of its chronic behavioral effects. They

measured in rats the suppression of drinking sweetened milk by

cocaine administration. Acute cocaine administration suppressed

the consumption of the milk in a dose-dependent manner. Tolerance

to daily cocaine (16 mg/kg, intraperitoneal administration) was

observed in a group of rats’given the drug prior to milk exposure,

but not in a group receiving cocaine after milk exposure. If the

tolerance had been the same in the two groups, then it could have

been due to the common effect of the drug; e.g., enhanced elimination which has been shown to occur in rats (Nayak et al., 1976).

However, the difference in effect suggests that some aspect of the

milk exposure in the presence of cocaine was important for the

development of tolerance. Similar findings have been reported for

amphetamine in rats (e.g., Schuster et al., 1966).

Tatum and Seevers (1929) noted an increased behavioral reaction to

cocaine with repeated administration in both dogs and rhesus

monkeys. They also noted conditioned changes that could be elicited

by the stimuli that preceded drug administration. Downs and Eddy

(1932a; 1932b) found increased responsiveness to cocain in the

form of convulsions and death in the rat, and an increased reaction

68
to a fixed dose in the dog as well. Post and Rose (1976) have shown

an increasing effect of daily 10 mg/kg doses of cocaine on

locomotor activity in the rat.

Finally, in a study using extremely large doses of cocaine in rhesus

monkeys (10-17 mg/kg intraperitoneal; twice per 24 hours), Post et

al. (1976) observed complex progressive changes in cocaine-induced

patterns of behavior. Severe stereotyped behaviors occurred during

a six-week period of administration; in some of their monkeys, this

pattern of behavior subsided and was replaced by dyskinesias and

inhibition of locomotor activity. In accordance with the results of

previous studies, convulsions tended to occur more often with

chronic administration.

These studies show that a complex set of changes in cocaine’s

behavioral effects may occur with the chronic administration of

cocaine. There is no easy guide for predicting the direction of the

changes that might occur following chronic cocaine administration.

Behavioral changes associated with chronic administration need to

be studied in situations in which the contribution of factors that

usually influence behavioral tolerance development may be more

fully examined (e.g., Thompson & Schuster, 1968). It is only then

that a full characterization can be made of these interesting

initial observations.

Direct Effects on Operant Behavior

Operant behavior can be described as behavior controlled by its

consequences: it is increased and maintained by the presentation or

termination of environmental events. If responding is maintained

by stimulus presentation, then we refer to the stimulus as a

positive reinforcer. If an event maintains behavior by its termination, then the event is a negative reinforcer. If the future

probability of a response is reduced by the presentation of a

consequence, the consequence is referred to as a punisher. The

administration of cocaine has been studied in situations in which

these different consequences control behavior and generalizations

have been drawn with respect to these drug-behavior interactions.

The organization of empirical effects will focus on these generalizations.

Profound alterations in operant behavior can also be produced by the

particular arrangement of the consequent event with respect to

responding. The same event may maintain behavior or suppress it,

depending on its schedule of presentation (Morse & Kelleher, 1970).

The schedule of presentation of reinforcers or punishers may also

affect the rate and pattern of behavior. There are a variety of

ways to arrange events to affect changes in behavior through their

schedules of delivery. These are basically derived from arrangements where responses bring about reinforcers on the basis of a

temporal requirement, a number requirement or some combination of

these two. In a fixed-interval schedule, for example, reinforce69
ment is delivered following the first response after a fixed

interval of time since the last reinforcement delivery. After this

schedule has been in effect for some period of time, it produces low

rates of responding that accelerate positively between deliveries

of the contingent stimulus. The final highest rate is sustained

until the next reinforcer is delivered. In fixed-ratio schedules,

reinforcement is delivered following the occurrence of a given

number of responses, regardless of the time since the last

reinforcement. In the latter case, if the response requirement is

reasonably small, a short pause occurs following reinforcement

delivery, after which responding resumes at a high sustained rate.

These patterns of responding occur with great regularity with these

schedules in rodents, pigeons and primates. The evidence below

provides numerous examples of these patterns.

Schedule-controlled performances may be used to examine the effect

of cocaine on a variety of rates and patterns of responding. Smith

(1964) examined the effects of cocaine on patterns of key-peck

responding under the schedules mentioned above when short periods

of food access were used as reinforcements for food-deprived

pigeons. He found that 0.3-3.0 mg/kg doses of cocaine increased

responding in the fixed-interval schedule while they decreased

responding in the fixed-ratio schedule. A similar range of doses

(0.1-1.0 mg/kg) of cocaine increased responding under fixedinterval schedules of food reinforcement in squirrel monkeys

(Barrett, 1976; Gonzalez & Goldberg, in press). Dose-related

decreases have been found in fixed-ratio responding maintained by

food reinforcement over a 0.3-3.0 mg/kg dose range in squirrel

monkeys (Gonzalez & Goldberg, in press) and rhesus monkeys (Woods &

Tessel, 1974; Johanson, in press a).

Gonzalez and Goldberg (in press) noted that cocaine and amphetamine

have similar qualitative and quantitative effects on these and

other schedule-controlled performances maintained by food delivery,

although d-amphetamine has a slightly longer duration of action.

Dews (1958) has formulated a general framework for the description

of drug effects on schedule-controlled responding, noting that many

drug effects depend upon the rate of ongoing responding. A typical

result is that of amphetamine which increases the lower rates of

responding controlled by fixed interval schedules while leaving

unchanged or decreasing the high rates associated with fixed-ratio

schedules of food delivery. The examples given above of cocaineinduced rate changes conform well to this rate-dependent analysis

of drug effects.

Barrett (1976) compared the effects of cocaine on fixed-interval

responding maintained by food to similar behavior maintained by

presentation of electric shock in squirrel monkeys. He found that

the effects of cocaine were similar for the two reinforcers.

Intermediate doses increased responding; higher doses reduced the

frequency of behavior maintained by shock and food by about the same

amount. Other drugs (e.g., pentobarbital) had markedly different

effects on behavior maintained by these reinforcers. Herling et al.

70
(1975) reported that under some circumstances, food- and cocainemaintained fixed- interval responding in rhesus monkeys may be

affected similarly by cocaine administration; in both situations,

rate of response was increased by moderate doses and decreased by

higher doses of cocaine.

Hutchinson and Emley (in press) found that 0.3-3.0 mg/kg of cocaine

increased responding that postponed the delivery of electric shock

in the squirrel monkey. The response used in this situation was

biting, a response elicited by electric shock in this species, as

described above. Spealman et al. (personal communication) compared

fixed-interval and fixed ratio schedules of negative reinforcement

based on electric shock delivery to similar schedules of food

delivery in squirrel monkeys. They found similar effects of cocaine

on the two types of reinforcement. These effects depended on

control rate of responding as determined by the schedules of

reinforcement.

The results of the experiments on schedule-controlled performances

suggest that cocaine may affect rates of responding maintained by

different reinforcers in the same way. Johanson (in press: a),

however, found that cocaine decreased food-reinforced fixed-ratio

responding at doses that did not affect fixed-ratio responding

maintained by the termination of stimuli associated with electric

shock. On the other hand, perphenazine in some situations reduced

responding controlled by the two reinforcers to a comparable

extent. Clearly, further experimentation is needed to clarify the

conditions under which these reinforcer-dependent differences will

be obtained with cocaine.

Large doses of cocaine (2.5-10 mg/kg), relative to those used in

primates, increase low rates of responding maintained by electrical

brain stimulation in rats. High rates of brain self-stimulation may

be unaffected at these doses (Crow, 1970; Wauquier & Niegemeers,

1974).

Behavior suppressed by punishment was increased by cocaine in

rodents over a 10-30 mg/kg dose range (Morpurgo, 1965) while

behavior maintained by negative reinforcement was decreased.

Smaller doses were ineffective in increasing behavior suppressed by

stimuli associated with electric shock (Hill et al., 1967). A

similar dose range was found to reduce the frequency of behavior

maintained by water reinforcement (MacPhail & Seiden, 1975). Taken

together, the experiments with rodents using these operant techniques are consistent with experiments in primates in suggesting

that low rate behavior may be increased by moderate doses of

cocaine, while higher doses may reduce high-rate behavior regardless of the nature of the reinforcer. Indeed, these cocaine-induced

effects indicate a strong dependence of the drug’s effect on the

rate of occurrence of operant behavior. With the exceptions noted,

it seems that cocaine affects behavior controlled by different

reinforcers in a similar manner as long as comparable rates of

behavior are involved.

71
INDIRECT BEHAVIORAL EFFECTS OF COCAINE

The following sections deal with situations in which cocaine is used

as a stimulus to bring about behavioral changes that are specific

products of conditioning history. We shall first examine the

interesting evidence that animals can recognize the ‘effects of

cocaine and can be taught to perform a response differentially in

the presence or absence of the drug. Within this procedure,

questions such as the following may be answered: What is the lowest

dose of cocaine that can be differentiated from saline? What drugs

are sufficiently similar to cocaine to be confused with it?

Another interesting use of cocaine is as a reward. In studies of

this kind, delivery of a dose of cocaine is contingent on the

performance of a response. The delivery of drug is said to be

reinforcing (rewarding) if the response that precedes drug administration increases in frequency. As we will see, this procedure

can answer questions such as: How strong a reinforcer is cocaine

relative to other drug and non-drug reinforcers? How can other

drugs affect cocaine-reinforced responding? and, equally important,

How is cocaine different from other reinforcers?

Cocaine as an Unconditioned Stimulus

Still another use of cocaine in conditioning is that of establishing

classically conditioned responses. Many drugs can serve as unconditioned stimuli for the formation of classically conditioned responses. Cappell and LeBlanc (in press) compared the effectiveness

of amphetamine, cocaine and morphine as unconditioned stimuli producing conditioned suppression of the drinking of sweetened water

in rats. While both morphine and amphetamine produced conditioned

suppression of drinking, cocaine, even in doses that have been shown

to decrease drinking directly (Woolverton et al., in press), did not

produce conditioned decreases in fluid intake. Clearly, further

experiments are necessary to examine the ability of cocaine to serve

as a stimulus for classically conditioned responses in these and

other contexts.

Cocaine as a Discriminative Stimulus

A discriminative stimulus is a feature of the environment which is

correlated with the presentation of a reinforcer. To determine

whether differences between environmental features can be used as

discriminative stimuli, behavior is reinforced in the presence of

one set of features and not reinforced in the presence of another.

When a difference in behavior occurs under the two conditions, one

may assume that the specified feature has become conditioned and

that the features have been discriminated. This "feature of the

environment" may be simply the presence or absence of a light in an

animal’s chamber, or a difference in wavelength of two lights.

72
Similarly, a discrimination may be based on differences in internal

cues, such as those produced by food or water deprivation.

Researchers have shown that a variety of drugs can serve as discriminative stimuli (e.g., Overton, 1971; Barry, 1974). Barry and

Kubena (1972) trained rats to press a lever for food reinforcement

following the injection of 4 mg/kg of tetrahydrocannabinol (THC);

following saline injections (in the absence of THC) responding was

punished with electric shock. Another group of rats was trained in

the same situation with the contingencies reversed. When cocaine

(10 or 20 mg/kg, intraperitoneal) was substituted for THC, both

groups of rats responded to cocaine as they did to saline. However,

this may be due either to differences between the attributes of THC

and cocaine, or to the use of inactive doses of cocaine.

Winter (1975) trained a group of rats to bar-press with mescaline

(10 mg/kg, intraperitoneal) and saline as the cues to the presentation of either food reinforcement or shock. Cocaine was assessed

for its stimulus equivalence to mescaline; if cocaine has effects

similar to mescaline, the group punished following mescaline should

also stop responding in the presence of cocaine, and the group

conditioned to respond following mescaline should, similarly, respond following cocaine. Cocaine (3, 10 and 30 mg/kg, intraperitoneal) failed to engender responding in the group trained to

respond following mescaline. The possibility that the doses of

cocaine were too small is discredited by the fact that rats trained

to respond in the presence of saline and refrain from responding

following mescaline, showed dose-dependent decreases in responding

over the range of cocaine doses administered. These results are

consistent with a direct rate-decreasing effect of cocaine and the

dosages were in the range found by MacPhail and Seiden (1975) to

reduce responding maintained by similar schedules of reinforcement.

Thus, behaviorally active doses were used by Winter, and we may

conclude that cocaine is not functionally similar to mescaline in

this behavioral situation.

Ando (1975) trained rats, catheterized for intravenous injection,

to respond for food following a 0.2 mg/kg injection of amphetamine.

Responding was reinforced for five minutes after the amphetamine

injection and was not reinforced following saline injections. Periods of amphetamine and saline alternated, with injections given

every half hour. Responding occurred rapidly after amphetamine but

not after saline. Cocaine (0.2 mg/kg) acted like amphetamine in

that it induced responding in the five-minute period following an

injection. Ando's procedure provides more rapid testing of different doses and drugs, and may allow the recognition of smaller doses

compared to other routes of administration. Unfortunately, the

technical aspects of intravenous catheterization of rats and other

small animals has not yet been developed sufficiently to permit

long-term catheter patency in a large proportion of subjects.

73
The literature associated with the discriminative properties of

cocaine is quite sparse, but the limited results are interesting.

from the studies noted above, cocaine appears to have stimulus

attributes more similar to amphetamine than to mescaline or THC.

These studies have used drugs other than cocaine as discriminative

cues and cocaine’s similarity to these agents has been explored. No

experiment using cocaine as the discriminative stimulus has been

done although this approach is equally important. As a result, many

questions remain unanswered. What are the dose and temporal

dimensions under which cocaine and amphetamine are equivalent? Can

animals be taught to discriminate cocaine from amphetamine, and, if

so, under what circumstances? The relationship between the discriminative properties of the drug and the other behavioral actions

of the drug (e.g., the many direct actions and the reinforcing

action) should be explored. Finally, as noted previously, since

tolerance is conferred to some behavioral actions of cocaine, do the

discriminative properties of cocaine also change during chronic

administration? These questions, which have yet to be analyzed in a

systematic manner, might be explored using discriminative stimulus

procedures such as those outlined here.

Cocaine as a Reinforcing Stimulus

If the frequency of a response increases when that response is

followed by cocaine delivery, the cocaine is said to function as a

reinforcer. A variety of species, routes of administration, doses

and response requirements have been examined to determine the

conditions under which cocaine acts as a reinforcer. Rats, guinea

pigs (Dougherty, personal communication), pigeons (Wenger, personal

communication), dogs (Risner, personal commnmication), squirrel and

rhesus monkeys and baboons are among the species that have been

tested. Indeed, the species generality has become sufficiently

wide that a negative finding in a particular species would induce

skepticism about the experimental conditions employed. However,

the conditions of cocaine delivery that have been studied have been

rather limited. The intravenous route is by far the most popular,

probably because it is so effective in producing positive results.

With the less popular routes of administration, we knew very little

about cocaine’s reinforcing effect.

In the most common experimental procedure, a simple response acts to

deliver cocaine. The response is usually the depression of a lever

that extends into the living space of the experimental subject.

Depending on other experimental conditions, it may be important to

examine whether the drug exerts direct behavioral effects on responding, so a second lever may be present that has no consequence

with respect to drug delivery. Were the cocaine to have an

important activity-increasing effect, for example, responding might

increase equally on the two levers. This has not been the case in

many experimental situations (e.g., Johanson et al., 1976a; Pickens

& Thompson, 1968).

74
When intravenous routes of delivery of cocaine are employed, completion of the reinforcement contingency activates a pump that

delivers drug directly into the blood through a chronic indwelling

venous catheter. A variety of rather ingenious techniques have been

devised to shield these catheters in monkeys (e.g., Deneau et al.,

1969; Herd et al., 1969), dogs (Jones & Prada, 1973), baboons

(Findley et al., 1972) and rats (Weeks, 1962). For intramuscular

administration, rhesus monkeys can be trained to accept an intramuscular injection (apparently to avoid aversive handling) and

subsequently can be taught to respond to turn on a light signaling

to the experimenter the time for a cocaine injection (Goldberg et

al., 1976). An oral route of administration has been examined in

rhesus monkeys with the cocaine delivered in candy (Siegel et al.,

1976), but it is not clear whether cocaine or the candy was the

functional reinforcer in this situation. This result may have more

to do with procedural detail than pervasive differences in results

depending upon route of administration. Using a chronic intragastric cannula, cocaine injections have been found to reinforce

lever-press responding in rhesus monkeys (Schuster, personal communication) . The oral and intragastric routes of administration

bear further study because of the marked differences in various

behavioral effects of cocaine by the oral as opposed to the intravenous route in man (e.g., Woods & Downs, 1973). The intranasal

route of administration has not been examined in animals, although

this appears to be the predominant mode of administration in man in

this country. A single study approached this route in rhesus

monkeys (Siegel et al., 1976) by encouraging the smoking of cocaine.

Water-deprived rhesus monkeys were rewarded with water for puffing

cocaine base in lettuce leaf cigarettes. When tested without the

water contingency, two of the three monkeys continued to smoke the

cocaine base cigarettes more than the cigarettes with lettuce

alone. Subsequently, they appeared to prefer cocaine-containing

cigarettes to plain cigarettes. Some cocaine was found to be

absorbed under these conditions, since the cocaine metabolite,

benzoylecgonine, appeared in the urine following cocaine intake.

Both the inhalation and intramuscular routes of administration have

a tremendous practical advantage over the relatively short-term

intravenous technique, due to the catheter problems mentioned previously. There are no reports of intraventricular or intracerebral

cocaine self-injection.

Although our information on different species is far from complete,

all animals that have been tested for reinforcing effects of cocaine

show a positive response. Each of these situations has important

behavioral parameters’ that influence the expression of the reinforcing effects of cocaine. These parameters will be discussed with

respect to the influence on the rate and pattern of the reinforcing

effect of cocaine.

DOSE AS REINFORCER MAGNITUDE: As noted previously, most, if not

all, of the behavioral effects of cocaine are dose-dependent. We

have seen in previous sections, for example, that the effects of

75
cocaine on schedule-controlled performances may be an increase or a

decrease depending on the dose. A moment’s reflection should

suggest that dose will be an important determinant of performance

when cocaine itself is used as a reinforcer. Too small a dose, of

course, will be totally ineffective; but as dose is increased, does

the rate of responding indicate an increased effect due to increased

reinforcing efficacy? The answer is yes, but this must be qualified

by stating the specific experimental conditions. An example of

experimental observation can be used to illustrate the point.

A monkey has been conditioned to self-inject cocaine. After each

series of 30 responses, the monkey obtains an injection of cocaine.

The rate of drug administration is entirely dependent on the speed

of the monkey’s responding. With experience, the monkey works at a

rapid pace ( 1 response per second) for a small intravenous dose

(e.g., 0.01 mg/kg) that is used as the reinforcer. When the dose is

decreased, the rate increases further but becomes more variable

across sessions. If the dose is decreased further, the rate of

responding drops considerably, indicating that the dose has been

reduced to a level that either has no discernible effect or has too

small an impact to maintain behavior. As the dose is increased

again, rates of responding also increase to a maximal rate above

which further dose increases lead to decreases in rates of responding (Downs & Woods, 1974). This type of relationship of dose

to self-injection rate has been reported for fixed-ratio schedules

of cocaine delivery in rodents and primates (e.g., Goldberg, 1973;

Pickens & Thompson, 1968) and for fixed-interval schedules of

cocaine delivery in primates (e.g., Balster & Schuster, 1973;

Goldberg & Kelleher, 1976). The dose that maintains the maximum

rate under these schedules depends on the parameters of the schedule

and whether or not another opportunity for self-injection occurs

immediately following the previous injection.

It is thought that the rate of cocaine-reinforced responding

increases because the higher doses are stronger reinforcers. With

further increases in dose, the appearance of direct rate-decreasing

effects may in some way limit the rates of responding. Cocaine can

decrease directly both fixed-interval and fixed-ratio schedulecontrolled performances maintained by other reinforcers as noted

previously. The use of schedules of reinforcement in which drug and

other types of reinforcement alternate allows the determination of

whether the rate-decreasing effects of the larger doses of Cocaine

are behaviorally specific to particular reinforcers (e.g., Balster

& Schuster, 1973; Tessel & Woods, 1975).

SCHEDULES OF COCAINE REINFORCEMENT: A schedule of reinforcement,

as noted above, specifies the rule under which responses are

followed by a consequence (e.g., Ferster & Skinner, 1957); in the

cases to be discussed in this section, the reinforcing consequence

is cocaine delivery. If responding is reinforced with intravenous

cocaine on a fixed-interval schedule, responding -- as with food

reinforcement -- shows a slowly accelerating rate of occurrence

that rises to a final rate sustained until cocaine delivery. This

76
has been demonstrated for cocaine in both the rhesus monkey (Balster

& Schuster, 1973; Goldberg & Kelleher, 1976; Pickens & Thompson,

1972) and in the rat (Dougherty & Pickens, 1973). A fixed-ratio

schedule of intravenous cocaine delivery generates high sustained

rates of responding if the requirement for cocaine delivery is a

modest number of responses (e.g., 10-60) with no temporal restrictions. As when food is delivered under fixed-ratio schedules, the

pattern of responding is a pause followed by a rapid sequence of

responses terminated by delivery of cocaine. Responding may exceed

one response per second under these schedules in rhesus and squirrel

monkeys (Downs & Woods, 1974; Goldberg, 1973; Goldberg & Kelleher,

1976). Thus, the pattern of responding maintained by these

schedules of cocaine delivery may be comparable to other reinforcing events. An excellent summary of schedules of cocaine injections

in squirrel and rhesus monkeys will soon be available (Goldberg &

Kelleher, 1977).

SCHEDULE-CONTROLLED PERFORMANCES OF PARTICULAR EKPERIMENTAL

INTEREST: from the variety of ways in which cocaine is potentially

useful as a reinforcer, experimenters interested in the examination

of schedule-controlled performances have centered special interest

on a few relatively complex procedures. The overall thrust of these

experiments has been to measure the reinforcing strength of cocaine

and to obtain a broad description of the variables that may interact

with cocaine as a reinforcer. A brief description of the procedures

will be given along with the concepts that have arisen from the

studies.

A technique that has shown promise in ordering reinforcer

magnitudes with reinforcers such as electrical brain stimulation or

sweetened milk in rodents is to increase the number of responses

required for each successive reinforcement delivery. The technique, which is called the progressive ratio schedule (Hodos, 1961;

Hodos & Kalman, 1963), may require 100 responses for the initial

reinforcer; then the requirement might double to 200, 400, 800, etc.

The critical measure of behavior is the highest ratio completed in a

given period of time, and this is used as an indicator of the

strength of the reinforcer. It is thought that the application of

this procedure will provide comparisons of the relative reinforcing

strengths of different cocaine doses as well as comparisons among

different drugs. Yanagita (1973) showed that rhesus monkeys completed larger ratios for larger doses of cocaine. Griffiths et al.

(1975), however, found the largest completed ratio to be constant

for baboons that were self-injecting cocaine in a variety of

different doses. The procedures were slightly different in these

studies, but as Brady and Griffiths (1977) point out, the major

difference was that the doses studied by Griffiths et al. (1975)

were larger than those used by Yanagita (1973).

Another technique used to measure the reinforcing strength of

different cocaine doses involves behavioral situations in which a

preference for or a choice between different doses of cocaine has

been determined. Often these situations involve a set of levers,

77
each of which delivers a different consequence (e.g., different

reinforcement magnitudes or different delays in reinforcement

delivery). Preference is measured by the relative responding

maintained by the different consequences; if the relative rate of

responding increases on the lever that delivers reinforcement more

often, a preference for that consequence is assumed. In a variety

of circumstances with both the baboon Brady & Griffiths, 1977)

and the rhesus monkey (Iglauer & Woods, 1974; Johanson & Schuster,

1975), a preference for the larger of two doses of intravenous

cocaine has been demonstrated. At very large doses, however, lack

of Preference has occasionally been noted (Johanson & Schuster,

1975; Llewellyn et al., 1976). These procedures and variations of

them may also provide important data on preferences for different

drug and non-drug reinforcers and may provide important ways of

assessing behavioral procedures that may affect preferences for

drug and non-drug reinforcers (e.g., Catania, 1975).

Another procedure that has been used for the assessment of cocaine

as a reinforcer is a second-order schedule of reinforcement (e.g.,

Kelleher, 1966). This is a schedule that uses one schedule requirement as a building block -- a unitary response requirement -- for a

second schedule. For example, a fixed ratio schedule could be used

as a building block; it could be reinforced on a second schedule,

perhaps a fixed interval. Continuing the example, a cocaine

injection would be presented for the first completed fixed ratio

after a fixed interval of time from the previous injection. Secondorder schedules may be used to examine long sequences of behavior,

which are largely maintained by stimuli which accompany the

reinforcement. delivery. In the example, a stimulus which

accompanies the drug injection when the ratio completed after the

interval has passed would also occur with the completion of each

fixed ratio within the fixed interval. Thus, it would be possible

to examine the ability of stimuli associated with drug injections to

maintain behavior that leads to these injections. Conditioned

stimuli associated with cocaine and other drugs have been shown to

have large effects in the maintenance of schedule-controlled performances in both rhesus and squirrel monkeys (Goldberg et al.,

1975). This technique holds considerable promise for investigation

of environmental factors affecting drug self-injection.

Recently, an international group convened under the auspices of the

Committee on Problems of Drug Dependence to evaluate the above

procedures in the preclinical assessment of the abuse potential of

new drugs. It was the consensus of the group that the methods

discussed in this section hold considerable promise in the evaluation of the abuse potential of both central stimulants and depressants (Unna & Thompson, in press). A full description of cocaine's

effects in these procedures will provide a good basis for comparison

with other drugs that may have different profiles of behavioral

effects.

ACCESS CONDITIONS TO COCAINE: When animals are conditioned to selfinject cocaine, the self-injection behavior may be restricted to a

78
certain time of day or a specified total number of injections or

some combination of these variables in order to limit the intake of

cocaine. This limitation of intake has been found necessary for

long-term experiments with intravenous cocaine self-injection,

since rhesus monkeys will go through bouts of severe intoxication if

their intake is not restricted (Deneau et al., 1969; Johanson et

al., 1976a). The state of intoxication includes profound to

complete anorexia, restlessness, stereotyped movement, piloerection, tremor, dysmetria, self-mutilation and mydriasis. During

these periods, which may persist unabated for days, severe central

stimulation may produce grand ma1 convulsions. heath can occur,

presumably following either the convulsive episodes or cardiovascular complications. A bout may also be terminated in exhaustion

and a period of abstinence, followed by another episode of cocaine

self-injection. In the monkey, these cycles often produce death

within one month, or, on occasion, in less than one week. Similar

cocaine-induced forms of intoxication have been described in

intravenous self-injection experiments in rats (Pickens & Thompson,

1971).

The particular parameters of chronic administration that induce

these toxic effects are not known. The possibility of species differences exists: Pickens and Thompson (1971) suggested that in

rats, amphetamine brings about gross toxicity more readily than

cocaine, while Johanson et al. (1976a) suggested that the reverse

holds true with the rhesus monkey. Regardless, in the latter

species -- when intravenous cocaine is available in an unlimited

fashion -- the drug kills with amazing speed and reliability. Yet,

this form of intoxication is reversed by limiting the periods for

cocaine administration. Most investigators have limited cocaine

access to a dose far smaller than that necessary to produce convulsions. Opportunities for self-injection are spaced far enough

apart to minimize cumulative drug effects. Quite limited access to

the drug can be successfully used. For example, single

intramuscular injections maintained responding in the rhesus monkey

when access to the drug was limited to alternate days (Goldberg et

al., 1976).

OTHER VARIABLES THAT AFFECT COCAINE-REINFORCED RESPONDING: Gollub

and Ysnagita (1974) reported that the longer the delay imposed

between the completion of a fixed-ratio requirement and its consequent intravenous injection, the slower the cocaine-reinforced

responding. Johanson (1975) described a preference situation,

however, in which rhesus monkeys chose a delayed injection over an

immediate injection. Procedural details of these preliminary

reports were not available to resolve these differences in effects.

A better understanding of delay of reinforcement might help explain

changes in quantitative effects with different routes of

administration.

Grove and Schuster (1974) demonstrated that electric shock delivered inmediately following the reinforced response suppressed

responding maintained by intravenous cocaine delivery in rhesus

monkeys. Johanson (1975) showed that the shock-induced suppression

79
of a sequence of responses leading to cocaine delivery could be

reversed by increasing the dose of cocaine available. These initial

findings may lead to important generalizations about the punishment

of drug-reinforced responding.

Only one experiment has been conducted on the influence of rate of

cocaine injection on reinforced responding. Balster and Schuster

(1973) showed that a given dose of intravenously injected cocaine

was more effective in maintaining fixed-interval performance the

more rapidly it was injected.

EFFECTS OF DRUGS ON RESPONDING MAINTAINED BY COCAINE REINFORCEMENT:

A wide variety of drugs have been examined for their effects on

cocaine-reinforced responding. These effects hold potential

interest for a number of reasons: the pharmacology of cocaine’s

behavioral effects, including the reinforcing effect, may be described in part through analysis of the manner in which different

drugs alter cocaine’s reinforcing effects. Further, a drug that

reduces the reinforcing effect of cocaine might be used to treat

problems of excessive cocaine use. Similarly, a drug that alters

the reinforcing effect of cocaine could be used to analyze the

behavioral and pharmacological actions of cocaine. As has been

mentioned, cocaine’s locomotor stimulating effect is thought to be

related to a potentiation of the effect of biogenic amines (e.g.,

norepinephrine, serotonin and dopamine).

Drugs which act to reduce the activity of catecholamine-containing

neurons have been shown to alter cocaine-reinforced responding.

For example, haloperidol is thought to act as an antagonist of

dopamine’s actions. It may increase cocaine-reinforced responding

at small doses while reducing cocaine-maintained responding at

larger doses (Gill et al., in press; Woods et al., in press). Other

drugs which share haloperidol’s property of blocking dopamine

receptors (e.g., pimozide, chlorpromazine, perphenazine and trifluorperazine) also modify cocaine-reinforced responding.1

 Drugs

that act to reduce adrenergic activity through different cellular

mechanisms (e.g., alpha-methyl-para-tyrosine and reserpine) also

bring about changes in cocaine-reinforced responding (Wilson &

Schuster, 1973a; 1974). Because doses of haloperidol and chlorpromazine that affect behavior maintained by other reinforcers

(e.g., food) also affect cocaine-reinforced responding, their

behavioral specificity in changing cocaine-reinforced responding

has to be examined in great detail.

Drugs that are known to potentiate the actions of biogenic amines by

interfering with their termination of action (e.g., pargyline and

imipramine) reduce cocaine-reinforced responding (Wilson &

1Gill et al., in press; Johanson et al., 1976b; Risner, 1977; Wilson

& Schuster, 1972, 1973a; Woods et al., in press.

80
Schuster, 1973a; 1974). The specificity of this effect on cocainereinforced responding has not been assessed. Taken together, these

results suggest that biogenic amines act as modulators of cocainereinforced responding. Further research is needed to delineate the

pharmacological and behavioral actions of these drugs on cocainereinforced responding.

The schedule of cocaine reinforcement is an extremely important

variable in determining the nature and magnitude of the effects of

chlorpromazine and haloperidol on cocaine-reinforced responding

(Woods et al., in press). It is likely that other variables (e.g.,

dose, pretreatment time and route of administration) interact in

complex manners to determine the direction and magnitude of these

drug effects.

Atropine, a drug which blocks some of the actions of the neurotransmitter, acetylcholine, has been shown to increase cocainereinforced responding in small doses. The quaternary form of the

drug, which does not readily pass the blood-brain barrier, and

consequently has little central action, did not increase cocaine

self-injection (Wilson & Schuster, 1973b). The effect of atropine

was similar to that described above for dopamine receptor blockers.

However, atropine did not reverse cocaine-induced decreases in

food-reinforced responding in rhesus monkeys whereas chlorpromazine

did antagonize this effect of cocaine (Wilson & Schuster, 1975).

This curious and interesting drug interaction deserves considerable

further investigation.

Propranolol in the squirrel monkey reduces cocaine-reinforced responding in a manner similar to that brought about by increasing the

cocaine dose. Moreover, doses of propranolol that decreased

cocaine-reinforced responding had no effect on behavior maintained

at comparable rates and patterns by food presentation (Goldberg &

Gonzalez, in press). Propranolol has been shown to reduce cardiac

output in the doses that reduced cocaine-reinforced responding and,

thus, it may have slowed the delivery of cocaine to sites of

inactivation or metabolism. This and other potential mechanisms of

propranolol effects were entertained by the authors.

Dougherty and Pickens (1974) investigated two drugs that may

influence metabolism of cocaine in a situation involving selfinjection by rats. They found that phenobarbital, an agent that

increases liver microsomal drug-metabolizing systems, increased

cocaine self-injection. Another drug, SKF-525A, which blocks this

same metabolism system in the liver, reduced cocaine self-injection. Since these effects are similar to those expected from

changes in the cocaine dose, the authors suggest that the effects

may have been due to altered metabolism of cocaine.

A variety of other drugs have been shown to reduce cocaine-reinforced responding, e.g., morphine, pentobarbital, d-amphetamine and

phenmetrazine (Wilson & Schuster, 1973a). The interpretation of

these findings will become clearer when the specificity of these

81
drugs has been assessed by comparing their effects on behavior

comparably controlled by non-drug reinforcers. For instance, it

may be that the doses of d-amphetamine required to reduce cocainereinforced responding are different than those needed to reduce

food-reinforced responding occurring at the same rate.

This section of the paper has dealt with an important area of research which has not yet yielded its full potential. For example,

in none of the research reported can one conclude that a drug

interacts with the reinforcing effects of cocaine in a selective

manner. Selective potentiation of its behavioral effects has been

demonstrated with propranolol; yet, even in this case, the reinforcing effects of the drug may not have been altered selectively.

COMPARISON OF COCAINE’S REINFORCING EFFECT TO THAT OF OTHER REINFORCERS: Many individuals believe that cocaine is an inherently

strong reinforcer; its reinforcing effect may in some way override

the effects of other stimuli. By implication, for example, when

pitted against cocaine, most stimuli would not be preferred. This

impression of the strength of the reinforcing effect of cocaine has

arisen from the observations of severely intoxicated states that

have been induced as a consequence of self-injection by the intravenous route of administration rather than a more appropriate analysis compatible with the concept of a reinforcing effect of the drug.

If we take the broader view, a variety of experimental conditions

are important to a consideration of the strength of cocaine’s

reinforcing effect relative to other events. The comparison of

cocaine’s reinforcing effects with other drugs and non-drug reinforcers is both an important theoretical and empirical issue which

has received little experimental attention. Thompson and Pickens

pointed out in 1970 that there were no direct experimental comparisons of cocaine to other reinforcers. All experiments addressing

the issue that have been done since that time have used intravenous

routes of delivery and have drawn comparisons between drugs so

delivered and food delivery. Ideally, a variety of events should be

compared across different behavioral conditions in order to arrive

at general conclusions. In addition, drugs and other interventions

should be studied to determine whether they modify the reinforcing

efficacy of cocaine and other events when they function as reinforcers. A multidimensional comparison of this kind is a complex undertaking and is by no means complete; nevertheless, there are a number

of conditions under which comparisons have been drawn between

cocaine and other events.

Unlimited Access: As mentioned previously, cocaine self-injection

patterns under conditions of unlimited access are erratic with

bouts of self-intoxication alternating with drug abstinence.

Deneau et al. (1969) noted that this pattern occurred with amphetamine and ethanol but not with narcotics or pentobarbital. With

cocaine, as with ethanol, this pattern of self-injection is probably terminated by the prolonged state of intoxication since it is

not sustained under limited drug access with either drug (Winger &

Woods, 1973; Woods & Schuster, 1970). Variables associated with the

termination of these bouts of self-injection have not otherwise

82
been identified. It is possible that prolonged exposure to cocaine

under limited but extensive access conditions may change the reinforcing value of cocaine.

Dose: A variety of procedures have been used to show that a larger

cocaine dose is preferred to a smaller, as mentioned previously.

Johanson and Schuster (1975) showed that cocaine was preferred to

methylphenidate; however, ah increase in the dose of methylphenidate reversed the preference in favor of methylphenidate.

Griffiths et al. (1975) found that cocaine could maintain higherbreaking points on progressive ratio schedules of drug delivery in

baboons than either secobarbital or methylphenidate. A variety of

doses and conditions for cocaine and comparison agents need to be

evaluated to arrive at an assessment of the generality of these

results.

Schedules of Reinforcement: Intravenous cocainemaintained fixedratio responding at higher maximal rates than codeine in the rhesus

monkey (Dawns & Woods, 1974) and a similar finding has been shown

with cocaine-pentobarbital comparisons in the rhesus monkey (Goldberg et al., 1971). Goldberg (1973) compared food and intravenous

cocaine deliveries as reinforcers on both ratio schedules and

second-order schedules of reinforcement in squirrel monkeys. He

found that the reinforcers could be used to maintain comparable

rates and patterns of responding on both types of schedules. Rut

the degree of equivalence depended both on the history of exposure

and, more importantly, on the magnitude of either food or cocaine

delivered. More recently, Goldberg (1976) has suggested that the

reinforcing effects of morphine and cocaine can be comparable under

second-order schedules of drug delivery.

The continuing examination of important issues associated with the

comparison of cocaine to other events as reinforcers is needed.

Indeed, it is quite unfortunate that more experiments focusing on

comparisons of this type have not been designed. Nevertheless, it

is clear that other variables must be evaluated when reinforcers are

compared; generalizations depend as much on conditions of cocaine

delivery as on any general property of cocaine as a reinforcer.

GENERAL CONSIDERATIONS

Details of the patterns of human cocaine self-administration are

essentially unknown. Anecdotal accounts suggest that the predominant route is intranasal, but there is virtually no reliable

information on amounts taken over periods of cocaine use in any

large group of individuals. (See Chapter 4, Byck & Van Dyke;

Chapter 5, Smith & Wesson; and, Chapter 6, Siegel, this volume.)

Consequently, it is impossible to evaluate the parallels between

cocaine self-administration in animals and in humans. Even a full

examination of cocaine self-administration in animals using the

primary route of administration used by man would be informative;

only a beginning has been made on that task.

83
Nevertheless, there are reasonable inductions from animal research

that in principle are applicable to human self-administration.

Severe cocaine intoxication is self-induced when the intravenous

route of administration is used and access to the drug is unlimited.

Limited access to the drug, routes of administration that delay

onset of action, and low doses each contribute to reductions in the

severity of self-induced intoxication.

It is important to examine in animals the conditions that induce

patterns of behavior that, although initially characterized by

insignificant drug-taking, may eventuate in severe self-intoxication. A much better description of factors that contribute to the

progression of drug-taking from sampling to occasional use to

severe chronic intoxication can be derived from such studies.

Important clues to these factors can be gathered from studies

exploring ways of potentiating the reinforcing potency of other

drugs. For example, investigators have found a variety of ways to

enhance the reinforcing properties of ethanol (e.g., Cotten, 1975).

By comparing these factors, it may be possible to examine those that

pertain generally to many drugs and those that are specific to

cocaine.

Cocaine clearly functions as an effective stimulus to reinforce

drug-taking behavior in animals. The conditions of cocaine delivery in relation to different behaviors are at least as important

to how behavior is changed by cocaine as is any inherent property of

cocaine. Studies of cocaine self-administration have shown repeatedly that either a great deal of behavior or very little can be

maintained by cocaine depending on the conditions of delivery. I t

may be that cocaine will turn out to be an effective reinforcer of

different behaviors under a much broader or different set of

conditions than other drugs. This supposition will be borne out

only by the systematic study of the drug as well as a reinforcer

under a wide set of environmental conditions.

The mechanisms of cocaine’s actions on behavior should be studied

using the behavioral procedures described above. It is not clear

whether any of the various behavioral actions of cocaine can be

separated. For example, is it possible to alter the reinforcing

effects of cocaine, leaving other effects of cocaine, e.g., the

ability to change food-reinforced responding, unaltered? In principle, studies of this kind should allow answers to questions that

have important clinical implications. For example, if drugs could

be shown to alter the doses of cocaine that reinforce and maintain

drug-taking behavior, these drugs could be used in a manner

analogous to the use of narcotic antagonist therapy for heroin

abuse. An important consideration in this type of therapy is

whether other behaviors are also affected by doses of drugs that

modify the reinforcing effects of the abused drug.

Though the question of whether cocaine’s behavioral actions may be

separated remains unanswered, questions about which of cocaine’s

specific physiological actions are most closely associated with its

behavioral actions can be raised. Cocaine brings about some of its

84
physiological effects by two prominent actions: it stabilizes

membranes, an action associated with its local anesthetic action;

and it potentiates the actions of biogenic amines. It may so act by

blocking uptake of these amines and it may release certain amines

as well (e.g., Kalsner & Nickerson, 1969). Collier (1968) has

speculated that the potentiation of the actions of norepinephrine

by cocaine may be related to its reinforcing actions. A careful

comparison of a variety of drugs, each of which has a different

physiological property in common with cocaine, would be helpful in

matching physiological mechanisms with behavioral effects.

The analysis of cocaine’s behavioral actions in animals has led to a

description of its effects in a variety of experimental contexts,

increasing our understanding of the complex actions of the drug.

The contribution of studies of this kind is especially important due

to the paucity of information on human subjects.

James H. Woods, Ph.D.

Departments of Pharmacology and

Psychology

University of Michigan

Ann Arbor, Michigan

I would like to acknowledge the good and considerable assistance of

James Grubman with the early stages of the paper; later, the kind

editorial assistance of Gail Winger, which is appreciated greatly,

and Kippy Pritula for her secretarial help throughout. I thank the

many researchers interested in cocaine who sent preprints and

reprints of their research papers to me. J.H.W.

85
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95

Chapter V WHAT ARE THE EFFECTS

OF COCAINE IN MAN?

Robert Byck, M.D. and Craig Van Dyke, M.D.

The question in the title my not be answered for the reader of this

essay. What we know for sure may strike the reader as mundane.

What is supported by strong evidence may impress the reader as

common knowledge.

This dilemma is not just a reflection of restricted research in

cocaine. It is rather a statement. of our inability to describe

fully the effects of any agent which alters complex human functions.

In order to prepare you for an answer we must first assess the

quality of the evidence. This can be phrased in terms of Source and

Surety.

laboratory reports in man represent sources of information about

Myths, street knowledge, animal studies and clinical or

cocaine. While surety is in part a function of source (e.g., we are

much less certain of the mythological infomation than we are of the

clinical information), it is also dependent on other factors. For

instance, multiple clinical reports are more certain than single

clinical reports. To say we know that an effect occurs means that

it has been demonstrated in a controlled experimental situation in a

number of independent laboratories. It also means that in clinical

or street reports the substance causing the effects can be positively identified. Ideally, the effect should be consistently seen in

non-laboratory situations and should be measurable in a reproducible fashion.

Why a laboratory experiment? Why many laboratories? Why a controlled experiment? The history of pharmacology and of psychopharmacology is filled with presumptive errors about the effects of

drugs. These errors were clarified only by repeated controlled

experiments.

Pharmacologists are concerned with the changing effects of drugs at

different dosages. A drug such as alcohol can make people relaxed

at one dose, sleepy at another, combative at another and psychotic

at another. Nor is every person affected in the same way by these

changing dosages. The effects of the surrounding environment

(setting) and of the psychological state and history of the subject

profoundly modify the action of a drug. Effects seen after chronic

use differ from those observed after a single dose -- often they are

opposite. Effects seen after injecting a drug often bear little

relationship to those seen after swallowing the same substance.

97
If an effect is measurable by standard instruments or scales,

laboratories can compare results. If not, we must, in each instance, make hopeful assumptions about the reliability of the

reporting investigators.

SURETY RATING

John Kenneth Galbraith (1975), writing on a subject somewhat unrelated to this article, said:

These are matters on which there is no proof, and it

is unbecoming, however customary, to substitute certainty of statement for hard evidence. But the

simple facts are worth a glance.

In order to elude the trap of certainty we have classified the

effects of cocaine by assigning a "surety rating" of one to seven to

statements made about the drug. The surety rating is numerical and

hierarchical. The hierarchy takes into account both the source and

surety of the information. For example, although animal experiments may conclusively demonstrate that an effect occurs, one can

only presume that this effect does occur in man since we know of

many interspecies differences in drug effects. We have summarized

in Figure 5-1 all the reported effects of cocaine in man.

Information in column one has been gathered from published research

articles where repeated measurements under controlled conditions

have shown consistent effects in wan. We can say that we "known

that this is an accurate description of the drug’s effects at a

specific dosage.

Column two encompasses reliable reports from the clinical literature that are consistent in their description and where the dosage

of cocaine is known.

Column three includes reports either of controlled experiments in

man that have not been replicated or laboratory experiments that are

strongly suggestive that the effects observed are probable. (Columns one and three are mutually exclusive.)

Column four indicates that the effects seen are reproducible in

animals; but, for a variety of reasons, either have not been

evaluated in man or -- for reasons of danger or ethics -- cannot be

replicated in man.

In column five effects which are anecdotal in the medical literature

are reported. Unpublished reports (referenced as "personal communication") are also included even if the experiments are well

controlled.

98
The sixth column includes popular reports of "Cocaine Effects" --

this is to say we do not know whether cocaine was really the active

agent and the "effects" may be distorted in the telling. Much of

this information cannot be evaluated by anyone at this time, but

some of it may be true.

The seventh column encompasses the real mythology of cocaine. Some

of this information is from highly reliable sources and is stated as

fact -- but there is no record of the evidence which produced the

"fact." The historical myths of the effects of coca chewing are

included as well as case reports from the older literature where the

reliability of the report, the journal and the subject are all open

to question. Some of these effects may occur but their inclusion in

the table is only for the purposes of completeness. Many are

probably untrue.

There is no way of stating that any effects except those in the

first two columns really occur in man as the result of cocaine administration. If we wish to improve our knowledge, the other

effects must be evaluated and the quality of the evidence improved.

There is certainly a temptation to include in the "known" effects of

a drug in man, those effects which have been seen only in laboratory

animals. We cannot rely on such data except in a supportive manner.

Certain pertinent effects on psychological phenomena cannot be

examined in animals and so the information about the effects of high

dosages and chronic usage must remain at the level of street reports

and myth. In those instances, in particular, the identity of the

drugs causing the effects is unclear. Therefore, in column six, we

have been careful not to ascribe to cocaine effects which may be the

result of polydrug usage.

Wherever information on human effects is available, we have broken

down the data by dosage, route and chronicity. Most drugs produce a

spectrum of effects which vary with the amount of drug available at

the receptor site. Thus, the some drug can both speed and slow the

heart rate, increase and decrease respiratory rate, or cause euphoria and dysphoria.

Dosage alone may not be a clear indicator of the effect to be

produced. The concentration of active drug in the blood (now

measurable with cocaine) is a closer approximation; but the reader

should be aware that even this is not a final answer. Long term

exposure to a drug may modify the body and so a drug can be acting in

a chemically changed organism.

bearing these caveats in mind, what can we say about the effects of

cocaine in man? This question will be answered in narrative form in

five parts: local effects, systemic effects, central nervous

system effects, social effects and absorption and metabolism; and

is also summarized in the first two columns of Figure 5-1. The

figure, of course, also presents the less certain "effects" of

cocaine which we cannot support with acceptable scientific evidence.

99
Figure 5-1 lists the reported effects of cocaine in man. In referencing this table we have tended to use single citations. Where

many references could be cited, we have used the original reference.

The use of early references does not imply that these studies were

not replicated in later investigations. We have treated columns one

and three as mutually exclusive. Information obtained from "personal communications" has been listed in column five, even if this

information resulted from controlled laboratory studies. Ashley

(1976) and Mortimer (1901; reprinted, 1974) provide good sources of

street knowledge, while most textbooks of pharmacology are good

examples of unverifiable information on the effects of cocaine in

man. For other reviews of cocaine the reader is referred to: Van

Dyke and Ryck (1977), Woods and Downs (1973) and Byck (1975).

References are listed by category and column number. For instance,

the reference for the multiple clinical reports of cocaine as au

effective local anesthetic is listed under Ia(2) (i.e., I= local

effects; a=local anesthesia; (2)=column (2). References for the

narrative section are listed separately.

100
FIGURE 5-1

Reported Effects of Cocaine

Categorized by Type and Reliability of Evidence (Surety)

101
Figure 5-1 (cont’d)

1. Reproductible in man + report that it occurs

2. Many clinical reports in man/reliable - report that it does not occur

sources

3. Laboratory reports in man/not

±

reports that it both occurs and does

not occur

4. Animal reports report that it increases

5. Single case report in man/reliable report that it decreases

source

report that it increases and then

6. Street knowledge decreases with higher dosages

report that it both increases and

7. Unverifiabale report, historical myth, decreases

or textbook dogma

report that there is no change

102
Figure 5-1 (cont’d)

LEGEND

1. Reproducible in man + report that it occurs

2. Many clinical reports in man/reliable

sources

3. Laboratory reports in man/not

replicated or adequately controlled

4. Animal reports

5. Single case report in man/reliable

source

6. Street knowledge

7. Unverifiable report, historical myth,

or textbook dogma

- report that it does not occur

reports that it both occurs and does

not occur

report that it increases

report that it decreases

report that it increases and then

decreases with higher dosages

report that it both increases and

decreases

report that there is no change

103
Figure 5-1 (cont’d)

LEGEND

1. Reproducible in man

2. Many clinical reports in man/reliable

sources

report that it occurs

report that it does not occur

3. Laboratory reports in man/not

replicated or adequalely controlled

4. Animal reports

5. Single case report in man/reliable

source

6. Street knowledge

7. Unverifiable report, historical myth,

or texbook dogma

reports that it both occurs and does

not occur

report that it increases

report that it decreases

report that it increases and then

decreases with higher dosages

report that it, both increases and

decreases

report that there is no change

104
Figure 5-1 (cont’d)

LEGEND

1. Reproducible in man

2. Many clinical reports in man/reliable

sources

report that it occurs

report that it does not occur

3. Laboratory reports in man/not

replicated or adequately controlled

reports that it both occurs and does

not occur

4. Animal reports report that it increases

3. Single case report in man/reliable report that it decreases

source

6. Street knowledge

report that it increases and then

decreases with higher dosages

report that it both increases and

7. Unverifiable report. historical myth, decreases

or textbook dogma

report that there is no change

105
Figure 5-1 (cont’d)

LEGEND

1. Reproducible in man

2. Many clinical reports in man/reliable

sources

3. Laboratory reports in man/not

replicated or adequately controlled

4. Animal reports

5. Single use report in man/reliable

source

6. Street knowledge

7. Unverifiable report, historical myth,

or textbook dogma

report that it occurs

report that it does not occur

reports that it both occurs and does

not occur

report that it increases

report that it decreases

report that it increaser and then

decreases with higher dosages

report that it both increases and

decreases

report that there is no change

106
Ia(1)

Ia(2)

Ia(4)

Ib(l)

Ib(4)

Ic(2)

Ic(4)

IIa(1)

IIa(2)

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Gutierrez-Noriega, C. and Ortiz, V.Z. Cocainismo experimental. I. Toxicologia general, acostumbramiento y

sensibilizacion. Revista de Medicina Experimental,

3:279-306 (1944).

Post, R.M., Kopanda, R.T. and Black, K.E. Progressive

effects of cocaine on behavior and central amine

metabolism in rhesus monkeys: Relationship to kindling and psychosis. Biological Psychiatry, 11:403-

419 (1976).

Vb(5) Byck, R. Personal communication.

Vc(3) Post, R.M., Gillin, J.C., Wyatt, R.J. and Goodwin, F.K.

The effect of orally administered cocaine on sleep

of depressed patients. Psychopharmacologia

(Berlin), 37:59-66 (1974).

VIa(3) Byck, R., Jatlow, P., Barash, P. and Van Dyke, C. Cocaine:

Blood concentration and physiological effect after

intranasal application in man. In Ellinwood, E.H.

and Kilbey, M.M. (eds.), Cocaine and Other Stimu1ants. New York, NY: Plenum Press, 1977, pp. 629-

646.

Resnick, R.B., Kestenbaum, R.S. and Schwartz, L.K. Acute

systemic effects of cocaine in man: A controlled

111
VIa(5)

VIb(4)

VIb(5)

VIc(4)

VIc(5)

VId(5)

VIf(5)

study by intranasal and intravenous routes. Science, 195:696-698 (1977).

Orr, D. and Jones, I. Anaesthesia for laryngoscopy. Anaesthesia, 23:194-202 (1968).

Young, D. and Clauber, J.J. Electrocardiographic changes

resulting from acute cocaine intoxication. American

Heart Journal, 34:272-279 (1947).

Koehntop, D., Liao, J.C. and Van Bergen, F.H. Pharmacological enhancement by cocaine, tropolene, aminophylline, and ketamine of epinephrine-induced arrhythmias during halothane-nitrous oxide anesthesia. American Society of Anesthesiologists Annual

Meeting, October, 1975.

Barash, P.G. Personal commication.

Eidelberg, E., Lesse, H. and Gault, F.P. Au experimental

model of temporal lobe epilepsy: Studies of the

convulsant properties of cocaine. In Glaser, G.H.

(ed.), EEG and Behavior. New York, NY: Basic Hooks,

1963, pp. 272-283.

Mayer, E. The toxic effects following the use of local

anesthetics. Journal of the American Medical Association, 82:876-885 (1924).

Lewin, L. Phantastica, Narcotic and Stimulating Drugs,

Their Use and Abuse. New York, NY: E.P. Dutton and

co., 1931.

Bergen, A. Personal communication.

Smith, D. Personal communication.

Messinger, E. Narcotic septal perforations due to drug

addiction. Journal of the American Medical Association, 179:964-965 (1962).

112
THE CONFIRMED PHRMACOLOGY OF COCAINE IN MAN

Local Effects

Still widely used today in otolaryngology and anesthesiology,

cocaine is an effective local anesthetic when applied topically or

injected near nerves. Cocaine constricts blood vessels and thereby

limits the amount of bleeding from surgical procedures as well as

limiting its own absorption. Cocaine dilates the pupil when applied

topically to the eye (Koller, 1884; Kuroda, 1915). The local

anesthetic effects of cocaine in man are more fully described in

Chapter 9.

Systemic Effects

We know that cocaine produces an increase in heart rate and blood

pressure in man. Resnick and co-workers (1977) administered

cocaine to 19 human volunteers. They found that 25 mg of cocaine

administered intranasally produced only minimal changes in systolic

blood pressure, while 100 mg intranasally produced significant

changes in heart rate and in both systolic and diastolic blood

pressure. When administered intravenously, 10 and 25 mg of cocaine

produced a significant increase in heart rate and systolic blood

pressure. They reported that the onset of these effects occurred in

2 minutes, peaked in 5-10 minutes after intravenous administration

and in 15-20 minutes after intranasal application. Byck et al.

(1977) reported similar results after intranasal application of

cocaine but noted the powerful modifying effect of psychological

factors on cardiovascular variables. Fischman et al. (1976)

studied nine human volunteers who received intravenous cocaine in

dosages of 4, 8, 16 and 32 mg. Dosages of 4 and 8 mg had no effect

on heart rate or blood pressure. However, after 16 mg of cocaine,

the mean heart rate increased from a predrug rate of 74 beats per

minute (BPM) to 100 BPM; and after 32 mg, from 74 BPM to 112 BPM.

These investigators reported that increases in the heart rate

occurred 2-5 minutes after intravenous administration, peaked at 10

minutes and returned to the predrug baseline rate at 46 minutes.

Similarly, the 16 and 32 mg dosages were the only ones that

increased systolic blood pressure. This increase in systolic blood

pressure was 10-15 percent above the predrug levels and occurred 10

minutes after drug administration. Post et al. (1974a) studied the

effect of intravenous cocaine in 12 depressed patients. They found

increases in both heart rate and systolic blood pressure following a

range of dosages from 2-16 mg. These four studies by independent

investigators indicate that cocaine increases the heart rate and

blood pressure in man when administered by either the intranasal or

intravenous route. The dosage and time effect relationships remain

unclear.

Few cardiac arrhythmias are reported with the clinical use of

cocaine (Orr & Jones, 1968; Young & Glauber, 1947). In one

113
experimental study, Fischman et al. (1976) reported no arrhythmias

in nine volunteers who received intravenous cocaine in dosages

ranging from 4-32 mg. Neither Resnick et al. (1977) nor Post et al.

(1974a) reported arrhythmias and none has been reported by Byck et

al. (1977).

CENTRAL NERVOUS SYSTEM EFFECTS

We know that in most people cocaine causes euphoria.1 This information is consistent with "street knowledge" and "textbook dogma."

There is no doubt that many individuals on the street get a pleasant

feeling from what is reputed to be cocaine and seek to repeat the

experience. Recently, three independent laboratories have begun to

describe the subjective effects of cocaine in man. Byck et al.

(1977) in a controlled series of experiments found significant

euphoria in man following intranasa1 cocaine in dosages ranging

from 13-130 mg. Resnick and his co-workers (1977) found that 25 mg

of intranasal cocaine and 10 and 25 mg of intravenous cocaine

produced a high and pleasant feeling in their volunteers. Fischman

et al. (1976) reported that intravenous cocaine produced subjective

effects that were similar to intravenous amphetamine and, in fact,

the subjects were often unable to identify whether they had received

cocaine or amphetamine. Whether the euphoria of cocaine is due to

the local anesthetic or sympathomimetic character of the drug is not

yet known.

Absorption and Metabolism

The rate of absorption of cocaine varies with the route of administration. Following intravenous injection, the total dose of

cocaine is present in the blood within a few minutes. Van Dyke et

al. (1976) found that, after topical application to the nasal

mucosa, the concentration of cocaine in the blood rapidly increases

for 20 minutes, peaks at 60 minutes and then gradually declines for

at least 3 hours after application. There is very little information on the absorption of cocaine after oral administration. Post

et al. (1974a; 1974b) did demonstrate changes in mood and sleep

patterns following daily oral dosages of 200 mg of cocaine in

depressed patients, indicating that cocaine shows activity after

oral administration. Woods et al. (1951), using much higher dosages

than those used in man, demonstrated in dogs that oral. cocaine was

absorbed. The psychopharmacological effects of coca chewing have

been extensively reported but never examined in a controlled manner.

1As discussed in Byck et al., 1977; Fischman et al., 1976;

Resnick et al., 1977; Post et al., 1974a.

114
We know that most of the absorbed cocaine is hydrolyzed in the body

to benzoylecgonine. The site of this hydrolysis is not known. I t

has always been presumed to be the liver (Ritchie & Cohen, 1975);

however, recent in vitro studies demonstrated that enzymes in the

plasma may play a role in the hydrolysis of cocaine (Jatlow et al.,

1976). Most cocaine is eliminated in the urine as benzoylecgonine.

This occurs within 24-36 hours after administration Nan Dyke et

al. in press; Wallace et al., 1976). The drug may also be

eliminated as free cocaine in the urine but this usually accounts

for less than 20 percent of the total dose. As would be expected,

more free cocaine is excreted when the urine is acidic (Fish &

Wilson, 1969)

The recent development by Jatlow and Bailey (1975) and Hawks (1974)

of sensitive and reliable assays to measure low concentrations of

cocaine in the blood has been a major breakthrough in helping us to

understand the pharmacology of cocaine in man. Its rate of absorption and sojourn in the blood after different routes of administration are now being studied, as are the metabolic pathways. These

assays will permit correlations between the concentration of cocaine in the blood and its psychological and physiological effects.

CONCLUSION

The reader may have an uneasy feeling that most of the actions and

effects of cocaine that seemed to be "known" are still open to

question. This is, in fact, the case. By the nature of the

acceptable evidence, we must concede that some "facts" about

cocaine’s effects in man will probably never be demonstrated. This,

however, does not give us the license to, "substitute certainty of

statement for hard evidence" since to do so would be, "unbecoming,

however customary."

Robert Byck, M.D. and

Craig Van Dyke, M.D.

Yale University School of

Medicine

Department of Pharmacology

115
REFERENCES

What are the Effects of Cocaine in Man?

Ashley, R. Cocaine: Its History, Uses and Effects. New York, NY:

Warner Books, Inc., 1975.

Byck, R. (ed.) Cocaine Papers: Sigmund Freud. New York, NY:

Stonehill Publishing Co., 1975.

Byck, R., Jatlow, P., Barash, P. and Van Dyke, C. Cocaine: Blood

concentration and physiological effect after intranasal

application in man. In Ellinwood, E.H. and Kilbey, M.M.

(eds.), Cocaine and Other Stimulants. New York, NY: Plenum

Press, 1977, pp. 629-646.

Ellinwood, E.H. and Kilbey, M.M. (eds.) Cocaine and Other Stimulants. New York, NY: Plenum Press, 1977.

Fischman, M.W., Schuster, C.R., Resnekov, L., Shick, J.F.E.,

Krasnegor, N.A., Fennell, W. and Freedman, D.X. Cardiovascular and subjective effects of intravenous cocaine administration in humans. Archives of General Psychiatry, 33:983-

989 (1976).

Fish, F. and Wilson, W.D.C. Excretion of cocaine and its metabolites in man. Journal of Pharmacy and Pharmacology,

21(Suppl.): 135S-138S (1969).

Galbraith, J.K. Money, Whence It Came, Where It Went. Boston, MA:

Houghton Mifflin Co., 1975.

Hawks, R.L., Kopin, I.J., Colburn, R.W. and Thoa, N.B. Norcocaine:

A pharmacologically active metabolite of cocaine found in

brain. Life Sciences, 15:2189-2195 (1974).

Jatlow, P., Barash, P.G., Van Dyke, C. and Byck, R. Impaired

hydrolysis of cocaine in plasma from succinylcholine sensitive individuals. Clinical Research, 23(3):255A (1976).

Jatlow, P.I. and Bailey, D.N. Gas-chromatographic analysis for

cocaine in human plasma, with use of a nitrogen detector.

Clinical Chemistry, 21:1918-1921 (1975).

Koller, C. Uber die Verwendung des Cocaine zur Anasthesierung am

auge. Weiner Medizinische Wochenschrift, 34: Nos. 43 and 44

(1884).

Kuroda, M. On the action of cocaine. Journal of Pharmacology and

Experimental Therapeutics, 7:423-439 (1915).

Mortimer, W.G. History of Coca The Divine Plant of the Incas.

1901, reprinted, San Francisco, CA: And/Or Press, 1974.

116
Orr, D. and Jones, I. Anaesthesia for laryngoscopy. Anaesthesia,

23:194-202 (1968).

Post, R.M., Gillin, J.C., Wyatt, R.J. and Goodwin, F.K. The effect

of orally administered cocaine on sleep of depressed patients. Psychopharmacologia (Berlin), 37:59-66 (1974b).

Post, R.M., Kotin, J. and Goodwin, F.K. The effects of cocaine on

depressed patients. American Journal of Psychiatry,

131(5):511-517 (1974a).

Resnick, R.B., Kestenbaum, R.S. and Schwartz, L.K. Acute systemic

effects of cocaine in man: A controlled study by intranasal

and intravenous routes. Science, 195:696-698 (1977).

Ritchie, J.M. and Cohen, P.J. Local anesthetics. In Goodman, L.S.

and Gilman, A. (eds). The Pharmacological Basis of Therapeutics, 5th Edition. New York, NY: Macmillan, 1975, pp. 379-

403.

Van Dyke, C., Barash, P.G., Jatlow, P. and Byck, R. Cocaine:

Plasma concentrations after intranasal application in man.

Science, 191:859-861 (1976).

Van Dyke, C. and Byck, R. Cocaine: 1884-1974. In Ellinwood, E.H.

and Kilbey, M.M. (eds.) Cocaine and Other Stimulants. New

York, NY: Plenum Press, 1977, pp. 1-30.

Van Dyke, C., Byck, R., Barash, P.G. and Jatlow, P. Urinary

excretion of immunologically reactive metabolite(s) after

intranasal administration of cocaine, as followed by enzyme

immunoassay. Clinical Chemistry, 1977, in press.

Wallace, J.E., Hamilton, H.E., King, D.E., Bason, D.J., Schwertner,

H.A. and Harris, S.C. Gas-liquid chromatographic determination of cocaine and benzoylecgonine in urine. Analytical

Chemistry, 48:34-38 (1976).

Woods, J.H. and Downs, D.A. The psychopharmacology of cocaine. In

Drug Use In America: Problem in Perspective. Appendix Volume

1: Patterns and Consequences of Drug Use. Washington, DC:

U.S. Government Printing Office, 1973, pp. 116-139.

Woods, L.A., McMahon, F.G. and Seevers, M.H. Distribution and

metabolism of cocaine in the dog and rabbit. Journal of

Pharmacology and Experimental Therapeutics, 101:200-204

(1951).

Young, D. and Glauber, J.J. Electrocardiographic changes resulting

from acute cocaine intoxication. American Heart Journal,

34:272-279 (1947).

117

Chapter VI COCAINE: RECREATIONAL

USE AND INTOXICATION

Ronald K. Siegel, Ph.D.

Cocaine is one of several alkaloids obtained from coca leaves

Erythroxylon Coca Lam. ). The function of alkaloids in plants is

generallV unknown as is the reason plants produce them. Alkaloids

taste bitter, often produce numbing sensations, and are physiologically active with psychologic, teratogenio and toxic effects.

They act as extremely effective feeding deterrents; it has been

argued that naturally occurring plant drugs such as cocaine are

justified evolutionarily by their potentially maladaptive effects

on herbivores (Bever, 1970; Eisner & Halpern, 1971). The major

questions concerning the use of cocaine alkaloid by humans are: 1)

Why did man bypass these deterrent effects and initiate use of

cocaine? 2) Why is use of cocaine maintained? and 3) What are the

consequences of such continued use? These questions are addressed

in this chapter. It will presently be seen that the psychological

intoxication resulting from cocaine use is a primary reason for its

continued use. The nature and extent of this intoxication in a

group of contemporary users will also be explored. These users

reflect social-recreational patterns of intranasal use, and they

differ substantially from more compulsive intravenous users discussed elsewhere in this volume (cf., Smith & Wesson, Chapter 6).

DISCOVERY AND INITIAL USE

Folklore and mythology are replete with examples of man’s discovery

of plant alkaloids through observation and modeling of animal

behavior (cf., Siegel, 1973). The legendary discovery of coffee,

purportedly around 900 A.D., was made by an Abyssinian tending his

herd of goats. The herder noticed that his animals became

abnormally "frisky" after eating the bright red fruit of a tree that

was later isolated and identified as coffee (Taylor, 1965). In

Yemen, another herder discovered that his goats exhibited signs of

extraordinary stimulation after eating certain leaves. The

shepherd tried the leaves himself and found them quite stimulating

even after a day’s work. Since that time the use of those leaves

(qat leaves which contain the alkaloids cathine, cathedine, and

cathenine) has spread through the entire country (Abdo Abbasy,

1957).

Similarly, several stories are told of coca’s discovery based on

modeling of animal behaviors. One story -- told by an informant

from Huanuco, Peru -- claims that coca was first used by pack

animals traveling in the mountains and deprived of their normal

forage. The coca leaves sustained the animals, and humans quickly

119
copied the coca-eating behavior. Indeed, Mortimer (1901; reprinted, 1974) notes that coca was used by man, and perhaps by beast,

when traveling in the mountains where ingestion was probably induced by irregular eating, improper diet and lack of oxygen at higher

altitudes. Such use is similar to that of peyote used in small

doses by Huichol Indians traveling in the Sierra Madre mountains of

Mexico (Lumholtz, 1902). Recent nutritional analysis has revealed

that since 100 grams of coca leaves contains 305 calories, 18.9

grams of protein and 46.2 grams of carbohydrates, and satisfies the

Recommended Dietary Allowance for calcium, iron, phosphorus, vitamins A, B2

 and E(Dukeetal., 1975), the coca leaves could, indeed,

have sustained Peruvian travelers. However, the full complement of

nutrients present in coca leaf may not be fully absorbed in the

normal chewing-sucking extraction employed by man.

Another story told by informants from Cuzco and Lima, Peru, claims

that a number of birds and insects are fond of coca seeds and leaves

and the speed with which they devour the plant suggested the

stimulant properties to early man. Mortimer (1901; reprinted,

1974) indicated that ants and other insects avidly devoured the

leaves but there was no indication of psychoactive effects from this

ingestion. However, he did note that "the birds are great lovers of

coca seeds, and when these are lightly sown on the surface of the

nursery it is necessary to cover the beds at night with cloths to

guard against ‘picking and stealing’...." One may speculate that

early man modeled his coca use after such observations, much like

the Greeks who adopted the habit of eating hempseeds -- and, later,

other parts of the cannabis plant -- after watching finches do so

(Schultes, 1970).

Man’s inevitable ecological encounters with coca would have brought

him into contact with the highly reinforcing properties of the

cocaine alkaloid. Independent of the nutritional value, the

psychoactive effects are considerably more direct and immediate.

Animal studies are rich with examples of cocaine’s powerful psychoactive and reinforcing effects (cf., Preclinical Behavior, Chapter

4). Lewin (1931) reports a case of an animal modeling human use:

The case is, however, on record of a monkey which

became a cocaine-eater through imitation...The animal

searched the pockets and the cupboards of its mistress for cocaine, which it voraciously consumed.

The consequences were the same as in men.

MAINTENANCE OF USE

These consequences or effects are undoubtedly responsible for maintaining cocaine use. The effects can be interpreted as a state of

intoxication with high reinforcement potential. Indeed, animals

such as rats and monkeys, having once experienced unlimited access

to cocaine, will self-administer the drug until they die, often

ignoring food and water. While many non-pharmacologic factors

120
(e.g., individual and environmental variables) may affect man’s use

of a drug such as cocaine, psychological intoxication appears to be

the primary reinforcing effect.

Freud described the intoxication in Uber Coca, his famous 1884

monograph on coca:

The psychic effect (of cocaine) consists of exhilaration and lasting euphoria, which does not differ in

any way from the normal euphoria of a healthy

person....One senses an increase of self-control and

feels more vigorous and more capable of work; on the

other hand, if one works, one misses the heightening

of the mental powers which alcohol, tea, or coffee

induce. One is simply normal, and soon finds it

difficult to believe that one is under the influence

of any drug at all....Long-lasting. intensive mental

or physical work can be performed without fatigue; it

is as though the need for food and sleep, which other

wise makes itself felt peremptorialy (sic) at certain

times of the day, were completely banished. (Byck,

1974)

Aleister Crowley (1917) offers a more romantic description of

cocaine intoxication:

The melancholy vanishes, the eyes shine, the wan

mouth smiles. Almost manly vigor returns, or seems

to return. At least faith, hope and love throng very

eagerly to the dance; all that was lost is

found....To one the drug may bring liveliness, to

another languor, to another creative force, to

another tireless energy, to another glamor, and to

yet another lust. But each in his way is happy.

Think of it!--so simple and so transcendental! The

man is happy!

Throughout the 19th and 20th centuries, the literature on coca and

cocaine contained many references to the reinforcing nature of this

intoxication. Even current patterns of recreational use appear to

be initiated and maintained by the psychoactive effects (Phillips,

1975). A number of recent studies of cocaine users have confirmed

the experience of positive drug effects which appear to maintain

continued use. Ashley (1975) interviewed and observed 81 cocaine

users and found that they experienced euphoria, sexual stimulation,

increased energy and a reduction in fatigue and appetite. In

another study of 17 cocaine users, Grinspoon and Bakalar (1976)

reported additional phenomenological data on the intoxication and

these authors emphasized their agreement with reports from literary

sources and other studies (cf., Petersen, Chapter 1 this volume).

121
In yet another interview study with 32 intranasal cocaine users, the

subjective effects reported included a subtle exhilaration, increased energy and sociability, and a pleasant feeling of wellbeing and mastery (Waldorf, pers. comm., 1976).

CONSEQUENCES OF CONTINVED USE

Despite the obvious appeal and romantic attraction of this state of

intoxication, the consequences of continued use have been the

subject of over a century of research and debate. Most researchers

agree that the pleasurable effects diminish with continued use and

are replaced by an increasing number of adverse effects which can

Only be alleviated through its cessation. Crowley (1917, reprinted

1973) describes this state in a highly stylized account:

But to one who abuses cocaine for his pleasure nature

soon speaks, and is not heard. The nerves weary of

the constant stimulation; they need rest and food.

There is a point at which the jaded horse no longer

answers whip and spur. He stumbles, falls a quivering heap, gasps out his life....So perishes the slave

of cocaine. With every nerve clamoring, all he can do

is to renew the lash of the poison. The pmarmaceutical effect is over; the toxic effect accumulates . The nerves become insane. The victim begins

to have hallucinations.... And alas! The power of

the drug diminishes with fearful pace. The doses

wax; the pleasures wane. Side-issues, invisible at

first, arise; they are like devils with flaming

pitchforks in their hands. (Crowley, 1917)

Unfortunately, the language of this passage and others like it, with

its connotations of cocaine addiction and psychosis, have influenced many of the medical and scientific opinions to date. With a

similar "data base" of self-experimentation, Freud described the

state as one of agitation characterized by persecution and hallucinations, but he used less emotional language for his observations

(Freud, 1887). Others call the condition one of "delirium"t (e.g.,

Mantegazza, 1859) or "extreme alarm due to false impressions"

Grinspoon & Bakalar, 1976). But for most, the critical diagnostic

features of this state are the hallucinations, and the presence of

tactile hallucinations are the most conspicuous.

(Lewin, 1931). Still others write about mania and psychoses (cf.,

One of the more consistent findings is that continued use is

associated with tactile hallucinations of animals moving in the

skin, or bugs or insects moving under the skin. This phenomenon was

described by Magnan and Saury (1889) and has since been known as

"Magnan’s sign" or "cocaine bugs." Magnan and Saury noted that

122
these symptoms are the first hallucinatory phenomena to develop

with chronic use while hallucinations of sight, hearing and smell

come later. Although Magnan’s sign and allied symptoms are usually

associated with chronic use, a number of hallucinatory experiences

have been reported with large acute doses of cocaine (e.g.,

Mortimer, 1901; reprinted, 1974; Eggleston & Hatcher, 1919).

According to Magnan and Saury, the hallucinations subsequently lead

to difficulties in thinking and orientation.

Indeed, the diagnosis of psychosis often emerges from the presence

of these tactile sensations, independent of other changes. But

psychosis involves more than hallucinations and usually implies

dysfunction in an individual’s mental processes, emotional responses, memory, communication skills, sense of reality and behavior. Furthermore, psychosis is often characterized by regressive

behavior, inappropriate mood, diminished impulse control and delusional thinking (cf., American Psychiatric Association, 1969). The

presence of such a wide range of phenomena in cocaine intoxication

is less clear than the presence of hallucinations. Indeed, descriptions of cocaine hallucinations often include references to

clear mental ability (e.g., Mantegazza, 1859).

VARIABLES AFFECTING USE AND INTOXICATION

The precise description of this state of cocaine intoxication

requires information about concomitant variations between the characteristics of the behavior and of the drug. 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 relations, 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 the limited knowledge

about cocaine, the presence of such a myriad of interacting

variables should temper a desire to simplify use and intoxication

with succinct labels such as "euphoria," "mania" or "psychosis."

The study described below was undertaken in an attempt to elucidate

some of these variables in relation to the psychological

intoxication.

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 85 social-recreational cocaine users

were eventually selected for the study. All subjects in the sample

met the initial requirement of having used a minimum of 1 gram of

cocaine per month for 12 months (range = 1-4 grams). All subjects

123
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 (EWI) (El-Meligi &

Osmond, 1970), in-depth interview, physical examination (for most

subjects) and visual imagery and perception tests. Two additional

groups of subjects were recruited for interview and questionnaire

study only. One group consisted of 14 female social-recreational

users who all satisfied the 1 gram per month minimum requirement.

The second group consisted of both male and female experimental

users (n=19) who had only used cocaine 10 times or fewer with a

total intake of no more than 1 gram.

Unless otherwise specified, the data discussed below are from the

group of 85 male social-recreational users.

PREPARATIONS AND PURITY

All subjects used the hydrochloride salt of cocaine available

through illicit markets. The LAC-USC Medical Center street drug

analysis laboratory has found that the average purity of street

cocaine in the Los Angeles area is 63 percent (Montgomery, personal

communication, 1976). Another street drug assay laboratory in

Northern California (Pharm Chem, Palo Alto) found that the average

street cocaine was 53 percent for samples received in that area.

The most common adulterants in these samples are sugars (lactose,

mannitol and inositol); local anesthetics (procaine, lidocaine,

benzocaine and tetracaine); and, albeit rarely, other drugs (amphetamine, caffeine, phencyclidine, acetaminophen, salicylamide,

pemoline and heroin). Several other non-drug adulterants may be

present, such as flour and talc, but analysis for these is rarely

done (Perry, 1974). Of the 85 subjects, 4 had used the free base of

cocaine (primarily for smoking as discussed below) while 6 had

occasionally chewed coca leaves, primarily during travels in South

America.

MULTIPLE DRUG USE

All subjects had histories of multiple drug use. Concomitant with

their use of cocaine, 85 percent were using alcohol; 66 percent,

cannabis preparations; 57 percent, caffeine (coffee, tea, chocolate

and cola beverages); 8 percent, amphetamines; and 5 percent, hallucinogens other than cannabis. Surprisingly, the figure for caffeine is considerably below national averages, which are estimated

to be as high as 90 percent for adults (Gilbert, 1976). It is

possible that this represents a substitution of cocaine for caffeine as a stimulant of choice. Furthermore, caffeine interacts

with drugs that affect neural transmission and this interaction

124
with cocaine may have undesirable or non-preferred effects on

users.

Prior to their cocaine use, subjects reported experiences with

amphetamines and related stimulants (27 percent), barbiturates (20

percent), hallucinogens other than cannabis (10 percent) and

opiates (2 percent). All subjects had tried cannabis in the past.

During the 12 month period of the survey, all 85 subjects reported

that cocaine was their recreational drug of choice and 73 subjects

identified themselves as regular cocaine users and only casual

users of other drugs. The average frequency of drug use per week

was: caffeine, 5x; cocaine, 3x; alcohol, 2x; and marihuana or other

cannabis preparations, 0.25x (1/4x).

ROUTES OF ADMINISTRATION

All subjects employed the intranasal route of self-administration

while a few (n=12) had also experimented with smoking cocaine on

tobacco or marihuana cigarettes and chewing coca leaves (n=6). One

subject had several experiences with intravenous, intramuscular and

subcutaneous injections of cocaine. Four subjects had experimented

with topical applications of cocaine to the genitalia.

DOSAGES

When cocaine was used intranasally, subjects self-administered one

"cokespoonful" per nostril or one "line" per nostril. The amount of

pure pharmaceutical cocaine hydrochloride (crushed, flaky crystals)

in commercially available "cokespoons" has been determined to range

from 5-10 mg for a level cokespoon. Assuming an average street

purity of roughly 58 percent, this amounts to an average intranasal

dose of 8.7 mg (total for both nostrils) per administration. The

average" "line" of cocaine is about 1/8 inch wide by 1 inch long

(Gottlieb, 1976) and amounts to approximately 25 mg of cocaine if

pure or 14.5 mg of cocaine if street cocaine. When cocaine

hydrochloride was used for smoking, small amounts were placed on the

burning end of a marihuana or tobacco cigarette or sprinkled

throughout the cigarette. When cocaine base was used with tobacco

or marihuana for smoking, users distributed approximately 1/3 gram

of base throughout a cigarette for each person smoking (cf. Siegel

et al., 1976). Cocaine base is an intermediate compound in the

manufacture of the hydrochloride salt and is less susceptible to

decomposition upon heating. It can be re-obtained from street

cocaine via simple chemical procedures.

125
DOSE REGIMES

While subjects in this sample used 1-4 grams of cocaine per month,

doses were not evenly distributed across time. Generally, subjects

purchased cocaine in gram quantities, sometimes referred to as

"bindles" or "spoons," although a spoon could vary from 0.5 to 2.0

grams (Lee, 1976). This amount was generally consumed in less than

one week (49 percent); some subjects used it within two days (34

percent). When cocaine was used intranasally, most subjects repeated the self-administration an average of 3 times per night,

usually at 15 or 30 minute intervals (range = 10 minutes to 2

hours ). When cocaine base was used for smoking, a cigarette

containing approximately 1 gram of cocaine base was smoked by two or

three persons over an average period of four hours.

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: The group of 19 subjects classified as

experimental users engaged in short-term, non-patterned trials of

cocaine with varying intensity and a maximum frequency of 10 times

(or a total intake of less than 1 gram). These users were primarily

motivated by curiosity about cocaine and a desire to experience the

anticipated drug effects of euphoria, stimulation and enhanced

sexual motivation. Their use was generally social and among close

friends. Only four of these individuals purchased their own cocaine

and these, together with two subjects given gifts of cocaine, were

the only ones who engaged in individual (non-social) trials. Most

(68 percent) expressed a desire to use cocaine more often but were

restricted by economic and supply considerations. The remainder

(32 percent) experienced little or no drug effect and felt no desire

to continue use. Interestingly, most of the experimental users

endorsed the street myth that cocaine is a subtle drug (cf.,

Phillips, 1975) but only those individuals who expressed a desire to

continue cocaine use also believed that cocaine gives a "kick" or

"rush." This latter finding suggests the importance of psychological set in determining drug reactions.

Social-Recreational Use: All 85 subjects in the formal study

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 subjects

126
started as experimental users and many (71 percent) engaged in

episodes of more frequent use (see below), although their primary

pattern was social-recreational. Most (75 percent) purchased their

own cocaine while the remainder shared use with others in social

settings. All 85 subjects experienced drug effects and varying

degrees of intoxication (described below).

When asked to rank all drugs in terms of recreational drugs of

choice, all users ranked cocaine first. However, when asked to rank

all drugs used in terms of potency in producing euphoria and

ecstasy, 69 percent of the males and 95 percent of the females

ranked cocaine first. Other drugs ranked above cocaine in this

category included LSD, marihuana and methamphetamine. Nonetheless,

cocaine retained popularity as a recreational drug of choice for

these reasons:

1) Cocaine was viewed by users as a social drug which

facilitated social behavior. Conversely, LSD and marihuana

were generally viewed as individually-oriented and asocial

drugs.

2) Cocaine was viewed by users as the "ideal" drug in terms

of convenience of use, minimal bulk, rapid onset of effects,

minimal duration of action with few side effects, a high

degree of safety and no after effects.

3) Cocaine was viewed by users as an exotic drug which had

appeal because of its rarity, high price and historicalcontemporary associations with popular and often high-status

folk heroes.

In connection with this latter attitude, users spent an average of

$30 on cocaine paraphernalia during the period surveyed compared to

only $4 on marihuana paraphernalia. While cokespoons, vials,

mirrors and other cocaine paraphernalia are more expensive than

marihuana rolling papers or pipes, users consistently claimed that

the cocaine paraphernalia was not essential to their drug use, but

represented a desire to share in the illicit status associated with

such devices.

Undoubtedly, these attitudes contributed to stable patterns of

social-recreational use which did not escalate to individually

oriented patterns of uncontrollable use. In addition, most users

felt that the high cost and inconsistent quality of street cocaine,

together with the short duration of action, were rate-limiting

determinants of cocaine use. They also felt that cocaine was not

addictive, except perhaps with intravenous use, and thus, socialrecreational intranasal use would not result in escalating patterns

of use. A number of these subjects were re-interviewed at various

times during the months following this study and none of them

manifested any signs of increased usage.

127
Circumstantial-Situational Use: Approximately 53 percent of

the males 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 perceived need or desire to achieve a known

and anticipated drug effect deemed desirable to cope with a specific

condition or situation. The motivations cited by male users, in

order of decreasing frequency, were: to increase performance at

work (89 percent); to enhance mood during periods of situational

depression (69 percent); and to enhance performance at play (e.g.,

sports, hiking, sex) (42 percent). Approximately 68 percent of the

females engaged in situational use and they cited the following

motivations: to enhance mood (90 percent); to increase performance

at work (particularly housework) (90 percent); to suppress appetite

(60 percent); and to enhance sexual performance (20 percent ) .

Intensified Drug Use: Fifteen males (18 percent) and two

females (14 percent) engaged in 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 performance. Nonetheless, users

here still referred to their intensified use as "runs" or "binges" --

-- terms normally used for periods of repeated dosing found in all

groups of cocaine users. Only this group of intensified users

reported hallucinations (discussed below) and tolerance to behavioral effects. Tolerance was chiefly reported as a lessening in

perceived stimulation and anti-fatigue effects with no loss in

euphoric effects. While behavioral tolerance to cocaine has been

demonstrated in three animal species, reports of tolerance in man

are still purely anecdotal at this time (cf., Grinspoon & Bakalar,

1976).

Compulsive Drug Use: None of the subjects studied engaged in

compulsive use, which is characterized by high frequency and high

intensity levels of relatively long duration, producing some degree

of psychological dependence.

PHENOMOLOGY AND INCIDENCE OF INTOXICATION EFFECTS

The acute physiological and psychoactive effects reported by social-recreational users did not differ substantially from those

described in the historical literature or elsewhere in this volume

(cf., Byck & Van Dyke, Chapter 5). Briefly, subjects repeatedly

sought and experienced euphoria (100 percent), stimulation (82

percent), reduced fatigue (70 percent), diminished appetite (67

percent), garrulousness (59 percent), sexual stimulation (13 percent), increased mental ability (12 percent), alertness (7 percent)

and increased sociability (6 percent). A number of mtoward effects

were also reported by users: restlessness (70 percent), anxiety (34

1Matsuzaki et al, 1976; Moerschbaecher, 1976; Whyte, 1976; Thompson, in press.

128
percent), hyperexcitability (28 percent), irritability (16 percent)

and paranoia (5 percent). Taken together, individuals reported

experiencing some positive effects in all intoxications and negative or untoward effects in only 3 percent of the intoxications.

The chronic effects reported by these social-recreational users

were also similar to those reported elsewhere (Grinspoon & Bakalar,

1976). In addition to acute intoxication phenomena, users experienced both desired and undesired effects. The desired effects

included: a generalized feeling of increased energy (65 percent),

increased sensitivity to acute effects of cocaine (60 percent) and

weight loss (21 percent). The undesired effects included: nervousness and irritability (44 percent), perceptual disturbances (44

percent), nasal problems (28 percent), fatigue or lassitude when

effects wore off (26 percent) and situational sexual impotency (4

percent). Overall, chronic positive or desired effects were experienced in all intoxications while negative effects were experienced in approximately 5 percent of the intoxications.

PERCEPTUAL CHANGES

Of the phenomena reported above, the perceptual changes are perhaps

the least understood but also among the most important in understanding the precise nature and form of cocaine intoxication.

Indeed, Post (1975) has suggested that cocaine users may manifest an

orderly progression of clinical syndromes including euphoria,

dysphoria and paranoid psychosis. Furthermore, the presence of

perceptual changes including hallucinations are key diagnostic

criteria in the determination of the psychotic phase. Therefore,

these perceptual changes were the subject of concentrated examination and testing in the study.

A total of 37 subjects (44 percent) experienced some perceptual

phenomena consisting chiefly of increased sensitivity to light,

halos around bright lights and difficulty in focusing the eyes.

Some of these subjects were experiencing chronic mydriasis caused

by cocaine-induced enhancement of norepinephrine tonically released

from sympathetic fibers that innervate the radial muscle of the iris

(Woods & Downs, 1973). The mydriasis may have contributed to these

perceptual effects. Several users also experienced exophthalmos

(protrusion of the eyeball) and cycloplegia (paralysis of the

ciliary muscle of the eye) which may have further contributed to

these effects.

All 37 subjects of this subsample experienced some lapses of

attention, but only 16 of these reported any difficulty in thinking

associated with such changes. Such experiences included difficulty

in maintaining attention during complicated tasks; difficulty in

maintaining thoughts during conversation; and general preoccupation

with personal problems. These effects are similar to what Post

(1975) has described as "inability to concentrate," a component of

cocaine dysphoria.

129
A total of 15 subjects (18 percent) reported hallucinatory experiences in several modalities including vision, touch, smell, hearing

and taste. These phenomena were first noticed after approximately

six months of recreational use and subjects usually became aware of

them only during episodes of intensified use. Subjects described

these events as pseudohallucinations, lacking the concomitant delusion that such events really existed. Pseudohallucinations are

characteristic of many drug intoxications (e.g., marihuana) and

differ from psychotic or true hallucinations which are accompanied

by delusions or beliefs that the perceptions are real (Siegel &

Jarvik, 1975).

Visual: Thirteen subjects (15 percent) reported visual hallucinations associated with the use of cocaine. Effects were

reported both with the eyes open and closed. In the eyes open

condition, subjects reported the sensation of object movement in

their peripheral visual fields. For example, subjects stated,

"Something just went by the corner of my eye," "Something just flew

by," "I feel like something or someone just moved over there," etc.

In dim illumination or with eyes closed, these sensations of

movement were extremely weak and often appeared only as flashes or

spots of light (cf., Wilson, 1973). Indeed, several subjects coined

the phrase "snow lights" to indicate the origin and nature of these

events. "Snow lights" were described as similar to, but less

intense than, the twinkling of sunlight as it is reflected from

frozen snow crystals. They were also described as similar to the

sparkling of cocaine (i.e., "snow") crystals.

During later stages of use, subjects reported seeing geometric

patterns in their peripheral visual field, usually only with open

eyes. These patterns were usually black and white and were composed

of straight lines, points and curves. Patterns reported by subjects

included stars, stripes, zigzags, herring-bones, checkerboards and

lattices. Such patterns are virtually identical to those patterns

seen as normal entopic phenomena as well as those experienced in

states of migraine. Subjects did not report "complex" hallucinations of fully formed or recognizable objects, although such reports are found in the literature (Woods & Downs, 1973).

Four subjects reported occasional polyopia. For example, one

subject saw a duplication of a painting hanging on the wall, another

subject claimed that a telephone dial appeared to have hundreds of

holes, etc. Three subjects experienced the rare phenanenon of

dysmegalopsia, including micropsia and macropsia, in which objects

and people appeared distorted in size. Only the subjects who smoked

cocaine base or injected cocaine had any dysmorphopsia. The single

subject who injected cocaine reported seeing an ashtray change into

a frying pan and then into a chicken! The phenomena of polyopia,

dysmegalopsia and dysmorphopsia are described by Kluver (1942) as

appearing in incipient toxic psychoses as well as in cocaine

intoxication. Such phenanena are also common in other states of

central nervous system excitation where zoopsia -- or hallucination

of animals -- are conspicuous (Wolf & Curran, 1935; Feldman &

Bender, 1970; Ey, 1973).

130
Tactile: Eleven subjects reported tactile hallucinations

after several days of intensified use. These hallucinations included, in order of occurrence: itching of the skin, primarily of

the hands but also including legs and back; the sensation of "moving

itchs" or foreign particles moving under the skin; the sensation of

small insects moving under or on the skin, primarily confined to the

face and hands but including all parts of the body; and the

sensation of objects or people brushing against the body. None of

the subjects reported any concomitant visual hallucinations; nor

did they believe that insects or objects were actually present,

although they often scratched or rubbed the skin. Thus, the

phenomena seen here appear to be simple pseudohallucinations.

Interestingly, one subject who had experience with smoking opium

and the consequent itching associated with opium-induced histamine

release, found the cocaine experience identical. S.A.K. Wilson

(1955) describes this paresthesia of pricking, "working" or "crawling" under the skin as eventually developing into hallucinations of

sight and hearing. However, none of the survey subjects experienced

this development. Subjects always described the tactile sensations

in terms of the similes "like," "as if," or "it is as though" and

they insisted that they never suffered from the delusion that

insects were, in fact, really present.

Olfactory: Six subjects reported olfactory hallucinations.

In most instances, subjects interpreted the perception of smells

and odors which were not consensually validated as simply an

increased awareness or sensitivity to smells actually present.

Smells reported included smoke, gasoline, natural gas, feces, urine

and garbage. At the time of examination, three of these subjects

had noticeable rhinitis (inflamed nasal mucous membranes) while a

fourth had several sores and scars on the interior nares. Such

damage to the nasal mucosa may also have caused degenerative changes

in olfactory receptors leading to abnormal firings (input) to the

olfactory bulb. The presence of "bad" or "foul" odors is strikingly

similar to those odors which precede uncinate fits which are also

linked to olfactory receptors as well as abnormal brain activity.

Auditory: Three subjects reported auditory hallucinations.

One of these experienced recurrent perceptions of a voice calling

his name when he was alone in the house. Another subject occasionally heard a noise "like" whispering which appeared to cane from

fans and ventilation ducts. The third subject heard whispering

while lying in bed alone at night. These whisperings, while

unintelligible, often kept the subject awake. Interestingly, he

interpreted the noises as "the sound of coke."

Gustatory: Three subjects reported strong gustatory (taste)

hallucinations occurring during acute intoxications. In every

case, these were negative hallucinations -- the subjects failed to

detect strong tastes in foods and drinks, tastes which others could

readily perceive. Such negative hallucinations may be associated

with olfactory changes as well as with attentional dysfunction.

131
HALLUCINOSIS OR PSYCHOSIS?

Taken together, the results of this study of perceptual changes in

users suggest an orderly progression of hallucinations from simple

"snow lights" through geometric forms to tactile sensations. The

subjects frequently described the "snow lights" and geometric patterns as being "like" insects, especially in their darting and

fleeting movements. Unlike previous accounts of "cocaine bugs,"

subjects did not see insects but did feel itchs and other sensations

which were "like" insects crawling on the skin. Nevertheless, none

of the subjects, while manifesting these behaviors, showed any

abnormal profiles on either the MMPI or the EWI. Indeed, the EWI

scales indicated some elevation of sensory perception scales with

no concomitant elevation of time perception, body perception, self

perception, perception of others, ideation, dysphoria or impulse

regulation (El-Meligi & Osmond, 1970). This latter configuration

would seem to indicate that the reported phenomenology may be simply

an acute psychopharmacologic effect of cocaine and not a symptom of

incipient psychosis. Since the dysphoria generally seen in the

development of cocaine clinical syndromes (Post, 1975) was not

present here, it is also possible that the recreational doses and

patterns of use reflected in this population of subjects were

insufficient to produce psychosis. Thus, the perceptual changes

suggest only the presence of an hallucinosis, events which users

found to be transient and which disappeared when they went from

periods of intensified use back to more moderate social-recreational use.

OVERVIEW

The initial use of cocaine by humans appears to have been the result

of accidental self-administration of coca, perhaps modeled from

animal use of the coca plant. Early coca use was initially

maintained by nutritional and psychoactive effects which were

instrumental in sustaining work activity. Use of cocaine itself in

the 19th and 20th centuries was primarily maintained by the reinforcement value of the intoxication state itself. This state is

characterized by euphoria and stimulation. Contemporary experimental use appears to be initiated by a curiosity about the drug and a

desire to experience the effects of euphoria and stimulation. Use

among social-recreational users is maintained by the social sharing

of this highly pleasurable experience. Some negative effects are

also reported among this group, and these include irritability,

perceptual disturbance, nasal problems and fatigue. When use is

intensified, negative effects, particularly perceptual changes, are

more noticeable. Such perceptual changes, which include "snow

lights" and geometric patterns in the visual modality, are pseudohallucinations which users can accurately judge as unreal.

Magnan's sign or "cocaine bugs" appear to be little more than

tactile sensations of itching. Among social-recreational users,

132
these pseudohallucinatory events appear to be more acute psychopharmacologic effects than signs of incipient psychosis. Psychometric instruments failed to detect the presence of dysphoria or

psychosis in this population. Adverse effects, including perceptual disturbances, seem to disappear when use is shifted from

intensified patterns back to more moderate recreational regimes.

In this sense, users are capable of titrating their doses so as to

circumvent adverse reactions. An important caveat is that these

effects are neither uniformly negative nor uniformly predictable.

The number of variables affecting their production is presently

unknown.

Ronald K. Siegel, Ph.D.

Department of Psychiatry

and Biobehavioral Sciences

University of California,

Los Angeles

133
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136
Chapter VII COCAINE: ITS USE FOR

CENTRAL NERVOUS SYSTEM

STIMULATION INCLUDING

RECREATIONAL AND MEDICAL USES

Donald R. Wesson, M.D. and David E. Smith, M.D.

Although the more common medical uses of cocaine (discussed in Chapter 9, Cocaine in Clinical Medicine) involve its local anesthetic

properties, the non-medical uses of cocaine are for its central

nervous system (CNS) effects. To a lesser extent, the CNS effects

of cocaine have been used medically, and periodically receive

renewed interest. This chapter considers the social-recreational

use patterns, followed by brief considerations of medicinal

applications.

SOCIAL-RECREATIONAL USE

The history and changing nature of cocaine use in American society

has recently been reviewed by a number of authors (Grinspoon &

Bakalar, 1976; Ashley, 1975). The use of cocaine appears to have

greatly increased over the past 10 years. Although its use is

common among heroin and other seasoned drug users, much cocaine use

occurs among young professionals and students not traditionally

associated with drug using subcultures. Among these latter groups,

cocaine is viewed as analogous to marihuana, and is considered to be

free of adverse reactions and dependence liability. The extent to

which these beliefs are justified involves consideration of patterns of use and dosage, as well as the pharmacological properties

of cocaine. Here we will consider caveats regarding the use

patterns and dosage, and leave a detailed discussion of pharmacological issues to other chapters of the monograph specifically

devoted to those questions.

Today "coke," "snow," "gold dust," "bernice," "lady," "she," "Dana

Blanca," "the rich man’s drug," or "the pimp’s drug" (all slang

terms for cocaine) is widely available and used at a cost of $500-

$1500 an ounce, or for about $60-$100 a gram.

Patterns of cocaine use and abuse cannot be completely replicated in

a laboratory setting. The subjective effect of any drug experience

is a complete interaction of expectations, setting and pharmacological effects of the drug, drug response, idiosyncracies of the

drug user, and many additional socio-cultural expectations. Drug

use rituals not generally duplicated in laboratory settings may

alter the subjective sensations of the drug experience.

Knowledge of patterns of cocaine use is derived primarily from

clinical descriptions of adverse drug reactions and descriptions of

use patterns through individual interviews by researchers. The

137
current approach is analogous to studying astronomy by sitting in a

cave and asking visitors from the surface to describe the stars.

The information thus derived is certainly subject to a marked

observer bias, and clinical reports are likely to emphasize the

bizarre or, at best, atypical reactions.

Naturalistic observations of cocaine use by trained observers are

needed to add perspective to understanding cocaine use patterns.

However, because of the variety of individuals who use cocaine, and

because of the variety of situations and settings in which cocaine

use occurs, extensive observation would be required to comprehensively describe current use. Although the interpretation of field

observations is subject to some ambiguity due to the interaction of

set and setting and possible contamination due to the presence of an

observer, the laboratory situation -- which attempts to control as

many variables as possible -- may also lead to erroneous conclusions. There is always the unknown effect of introducing recording

apparatus as well as the restrictions of laboratory settings, and it

is naive to discount the influence of such factors. Without doubt,

careful observation of cocaine use in a natural setting by trained

observers could allow greater understanding of patterns of use than

is now available. With the knowledge of as many variables as

possible, the laboratory researcher would be in a better position to

replicate patterns and dosages which are self-administered; and

therefore, complement the knowledge acquired in the laboratory with

relevance derived from field observations.

Cur observations and opinions regarding cocaine evolved from multiple contacts with cocaine users at the Haight-Ashbury Free Medical

Clinic, the San Francisco Polydrug Project, observations at rock

concerts, medical-legal consultations to the court, and by treating

drug abusers in our private practice. Although our observations

are, without question, subject to many of the limitations described

above, we believe that some reasonably reliable information about

current cocaine use has been developed as a result of these observations. The absolute frequency with which the described patterns

actually occur are unknown, and some of the patterns described may

well be the exception. Similarly, some of our toxicological

findings have not been verified by laboratory studies; therefore,

in certain situations, our conclusions may be at variance with

laboratory-derived results.

CONSIDERATIONS OF DOSAGE

The absolute single dose of cocaine as used in a natural setting can

only be estimated, but based on our analysis of material supplied by

patients ranges from 0-200 mg/ingestion. Adverse reactions to nonintraveneously administered cocaine are related primarily to

dosage, frequency and route of administration. It is reasonable to

assume that the amount of cocaine used per episode in a natural

setting occurs along a skewed bellshaped distribution as simulated

in Figure 6-1.

138
As indicated in the top section of Figure 6-1, the hypothetical

probability of adverse reaction to snorting cocaine is primarily a

function of dosage. If use patterns change, pushing the mean point

to the right, the probability of adverse reactions increases. In

our opinion, current human administration studies use substantially

less cocaine than the doses self-administered by users in a natural

setting, thus further confusing the issue of safety since dosage is

a major determinant of adverse drug effect. (It should also be

added that individual sensitivities to the untoward effect of the

drug may vary widely, so that a "safe" dose for one person may be a

dangerous one for another.)

Since cocaine’s effects are compared to those of other general

central nervous system stimulants like amphetamines, rather than

the opiates or marihuana, one would expect that the toxicity of

cocaine could qualitatively parallel that of amphetamines. Our

experience substantiates this premise, as we have seen cocaineinduced depressions, psychological dependence upon cocaine, acute

anxiety reactions to cocaine and cocaine psychosis -- all qualitatively similar to other CWS stimulants, such as the amphetamines.

PATTERNS OF USE

Oral Use

Although atypical of United States usage patterns, oral use of

cocaine can be found. In Peru chronic coca use is common. Andean

Indians chew coca leaves as a social ritual and mild stimulant and

members of upper socio-economic classes brew tea from coca leaves

(Weil, 1974). Far from chronic use, we have observed an expanded

interest among counter-culture groups in the United States in the

chewing of coca leaves for medicinal purposes as a social ritual,

and as a mild stimulant. This is interpreted as part of a broader

trend from synthetic drugs toward organic drug use.

Snorting

Cocaine is often absorbed through mucous membranes resulting in

local anesthesia of the membrane in addition to cocaine systemic

effects. The most common method of using cocaine is "snorting," a

special case of absorption through mucous membranes as the cocaine

is deposited on the mucous membrane lining of the nose. commonly,

cocaine is chopped with a razor blade on a piece of glass into a

fine powder and arranged into thin lines or columns, 3-5 cm long. A

line is then inhaled intranasally, usually through a rolled dollar

bill. One gram of cocaine normally produces about 30-40 lines of

cocaine so that each line contains approximately 25-30 milligrams.

139
FIGURE 6-1

An Illustration of the Hypothetical

Relation BetweeIn Dosage and

Frequency of Adverse Reaction

140
The user experiences 20-40 minutes of stimulation and sometimes

euphoria. Typically, the individual becomes talkative, and feels

energetic and self-confident. The effects of a single dose diminish

after 20-40 minutes, generally with no discernible after effects.

Occasional, single dose snorting rarely produces complications

sufficiently severe to require medical intervention.

Some individuals may continue to snort lines of cocaine every 10-20

minutes. Under these conditions, cocaine can accumulate in the body

and produce a state of extreme agitation with increased suspiciousness and even paranoid psychosis. Realistically, most individuals

are unable to afford the quantity of cocaine necessary to produce

such adverse reactions. However, we have seen situations in which

individuals with large sums of money and access to large quantities

of cocaine, such as drug dealers and musicians, have been able to

accrue sufficient amounts of cocaine to produce a cocaine psychosis

with associated violence, similar to the violence-associated stimulation seen in the high dose amphetamine abuse drug culture (Smith,

1968).

Further, repeated high dose intranasal abuse of cocaine has some

potential physical consequences -- such as a perforated nasal

septum -- although this condition is quite rare. Our accumulated

case experience has revealed only one instance of a perforated nasal

septum which was secondary to extreme high dose intranasal abuse of

cocaine.

In addition, as with the other stimulants such as the amphetamines

(Smith & Wesson, 1973; Smith, 1968), one may see a drug-induced

depression after prolonged high dose abuse of cocaine. This

depression can occur in individuals who do not have a history of

depression and is related primarily to dosage, duration of use and

route of administration, as demonstrated by the following case

example:

Case I

A 24-year-old white female worked as a secretary and had no history

of significant prior depression. She periodically used cocaine by

the intranasal route, and, at one point, was given an unusually

large quantity of cocaine. (The material was professionally analyzed by a street drug analysis laboratory in the San Francisco Ray

Area, which found it to contain 93 percent cocaine.) After "snorting" five to eight lines of the cocaine per night for several days,

she began waking up feeling depressed. To overcome this depression,

and go to work, she snorted one to two lines of cocaine in the

morning. By the end of the second week, she was progressively

developing severe anxiety, depression and increasing irritability

which was interfering with her interpersonal relationships. Her

concern over this drug-induced depression and anxiety faded in

approximately two days and she re-established her usual level of

positive affect and mood. Since this occurrence, she periodically

141
uses cocaine in social-recreational settings; however, she is careful to keep her dosage at a low enough level to avoid recurrence of

this drug-induced depression.

Absorption Through Other Mucous Membranes

Other methods of absorption include rubbing cocaine on the gums or

having cocaine blown from a straw onto the mucosal surface of the

back of the throat.

Cocaine can also be absorbed through the mucosa of the vagina and

sane individuals have incorporated this phenomena into their

cocaine usage. Some users report intercourse is prolonged, and

orgasms more intense after cocaine use. Occasionally males have

difficulty achieving erections but once acquired, are able to

sustain intercourse over an extended period of time. Some females

report being unable to have orgasm, but rather are able to achieve a

high, prolonged level of sexual excitation.

Intravenous Use

Cocaine may be injected alone or in combination with a longer

lasting euphoriant such as heroin. (Mixtures of cocaine and heroin

are called "speedballs.")

When cocaine is injected intravenously, the subject experiences an

intense "rush" which is not experienced when cocaine is ingested

orally or snorted. William Burroughs (1959) described the experience as follows:

When you shoot coke in the mainline there is a rush of

pure pleasure to the head...Ten minutes later you

want another shot.. . intravenous C is electricity

through the brain, activating cocaine pleasure

connections... There is no withdrawal syndrome with C.

It is a need of the brain alone.

Although Burroughs paid considerable tribute to cocaine, experienced users may not be able to initially distinguish the cocaine

rush from that produced by amphetamines. The distinction can be

made after a few minutes, however, because the effects of cocaine

dissipate much more rapidly than amphetamines (Kramer et al.,

1967).

Fischman et al., (1976) found that the cardiovascular and subjective effects of intravenously administered cocaine in humans was

similar to that of dextroamphetamine, and concluded that 10 mg of

dextroamphetamine generally had a subjective effect comparable to

that of 8-16 mg of cocaine.

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Cocaine is a popular drug among methadone maintenance clients since

cocaine will exert its stimulant actions even concurrent with

methadone. Chambers et al., (1972) in a study of methadone maintenance in Philadelphia, reported that cocaine was detected in 32 out

of 173 methadone maintenance clients within one month.

Chronic high dose use in an effort to maintain a constant euphoric

state increases the risk of medical sequelae. After a few days the

pleasurable effects give way to an intense anxiety state with gross

paranoid features, including auditory and visual hallucinations

similar to an amphetamine psychosis.

Adverse reactions also may occur when the individual changes route

of administration, as demonstrated by the following case:

Case II

A 19-year-old white male had been experimenting with a variety of

drugs, including snorting cocaine for approximately two years. He

had used cocaine exclusively in a recreational setting and indicated that he found nothing but pleasure in the drug experience and

never had any problem, nor had he escalated his dose. One day a

group of friends were injecting cocaine and they persuaded him to

try this route of administration. As he had had no difficulty with

cocaine previously, and as a result of curiosity and peer group

pressure, he decided that he would experiment with injection.

Following the intense stimulation and rush he became acutely

anxious and frightened. Upon arrival at the Medical Section of the

Haight-Ashbury Free Medical Clinic, he was found to have a very

rapid pulse rate as well as a hyperventilation administered;

anxiety. He was treated with 10 mg of i.v. Valium(R) adminestered

slowly with reassurance. To cease the carpopedal spasms he had

developed as a consequence of his hyperventilation syndrome, he was

told to breathe into a paper bag which increased his carbon dioxide

levels. The acute anxiety and its subsequent sequelae faded in

approximately three hours. Follow-up indicated no recurrences or

further experimentation with intravenous injection of cocaine by

this individual. This use of intravenous sedative hypnotic medication is controversial and some critics of this approach use oral

medication only while others stress reassurance alone without medication. We would recommend intravenous Valium(R) only after nonpharmacological intervention has failed.

Case III

A 31-year-old white male law student in his fourth year of law

school had a long history of experimental drug use including alcohol

(his first drug), marihuana and LSD; but at no time had he abused a

psychoactive drug. Approximately two years ago he was introduced

to cocaine in a social setting by a group of friends and fellow law

143
students. He became a regular recreational user of cocaine and in a

social setting during an evening would chop up and snort between 10

and 20 lines of cocaine in the usual fashion. (Often, as with this

case, cocaine is used in a recreational setting along with alcohol

and marihuana.) With this law student, the pattern of recreational

cocaine use continued for sane time, but moved to a more daily

pattern when he found that the inhalation of cocaine stimulated his

performance and ability to study at night, something he found

desirable because he had begun to prepare for the bar examinations.

One evening a female friend with whom he was periodically having

sexual relations produced a needle and syringe and indicated that

the injection of cocaine produced a pleasurable, orgasmic-like

"rush." The law student injected the cocaine simultaneously with

his female sexual acquaintance and found the orgasmic "rush" quite

desirable. Over a several month period he escalated his intravenous

cocaine use on a daily basis, injecting from approximately 10 p.m.

until 7 a.m., on a 15 minute to 1 hour repeated schedule, using

approximately 2g of cocaine per night.

Despite the fact that the law student was independently wealthy as a

result of a family inheritance, he found that he was rapidly

consuming his inheritance as his cocaine habit was costing him $50-

150 per day. As a consequence he began dealing cocaine to his

friends in order to help support his own habit. While the injection

of cocaine involved both male and female figures, he would almost

invariably inject with a woman in a sexual context, although he

reported that as he became more deeply involved with cocaine, his

libido dropped dramatically; for both he and his female sexual

partners, the orgasmic effects of the cocaine injection became a

substitute for actual sexual intercourse.

One evening he injected a female friend in his usual fashion (he

would first inject the woman and then himself). She suddenly had a

series of seizures, became comatose, required mouth-to-mouth resuscitation and was subsequently transported to an emergency roan.

During this particular cocaine run, he also experienced the first

evidence of a cocaine psychosis, with auditory and visual hallucinations and extreme paranoia. The negative effects both to himself

and to his girlfriend were quite shocking because he had believed

cocaine to be as free of adverse consequences as marihuana. Because

of these two episodes, he decided to quit cocaine use and seek

treatment. During the "withdrawal period" he experienced difficulty sleeping and a severe drug induced depression associated with

anxiety that lasted for approximately one week. Most depressive

symptoms gradually abated; however, the anxiety continued along

with an urge to use cocaine late in the evening at the time for his

previous cocaine runs.

To help with the anxiety, depression and sleep disorder, 10 mg of

Valium(R) p.o, was administered each night. As there was no

evidence of a prolonged underlying depression which preceded the

cocaine abuse or that lasted following the "fade out" period of the

144
drug-induced depression, no tricyclic antidepressants were administered. He made a decision to self-medicate the lethargy and

reactive depression with the intranasal use of cocaine which he

resumed on a daily basis. He expressed great surprise at the toxic

effects of cocaine, but was also quite ambivalent about whether he

would completely discontinue cocaine.

DEPENDENCE AND TOXICITY

Although psychological dependence on cocaine does occur, whether

cocaine produces true physical dependence remains a question. I f

deprived of the drug, the cocaine user does not experience withdrawal symptoms such as those experienced by heroin or barbituate

addicts. However, the depression following cocaine use may be

viewed as a withdrawal state.

The degree of drug-induced depression is dose related and, as

described by Blum (1976) and Axelrod (1970), the central stimulant

action of both the amphetamines and cocaine is attributed to its

effects on brain biogenic amines, especially catecholamines. The

mental depression and fatigue which characterizes the depression to

large doses of both amphetamine and cocaine in humans may be

associated with temporary depletion of catecholamines in the central nervous system. Blum (1976) has also suggested that a mild

functional deficiency of any dopamine or 5-hydroxyltryptamine in

the central nervous system may serve as a biochemical basis for the

drug-induced depression to cocaine.

TREATMENT OF TOXICITY

Treatment of cocaine toxicity is accomplished on a symptomatic

basis. A sedative such as diazepam (Valium(R) can be administered

orally for acute anxiety and drug-induced depression in dosages of

10-40 mg in repeated doses as indicated. Prolonged depression

indicative of an underlying mood disorder can be treated by

tricyclic antidepressants and appropriate psychotherapeutic intervention as indicated (Smith, 1976)1

. With a severe overdose,

hospitalization with respiratory assistance and a life support

system (described in detail in "Cocaine in Clinical Medicine") may

be necessary. Once cardiopulmonary function is assured, prognosis

for the recovery from an overdose is greatly increased. Within a

few hours, life-threatening signs disappear. After recovery,

psychological support is of the utmost importance. For the rare

case of cocaine stimulant psychosis, psychiatric hospitalization

may be indicated.

1

See however Barash, Chapter 9, this volume for a caution on the

potentiating effect of tricyclic antidepressants on cocaine.

145
In general, we find that the cocaine psychosis is of much shorter

duration than the amphetamine psychosis. Therefore, if medication

is needed, we recommend repeated small doses of Valium(R) to deal

with the agitation and anxiety. If the psychosis persists, we

recommend increasing the dose of Valium . If it continues for

several days then the phenothiazine tranquilizers should be used

with additional evaluation in order to determine if the cocaine has

precipitated an underlying, endogenous psychotic disorder.

As with any stimulant, cocaine is often used in association with

other drugs, very often in an upper-downer cycle (Smith & Wesson,

1973) with the secondary drug usually being a sedative-hypnotic in

order to deal with sane of the stimulant side effects of cocaine.

Cur experience has been, that the individual is able to titrate his

stimulant and sedative use to minimize negative consequences, particularly if the drug is taken in a social-recreational setting.

However, our court work has revealed situations in which young,

particularly working-class adults, have been arrested for drunk

driving and found to have intoxicating levels of alcohol. In

interviewing these individuals, either through our field research

or medical-legal consultation, we have occasionally found that

their intoxication was actually a secondary drinking pattern with

the primary social drug being cocaine. None of the laboratory

examinations of biological fluids were tested for cocaine and the

client was almost always attempting to hide his primary pattern of

cocaine use, both from the court and from his defense attorney.

Consequently, rarely has the primary pattern of cocaine use been

implicated in this upper-downer cycle in which the secondary drug, a

sedative-hypnotic, apparently leads to the negative social consequences. Because much of our contact with the cocaine user, as well

as the abuser, has occurred outside of any treatment system, we feel

that much of the cocaine abuse that is occurring at the street level

is hidden from scientific or public analysis to date. This dearth

of information actually perpetuates the belief that because the

known incidence of cocaine abuse is small, the drug per se has a low

abuse potential.

DRUG DECEPTION

Because of its high price and its distribution through black market

channels, less expensive, more available materials are likely to be

misrepresented as cocaine. This "drug deception" is, in fact,

fairly common. Much of what is sold as cocaine is actually

amphetamines, or other white (and sometimes brown) substances.

Common substitutions for cocaine -- as analyzed by street drug

analysis programs -- are amphetamines, tetracaine, or other local

anesthetics, such as procaine (Novocain 1 and lidocaine (Xylocaine(R)). While data from street drug analysis programs document

the existence of deception, they do not necessarily provide

accurate estimates of its prevalence. Drugs are usually submitted

for analysis because the owner suspects that the drug has been

146
misrepresented. Therefore, samples which are analyzed are not

generally a random sampling of cocaine within the community.

Nevertheless, review of data on cocaine samples submitted to a

street drug analysis laboratory in Palo Alto, California (Perry,

1975), indicates that approximately 73 percent of the cocaine

samples submitted for analysis was pure cocaine, while another 21

percent consisted of cocaine infiltrated with synthetic local anesthetics and the remaining 6 percent contained other drugs such as

amphetamines, caffeine, phencyclidine or no drug at all. A review

of the monthly survey done at the Los Angeles County Hospital Drug

Investigation Laboratory (Ritzlin & Lundberg, 1976) showed that of

10 cocaine samples submitted for analysis, 6 contained cocaine. Of

the other four, one contained a cocaine/lidocaine combination, one

a cocaine/mannitol combination, another contained pure lidocaine,

and one was pure heroin. The latter finding of heroin-cocaine

mixtures causes both confusion and concern. Presently, cocaine

costs more than heroin and an increasing number of analyzed samples

are found to have been adulterated with heroin. In addition, the

phenanenon of "speed-balling," utilizing both heroin and cocaine,

is growing more popular. This may produce difficulty in managing an

overdose episode. For example, if an individual snorts or injects a

large quantity of material he believes to be cocaine, but, in fact,

contains heroin, the overdose experienced may be different than one

would expect from ingesting pure cocaine. Treatment of heroin

overdose is accomplished with intravenous naloxone, an opiate

antagonist, which would have no effect on the cocaine stimulant

symptoms. The combination of cocaine and heroin can result in some

individuals being exposed to heroin who would probably not otherwise seek a heroin experience, as occurred in the following case

example.

Case IV

A 35-year-old white female architect intermittently snorted cocaine

in a social-recreational setting, but was introduced to a mixture of

cocaine and heroin by a rock musician. She found the heroin prolonged and altered the effects of cocaine which she snorted, and

produced an encouraging drug effect which was somewhat like an "acid

trip." She snorted this mixture of cocaine and heroin each evening

for approximately two weeks, but found that it was disrupting her

work, producing a drug-induced depression and raising concerns in

her mind about becoming addicted to heroin since she found the

caubination so pleasurable. As a result, she discontinued her use

and had a moderate drug-induced depression which she thought might

be a mild abstinence syndrome. Neither required treatment or

medical intervention. Even when examining what appear to be

specific drug patterns, it cannot be assumed that the desired

effects are the same for all individuals.

147
Case V

Interviews were done with 15 high dose intravenous cocaine and

heroin abusers in a notorious drug dealing house in the Mission

District of San Francisco. Of the 15 individuals, 4 indicated that

intravenous injection of cocaine was the drug of choice because of

the "orgasmic rush" they received when they injected, and the fact

that it stimulated them to stay active. They mixed cocaine with

heroin in order to calm some of its side-effects and to enhance the

pleasurable effects of the cocaine.

The other 11 individuals indicated that the nodding, stoned effect

of heroin was much more attractive to them and they did not like the

"speedy" effect of the cocaine. They used cocaine combined with

heroin only occasionally to have some diversity in their drug

experience. Despite the fact that all 15 had experienced adverse

drug effects with both cocaine and heroin, none had any interest in

stopping their intravenous drug abuse.

MEDICAL USES OF COCAINE

Because of its euphoric effects, cocaine can alleviate a depressed

mood. Freud had considered its use for this purpose, and felt it

could be a useful psychotherapeutic drug. (Cf., Petersen, Chapter 1

this volume)

Grinspoon and Bakalar (1976) reviewed subsequent uses of cocaine

for its CNS effects, and categorize three applications:

1) treatment of mental disorders – mainly depression and

catatonic stupor;

2) diagnostic aids for mental disorders; and

3) model psychosis (schizophrenia, paranoid’type).

The use of cocaine (and stimulants in general) in the treatment of

depression has been generally disappointing. It is clear that

stimulants do not have any role in the treatment of most depressed

patients, however, one need not conclude that cocaine is completely

without value in every case.

While the authors would not presently advocate cocaine for the

treatment of any mental disorder, we believe the potential role of

cocaine in selected cases who have not responded to conventional

treatment should be re-explored using modern evaluation techniques.

The abuse potential, per se, should not necessarily preclude considerations of use. Severe depression unresponsive to treatment

can be incapacitating and life-threatening, and can justify treatment techniques with considerable risk of addiction. Responsible

use dictates control against diversion and close clinical monitoring and control.

148
Recently, cocaine has received sane use in the United States as a

modified Brompton’s Solution (containing methadone, cocaine and

alcohol) for the treatment of pain from terminal cancer. The CNS

stimulant effects are thought to decrease the clouding of consciousness produced by the methadone, and to potentiate its analgesic effects.

DISCUSSION AND SUMMARY

In summary, cocaine is a central nervous system stimulant of

moderately high abuse potential. At the present time the preferred

route of administration is intranasal and the dosage patterns are

relatively low. The social rituals surrounding the drug endorse

primarily recreational use while the high cost and low availability

of the drug produce the current low rate of cocaine abuse in the

United States.

Unfortunately, the difference between current abuse versus abuse

potential is a concept not well understood by many laboratory

scientists, drug experts who do not see cocaine abuse in their

treatment programs, or by the general public. For example, a recent

"San Francisco Chronicle" featured a story on cocaine which included the following quotes from an expert in the drug field:

...cocaine is less harmful than many other legal and

illegal drugs popular in America.

Most of the evidence is that there aren’t any adverse

effects to normal cocaine use. It looks to be much

safer than barbiturates and amphetamines, and there’s

no evidence it has the body effects of cigarettes or

alcohol.

If I were going to go out and sell a drug to the

public, it would probably be cocaine. We might be

better off using it as a recreational drug than

marihuana. Rut we have a cultural bias against

routes of administration. As long as you can drink it

or smoke it, it’s OK in our society. That’s why

marihuana is making it. But using it in the nose or

with a needle just isn’t accepted. That may prove to

be the biggest obstacle for cocaine.

San Francisco Chronicle

Thursday, October 21, 1976,

Page 4)

149
We believe the closest pharmacological parallel to cocaine is

neither marihuana nor alcohol, but rather amphetamines. In projecting the abuse "potential" of cocaine, it would be better to look

at the consequences of amphetamine use -- whether swallowed, snorted or injected -- in helping to resolve the major debates now

surrounding street use and abuse of cocaine.

Although most cocaine use, even in a social recreational setting,

does not produce adverse medical or psychological consequences, one

should not necessarily conclude that cocaine use is harmless. In

considering the risk to the individual, one must also consider that

at least some individuals must contact the illicit drug marketplace

to obtain cocaine and may, thus, be exposed to criminal activities.

The high cost of cocaine may drain an individual of financial

resources. Also, drug-induced depressions and psychosis may

occasionally occur.

The combination of cocaine with alcohol or other central nervous

system depressants has the effect of combining the poor judgment of

sedative intoxication with a high energy level of cocaine, a

combination which we have observed to have serious consequences in

some individuals.

Thus, we view cocaine to be a drug of moderately high abuse

potential, similar to that of amphetamines; but with socio-cultural

variables that prevent its widespread abuse, including the set and

setting in which the drug is usually taken, and the route of

administration which is primarily nasal "snorting" rather than

intravenous "shooting." Most users now use cocaine by the intranasal route at moderately low dosages, while a relatively small

percentage use cocaine intranasally or intravenously at high

dosages. However, if the drug were more readily available at a

substantially lower cost, or if certain socio-cultural rituals

endorsed and supported the higher dose patterns, more destructive

patterns of abuse could develop.

David E. Smith, M.D.

Haight-Ashbury Free Medical Clinic

and SanFrancisco Polydrug

Research Project

and

Donald R. Wesson, M.D.

San Francisco Polydrug Research

Project

150
REFERENCES

Cocaine: Its Use for Central Nervous System Stimulation

Including Recreational and Medical Uses

Ashley, R. Cocaine: Its History, Uses and Effects. New York, NY:

St. Martin's Press, 1975.

Axelrod, J. Amphetamine metabolism, physiological disposition and

it effects on catecholamine storage. In Costa, E. and

Garattini, S. (eds.) International Symposium on Amphetamines

and Related Compounds. New York, NY: Raven Press, 1970, pp.

207-216.

Blum, K. Depressive states induced by drugs of abuse: Clinical

evidence, theoretical mechanisms and proposed treatment.

Part II. Journal of Psychedelic Drugs, 8(3):235-262 (1976).

Burroughs, W.S. Naked Lunch. New York, NY: Grove Press, 1959, pp.

64-65.

Chambers, C.D., Taylor, W.J.R. and Moffett, A.D. The incidence of

cocaine abuse among methadone maintenance patients, International Journal of the Addictions, 7(3):427-441 (1972).

Fischman, M.W., Schuster, C.R., Resnekov, L., Shick, J.F.E.,

Krasnegor, N.A., Fennell, W. and Freedman, D.X. cardiovascular and subjective effects of intravenous cocaine administration in humans.

989 (1976).

Archives of General Psychiatry, 33:983-

Freud, S. The Cocaine Papers. Vienna, Austria: Dunquin Press,

1963.

Grinspoon, L. and Bakalar, J.B. Cocaine: A Drug and Its Social

Evolution. New York, NY: Basic Books, 1976.

Kramer, J.C., Fischman, V.S. and Littlefield, AC. Amphetamine

abuse: Pattern and effects of high doses taken intravenously. Journal of the American Medical Association,

201(5):305-309 (1967).

Martin, R.T. The role of coca in the history, religion and medicine

of South American Indians. Economic Botany, 24:422-438

(1970).

Perry, D.C. Heroin and cocaine adulteration. Clinical Toxicology,

8(2):239-243 (1975).

Ritzlin, R.S. and Lundberg, G.D. Street Drug Identification ProLAC - USC Medical Center Drug Investigation Laboratory,

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Smith, D.E. Acute amphetamine toxicity. Journal of Psychedelic

Drugs, 11(2): 49-54 (1969).

Smith, D. Polydrug abuse and comprehensive treatment intervention.

Presentation at the National Drug Abuse Conference in New

York, March, 1976.

Smith, D. and Wesson, D. (eds.). Uppers and Downers. Englewood

Cliffs, NJ: Prentice-Hall, 1973.

Weil, A.T. The green and the white. Institute of Current World

Affairs Newsletter, March 20, 1974.

152
Chapter VIII

THE FORENSIC TOXICOLOGY

OF COCAINE

Bryan S. Finkle, Ph.D. and Kevin I. McCloskey, Ph.D.

The general purpose of this study-report is to assess the role of

cocaine in post-mortem, medico-legal investigations, and a primary

objective to determine whether cocaine has caused a significant and

growing number of sudden, unexplained deaths. The significance can

be evaluated in terms of either the absolute number of deaths

directly attributable to cocaine ingestion or relative to the

fatalities caused by other abused and misused drugs. A total of

only 111 fatalities in which cocaine was involved occurred at 27

study sites between 1971 and 1976. Of these, 26 involved cocaine

alone. The population base of these sites totaled 62.9 million.

The report is a retrospective, collaborative survey aimed at

answering the above question, and provides incidental data and

information which may assist forensic toxicologists and pathologists in their search for a more rational approach to the analysis

and interpretation of "cocaine cases." It is not designed or

intended as a review of cocaine toxicology-pharmacology, nor as a

critique of analytical toxicology methods, much less an evaluation

of toxicology laboratories’ staffs or individual protocols.

The study was prompted by a growing volume of professional publicity

during the past two years that a massive resurgence of cocaine

availability and non-medical use was underway. This publicity has

aroused controversy concerning the drug’s toxicology, between advocates of its recreational use, who claim it is completely safe, and

opponents who cite the historical record and apparent dangers

indicated by data from the Drug Abuse Warning Network (DAWN) and the

experiences of professionals working in drug abuse treatment and

rehabilitation programs. Toxicological data to support or refute

these claims were not available, and although coroner and medical

examiner’s offices are only concerned with fatal cases -- and

therefore this report ignores overdose intoxications and adverse

reactions in which the subject recovers -- the data on fatalities do

provide a means of examining some medical hazards of cocaine use.

If cocaine is widely available and abused, and also toxic, it will

inevitably cane to the attention of forensic pathologists and

toxicologists. Sudden, unexplained deaths are subject to extensive

medical and circumstantial investigation to determine manner and

cause of death and, as such, can often provide accurate, objective

153
information to elucidate problems such as cocaine use. For any drug

used and abused for recreational purposes there will be an accompanying body of folk-lore and case-law which serves to support all

shades of subjective opinion but seriously clouds and hinders

scientific knowledge. Data from cases subject to post-mortem,

medico-legal investigation can shed important light through the

cloud and help clarify misconceptions. This is an important

justification for the rationale of this report.

Although books and papers continue to be published describing

apparently new aspects of cocaine,1 fatalities from the drug are

certainly not new. As early as 1891, Mattison discussed cocaine

poisoning and reported four well documented fatalities which occurred in 1887 and three in 1888. Mayer (1924) documented 21 deaths

attributed to cocaine, and all editions of Webster’s (1930) classic

text, Legal Medicine and Toxicology discuss fatal cocaine poisonings from the turn of the century through the 1920’s. Cocaine is

not a benign drug, a fact which is clearly supported by its known

pharmacology (Goodman & Gilman, 1975; Byck & Van Dyke, Chapter 5

this volume). Although used clinically as a local anesthetic, its

systemic effects as a potent central nervous system, cortical

stimulant are most relevant in evaluating its toxicity. After a

toxic dose, the subject is likely to be excited, confused and suffer

seizures (an early effect of central stimulation) followed rapidly

by depression, eventually involving the medullary centers, such

that death may result from respiratory failure. Yet, no major

toxicological study of cocaine deaths has been attempted in recent

years, although isolated cases have been reported in the medical

literature since 1970.2

DESCRIPTION AND SCOPE OF DATA COLLECTION

The data collection and evaluation were carried out between midAugust 1976 and January 1977, and were designed to address the

general questions discussed above, and to document in detail any

fatal cases in which cocaine was the specific causative agent.

Background information on each victim and the circumstances

surrounding death were gathered in order to isolate common factors

or trends which might be useful in predicting cocaine fatalities.

Toxicologists and pathologists from the medical examiners’ and

coroners’ offices at 27 sites across the United States and Canada

participated in the study. The sites and jurisdictions are shown in

1Ashley, 1975; Gay et al., 1975; Mule, 1976; Van Dyke & Byck, 1976.

2De Vito, 1975; Pickett, 1970; Price, 1974; Wright-St. Clair, 1970.

154
Figure 8-1. Figure 8-2 presents the population of these jurisdictions and the number of cocaine-associated deaths investigated at

each site. A total of 62.9 million or 29.8 percent of the United

States population was covered by these sites. The large percentage

is not only statistically useful, but it includes all sites from

which cocaine deaths had been reported to DAWN, and also sites such

as New York City and Los Angeles, where drug abuse is recognized as

a social problem. This bias was offset by including sites thought

less likely to yield cases, but which provided a balanced national

geographic and demographic picture. Almost all of the toxicologists and pathologists interviewed were aware of the "cocaine

problem" and, therefore, on guard for its potential involvement in

their cases.

Two instruments were used to gather data at each site. One

(Appendix A, page 178) provided information concerning analytical

toxicology and laboratory resources and the other (Appendix B, page

179) was used to record individual case data. Appendix B includes

definitions for each question and alpha-numeric coded answers. By

using the codes, the questionnaire could be completed rapidly and

the data entered directly into a mini-computer for analysis. The

study included only those cases in which cocaine and/or its metabolites were detected and identified by toxicological analysis. Data

were collected by reviewing the case files at each site. Only the

information indicated on the forms was recorded and the anonymity

and confidentiality of the deceased were scrupulously maintained.

None of the data can be traced from this report to any individual

case.

The total number of fatalities on which data was finally collected

which in any way involved cocaine was 111. Figure 8-2 shows the

breakdown by site. There were sane surprising results. While the

relatively high number of cases from New York City and Los Angeles

County was expected, the absence of any cases from Philadelphia,

Minneapolis and Las Vegas, and the small number of cases from Wayne

County (Detroit) and Cook County (Chicago) -- one and three respectively -- were notable, since these areas all have acknowledged drug

abuse problems. Similarly, the finding that the number of cases

from Utah and New Mexico virtually matched the number from urban

areas of California and Florida was very striking. Information from

interviews with forensic scientists and law enforcement officials

at several sites confirmed the local case incidence and the overall

inference that cocaine use and subsequent fatal episodes is not

uniform for urban or rural areas throughout the United States. Its

occurrence was not reliably predictable from general demographic

considerations or drug abuse histories for particular areas.

The finding of 111 cocaine-related fatalities in a 5-year period

represents a relatively low incidence when compared with fatalities

attributed to almost any other major drug of abuse -- e.g., heroin

or barbiturates -- but, more importantly for this study, it is a

155
FIGURE 8-1

COCAINE SURVEY SITES

U.S. SURVEY POPULATION = 62.9 MILLION

(29.8% OF U.S. POPULATION)
FIGURE 8-2

COCAINE SURVEY: PARTICIPATING SITES, JURISDICTION POPULATION

AND INVESTIGATED COCAINE ASSOCIATED DEATHS

SITE

Alabama State (AB)

Alameda County, CA (LA)

Clark County, NV (LV)

Cook County, IL (CO)

Dade County, FL (DD)

Dallas County, TX (DL)

Hennepin County, MN (HC)

Illinois State, (IL)

Los Angeles County, CA (LA)

Maryland State (MR)

Minnesota State (MI)

Montreal, Province of Quebec

New Mexico State (NM)

New York City, NY (NY)

North Carolina State (NC)

Orange County, CA (OC)

Oregon State (OR)

Philadelphia County, PA (PH)

Rhode Island State, (RI)

San Diego County, CA (SD)

San Francisco County, CA (SF)

St. Louis, Missouri County, MO (SL)

Toronto, Province of Ontario

Utah State, (UT)

Vancouver, Province of British Columbia

Washington, DC (DC)

Wayne County, MI (WC)

TOTAL

JURISDICTION

POPULATION

(x106)

3.5

1.1

0.3

5.4

1.5

1.3

1.0

6.0

7.0

4.0

3.0

6.0

2.1

7.6

5.0

1.5

2.0

2.0

1.0

1.4

0.7

0.6

8.3

1.2

2.0

0.7

3.0

79.2

DOCUMENTED COCAINE

ASSOCIATED DEATHS

(1971-1976)

2

6

0

3

6

2

0

0

10

5

0

6

5

31

1

8

0

0

0

5

5

0

2

6

0

7

1

111

157
FIGURE 8-3

SEGREGATION OF STUDY CASES

ACCORDING TO DRUG OR NON-DRUG DEATHS

TOTAL CASES INVOLVING COCAINE

111

DRUG DEATHS NON-DRUG DEATHS

86 25

DRUG COMBINATIONS COCAINE ONLY KNOWN CAUSE UNKNOWN

60 26 22 3

INVOLVED MORPHINE

(Heroin use)

28

OTHER DRUGS

32
small number for useful statistical analysis. This is particularly

true since of the 111, death was caused by drugs in 86 cases and by

cocaine alone in only 26 cases (see Figure 8-3). Although the data

gathered were uniform and therefore appropriate for analysis, the

study encompassed a highly specialized population -- fatalities

involving cocaine -- and, therefore, great care was taken not to

extrapolate from the data in an attempt to establish a perspective

or assessment of cocaine use generally. However, with these

limitations in mind, many useful facts and conclusive statements

can be made from the study cases. As shown in Figure 8-3, 25 cases

(22.5 percent of the total surveyed) were fatalities with a cause

other than drugs. Although cocaine and sometimes other drugs were

detected in these victims, they did not occur in concentrations

considered sufficient to cause death. In any event, 60 percent of

these cases were either homicides or suicides and almost all of them

(21) were violent deaths via gunshot or stab wounds.

The increasing frequency of cocaine’s presence in sudden, unexplained death cases is indicated in the following table:

OCCURRENCE OF COCAINE CASES BY YEAR*

1971 1972 1973 1974 1975 1976

2 3 11 25 37 29(58**)

*Total cases for all study sites, 1971-1976

**Extrapolated figure to December 31, 1976

The increase is sharp but care must be taken before inferring at

face value that the figures indicate a dramatic increase in cocaine

use. Other influences, such as the awareness of medico-legal

investigators of cocaine use and improvements in analytical methods

available to toxicologists during the past five years, may have

contributed to the apparent rise in the incidence of cases involving

cocaine.

HISTORY OF THE DECEASED

A general inspection and overview of the survey cases reveals that

the deceased were principally young, white males. The great

majority were less than 30 years old, and almost 2/3 were Caucasian

with an approximate 3:1 bias in favor of males.

Figure 8-4 shows the distribution of age groups as a percentage of

total cases. Although more than a quarter were 26-30 years old, 51

percent were in their 20’s and 68.5 percent were under 30. There

was a negligible number of cases (3) older than 40 years. Further

159
1 Case = 0.9%
analysis of the data did not show any other significant trends

related to age. For example, the 26 cases involving only cocaine

were almost evenly distributed between ages 16 and 35; and for those

28 cases associated with heroin used, as indicated by the detection

of morphine in the post-mortem blood and tissues, there was no

discernible difference from the overall pattern shown in Figure 8-

4 .

The racial characteristics of the victims were known in all but four

cases. Caucasians accounted for 63.1 percent (70 cases) of the

toal, 22.5 percent (25 cases) were black and 10.8 percent (12

cases) were of Spanish-American descent. There were no NativeAmerican Indians or Asian-Americans. Caucasians were represented

in greater proportion (80.8 percent, 21 cases) than blacks (11.5

percent, or 3 cases) in the 26 cocaine-only cases, whereas the

opposite was true for those victims involved with heroin use --

almost a third (32.1 percent, or 9 cases) were black, while 57.2

percent (16 cases) were caucasian. Spanish-Americans were represented in all categories in about the same proportion as in the

total survey.

As mentioned earlier, there was a marked bias toward males among the

deceased:

Males

Females

Number of cases Percent of total

81 73.0

30 27.0

111 100.0

Male/female ratio = 2.7

Similar male/female ratios occurred in the cases involving only

cocaine (2.9) and in those involving morphine (2.5), while a greater

preponderance of males was reported among the non-drug deaths (m/f =

5.25).

The occupational status of the deceased was known for 69 of the 111

cases. Of the 69, 77 percent were employed at the time of their

deaths. Approximately 35 percent could be classified as manual

blue-collar workers. Relatively few professionals -- medical or

clerical personnel -- or students were represented. Occupation was

known for half of the cocaine-only deaths but no particular group

predominated.

In order to determine the previous health and drug use experience of

the deceased, their medical and psychiatric history was evaluated

whenever possible. This information was generally available as

161
part of the investigator’s case report to the medical examiner or

coroner. For the purposes of this study, medical and psychiatric

history was defined by the 12 categories as shown in Appendix B,

page 179, items 10 and 12. The categories in these items were

assembled from common medical ailments and typical conditions

associated with emotional disturbance, and new categories were

added in keeping with case findings as the survey proceeded. By the

definition of item 10 the total sample population was generally

medically healthy prior to demise. There was no defined history of

recent acute or chronic illness for 85.6 percent of the cases. For

the remaining individuals who did have a medical history, there was

no marked single ailment or class of diseases. In all but 2 of the

26 cases involving only cocaine, there was no medical history.

In contrast with the positive medical histories, 61.3 percent (68

cases) of the deceased had, a "psychiatric history" as defined by the

criteria in question 12.1 It is important to note that of those

with a psychiatric history, the problems were almost exclusively

related to drug abuse or misuse, with a conspicuously low incidence

of alcohol abuse (only 2.4 percent of the 86 drug death cases).

Morphine, resulting from heroin use, was the drug most commonly

detected in combination with cocaine, occurring in 33 percent (28)

of the drug-death cases. Lidocaine (encountered as the usual

"cutting agent" for cocaine, and not as a medical treatment for the

victims), methadone and hypnotic sedatives were the only other

drugs frequently associated with the study cases. There were fewer

than five occurrences each for diazepam, amitriptyline, phenothiazines and propoxyphene -- drugs often used to treat tension,

depression and neuroses. Only 1.2 percent of the victims (one case)

had a history of attempted suicide, which is consistent with the low

incidence of deaths classified as suicide (16 or 14.4 percent).

Twenty-three of the 111 deceased had a known, documented history of

cocaine abuse; of these, 19 (21 percent of the total) were classified by the pathologist as victims of accidental drug-caused deaths

(26.7 percent of drug-caused deaths; see Figure 8-5). The causes of

death for the remaining cocaine abusers were: natural -- 1; homicide

-- 2; suicide -- 1 (gunshot wound). As might be anticipated, the

proportion of these cases in which cocaine was ingested nasally was

much higher than for the survey population as a whole (see Table 31,

but, surprisingly, so was the proportion of cases (56.5 percent; n =

13) in which cocaine was injected intravenously. Throughout this

discussion, intravenous use of cocaine, knowingly or otherwise, was

revealed as a common Occurrence, even among identified cocaine

abusers, as illustrated in Figure 8-6. This is consistent with the

reports of Wesson & Smith on street use of cocaine (cf., Chapter 6

this monograph). None of the known cocaine abusers in the study had

any reported medical history, in contrast with 14.4 percent of the

total cases; nor did they have any notable psychiatric history other

than drug abuse.

1The reader should note that inclusion in this category might

reflect no more than that the deceased had been reported to have

used marihuana. . .or even cocaine--Eds.

162
FIGURE 8-5

CASES INVOLVING PRIOR HISTORY OF DRUG ABUSE

PRIOR HISTORY N

Heroin Abuse 30 34.8

Cocaine Abuse 2 3 26.7

Unspecified-Drug Abuse 22 25.6

Alcohol Abuse 2 2.3

PERCENT OF DRUG

DEATH CASES*

*Percentage values do not tally because of overlap between

categories.

163
FIGURE 8-6

ROUTE OF ADMINISTRATION OF COCAINE FOR VARIOUS CATEGORIES OF THE SURVEY CASES

PERCENT OF

PERCENT OF PERCENT OF CASES DECEASED

ROUTE OF PERCENT OF COCAINE-ONLY DRUG COMBINATION HAS HISTORY OF

ADMINISTRATION TOTAL SURVEY CASES N DRUG DEATHS N DEATHS N COCAINE ABUSE N

Undeterminable 54.1 60 15.4 4 56.8 34 17.4 4

Intravenous 31.5 35 61.5 16 30.0 18 56.5 13

Nasal 7.2 8 7.7 2 8.3 5 17.4 4

Oral 6.3 7 15.4 4 3.3 2 8.7 2

Rectal 0.9 1 – – 1.6 1 – –

111 26 60 23
FIGURE 8-7

CLASSIFIED MANNER OF DEATH FOR TOTAL SURVEY CASES

MANNER

Suicide

Accident

Homicide

Natural

Undetermined

TOTAL

NUMBER OF CASES

16 (14.4%)

48 (43.2%)

13 (11.7%)

5 (4.6%)

29 (26.1%)

111

165
ATTENDANT CIRCUMSTANCES IN COCAINE ASSOCIATED DEATHS

The manner of death for all the study cases, as classified by the

medical examiner or coroner, is shown in Figure 8-7. The high

number of accidental deaths and those of undetermined cause is

notable because it clearly indicates the unintentional aspect and

the appropriately conservative view taken by most pathologists when

assessing deaths involving drugs of abuse. In addition, it indicates that the study population as a whole cannot be generally

characterized as suicides. Although the proportion of cases classified as accidental or undetermined was the same among those

involving only cocaine as for the total cases, the proportion of

suicides was higher -- 22.9 percent. There is no obvious explanation for this. In cases involving heroin use, only 1 out of 28 (as

compared to 16 cases of the 111 total) was a suicide, and accidental

deaths comprised 71.4 percent of the heroin users. This is again

indicative of pathologists’ cautious approach toward classifying

sudden deaths involving opiate narcotics.

The route of administration of the cocaine is shown in Figure 8-6.

For slightly over half of the cases (54.1 percent), these data could

not be determined. When information was available it generally came

from up to three sources: a) witnesses’ statements; b) pathologytoxicology findings at autopsy, such as injection sites, needle

tracks or cocaine detection on nasal swabs; and c) drug injection

paraphernalia found with the body. It is perhaps important to

reiterate that, as indicated in Figure 8-6. intravenous selfadministration is frequently used. This is particularly true for

those cases in which morphine was detected; however, there was no

means of determining whether the drugs were acquired and used as a

single powder or as separate preparations. In a total of 28 cases --

- a quarter of the total sample or one-third of the drug deaths --

morphine, related to heroin use, was detected analytically. The

evidence for a relationship between heroin and cocaine use, at least

for this post-mortem population, is, therefore, persuasive.

There was a significant bias towards the oral route for those cases

involving only cocaine. Oral ingestion was documented for 15.4

percent of these cases, but most of these were suicidal ingestions

of large amounts of the drug or accidental deaths in which the

packaged drug was swallowed for smuggling purposes or to elude

detection when arrested. Nasal insufflation was the route of

cocaine administration for 7.7 percent (2 cases) of this group, a

figure which closely matches the incidence for the total sample, and

refutes the common assumption by drug users that this route is

invariably safe. There is neither sound pharmacology nor case data

in the study to support this opinion.

There was nothing remarkable about the location at which the cocaine

use or fatal incident took place. Private residences (house or

apartment) accounted for 65.9 percent, and 9.4 percent occurred at a

motel or hotel. Only 11.8 percent (10) of the drug-death cases

166
reached a hospital before they died. This small number of hospital

cases is undoubtedly a reflection of the short survival time seen in

a majority of the total study cases and illustrates the potency of

the drug.

The range of survival times following cocaine ingestion or the

recorded interval between the last time the deceased was seen alive

and was found dead is depicted in Figure 8-8. One case is

equivalent to 1.7 percent of the total drug-death cases comprising

the graph. The earlier time intervals are undoubtedly the most

accurate because for the longer periods, particularly beyond 10

hours or overnight, it becomes increasingly likely that death

occurred earlier and the body remained undiscovered. Within these

constraints it can be seen from Figure 8-8 that almost two-thirds of

the victims (65 percent) died in less than five hours and most of

these (31.7 percent of the total drug-deaths) died in the first hour

following ingestion. The peak in the 9-10 hour period results from

the classification of overnight deaths in this interval; for many of

them the time interval may have been shorter. For the 26 cases

involving only cocaine the time interval distribution is significantly truncated; 73.9 percent of these victims died in less than 2

hours and more than half within one hour. The pattern for cases

involving morphine was not discernibly different from the overall

distribution. There was no correlation between survival time and

route of drug administration. All routes, including nasal ingestion, were represented among the rapid deaths (less than five

hours), highlighting again the potential for insufflation of the

drug to produce toxicity.

Although terminal symptom were reliably observed and reported for

only half of the deaths involving only cocaine (13 of 26 cases),

they were remarkably consistent. The symptoms were entirely central nervous system mediated -- usually seizures followed by respiratory arrest, coma and death. Cardiac arrest was reported in three

instances. These observations present a consistent picture of the

principal pharmacological actions of cocaine. Almost no other

signs or symptoms (e.g., vomiting or dizziness) were reported.

ANALYTICAL TOXICOLOGY METHODS FOR COCAINE, USED AT THE SURVEY SITE

All but two of the toxicology laboratories at the 24 U.S. sites

currently use routine analytical screening methods which would

detect cocaine if present in the autopsy specimen tested. Not less

than 5 mls of blood or urine was generally the sample of choice with

stated sensitivity limits for cocaine in the range 1.0-2.0 mcg/ml.

Three sites included liver tissue samples in the initial drug

screening analysis for cases in which no specific drugs were

suspected. Immunological methods applied to urine samples were

usually employed followed by thin layer chromatography (TLC) and

gas chromatography (GC), with ultraviolet spectrophotometry avail167
1 Case = 1.7%
able at two sites. The Enzyme Multiplication Immunological Technique (EMIT(R)) was used at nine laboratories and radioimmunoassay

) (EMIT(R) at one other site. ) has the advantage of rapid direct

testing of the sample and detection of the cocaine metabolite

benzoylecgonine. However, for practical purposes it is insensitive

to parent cocaine. It has been in use at most of the nine sites

since 1974. The other methods used all require extraction of the

drug and/or metabolite from the biological sample before

chranatographic analysis. At 11 laboratories benzoylecgonine was

included but the remaining 16 sites relied upon detection of the

parent cocaine. XAD-2 resin was used at two sites to separate the

drug from the biological matrix. All of the others used organic

solvent extraction after adjusting the sample to approximately pH 9

with buffer. Some saturated the aqueous sample with salt before

extraction to improve recovery of the drug and metabolite.

Chloroform, n-butyl chloride or diethyl ether were the most

commonly used solvents. Cocaine was often back-extracted into

dilute acid and recycled with solvent as a purification step before

chrauatography. It was noted that the stability of cocaine in

hydrochloric acid greater than 0.5N was not reliable. The

degeneration of cocaine in biological samples in vitro by

hydrolysis was also cause for concern. Sodium fluoride, as

recommended by Jatlow et al. (1976), should be used as a

preservative to prevent this problem.

Quantitative analysis for cocaine and/or its metabolite was

generally achieved using gas chromatography and an internal

standard. At only four sites were other techniques employed:

ultraviolet spectrophotometry, 2; EMIT (R), 1; and GC-mass

spectrometry, 1. It is interesting that although GC-MS was

available at 12 of the 27 survey sites, it was used routinely at

only 1 for quantitative work, by multiple ion monitoring. The

instrument was used at all sites for specific, qualitative

identification purposes. Eight different internal standards were

in use: nalorphine, imipramine, mepivacaine, methaqualone,

cholestane, trihexyphenidyl, lidocaine and SKF-525A. The common

use of lidocaine as a "cutting agent" is a caution against its use

as an internal standard for cocaine analysis, and a number of

collaborators expressed dissatisfaction with SKF-525A due to

unpredictable variations in its extraction characteristics and its

susceptibility to thermal degradation during GC analysis.

Excellent critical reviews of available analytical methods, discussing their advantages and limitations, have been written by

Jatlow (1976) and Bastos and Hoffman (1976). The extraction

procedure followed by GC-MS qualitative and quantitative analysis

described and used by Hawks (Hawks et al., 1974; Mule, 1976) might

be considered state-of-the-art and is potentially useful for

toxicologists at almost half of the study laboratories. For those

with GC there are a number of published, proven methods;1the method

described by Jatlow and Bailey (1975) requires a nitrogen detector,

while Jain et al. (1977) described a procedure using a simple

derivatization technique which allows the use of flame ionization.

1Blake et al., 1974; Jain et al., 1977; Jatlow & Bailey, 1975;

Wallace et al., 1976.

169
Practical means for the analysis of cocaine and its primary metabolite are available and were in use at almost all of the study sites.

It is almost certain that at 22 of the 27 laboratories collaborating

in the study, cocaine involvement in a fatal case would have been

detected, especially since the advent of immunological testing in

1973-74. The high percentage of study cases in which cocaine was

suspected by the investigator or pathologist prior to toxicological

analysis adds to this confidence. Similarly, the credibility of

sites reporting no cocaine cases during the 5 to 6 year period is

also supported by this fact. Initial screening methods should be

capable of detecting less than 1.0 mcg/ml cocaine in blood, based on

known maximum blood concentrations following effective doses of the

drug and the number of study cases in which the blood level was less

than 1.0 mcg/ml.

FATAL BLOOD AND TISSUE CONCENNTRATIONS

As seen in Figure 8-3 above, 86 of the 111 study cases were

classified as drug-deaths; however, quantitative cocaine blood

concentrations were determined for only 53 of these. The distribution of these concentrations as a percentage of the drug-death cases

is shown in Figure 8-9 (one case = 1.9 percent of the total).

Almost three-quarters of the cases (70 percent) had blood concentrations lower than 4.0 mcg/ml, with one-third between 1.0 and 4.0

mcg/ml and 36 percent 1.0 mcg/ml or lower. Only 4 of the 53 cases

had blood levels higher than 10 mcg/ml, one of which had the

remarkably high value of 25-26 mcg/ml. The routes of administration

for this group were either intravenous or unknown.

Blood cocaine concentrations were reported for 23 of the 26 cases in

which only cocaine was involved (see Figure 8-10). Because of the

small number of cases, inferences must be cautious, but there is a

trend towards higher blood concentrations in these cases than in all

of the drug-death cases; 70 percent of all drug-deaths had concentrations lower than 4.0 mcg/ml, while among cases involving only

cocaine, 70 percent of the cases were not accounted for until

concentrations up to 9.0 mcg/ml are included. Similarly, only 7.5

percent of the total drug-deaths had blood levels higher than 10

mcg/ml, while among the cocaine-only deaths, 17.3 percent were

above this level.

In order to assess the significance of the blood concentrations in

fatal cases, reported values from controlled animal and human

clinical studies can be used for comparison. A regimen of injections which culminated in convulsions and death within 30 days for

monkeys, and the accompanying milligram/kg doses have been reported

by Deneau et al. (1969). Approximately 40 mgs of cocaine every 4

hours, with a maximum daily intake of 80-100 mgs/kg, precipitated

convulsions. Van Dyke et al. (1976) reported plasma concentrations

in the range 120-474 nanograms/ml which persisted for 4-6 hours for

humans receiving 1.5 mg/kg cocaine applied to their nasal mucosa,

and ‘similar data have been reported by Byck et al. (1976) in a

170
1 Case = 1.9%
1 Case = 4.3%
variety of human patients. The highest blood concentrations

reported for humans following "large" (100-200 mgs?) i.v. street

doses were in the range 3-7 mcg/ml, and for monkeys receiving 15

mgs/kg i.p., concentrations were 0.7-1.0 mcg/ml. Obviously, many

factors, such as the ability of an individual to hydrolyze cocaine

to benzoylecgonine by plasma cholinesterase, can affect these broad

estimated ranges. Jatlow et al. (1976) has reported possible

impairment of this metabolic pathway in succinylcholine sensitive

individuals, which could result in unusually elevated plasma cocaine concentrations.

Liver tissue concentrations of cocaine relative to blood levels

have been analyzed to determine whether blood:liver ratios are a

practical indicator of toxicity, making the liver a useful toxicological specimen, particularly since cocaine is one of the few drugs

which undergoes metabolism in blood with a halflife of approximately 1.5 hours. Data for the survey cases are shown in Figure 8-11.

Reliable determinations of both blood and liver concentrations were

available for only 15 cases. Blood concentrations were generally

higher than liver concentrations, with a reversal in only 5 of the

15 cases. Figure 8-11 suggests that blood analysis is more desirable. For cases involving only cocaine, the mean blood/liver ratio

was 1.4, and the blood concentration was higher than that of the

liver in all of these cases.

Only two other drugs, morphine and alcohol, were considered in

evaluating the significance of the toxicological findings in the

111 study cases. Morphine was detected in 28 cases, all of which

were classified as drug-deaths. Blood cocaine concentrations were

significantly lower in this subset than in either the survey cases

as a whole or the cocaine-only cases; all 28 were lower than 4.0

mcg/ml and almost 60 percent were between 1.0 and 4.0 mcg/ml. There

is little doubt that the presence of morphine was an important

factor in toxicity in these cases.

Although alcoholism and alcohol abuse were not prevalent in the

medical and psychiatric histories of the survey population, alcohol

was detected in 22 (25.6 percent) of the 86 drug-death cases. In

six of these (approximately 7 percent), the only substances detected were alcohol and cocaine. Blood alcohol concentrations for the

22 cases ranged from 0.02 to 0.43 percent. Quitting the 0.43

percent figure, the mean for the sample was 0.10 percent and the

median, 0.12 percent, concentrations which would cause significant

central nervous system depression and add to the adverse CNS effects

of cocaine. The presence of ethanol in pharmacologically effective

concentrations is important, but the generalization that alcohol in

combination with cocaine is a dominant or predictable factor in

cocaine-associated deaths is not justified.

There were only eight cases in which both alcohol and morphine in

addition to cocaine were detected in significant amounts.

173
FIGURE 8-11

174
FORENSIC PATHOLOGY

All but 2 (1 who died from natural causes and 1 from gunshot wounds)

of the 111 study cases were suspected by the pathologist and/or

investigator to involve drugs, and in no less than 100 cases cocaine

was anticipated. Of the 86 deaths classified as drug fatalities 90

percent were subject to a complete medico-legal autopsy and for 70

percent of the 86 the autopsy was carried out within 24 hours; 20

percent were performed within 6 hours of discovery or report of the

death. This prompt response by medical examiners and coroners is

particularly important because-of the potential in vitro degradation of cocaine. For those cases in which only cocaine was detected

86 percent were autopsied within 24 hours. The gross observations

by the pathologist at autopsy were generally non-specific, consisting almost uniformly of pulmonary edema, and massive pulmonary,

visceral and cerebral congestion. For the cocaine deaths a high

percentage showed evidence of recent intravenous self-administration correlating with the high incidence of i.v. drug use reported

for this group of victims by witnesses and investigators. In the

cases with an authenticated prior history of cocaine use the

pathologist obtained nasal swabs for analysis and carefully examined the nostrils, nasal cartilage, cavity and nasopharynx. It is

interesting that not one of the deceased had a perforated nasal

septum. It has been reported that Ear, Nose and Throat Surgeons at

Yale University School of Medicine and Hospital have never seen a

case of nasal necrosis resulting from cocaine use (cf., Barash,

Chapter 9 this volume). Apparently the incidence of perforated

nasal septum as an effect of intranasal cocaine use has been

exaggerated.

The pathologist’s microscopic study of autopsy specimen sections

were all either reported as unremarkable or confirmed the gross

observations.

FATALITIES INVOLVING NASAL ADMINISTRATION OF COCAINE

Of the 111 cases in the study, 8 reported "snorting," "sniffing

coke" or insufflation -- all nasal administrations -- as the route

of administration. Although cocaine was shown to be present, the

immediate cause of death in one of the eight cases was determined to

be due to factors other than drugs. Of the remaining seven cases,

cocaine was the only drug detected in two of these drug deaths. As

shown in Figure 8-6, this is 7.7 percent of the 26 cocaine-only

cases. The manners of death for the eight cases were classified as

follows: "Accidental (4), "Undetermined" (31, and "Natural" (1);

there were no suicides. Of the seven drug-caused deaths, two

involved cocaine alone; two involved only cocaine and lidocaine;

and three involved only cocaine and morphine (heroin).

175
Nasal swabs taken at autopsy were positive in one of the two

cocaine-only cases. For the two fatalities in which lidocaine was

detected, lidocaine had been used to "cut" the cocaine, and the

powdered mixture was sniffed. No medical treatment had been given

in these cases, eliminating the possibility that lidocaine had been

mistakenly administered to the victims as an emergency medical

measure. The Drug Enforcement Agency (DEA) reports that lidocaine

or procaine is sometimes mixed with heroin and/or cocaine for sale.

Consequently, finding these drugs or their metabolites in postmortem analysis does not differentiate the dose-form or

formulation, and it is virtually impossible to assign separate

toxicological significance to each of the drugs in any of the cases.

The post-mortem blood concentrations of cocaine were high, however,

ranging from 2.8 to 5.9 mcg/ml. There was only 1 case in the

nanogram range -- at 200 nanograms/ml. This is in sharp contrast to

reports that nasal administration of single doses between 20 and 40

mg results in maximum plasma concentrations of approximately 50-100

nanograms/ml (Byck et al., 1976) and doses as high as 1.5 mg/kg

provide peak concentrations of approximately 120 - 500 nanograms/ml

after 15-60 minutes (Van Dyke et al., 1976).

Although intravenous self-administration was the predominant route

in the survey cases, and only seven confirmed deaths were associated

with nasal insufflation, the data underscore the possibility of

achieving very high, toxic blood concentrations by nasal administration of the drug. Therefore, it cannot be assumed that use of

this route is a guarantee of safety.

SUMMARY AND CONCLUSIONS

This retrospective, collaborative study involved 27 medical

examiners’ and coroners’ offices from the United States and Canada.

The geographic area surveyed included 62.9 million individuals or

29.8 percent of the U.S. population and provided only 26 cases in

which cocaine was the only drug detected. This is not a large number, either absolutely or relative to the number of other drug

fatalities from, e.g., sedative-hypnotics, analgesics and opiate

narcotics. However, there is evidence that the number of cocaine

deaths is increasing.

There were a total of 111 sudden, unexplained deaths in which

cocaine was involved. Drugs were causative in 86 cases. (The full

spectrum of the 111 study fatalities included some accidental and

suicidal deaths from a variety of causes other than drugs. There

are 25 such cases.) The national picture of cocaine deaths is not

uniform and many cities and counties with major drug abuse problems

did not report any fatal cocaine cases. The incidence of cocaine

related deaths is not, therefore, predictable from geographic

characteristics.

176
The deceased population consisted predominantly of young, white

males, many with a record of opiate narcotic abuse. Most were less

than 30-years-old, males out-numbered females almost 3 to 1 and the

subjects were employed in a variety of blue-collar jobs at the time

of their deaths.

The 111 victims in the study were medically healthy prior to death

and without known significant psychiatric problems other than drug

abuse. Alcoholism and heavy use of tranquilizers were not evident,

although many of the subjects were certainly drinkers.

The manner of death for almost half of the deceased was classified

as accidental and for approximately a quarter, as undetermined.

Suicides were rare.

There were a significant number of heroin users among the victims,

as indicated by case histories, route of administration of the drug

and post-mortem toxicological data; 35.3 percent had a history of

heroin use, 61.5 percent of the cases involved only cocaine and 30.0

percent of the drug combination deaths involved the intravenous

route. Morphine was detected analytically in one-third of the 86

drug-deaths.

Lidocaine was occasionally detected analytically and was apparently

used as a "cutting agent" for cocaine. Alcohol was present in

significant concentrations in about one-quarter of the drug-deaths

with a mean blood value of 0.1 percent.

Fatal toxicity from cocaine is rapid, with extremely fast onset of

symptoms. Two-thirds of the victims died in less than five hours

and one-third within the first hour following ingestion of the drug.

There is no evidence from the study that any particular route of

administration played a dominant role with respect to survival

time. Terminal symptoms, when observed, were CNS-mediated and

generally involved seizures followed by respiratory arrest.

Analytical toxicological methods adequate for detection and quantitative determination of cocaine and/or its primary metabolites in

post-mortem biological specimens were available at all laboratories. Immunological techniques (EMIT(R)) an gas chromatography

following solvent extraction or column chromatography separation,

were the most common. Sensitivity limits for a 5 ml blood sample

were generally in the range 1.0-2.0 μg/ml of cocaine. Benzoylecgonine was never analyzed quantitatively.

In 70 percent of the 86 drug-death cases the blood concentrations of

cocaine were lower than 4.0 mcg/ml and in more than one-third they

were 1.0 mcg/ml or lower. For fatalities involving only cocaine, 70

percent of the cases had blood concentrations lower than 9.0 mcg/ml.

Blood concentrations were generally higher than corresponding liver

tissue values, confirming blood as the sample of first choice for

analysis, although the in vitro instability of cocaine, requires

that the blood sample be preserved by sodium fluoride.

177
Cocaine involvement was suspected in most of the study cases by the

investigator or pathologist prior to analysis. Complete and prompt

autopsies were performed, often including examination of nasal

passages. No instance of perforated nasal septums was found. With

the exception of injection sites, gross observations and microscopic findings were unremarkable and without diagnostic character.

For seven of the study cases classified as drug-caused deaths it was

established that the cocaine was ingested intranasally. The blood

concentrations in six of these cases were very high: 2.8-5.9

mcg/ml, one case had the minimum concentration of 200 nanograms/ml.

The overall study findings and these seven cases in particular

clearly refute the assumption that nasal insufflation of cocaine is

completely safe. There is no pharmacological or toxicological

rationale to suggest that toxic circulatory system concentrations

of the drug cannot be achieved by this route.

This report should not be construed as an assessment of cocaine use

in the U.S.A. and Canada. Aside from the fact that this was not the

purpose of the study, the deceased population does not reflect

general use of the drug. Notwithstanding this limitation, the study

does indicate that drug abusers are dying from the use of cocaine

either alone or, more commonly, in combination with morphine.

Bryan S. Finkle, Ph.D. and

Kevin L. McCloskey, Ph.D.

Center for Human Toxicology

University of Utah

Salt Lake City, Utah

178
ACKNOWLEDGMENTS

It would not have been possible to conduct this study without the generous,

professional support of many Forensic Scientists, and also librarians, technical

and clerical staff at each of the laboratory survey sites. The work and contributions of the following individuals are gratefully acknowledged:

Alabama State

Alameda County, California

Clark County, Nevada

Cook County, Illinois

Dade County, Florida

Dallas County, Texas

Hennepin County, Minnesota

Illinois State

Los Angeles County, California

Maryland State

Minnesota State

Montreal, Province of Quebec

New Mexico State

New York State

N. Carolina State

Orange County, California

Oregon State

Philadelphia County, Penn.

Rhode Island State

San Diego County, California

San Francisco County,

California

St. Louis, Missouri County

Toronto, Province of Ontario

Utah State

Vancouver, British Columbia

Washington, D.C.

Wayne County, Detroit, Mich.

June K. Jones

Philip Reynolds &

Allan B. McNie

Thorne J. Butler

George N. Christopoulos

Arthur J. Fisk

James C. Garriott

Robert DeGregory

John J. Spikes

George R. Nakamura &

Thomas T. Noguchi

Yale H. Caplah

Lowell C. VacBerkom

Jean Jacques Rousseau

Jimmy C. Standefer

Milton L. Bastos

Arthur J. McBay &

R. Page Hudson

Robert H. Cravey

John P. Aitchison

Jane H. Speaker

Richard J. Bushee, Jr.

& William Q. Sturner

Richard F. Shaw

James A. Wright &

Boyd G. Stephens

George E. Gantner

George Cimbura &

Douglas M. Lucas

Ladislav Kopjak

Edwin J. Fennel1 &

Mel Y.W. Yip

Robert F. Reisch &

James L. Luke

Joseph R. Monforte &

Werner U. Spitz

Forensic Toxicologist

Forensic Toxicologist

Forensic Pathologist

Forensic Pathologist

& Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Pathologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Pathologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Pathologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Pathologist

Forensic Pathologist

Forensic Toxicologist

Laboratory Director

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Toxicologist

Forensic Pathologist

Forensic Toxicologist

Forensic Pathologist

B.S.F.

K.L. McC.

179
Appendix A

DATA COLLECTION INSTRUMENT

From Chapter 8, The Forensic Toxicology of Cocaine

The following instrument was used by Drs. Finkle and

McCloskey to gather information on analytical toxicology and laboratory procedures during their study of the incidence of cocainerelated deaths in 27 U.S. and Canadian sites over the past five

to six years.

180
APPENDIX A

Chapter 8

The Forensic TOxicology

CENTER FOR HUMAN TOXICOLOGY - COCAINE DRUG STUDY of Cocaine

DATA COLLECTION INSTRUMENT

ANALYTICAL TOXICOLOGY - METHODOLOGY

DRUG: COCAINE (CURRENT) OBTAIN COPY OF PROCEDURE

METHOD OF EXTRACTION (BLOOD & TISSUES)

METHOD OF IOENTIFICATION

METHOD OF QUANTITATION

LIMIT OF SENSITIVITY

PRECISION ACCURACY RECOVERY

CHANGES IN METHODS: NOTE ALL METHODS USED BETWEEN 1971 - 1976

IS COCAINE INCLUDED IN INITIAL SCREEN ANALYSIS

DESCRIBED SCREEN PROCEDURE OBTAIN COPY

LAB. FACILITIES:

SPACE STAFF

CAPITAL EQUIPMENT (DATES) 

181
Appendix B

FORM AND DATA CODES

From Chapter 8, The Forensic Toxicology of Cocaine

The following instruments were used by Drs. Finkle and

McCloskey to record individual case data, including definitions for

each question and alpha-numeric coded answers, during their study

of the incidence of cocaine-related deaths over the past five to six

years in 27 U.S. and Canadian study sites.

182
Appendix B

Survey Form

Official Cause of Death

History of Deceased

Circumstances of Death

Pathology and Toxicology

Data codes

1.

2.

3 .

4.

5 .

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18:

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36.

Manner

Cause of Death, Drug

Cause of Death, Cocaine

Occupation

Age

Sex

Race

Weight

Medical History

Specific (medical history)

Psychiatric History

Specific (psychiatric history)

Cocaine

Source

Route

Other Drugs

Location

Time Last Seen Alive or With

Drugs

Suicide Incidence

Specific (suicide evidence)

Terminal Symptoms

Type (of terminal symptoms)

Specific (terminal symptoms)

Treatment (immediately prior to

death)

Type (of treatment)

Drugs (used in treatment)

Autopsy

Time (between death and autopsy)

Specimen Conditions

Blood Source

Approximate Cause of Death

Gross

Microscopic (findings)

Cocaine only

Ethyl Alcohol

Cocaine and Ethyl Alcohol

183
CENTER FOR HUMAN TOXICOLOGY

NATIONAL DRUG SURVEY

APPENDIX B

Chapter 8

CHT No.

AGENCY No.

YEAR OF DEATH.

OFFICIAL C. 0. D.

1. MANNER

4. OCCUP.

5. AGE

6. SEX

2. C.O.D., DRUGS 3 . C.O.D., COCAINE

HX OF DECEASED

7. RACE 11. PSYCH. HX.

8. WT. 12. SPECIFIC

9. MED. HX.

10. SPECIFIC

CIRCUMSTANCES OF DEATH

13. COCAINE 18. TIME(L.S.A-D) 23. SPECIFIC

14. SOURCE 19. SUIC. INDIC.

15. ROUTE 20. SPECIFIC 24. TREATM.

16. OTHER DRUGS 21. TERM. SYMP. 25. TYPE

17. LOCATION 22. TERM. SYMP. TYPE 26. DRUGS

PATHOLOGY & TOXICOLOGY*

27. AUTOP. 31. APPR. C.O.D. 35. ETOH

28. TIME(D.-A.) 32. GROSS 36. COCAINE & ETOH

29. SPEC. COND. 33. MICRO

30. BLD. SOURCE 34. COCAINE ONLY

-----------------------------------------------

(mgs)+ DRUG BLOOD LIVER URINE BILE G. CTN.

COCAINE

ALCOHOL

*CONCENTRATION IN MICROGRAMS/ML OR MICROGRAMS/GM.

+G. CTN = TOTAL WT. OF DRUG IN MGS

184
APPFNDIX B, cont'd.

Chapter 8

DATA CODES The Forensic Toxicology

of Cocaine

OFFICIAL C.O.D. (CAUSE OF DEATH): Official Cause of Death as stated on final

Death Certificate. If unknown, write U.

1. MANNER: Officially determined manner of death as stated on final Death

Certificate.

CODE: S = SUICIDE

A = ACCIDENT

N = NATURAL

H = HOMICIDE

U = UNDETERMINED

2. C.O.D., DRUGS: Are drugs mentioned in official C.O.D.

CODE: Y = YES

N = NO

U = C.O.D. UNKNOWN

3 . C.O.D., COCAINE: Is Cocaine specifically mentioned in official C.O.D.

CODE: Y = YES

N = NO

U = UNKNOWN

4. Occup.: Occupation of the deceased. Select one - -

CODE: 01 = BLUE COLLAR WORKER OR MANUAL LABOR

02 = CLERICAL

03 = HOUSEWIFE

04 = STUDENT

05 = PROFESSIONAL

06 = PARAMEDICAL (e.g. NURSE, NURSE'S AID. HOSP. ORDERLY,

LAB. TECH.)

07 = MILITARY

08 = RETIRED

09 = UNEMPLOYED

10 = OTHER

11 = UNKNOWN

5. AGE: Age of Deceased.

CODE: 01 = 0-5 YEARS OF AGE

02 = 6-10

03 = 11-15

04 = 16-20

05 = 21-25

06 = 26-30

07 = 31-35

08 = 36-40

09 = 41-45 YEARS OF AGE

10 = 46-50

1 1 = 51-55

12 = 56-60

13 = 61-65

14 = > 65

15 = UNKNOWN

6 . Sex: Sex of Deceased.

CODE: M = MALE

F = FEMALE

U = UNKNOWN

185
7. RACE: Ethnic origin of Deceased.

CODE: C = CAUCASIAN

B = BLACK

A = ASIAN - AMERICAN

S = SPANISH SURNAME

N = NATIVE AMERICAN

U = UNKNOWN

8. WT: Body weight of Deceased.

CODE: 01 = 0.50 lbs

02 = 51-100 lbs

03 = 101-150 lbs

04 = 151-200 lbs

05 = > 200 lbs

06 = UNKNOWN

9. MED. HX.:

10. SPECIFIC:

Pertinent medical history of the deceased relative to the

cause of death.

CODE: Y = DECEASED HAD RECENT MEDICAL HISTORY.

N = NO PERTINENT MEDICAL HISTORY KNOWN.

Specify particulars of medical history. Select one or more

categories.

CODE: 0 1 =

0 2 =

0 3 =

0 4 =

0 5 =

06 =

07 =

08 =

0 9 =

1 0 =

11 =

12 =

1 4

13 =

=

1 5 =

RECENT HOSPITALIZATION (INCLUDES REST HOMES)

RECENT SURGERY

RECENT DENTAL PROCEDURES

RECENT PROCEDURE REQUIRING ANESTHETIC

RECENT INJURY OR CHRONIC ILLNESS (e.g. TRAUMA, MUSCULAR

INVALID OR SKELETAL INJURY)

GASTROINTESTINAL HX.

CARDIOVASCULAR HX.

DRUG ABUSE TREATMENT

EPILEPSY

PREGNANCY

OTHER

UNKNOWN

CARCINOMA

DIABETES

11. PSYCH. HX: Indications of recent psychiatric or emotional disturbances of

the deceased, as defined by categories listed in Number 12.

CODE: Y = INDICATIONS WERE PRESENT

N = NO INDICATIONS PRESENT

12. SPECIFIC: Specific indications of recent emotional disturbances. Select

one or more categories.

CODE: 01 = RECENT OR CHRONIC PSYCHIATRIC TREATMENT

02 = RECENT DESPONDENCY

03 = PRIOR SUICIDE ATTEMPTS

04 = COCAINE USE MEDICAL

05 = HEROIN ABUSE (e.g. PARAPHERNALIA FOUND, METHADONE

MAINTENANCE, ETC.)

06 = COCAINE ABUSE (e.g. NON-MEDICAL SELF-MEDICATION,

'RECREATIONAL')

07 = PSYCHOTROPIC ABUSE (LSD, PCP, MARIJUANA, ETC.)

08 = ALCOHOL ABUSE OR MISUSE

09 = GENERAL OR UNSPECIFIED DRUG MISUSE OR ABUSE

(SEDATIVES, AMPHETAMINE, ETC.)

186
12. SPECIFIC (Cont'd)

CODE: 10 = MENTAL RETARDATION OR NEUROLOGICAL IMPAIRMENT

11 = OTHER INDICATIONS

12 = OLD NEEDLE TRACKS

13. COCAINE: Cocaine was known to be available to the deceased.

CODE: Y = WAS AVAILABLE

N = NO INDICATIONS OF AVAILABILITY

14. SOURCE: Origin of the cocaine available to deceased.

CODE: P = PRESCRIPTION OF DECEASED

0 = PRESCRIPTION FOR SOMEONE OTHER THAN THE DECEASED

I = ILLICITLY OBTAINED

U = UNKNOWN

15. ROUTE: Apparent route of administration for cocaine used by deceased.

CODE: 0 = ORAL

V = INTRAVENOUS

M = INTRAMUSCULAR

S = NASAL

T = OTHER

U = UNKNOWN

16. OTHER DRUGS: Other medications known to be available to the deceased.

Select one or more.

CODE: 01 = LIBRIUM

02 = ELAVIL

03 = MELLARIL

04 = TRIAVIL

0 5 = MILTOWN

0 6 = THORAZINE

0 7 = DALMANE

0 8 = SECONAL

0 9 = NEMBUTAL

10 = CHLORAL HYDRATE

11 = TUTNAL

12 = PHENOBARBITAL

13 = PLACIDYL

14 = PROPOXYPHENE

17. LOCATION: Location where the deceased expired.

15 =

16 =

17 =

18 =

19 =

2 0 =

21 =

22 =

2 3 =

2 4 =

2 5 =

2 6 =

27 =

UNSPECIFIED BARBITURATES

DORIDEN

APC & CODEINE

PENICILLIN

DRUGS OF ABUSE (e.g. LSD,

MARIJUANA, PCP. ETC.)

OTHERS

UNKNOWN

METHAQUALONE

METHADONE

EQUANIL

TRANXENE

VISTARIL

HYDROXYZINE

CODE: 01 = RESIDENCE (HOUSE OR APARTMENT) 05 = HOSPITAL

02 = MOTEL OR HOTEL 06 = OUT-OF-DOORS

0 3 = AUTOMOBILE 0 7 = OTHER

0 4 = REST HOME 08 = UNKNOWN

187
18. TIME (LSA-D): Estimate of time interval between 'last seen alive' or

when drugs were ingested and death.

CODE: O1= 0.0 -

02 =

03 =

04 = 1.1 -

05 =

0.25 -

0.51 -

2.1 -

3.1 -

4.1 -

5.1 -

6.1 -

7.1 -

8.1 -

9.1 -

(also 'overnight')

0.25 hr 13 = 10.1 - 11.0 hr

0.50 hr 14 = 11.1 - 12.0 hr

1.0 hr 15 = 12.1 - 13.0 hr

2.0 hr 16 = 13.1 - 14.0 hr

3.0 hr 17 = 14.1 - 15.0 hr

4.0 hr 18 = 15.1 - 16.0 hr

5.0 hr 19 = 16.1 - 17.0 hr

6.0 hr 20 = 17.1 - 18.0 hr

7.0 hr 21 = 18.1 - 24.0 hr

8.0 hr 22 = 24.1 - 72 hrs

9.0 hr 23 > 72 hrs

10.0 hr 24 = UNKNOWN

25 = HOSPITALIZATION

06 =

0 7 =

08 =

09 =

10 =

1 1 =

1 2 =

, >24 hr

19. SUIC. INDIC: Indications that death may have been a suicide.

CODE: Y = INDICATIONS PRESENT

N = NO INDICATIONS

20. SPECIFIC: Specific evidence of suicide. Select one or more.

CODE: N = SUICIDE NOTE

S = VERBAL STATEMENTS

A = ACTIONS (e.g. CUT WRISTS, HIDING. ETC.)

P = PRIOR ATTEMPTS

21. TERM. SYMP: Presence of symptoms relative to drug ingestion observed

in the deceased prior to death.

CODE: Y = SYMPTOMS WERE OBSERVED

N = NO SYMPTOMS OBSERVED

22.

23.

TYPE:

SPECIFIC:

Specify type of terminal symptoms observed. Select one or more.

CODE: C = INVOLVED CNS

V = INVOLVED CARDIOVASCULAR SYSTEM

P = PERIPHERAL MANIFESTATIONS

Specific terminal symptoms observed. Select one or more.

CODE: 01 = COMA

02 = RESPIRATORY ARREST

03 = CARDIAC ARREST

04 = SEIZURES

05 = INTOXICATION (e.g. DISORIENTATION. ATAXIA.

SLURRED SPEECH. ETC.)

06 = CARDIOVASCULAR COLLAPSE

07 = SYNCOPE

08 = VOMITING

09 = HALLUCINATIONS

10 = OTHER

24. TREATM.: Deceased received emergency medical treatment immediately

prior to death.

CODE: Y = DECEASED RECEIVED TREATMENT

N = NO RECORD OF DECEASED RECEIVING TREATMENT

188
25. TYPE: Type of emergency treatment received by deceased.

Select one or more.

CODE: 01 = CARDIOPULMONARY RESUSCITATION (CPR)

02 = DEFIBRILLATION

03 = CLOSED CHEST MASSAGE

04 = RESPIRATORY ASSISTANCE

05 = GASTRIC IRRIGATION

06 = DIALYSIS

07 = OTHER

08 = UNKNOWN

26. DRUGS: Drugs used in the course of emergency treatment.

Select one or more.

CODE: 01 = VALIUM

02 = LIDOCAINE

03 = NARCAN

04 = ISUPREL

05 = EPINEPHRINE, PHENYLEPHRINE

06 = CARBONATE

07 = OTHER

08 = UNKNOWN

27. AUTOP.: Type of autopsy performed.

CODE: C = COMPLETE

P = PARTIAL

E = EXTERNAL ONLY

U = UNKNOWN

28. TIME (D-A): Time interval between death and autopsy.

CODE: 01 = O-6 hrs

02 = 7-12 hrs

03 = 13-18 hrs

04 = 19-24 hrs

05 = 25-48 hrs

06 = > 48 hrs

07 = UNKNOWN

29. SPEC. COND.: Condition of tissues and blood specimens.

CODE: F = FRESH

D = DECOMPOSED

E = EMBALMED

U = UNKNOWN

30. BLD. SOURCE: Site from which blood sample was collected.

CODE: J = JUGULAR

H = HEART OR GREAT VEINS

0 = OTHER PERIPHERAL SITE

F = FEMORAL

U = UNKNOWN

189
31. APPR. C.O.D.: Immediate suspected cause of death.

CODE: D = DRUG(S) OVERDOSE

N = NATURAL (DISEASE)

T = TRAUMA (e.g. STRANGULATION, AUTO ACCIDENT, CRUSHING,

BLOOD LOSS. BURNS, DROWNING, ETC.)

G = GUNSHOT WOUNDS

S = STABBING

E = ELECTROCUTION

0 = OTHER

U = UNKNOWN

32. Gross: Gross autopsy findings. Select one or more.

CODE: 01 = PULMONARY EDEMA & CONGESTION

02 = VISCERAL EDEMA & CONGESTION

03 = CEREBRAL EDEMA & CONGESTION

04 = MEDICATIONS IN GASTRIC CONTENTS

33. MICRO:

0 5 =

06 =

0 7 =

08 =

09 =

10 =

11 =

12 =

13 =

14 =

Microscopic

CODE: 01 =

02 =

03 =

04 =

ASPIRATION OF VOMITUS

INTERNAL INJURIES

'NEEDLE TRACKS'

'SUICIDE SCARS'

INDICATIONS OF DISEASE PROCESS

UNKNOWN OR NOT PERFORMED

VISCERAL CONGESTION

TRAUMA

UNREMARKABLE

CHEMICAL GASTRITIS

and bacteriological findings.

UNREMARKABLE

CONFIRMS GROSS FINDINGS

INDICATIONS OF DISEASE PROCESS NOT SUSPECTED

FROM GROSS AUTOPSY

UNKNOWN OR NOT PERFORMED

34. COCAINE ONLY: Laboratory analysis for cocaine and other drugs.

CODE: Y = ONLY COCAINE FOUND

N = OTHER DRUGS (INCLUDING ALCOHOL) WERE FOUND

35. ETOH: Laboratory analysis for ethyl alcohol

CODE: Y = ALCOHOL WAS PRESENT

N = ALCOHOL WAS NOT PRESENT

36. COCAINE & ETOH: Laboratory analysis for cocaine and ethyl alcohol.

CODE: Y = ONLY COCAINE AND ALCOHOL FOUND

N = EITHER COCAINE ALONE OR COCAINE IN

COMBINATION WITH DRUGS OTHER THAN ALCOHOL.

190
REFERENCES

Forensic Toxicology

Ashley, R. Cocaine: Its History, Uses and

St. Martin's Press, 1975.

Effects. New York, NY:

Bastos, M.L. and Hoffman, D.B. Detection and identification of

cocaine, its metabolites and its derivatives. In Mule, S.J.

(ed.), Cocaine: Chemical, Biological, Social, and Treatment

Aspects. Cleveland, OH: CRC Press, 1977, pp. 33-58.

Blake, J.W., Ray, R.S., Noonan, J.S. and Murdick, P.W. Rapid,

sensitive gas-liquid chranatographic screening procedure for

cocaine. Analytical Chemistry, 46(2):288 (1974).

Byck, R., Jatlow, P., Barash, P. and Van Dyke, C. Cocaine: Blood

concentration and physiological effect after intranasal application in man. In Ellinwood, E.H. and Kilbey, M.M. (eds.),

Cocaine and Other Stimulants. New York, NY: Plenum Press,

1977, pp. 629-646.

Deneau, C.W., Yanagita, T. and Seevers, M.H. Self-administration

of psychoactive substances by the monkey: A measure of

psychological dependence. Psychopharmacologia, 16:30-48

(1969).

De Vito, J.J. Cocaine Intoxication. Medical Times, 103(10):189

(1975).

Gay, G.R., Inaba, D.S., Sheppard, C.W. and Newmyer, J.A. Cocaine:

History, epidemiology, human pharmacology and treatment. A

perspective on a new debut for an old girl. Clinical Toxicology, 8(2):149-178 (1975).

Goodman, L.S. and Gilman, A. The Pharmacological Basis of Therapeutics. 5th Ed. New York, NY: Macmillan, 1975.

Hawks, R.L., Kopin, I.J., Colburn, R.W. and Thoa, N.B. Norcocaine:

A pharmacologically active metabolite of cocaine found in

brain. Life Sciences, 15:2189-2195 (1974).

Jain, N.C., Chinn, D.M., Budd, R.D., Sneath, T.S. and Leung, W.J.

Simultaneous determination of cocaine and benzoylecgonine in

urine by gas chromatography using "on-colunm" alkylation.

Journal of Forensic Sciences, 22(1):7-16 (1977).

Jatlow, P. Analysis of cocaine and its metabolites in biological

fluids. In Mule, S.J. (ed.) Cocaine: Chemical, Biological,

Social, and Treatment Aspects. Cleveland, OH: CRC Press,

1977, pp. 59-70.

191
Jatlow, P., Barash, P.G., Van Dyke, C. and Byck, R. Impaired hydrolysis of cocaine in plasma from succinylcholine sensitive

individuals. Clinical Research, 23(3):255A (1976).

Jatlow, P.I. and Bailey, D.N. Gas chromatographic analysis analysis for cocaine in human plasma, with use of a nitrogen

detector. Clinical Chemistry, 21(13):1918 (1975).

Mattison, J.B. Cocaine poisoning. Medical and Surgical Reporter,

65:645 (1891).

Mayer, E. The toxic effects following the use of local anesthetics. Journal of the American Medical Association, 82:8 76-

885 (1924).

Mule, S.J. (ed.) Cocaine: Chemical, Biological, Social, and

Treatment Aspects. Cleveland, OH: CRC Press, 1977.

Pickett, R.D. Acute toxicity of heroin alone and in combination

with cocaine or quinine. British Journal of Pharmacology,

40:145 (1970).

Price, K.R. Fatal cocaine poisoning. Journal of the Forensic Science Society, 14(4):329 (1974).

Van Dyke, C. and Byck, R. Cocaine: 1884-1974. In Ellinwood, E.H.

and Kilbey, M.M. (eds.), Cocaine and Other Stimulants. New

York, NY: Plenum Press, 1977, pp. 1-30.

Van Dyke, C., Barash, P.G., Jatlow, P. and Byck, R. Cocaine:

Plasma concentrations after intranasal application in man.

Science, 191:859-861 (1976).

Wallace, J.E., Hamilton, H.E., King, D.E., Bason, D.J., Schwertner,

H.A. and Harris, S.C. Gas-liquid chromatographic determination of cocaine and benzoylecgonine in urine. Analytical

Chemistry, 48(1):34-38 (1976).

Webster, R.W. Legal Medicine and Toxicology, Philadelphia, PA:

Saunders, 1930.

Wright-St. Clair, R.E. Poison or medicine. New Zealand Medical

Journal, 71:224 (1970).

192
Chapter IX

COCAINE IN CLINICAL MEDICINE

Paul G. Barash, M.D.

Cocaine has been used in medical practice for centuries. Although

the South American Incas, 800-1200 years ago, probably used

cocaine-filled saliva for such complex neurosurgical procedures as

trephinization (Gay, 1975), the local anesthetic effects were

largely ignored until the 19th century. In the period of 24 years,

from 1860-1884, a series of events ushered in one of the greatest

medical discoveries of the century (Becker, 1963): Alfred Niemann

(1860) extracted the active principle, an alkaloid, and named it

cocaine. Von Anrep (1879), commenting on cocaine’s possible

medical application, noted its anesthetic effect following topical

application (tongue) and infiltration (skin). However, it took

Carl Koller (1884), a young ophthalmologist who had spent years

searching for a local anesthetic for eye surgery, to realize the

enormous contribution cocaine could make to anesthesia and surgery.

Following Keller’s discovery, Jellinek (1884) demonstrated

cocaine’s unique qualities, as a topical anesthetic and vasoconstrictor of the upper and lower respiratory tract. In short

order, Halsted (1885) demonstrated the use of cocaine for nerve

block anesthesia, Corning (1885) used cocaine for peridural anesthesia, and Quincke (1898) induced spinal anesthesia with cocaine.

With the synthesis of procaine in 1905, newer, less toxic agents

supplemented cocaine. However, nearly a century after its introduction to modern clinical medicine, cocaine continues to be the

only drug capable of causing both intense vasoconstriction and

local anesthesia. The resurgence of research in the physiology and

pharmacology of cocaine offers the 20th century clinician a unique

opportunity to have an important drug impartially m-evaluated.

INDICATIONS

The only currently accepted indication for the use of cocaine is as

a topical local anesthetic and vasooonstrictor of mucous membranes

(Local Anesthetics, 1973; Ritchie, et al., 1970). (Local anesthesia is defined as the reversible loss of sensation in a circumscribed area. Topical anesthesia is produced by surface application of the local anesthetic agent.) Cocaine is applied when

anesthesia and vasoconstriction of the nose, throat, larynx and

lower respiratory passages are required. Without vasoconstriction,

193
blood loss may be considerable from the highly vascular areas of the

respiratory tract. Further, bleeding obscures the operative field,

and may thus render surgery difficult.

Cocaine is no longer recommended for use as an ophthalmologic

anesthetic because repeated use may be followed by the toxic effects

of clouding, pitting and ulceration of the cornea; these are further

aggravated by the concomitant loss of the normal protective ocular

reflexes.

DOSAGE

Upper limits for the dose of cocaine vary and are somewhat arbitrary. Despite the fact that the AMA Drug Evaluation Handbook

(Local Anesthetics, 1973) suggests a maximum dose of 1 mg/kg,

standard reference textbooks in pharmacology and anesthesia indicate that the maximal safe dose is 200 mg (= 3mg/kg). Reports of

lethal dosages in medical practice range from 22 mg (submucosal

injection) to 2,500 mg (subcutaneous injection) (Van Dyke & Byck,

1977).

A consensus emerges from the literature: solutions of cocaine more

concentrated than 20 percent should not be used (Ritchie et al.,

1970; Reynolds, 1972). Further, 5-10 percent solutions appear more

appropriate and minimize the potential of toxic reactions (Campbell

& Adriani, 1958). Corssen (1973) using cultured human respiratory

epithelim, demonstrated that 10 percent cocaine solution causes

reversible cessation of ciliary activity (A similar effect was

noted with five percent lidocaine.) If a four percent cocaine

solution is used, the latent period (time from application to onset

of anesthesia and vasoconstriction) is 4.0 minutes and the duration

is 10.2 minutes; with a 10 percent solution latency decreases to 2.0

minutes but duration of action increases to 31.5 minutes (Adriani et

al., 1964). Von Dyke and others have demonstrated plasma cocaine

concentrations peak within 60 minutes after mucosal application and

can persist in the plasma for 180-360 minutes (Van Dyke et al.,

1976).

Many factors affect selection of the appropriate dose for a given

patient. No absolute dose range can be unequivocally recommended

since tolerance varies from patient to patient depending on such

factors as physiologic status and the ability to metabolize and

excrete the drug. Since cocaine is usually applied to the highly

vascular areas of the upper and lower respiratory tract, rapid

intravascular absorption oan occur. Thus more dilute solutions (5-

10 percent cocaine) should be used if large areas are to be

anesthetized. Patients with a decreased cardiovascular and metabolic reserve (elderly and debilitated) should have the dose

1As discussed in Ritchie et al., 1970; Pharmacology of drugs used

in local analgesia, 1973; Dripps et al., 1972.

194
reduced appropriately. Recently Jatlow et al. (1976) demonstrated

in vitro that serum of patients with pseudocholinesterase

deficiency are unable to metabolize cocaine. Until further in vivo

information is available, caution should be used in administering

cocaine to this group of patients.

When patients are receiving a number of drugs simultaneously, drug

interaction with cocaine can be potentially lethal. Since cocaine

interferes with the re-uptake of norepinephrine and potentiates the

effects of exogenous catecholamines, it should be used with caution

in patients receiving tricyclic antidepressants, reserpine, and the

monoamine oxidase inhibitors guanethidine, methyldopa and dopamine

(Smith, 1973; Davis et al., 1973). The interaction of cocaine with

general anesthetics in humans is not well documented. Orr, using

thiopental anesthesia with topical cocaine for laryngoscopy,

reported that 7/20 patients had significant ectopic ventricular

arrhythmias: 3 required intravenous propanolol for reversion to

sinus rhythm (Orr & Jones, 1968). However, not only was this study

poorly controlled, but the hypercarbia that was present may have

caused the arrhythmias.

Recently, two reports demonstrated the relative safety of cocaine

in conjunction with halothane, a widely used potent inhalation

anesthetic which sensitizes the myocardium to catecholamines.

Anderton observed atrial and ventricular extrasystoles in 2/45

patients following topical application of 35 mg cocaine for nasal

surgery (Anderton & Nassar, 1975). The arrhythmias resolved in 10

minutes without requiring any specific treatment. For the entire

group, no significant changes in pulse rate or systolic blood

pressure were observed. Van Dyke and colleagues (1976), using

cocaine for topical vasoconstriction in patients with acquired

organic heart disease, noted no significant adverse effects.

Simultaneous administration of epinephrine, as "cocaine mud"

(cocaine flakes and 1:1000 epinephrine) to potentiate the already

present intense vasoconstriction is extremely hazardous and has

been condemned (Smith, 1973; Myer, 1924; Schenk, 1975). Anderton

and Nassar (1975) have shown in a double blind study that doses as

low as 20-50 mg produce excellent surgical conditions and were

associated with minimal blood loss during surgery. Cocaine should

probably be avoided when hypermetabolic disease states such as

hyperthyroidism or pheochromocytoma are present Parenthetically,

if premeditation is required, diazepam (Valium(R)) might be an excellent choice, since it elevates the threshold for seizure

activity and thus may exert some protective effect if an actual or

relative overdose is administered (DeJong & Heavner, 1971, 1974).

ADVERSE SYSTEMIC REACTIONS

Contrary to popular opinion, most untoward reactions to local

anesthetics are not due to allergy. In a recent review of the world

literature Van Dyke and Byck (in press) were unable to find a single

documented case of anaphylactic response to cocaine. Although

195
poorly documented, the report by Dripps et al. (1972) described an

anaphylactic reaction in a patient with multiple allergies who

developed bronchospasm and cardiac arrest following topical application of cocaine. Moore (1969) has stated that 98 percent of toxic

reactions to local anesthetics are caused by intravascular injection or rapid absorption of the drug. Thus, toxic reactions to

cocaine are apparently due to: 1) overdose (actual or relative), 2)

rapid intravascular absorption or 3) allergy (extremely rare).

Systemic reactions to cocaine are manifested by signs of adrenergic

stimulation of the cardiovascular and central nervous systems.

These can be divided into progressive stages.1 In the first stage,

(early stimulation) euphoria gives way to cortical stimulation

manifested by excitement, emotional lability, restlessness and

apprehension. Nausea and vomiting with abdominal pain may ensue,

and finally muscular twitching is noted. Stimulation of the

cardiovascular system parallels these neurological findings. As a

result of medullary stimulation, there 'appear hypertension, tachycardia and skin pallor. Further stimulation of the central nervous

system is manifested in tonic and clonic seizures. The sympathetic

cardiovascular response is followed by ventricular arrhythmias. As

a result of the central nervous system dysfunction, respiratory

involvement occurs. An increase in rate and depth of breathing are

followed by dyspnea and cyanosis. As respiratory failure occurs in

the final stage (pre-morbid depression), unconsciousness occurs,

followed by loss of reflexes, blood pressure and pulse. As a result

of hypoxia, ventricular arrythmias continue and circulatory failure

ensues.

HOSPITAL TREATMENT OF COCAINE TOXICITY

Treatment is directed at prevention. First, the recommended guidelines with modification of dose for the individual patients should

be used. Second, cocaine should be used in situations where personnel experienced in resuscitation and basic life support are available.2

Preparation is the key to successful resuscitation. Basic equipment

required includes:

1) AMBU(R) positive pressure ventilation unit with appropriate size face masks and oropharyngeal airways.

2) Oxygen

3) Suction

4) A stretcher capable of Trendlenberg positioning.

5) EKG monitor and defibrillator

1As discussed in Gay et al., 1975; Ritchie et al., 1970; American

Medical Association, 1973.

2Moser, R.H. (ed.) Standards for cardiopulmonary resuscitation

(CPR) and emergency cardiac care (ECC). JAMA, 227 (suppl):835-886

196
6) Intravenous infusion

7) Medications.1

When an adverse reaction occurs, clear any possible airway obstruction and institute positive pressure ventilation with the

AMBU(R) bag. If supplemental oxygen is avilable, use it. Place

the patient in Trendlenberg position (30° head down) to augment

venous return to the heart and facilitate suctioning of the airway

to prevent aspiration.

are noted, administer diazepam (Valium(R)) 2.5-5.0 mg, or secoAs central nervous system manifestations

barbital (Seconal(R)) 25-50 mg (an intravenous route is preferred

over intramuscular administration). Alternatively, thiopental (50-

75 mg) should be administered intravenously. Diazepam is now the

treatment of choice for local anesthetic seizures (DeJong &

Heavner, 1971, 1974). Although these drugs must be titrated to

effect, the suggested upper limits of intravenous dosage are:

diazepam 0.5 mg/kg (during an 8 hour period); secobarbital 3 mg/kg;

and thiopental 3-5 mg/kg. If seizures continue, long acting nonpolarizing muscle relaxants (curare or pancuronium) may be required. At this stage advanced life support will be required.

When ventricular arrhythmias are present without signs of central

nervous system involvement, e.g. under general anesthesia, lidocaine (Xylocaine(R)) may be used in a bolus of 50-100 mg intravenously, and repeated with a 50 mg bolus, or by continuous infusion

if necessary. If cardiac involvement continues or lidocaine is

contraindicated due to seizure activity) the beta-blocker propanolol (Inderal(R)) can be administered (0.5-1.0 mg intravenously,

maximum=5mg). Propanolol offers the possible therapeutic advantage of treating the systemic effects of the hypermetabolic state.

Temperature should be monitored in anticipation of hyperthermia.

In documentation of the safety of cocaine, a recent survey of 741

plastic surgeons demonstrated the excellent record of cocaine as a

local anestheic in clinical practice (Feehan & Mancusi-Ungaro,

1976). some 80 percent (592) of the respondents currently used

cocaine for nasal surgery. This group reported that cocaine was

used in approximately 93,000 operations. Mild reactions were

observed in only 224 patients (0.24 percent) and severe reactions in

only 14 cases (0.015 percent). There were no fatal reactions in

93,004 patients.

Debate continues as to whether cocaine should be removed from the

U.S. Pharmacopeia. Deletion from this official compendium would

eliminate the availability of this unique drug to medical practit ioners . At present, no local anesthetic is totally devoid of

undesirable properties. Although cocaine cannot be autoclaved or

1Moser, R.H. (ed.) Standards for cardiopulmonary resuscitation

(CPR) and emergency cardiac care (ECC). JAMA, 227 (suppl):835-886

197
used for infiltration nerve block anesthesia, it possesses many

other properties of an "ideal" local anesthetic agent: Cocaine has

a short latency period with a duration of action suited to most

otolaryngologic procedures requiring local anesthesia. In concentrations used clinically, there appear to be no signs of permanent

mucosal or nerve damage. Since cocaine also produces vasoconstriction, addition of other vasoconstrictor drugs (with their potential

for toxic reactions), is not required.

The major area of controversy is the margin of safety of cocaine in

clinical medicine. Although sporadic reports of fatalities exist,

there is a paucity of data in the medical literature on the

incidence of morbidity and mortality associated with the use of

cocaine (Feehan & Mancusi-Ungaro, 1976).

As with any anesthetic, successful use of cocaine requires adequate

preanesthetic evaluation of the patient, adherence to the appropriate dosage schedule, and the ability and equipment to manage the

adverse systemic reaction. With these safeguards, cocaine has an

excellent record of safety.

Paul G. Barash, M.D.

Department of Anesthesiology

Yale University School of Medicine

New Haven, Connecticut

198
REFERENCES

Cocaine in Clinical Medicine

Adriani, J., Zepernick, R., Arens, J. and Authment, E. The comparative potency and effectiveness of topical anesthetics in man.

Clinical Pharmacology and Therapeutics, 5:49-62 (1964).

American Medical Association. Department of Drugs. Local Anesthetics. In AMA Drug Evaluations (2nd Ed.). Acton, MA:

Publishing Sciences Group, 1973, pp. 212-213

Anderton, J.M. and Nassar, W.Y. Topical cocaine and general

anaesthesia: An investigation of the efficacy and side

effects of cocaine on the nasal mucosa. Anaesthesia, 30:809-

817 (1975).

Becker, H.K. Carl Koller and cocaine.

32:304-373 (1963).

Psychoanalytic Quarterly,

Campbell, D. and Adriani, J. Absorption of local anesthetics.

Journal of the American Medical Association, 168:873-877

(1958).

Corssen, G. Toxic effects of local anesthetics on human respiratory

epithelium. Canadian Anaesthetists Society Journal, 20:17-20

(1973).

Davis, R.S. and McNeil, J.H. Cardiac effects of cocaine and certain

antihistamines and antidepressants. Archives Internationales

de Pharmacodynamie et de Therapie, 201:262-279 (1973).

DeJong, R.H. and Heavner, J.E. Diazepam prevents local anesthetic

seizures. Anesthesiology, 34:523-531 (1971).

DeJong, R.H. and Heavner, J.E. Diazepam prevents and aborts

lidocaine convulsions in monkeys. Anesthesiology, 41:226-230

(1974).

Dripps, R.D., Eckenhoff, J.E. and Van Dam, L.D. Introduction to

Anesthesia. The Principles of Safe Practice. Local Anesthetics. Philadelphia, PA: Saunders, 1972, pp. 213-217.

Feehan, H.F. and Mancusi-Ungaro, A. The use of cocaine as a topical

anesthetic in nasal surgery: A survey report. Plastic and

Reconstructive Surgery, 57:62-65 (1976).

Gay, G.R., Inaba, D.S., Sheppard, C.W. and Newmyer, J.A. Cocaine:

History, epidemiology, human phamacology and treatment. A

perspective on a new debut for an old girl. Clinical Toxicology, 8:149-178 (1975).

199
Jatlow, P., Barash, P.G., Van Dyke, C. and Byck, R. Impaired

hydrolysis of cocaine in plasma from succinylcholine sensitive individuals. Clinical Research, 23(3):255A (1976).

Lee, J.A. and Atkinson, R.S. (eds.), Pharmacology of drugs used in

local analgesia. Synopsis of Anaesthesia, 7th Ed. Bristol,

England: John Wright & Sons, Ltd., 1973, pp. 336-338.

Mayer, E. The toxic effects following the use of local anesthetics.

Journal of the American Medical Association, 82:876-888

(1924).

Moore, D.C. Complications of regional anesthesia. In Bonica, J.J.

(ed.), Regional Anesthesia. Philadelphia, PA: Davis, 1969,

pp. 217-253

Moser, R.H. (ed.) Standards for cardiopulmonary resuscitation

(CPR) and emergency cardiac care (ECC). Journal of the

American Medical Association, 227(suppl):835-868 (1974).

Orr, D. and Jones, I. Anaesthesia for laryngoscopy: A comparison

of the cardiovascular effects of cocaine and lidocaine.

Anaesthesia, 23:194-202 (1968).

Reynolds, F. The pharmacology of local analgesic drugs. In Wylie,

W.D. and Churchill-Davidson, H.C. (eds.), A Practice Anesthesia. London, England: Lloyd-Luke Ltd., 1972, pp. 1170-

1172.

Ritchie, J.M., Cohen, P.J. and Dripps, R.D. Cocaine, procaine and

other local anesthetics. In Goodman, L.S. and Gilman, A.

(eds.), The Pharmacological Basis of Therapeutics. New York,

NY: Macmillan, 1970, pp. 367-377.

Schenck, N.L. Local anesthesia in otolaryngology: A re-evaluation. Annals of Otology, Rhinology and Laryngolcgy, 84:65-73

(1975).

Smith, R.B. Cocaine and catecholamine interaction: A review.

Archives of Otolaryngology, 98:139-141 (1973).

Van Dyke, C., Barash, P., Jatlow, P. and Byck, R. Cocaine: Plasma

concentrations after intranasal application in man. Science,

191:859-861 (1976).

Van Dyke, C. and Byck, R. Cocaine: 1884-1974. In Ellinwood, E.H.

and Kilbey, M.M. (eds.), Cocaine and Other Stimulants. New

York, NY: Plenum Press, 1977, pp. 1-30.

200
Chapter X

CHARACTERISTICS OF CLIENTS ADMITTED

TO TREATMENT FOR COCAINE ABUSE

Eduardo Siguel, Ph.D.

Although the abuse of cocaine is usually obscured by the more

prominent difficulties associated with other types of drug abuse,

some information about its abuse is available through the Client

Oriented Data Acquisition Process (CODAP). CODAP is a data collection system developed and operated by the National Institute on Drug

Abuse which obtains information from drug abuse treatment facilities that receive Federal funding. These facilities provide about

50 percent of all drug abuse treatment in the United States, and

include about 1,500 clinics across the nation. Thus, CODAP provides

a broad data base to assess the characteristics of clients in

treatment. The data in this report are derived from 1975-1976

admissions to the 1,500 clinics which participate in CODAP. As a

result, the characteristics of clients who report cocaine as a

problem can be described using statistics obtained from this data

base. Caution should be used in interpreting these statistics since

the sample is probably not representative of cocaine users generally. It can, however, be considered representative of cocaine users

in Federally supported treatment facilities. For a comprehensive

description of CODAP and additional data on cocaine users, the

reader is referred to the references at the end of this section.

Of the approximately 55,000 patients admitted to CODAP clinics each

quarter, 1.2 percent report cocaine as their primary drug of abuse.

The typical cocaine abuser (See Figure 10-l) is: male (82 percent),

white (51 percent), without prior treatment experience (67 percent), a voluntary admission to treatment i.e., not referred by the

judicial process, (65 percent), unemployed (75 percent), has a

formal education higher than the ninth grade (80 percent) and was

admitted to treatment between ages 18 and 25 (57 percent).

Among those who report cocaine as a primary problem at admission,

about 50 percent report no other drug problem. Of the remaining

cocaine clients about 20 percent report marihuana as a secondary

drug problem, 10 percent barbiturates or amphetamines, 9 percent

opiates, 4 percent alcohol and the rest (7 percent) such other drugs

as the inhalants or the hallucinogens.

201
Although the percentage of clients in treatment who report cocaine

as their primary drug problem is low, among those who report other

drugs as the primary problem, cocaine plays a slightly more

prominent role. As a secondary or tertiary drug problem, it is

reported by 5.5 - 6.0 percent of the clients. Among clients who

have a primary drug problem other than cocaine, cocaine is mentioned

as a secondary drug problem by 4 percent of the approximately 55,000

quarterly admissions. Among clients who report heroin as the

primary drug problem, 6.0 percent report cocaine as a secondary drug

problem.

When cocaine abuse is examined from a racial or ethnic standpoint,

the frequency with which it is reported roughly parallels the ethnic

and racial composition of the nation as a whole. The largest group

of abusers is white, followed by Black, Puerto Rican, Mexican

American and Cuban. However, if cocaine abuse is viewed within

different race/ethnic groups the ordering is altered with Cubans

having the highest rate of abuse at 6.5 percent. This particular

result is normally obscured since Cubans are often grouped with

Mexican Americans and Puerto Ricans into one Spanish-speaking

ethnic group. It should also be noted that although Cubans have the

highest rate of cocaine abuse for those in treatment, cocaine use

still ranks fourth behind opiates, marihuana and amphetamines in

this ethnic group.

In the attempt to explain patterns of drug abuse, and to target

prevention and treatment programs, one must know the age at which

clients in treatment use a drug for the first time. The peak age

groups for the first use of cocaine is between 16 and 17 years (See

Figure 10-2). Looking at age of first use cumulatively, the data

shows 20 percent of those in treatment began use before the age of

15, and almost 70 percent began before they were 20 years old.

Thus, initial use of cocaine occurs mainly among youth. In addition, cocaine abuse follows a pattern which seems to be closer to

the first use of opiates rather than that of alcohol, marihuana and

the inhalants. Use of alcohol, marihuana and the inhalants

typically begins at an earlier age than does use of cocaine and the

opiates.

Cocaine abusers in treatment are similar in some ways but also

different from those in treatment who abuse other drugs. If one

compares individuals treated in both inpatient and outpatient

environments, 95 percent of cocaine abusers versus 60% of abusers of

other drugs are treated in drug free modalities.1 Cocaine users

1Drug free modality - a treatment regimen which does not include any

chemical agent or medication as the primary part of the drug

treatment.

202
complete treatment at a higher rate than opiate users and at about

the same rate as drug users overall. Cocaine users drop out of

treatment at a rate which is similar to all other drug users in

treatment but transfer at a slightly lower rate than the other drug

categories.

The results obtained from CODAP data are valuable for planning

strategies for drug abuse prevention and for allocating resources

for the treatment of drug abusers.

Eduardo N. Siguel, Ph.D.

Division of Scientific and

Program Information

National Institute on

Drug Abuse

203
FIGURE 10-1

DISTRIBUTIONS OF SELECTED CLIENT CHARACTERISTICS

FOR CLIENTS ADMITTED WITH PRIMARY DRUG PROBLEM OF COCAINE

(in percent)

(Based on Admissions During April-June, 1976)

Table I: Age at Admission (in years)

<18 18-20 21-25 26-30 31-44 > 4 4

9.8% 19.8 36.9 22.0 10.5 0.9

Table II: Age at First Use (in years)

<14 14-15 16-17 18-20 21-25 26-30 > 30

6.4 12.7 20.0 30.6 18.6 7.5 4.2

Table III: Race of Clients

White Black Am. Indian Asian-Am. P. Rican Mex. Am. Other

51.0 38.6 0.2 0.5 5.3 2.1 1.4

204
Figure 10-1, cont'd

Page Two

Table IV: Sex of Clients

Male Female

82.1 17.9

Table V: Number of Previous Treatments*

None 1 Treatment 2 Treatments >2 Treatments

66.7 20.5 6.4 6.4

*Individuals may have been in treatment for reasons other than cocaine abuse.

Table VI: Number of Other Drug Problems

1 2 >2

23.0 28.4 48.6

Table VII: Employment Status at Admission (Clients 18 and Older)

Employed Full-time

Employed Part-time

Unemployed

17.4

6.3

76.3

205
Figure 10-1, cont'd

Page Three

Table VIII: Enrollment in Educational Program

Table IX: Enrollment in Skill Development Program

Yes

No

5.5

94.5

Table X: Last Year of Formal Education Completed (Clients 18 and Older)

Years of Education

0-9 10-11 12 12+

14.6 31.0 31.6 22.8

206

Yes 16.5

No 83.5
Figure 10-1, cont'd

Page Four

Table XI: Legal Status at Admission

Voluntary 64.5

Federal Non-Voluntary 11.6

State Non-Voluntary 13.3

Local Non-Voluntary 10.6

N.B. The row percents of Tables I, II, III, IV, V, VI and X add to 100%; the column

percents of Tables VII, VIII, IX and XI add to 100% except for rounding errors.

207
FIGURE 10-2

DISTRIBUTION OF AGE OF FIRST USE FOR

CLIENTS WITH COCAINE AS THE PRIMARY

DRUG OF ABUSE WHO WERE ADMITTED TO

TREATMENT IN 1975
Figure 10-3 DISTRIBUTIONS OF ADMISSIONS BY SELECTED PRIMARY DRUGS

OF ABUSE AND MODALITY/ENVIRONMENT AND OF DISCHARGED

CLIENTS BY SELECTED PRIMARY DRUG OF ABUSE AND REASON

FOR DISCHARGE.

NOTE: The percents shown in each row for admissions and for discharges add to 100% (except for rounding error).

209
REFERENCES

Characteristics of Clients Admitted to

Treatment for Cocaine Abuse

Siguel, E. N. and Spillane, W. H. The epidemiology of drug abuse:

A new data base, new techniques and new findings. The

Proceedings of the Social Statistics Section of the American

Statistical Association, 1976.

National Institute on Drug Abuse – Statistical Series (Available

Quarterly). Washington, DC: Alcohol, Drug Abuse and Mental

Health Administration, Public Health Service, U.S. Department

of Health, Education, and Welfare.

210
AUTHOR INDEX

Abdo Abbasy, M., 119

Adriani, J., 194

American Medical Association, 193-194, 196

American Psychiatric Association, 123, 169

Anderton, J.M., 195

Ando, K., 73

Andrews, G., 17, 21, 27-28

Archer, S., 50, 56

Arens, J., 194

Aschenbrandt, T., 22

Ashley, R., 17, 27, 29, 32,

100, 121, 137, 154

Aulik, D., 120

Authment, E., 194

Axelrod, J., 145

Aynilian, G.H., 47

Backenheimer, M.S., 47

Baden, M.M., 54

Bailey, D.N., 55, 115, 169

Bakalar, J.B., 17, 121-122,

128-129, 137, 148

Balster, R.L., 74, 76-77,

80

Barash P.G., 57 113-115,

169-170, 176, 194-195

Barrett, J.E., 70

Barry, H., 73

Bason, D.J., 55, 115, 169

Bastos, M.L., 54-55, 169

Becker, H.K., 193

Bedford, J.A., 65

Bell, E.C., 71

Bender, M.B., 130

Besemer, D., 55

Bever, O., 119

Black, K.E., 69

Blake, J.W., 55, 169

Block, R., 50, 54, 67

Blum, K., 145

Blumberg, H., 66

Bonese, K., 74, 79, 80

Brady, J.V., 77-78, 83

Brewster, J.M., 75, 125

Brown, H.H., 54

Braun, J., 48

Budd, R.D., 169

Brungraber, E.G. 55

Buelke, J., 65

Bulligan, D., 54

Burchard, R.E., 47

Burroughs, W.S., 142

Byck, R., 21-26, 100, 113-115,

121, 154, 169-170, 176, 194-

195

Campbell, D., 194

Cappell, H., 72

Catania, A.C., 77

Chambers, C.D., 143

Chessick, R.D., 64

Chinn, D.M., 169

Christie, J.E., 66

Clayton, R.R., 7

Cohen, P.J., 115, 193-194, 196

Colburn, R.W., 50, 67, 169

Collier, H.O.J., 85

Corssen, G., 194

Costa, E., 65

Cotten, M.deV., 84

Crow, T.J., 66, 71

Crowley, A., 121-122

Curran, D., 130

Davis, J.M., 55

Davis, R.S., 195

DeJong, A.W.K., 47

DeJong, R.H., 195, 197

Dekirmenjian, H., 55

Deneau, G.W., 63, 75, 79, 82,

170

De Vito, J.J., 154

Dews, P.B., 65, 70

Dockens, W., 68

Dougherty, J., 74, 77, 81

Downs, A., 68

Downs, D.A., 11-13, 64, 70, 75-

77, 83, 100, 129-130

Dripps, R.D., 193-194, 196

Duke, J.A., 47, 120

Eckenhoff, J.E., 194, 196

211
Eddv. N.B.. 68

Eggleston, C., 123

Einhorn. A.. 48

Eisner, T., 119

El-Meligi, A.M., 124, 132

Emley, G.S., 65, 71

Ey, H., 130

Farnsworth, N.R., 47

Feehan, H.F., 197-198

Feldman, M., 130

Fennell, W., 113-114, 142

Ferster, C.B., 76

Findley, J., 75

Findley, J.D., 77, 83

Fish, F., 115

Fischer, R., 65-66

Fischman, M.W., 113-114,

142

Fischman, V.S., 142

Fodor, G., 50, 53

Fog, R., 65

Freedman, D.X., 113-114,

142

Freud, S., 13, 121-122

Gagliano, J., 18

Galambos, E., 66

Galbraith, J.K., 98

Gay, G.R., 154, 193, 196

Genter, W.A., 47

Gershon, S., 65

Gilbert, R.M., 124

Gill, C.A., 80

Gillin, J.C., 114

Gilman, A., 154

Glauber, J.J., 113

Goldberg, D.M., 71, 75, 79

Goldberg, S.R., 67, 70-71,

75-79, 81, 83

Gollub, L., 79

Gonzalez, F.A., 70, 81

Goodman, L.S., 154

Goodwin, F.K., 113-114

Gottlieb, A., 125

Griffiths, R.R., 77-78, 83

Grinspoon, L., 17, 121-122,

128-129, 137, 148

Gropetti, A., 65

Grove, R.N., 79

Gutcher, K., 77, 83

Guttmacher, H., 21

Guzman, M., 65-66

Halpern, B.P., 119

Hamilton, H.E., 54-55, 115,

169

Hammer, R.H., 55

Hardegger, E., 50

Hardinge, M.G., 64

Harris, S.C., 55, 115, 169

Hatch, R.C., 65-66

Hatcher, R.A., 123

Hawks, R.L., 50, 56-57, 67, 115,

169

Heavner, J.E., 195, 197

Herling, S., 70, 80-81

Herd, J.A., 75

Hill, H.E., 71

Hill, H., 80

Hodos, W., 77

Hoffman, D.B., 169

Hoffmeister, F., 83

Holbrook, J.M., 65

Holz, W.C., 80

Hutchison, R.R., 65, 71

Hurkmans, J.A., 66

Iglauer, C., 78

Ikeda, C., 66

Inaba, D.S., 154, 193, 196

Jain, N.C., 169

Jarvik, M.E., 75, 125, 130

Jatlow, P., 55, 57, 113-115,

169-170, 176, 194-195

Javaid, J.L., 55

Johanson, C.E., 70-71, 74, 78-

80, 83

Johnon, C.A., 75, 125

Johnston, L.D., 7

Jones, B.E., 75

Jones, E., 23, 25 , 23, 25

Jones: I., 113, 195

Jones, L.G., 75

Journal of the American Medical

Association, 29, 196, 197

Jukofsky, D., 54-55

Kalman, G., 77

Kalsner, S., 85

Kandel, D., 68, 72, 80

Kelleher, R.T., 67, 69, 71, 75-

7 8

Kestenbaum, R.S., 113, 114

King, E.E., 54-55, 115, 169

Kibbe, A.H., 65

212
Kluver, H., 130

Koller, K., 113, 193

Koontz, S., 55

Kopin, I.J., 50, 67, 169

Kotin, J., 113-114

Kramer, J.C., 142

Krasnegor, N.A., 113-114,

142

Kubena, R.K., 73

Kuroda, M., 113

Lal, H., 64

LeBlanc, A.E., 72

Lee, D., 52-53, 126

Leung, W.J., 169

Lewin, L., 120, 122

Littlefield, D.C., 142

Llewellyn, M.E., 78

Lumholtz, c., 120

Lundberg, G.C., 147

MacPhail, R.C., 71, 73

Mader, H., 48

Magnan V., 122-123

Mancusi-Ungaro, A., 197-

198

Mantegazza, P., 21-22,

122-121

Martin, R.T., 38, 47

Martindale, W., 27

Matsuzaki, M., 68, 128

Mattison, J.B., 154

Mayer, E., 12, 154, 195

McLaughlin, G.T., 29

McMahon, F.G., 114

McNeil, J.H., 195

Meola, J.M., 54

Misra, A.L., 50, 54, 67-

68, 128

Mockey, N., 55

Moerschbaecher, J.M., 128

Moffett, A.D., 143

Molnar, J., 66

Monardes, N., 19

Moore, D.C., 196

Moore, J.M., 55

Morpurgo, C., 71

Morse, W.H., 69, 75, 78-79

Mortimer, W.G., 17, 20-21,

27, 47-48, 100, 120. 123

Mule, S.J., 50, 54-55, 67-

68, 128, 154, 169

Muller, E., 48

Muller, W., 48

Munkvard, I., 65

Murdick, P.W., 55, 169

Musto, D., 28

Naimzada, M.K., 65

Nash, J., 41

Nassar, W.Y., 195

National Commission on Marihuana

and Drug Abuse, 126

Nayak, P.K., 50, 54, 67-68

Newmyer, J.A., 154, 193, 196

Nickerson, M., 85

Nicolich, M.J., 47

Niegemeers, G.J.E., 71

Noonan, J.S., 55, 169

O'Donnell, J.A., 7

Orr, D., 113, 195

Osmond, H., 124, 132

Ott, H., 50

Overton, D., 73

Panzik, H.L., 55

Patel, M.N., 67

Peregrino, L., 75

Perry, D.C., 124, 147

Peterson, D.I., 64

Pfeifer, A.K., 66

Phillips, J.L., 121, 126

Phillips, R., 55

Pickens, R., 74, 76-77, 79, 81-

8 2

Pickett, R.D., 154

Plowman, T., 120

Pontani, T.B., 54

Popanda, R.T., 69

Post, R.M., 65, 69, 113-114, 129,

132

Prada, J., 75

Price, K.R., 154

Randrup, A., 65

Ray, R.S., 55, 169

Resnekov, L., 113-114, 142

Resnick, R.B., 113-114

Reynolds, F., 194

Risner, M., 74, 80

Ritchie, J.M., 115, 193-194, 196

Ritzlin, R.S., 147

Robinson, W.W., 75, 77, 83

Room, R.G.W., 7

Rose, H., 65, 69

San Francisco Chronicle,

149

213
Saury, 122-123

Scheel-Kruger, J., 66

Schenk, N.L., 195

Schlichting, U.U., 83

Schubert, B.C., 47

Schultes, R.E., 120

Schuster, C.R., 68-69, 72,

75-83, 113-114, 142

Schwartz, L.K., 113-114

Schwertner, H.A., 54-55,

115, 169

Sears, Roebuck & Company,

28

Seevers, M.H., 63, 65, 68,

75, 79, 82, 114, 170

Seiden, L.S., 71, 73

Sheppard, C.W., 154, 193,

196

Shick, J.F.E., 113-114,

142

Siegel, R.K., 75, 119, 125,

130

Simons, F., 65

Skinner, B.F., 76

Slatin, G.T., 7

Smith, C.B., 65-66, 70

Smith, D.E., 141, 145-146

Smlith, R.B., 195

Sneath, T.S., 169

Solomon, D., 17, 21, 27-28

Spealman, R.D., 67, 71

Spingler, P.J., 68, 128

Streit, F., 47

Tatum, A.L., 63, 65, 68

Taylor, N., 119

Taylor, W.J.R., 143

Templeton, J.L., 55

Tessel, R.E., 70, 76

Thoa, N.B., 50, 67, 169

Thompson, D.M., 128

Thompson; T., 69, 74, 76-

79, 82

Unna, K., 78

Vadlamani, N.L., 67

Valanju, N.N., 54

Valanju, S.M., 54

Villareal, J.E., 65-66

Van Dam, L.D.; 194, 196

Van Dyke, C., 57, 100, 113-115,

154, 169-170, 176, 194-195

Van Rossum, J.M., 65-66

Van der Schaat, J.B., 66

Verma, S.K., 54

Voss, H.L., 7

Wallace, J.E., 54-55, 115, 169

Wallach, M.B., 65

Wauquier, A., 71

Webster, R.W., 154

Weeks, J.R., 75

Weil, A.T., 139

Wesson, D., 141, 146

Whyte, A.A., 128

Wikler, A., 71

Willsman, J.J., 47

Williams, E.H., 29

Willstatter, R., 48

Wilson, M.C., 65, 80-81

Wilson, R.A., 130

Wilson, S.A.K., 131

Wilson, W.D.C., 115

Winger, G.S., 80-82

Winter, J.C., 73

Wittke, W., 83

Wohler, V., 48

Wolf, H.G., 130

Wolf, H.G., 130

Woods, J.H., 11-13, 25, 64, 70,

75-78, 80-83, 100, 129-130

Woods, L.A., 114

Woolverton, W., 68, 72

Wright-St. Clair, R.E., 154

Wyatt, R.J., 114

Yanagita, T., 63, 75, 77, 79, 82,

170

Young, D., 113

Zepernick, R., 194

Zirkle, C., 80

214
abuse potential, 149-150

addiction (see also cocaine

dependent and cocaine habit),

25, 127

adrenergic stimulation, 196

adulterants, 5, 52, 124, 146,

162, 176-177.

adverse systemic reactions,

195

age

related to cocaine deaths,

159

of cocaine users, 202

aggression, 65-66

alcohol, 25, 40, 124-125, 143-

144, 146, 149-150, 162, 173,

177, 201-202

alertness, 102

alkaloids, 119, 193

allergy, 195-196

alpha-methyl-para-tyrosine,

66. 80

American Medical Association,

29, 194

AMBU(R), 196-197

amphetamines, 32, 65, 68, 70,

72-73, 79, 82, 114, 124-125,

139, 141-142, 145-147, 149-

150, 201

analgesic, 18, 149, 176

analytical methodology, 53-58,

159, 167, 177

anaphylactic response, 195-196

anesthetic quality of cocaine,

10, 24-25, 52, 101, 113, 124,

137, 13, 154, 193-198

anesthetics (other than cocaine), 146-147

anxiety, 128, 139, 141, 143-

144, 146

appetite, 11, 103, 121, 128

arrhythmias (see also ventricular arrythmias), 105, 113,

195

atropine, 66, 81

attention lapse, 129

auditory hallucinations, 131

SUBJECT INDEX

barbiturates, 125, 145, 149,

155, 201

behavioral actions of cocaine

metabolites, 67

behavioral effects of cocaine

in animals, 63-85

benzoylecgonine, 50, 54-55,

67, 75, 115, 169, 173, 177

benzoylnorecgonine, 67

bindles (see spoons)

binges (see dose)

blood concentrations, 170, 173

blood pressure, 101

blood vessel size, 101

Bolivia, 36-39, 47, 52

brain biogenic amines, 145

Brompton’s Solution, 149

caffeine, 124-125, 147

cancer treatment (see also

Brompton’s Solution), 149

cannabis (see also tetrahydocannabinol and marihuana),

43-44, 120, 124-125

cardiovascular effects (see

also heart rate), 142

carpopedal spasms, 143

cases of cocaine use, 141-143,

147-148

catecholamines, 145

central nervous system effects,

52, 102-104, 113-115, 137-

150

cerebral congestion, 175

chemistry of cocaine, 47-58

China, 43

chloroform, 169

chlororamazine, 80-81

cholestane, 169

chronic administration in

animals, 68

chronic use in man, 57, 129

circulatory failure, 196

cirumstantial-situational use

of cocaine, 128

215
client-Oriented Data Acquisition Process, 13, 201-210

coca, 5, 17-24, 27, 31, 35-44,

47, 57, 119, 132, 139

coca

as an anesthetic, 5, 23-24,

42

coca

chewing of, 5, 17-19, 37-41,

47, 114, 120, 124-125, 139

coca

cultivation of, 18-19

coca

stimulant effect of 27, 41,

48

coca

therapeutic uses of, 22-23,

36, 40, 43

coca

to reduce hunger and thirst,

4 0

coca

to reduce muscular exhaustion, 40

coca cigarettes, 27

Coca Cola(R), 28,47

coca poultices, 36

coca teas, 36-37

coca wines, 27

cocaine dependent (see also

cocaine addiction and cocaine habit), 25-26

cocaine habit (see also cocaine addiction and cocaine

dependent), 26

cocaine-induced depression

(see also mood), 114, 139,

141, 144-145, 147, 154

cocaine – the material (see

also chemistry), 47-58

cocaine mud, 195

cocaine psychosis, 11-12, 106,

123, 129, 132-133, 139; 141;

144, 146

CODAP (see Client-Oriented

Data Acquisition Process)

cokespoons (see spoons), 125

cola drinks 28, 47

Colombia, 36, 38-39, 52

column chromatography separation, 177

comatose, 144

Commissioners on Uniform State

Laws, 30

Comprehensive Drug Abuse Prevention and Control Act of

1970, 30

compulsive drug use, 128

conditioned behavior, 63-64

convulsions, 69, 106

coroners, 153-154

core temperature, 101

cortical stimulation, 196

cost of cocaine, 5, 13, 32,

127, 137, 144

cutting agent (see adulterants)

cyanosis, 196

cycloplegia, 129

d-amphetamine, 81-82

DAWN (see Drug Abuse Warning

Network)

death related to cocaine, 12,

64, 68, 79, 153-190

demographic considerations

in cocaine fatalities, 155

dependence

reinforcing stimulus, 105

tolerance, 105

physical dependence, 105

psychological dependence,

139, 145, 148

depression (see mood)

dextroamphetamine 142

diazepam (Valium(R)), 143-146,

197

diethyl ether, 169

discriminative stimulus, 72-

74

dopamine, 145, 195

dose

in animals, 64-65, 68, 70-

71, 75-78, 80, 83

in man, 125-126, 128, 137-

139. 141, 144. 194

drowsiness, 102

Drug Abuse Warning Network

(DAWN), 7, 12, 153-155

drug free treatment, 202

dyskinesias, 69

dysmegalopsia, 130

dysmorphopsia, 130

dyspnea, 196

dysphoria, 129

ecgonine, 48, 67

216
Ecuador, 36

effects of cocaine in man, 9,

97-115

EMIT(R), 55 169 177

environmental effects, 64

Enzyme Multiplication Immunological Technique

(see EMIT(R))

epinephrine, 195

ethanol, 82, 84

ethnic characteristics

of cocaine users, 202

euphoria, 114, 121, 128-129,

132, 141, 143, 148, 196

Europe, 20-21

eye (see opthalmology)

exophthalmos, 129

experimental use, 126

federal legislation restricting coca and cocaine, 30

forensic toxicologists, 153,

179

forensic toxicology, 153-190

Freud, Sigmund, 11, 13, 22-25,

27-28, 121

GC (see Gas Chromatography)

GC-MS (see Gas Chromatography

-Mass spectrometry)

GLC (see Gas Liquid Chromatography)

Gas Chromatography, 167, 169,

177

Gas Chromatography-Mass Spectrometry (GC-MS), 56, 169

Gas Liquid Chrauatography

(GLC) , 55-56

geographic characteristics

of cocaine deaths, 176

glaucoma, 24

glucose as an adulterant of

cocaine, 52

guanethidine, 195

gustatory hallucinations, 131

Haight-Ashbury Free Medical

Clinic, 138

half-life of cocaine, 57, 173

hallucinations, 25, 122-123,

128-132, 143-144

hallucinogens 124-125, 201

haloperidol, 60-81

halothane, 195

Harrison Narcotics Act of 1914,

30

heart rate, 101, 113

heart strength, 101

heroin, 9, 13, 53, 84, 124, 137,

142, 145, 147-148, 155, 161,

175-177

hospital treatment, 196

hydrochloride salt, 48, 52, 124-

125

hyperactivity, 66

hypertension, 196

hyperthyroidism, 195

hyperventilation, 143

hypoxia, 196

imipramine, 80, 169

Incas, 18-19, 35-36, 40

India, 43

Indians

Andean, 19-20, 36, 40

Brazilian, 39

of the Sierra, 5, 39, 40

indirect behavioral effects,

72

injected (see also intravenous), 8, 125, 143-144, 148,

150, 162, 166

inositol, 124

intensified drug use, 128

interaction with other drugs,

66, 195

intravenous

in animals, 65-83

in man, 8, 25, 113-114,

125, 127, 142-144, 148,

150, 162, 166

intoxication, 25, 122-123,

128

intramuscular (see injected)

intranasal administration, 8,

83, 114, 122, 125-126, 139,

141, 143-145, 147, 149-150,

162, 166-167, 175-176, 178

iproniazid, 66

LSD (see also hallucinogens),

9, 127, 143

217
lactose, 52, 124

laryngoscopy, 195

larynx (see also laryngoscopy)

193

laws prohibiting or restricting distribution of cocaine,

29-30

lidocaine, 52, 146-147, 162,

169, 175-177, 194, 197

limestone, 17, 35, 38

line (see dose)

liver tissue concentration,

173

locomotor activity, 64-67, 69

macropsia, 130

mannitol, 52, 124

marihuana, 1, 6, 12, 125, 127,

130, 137, 139, 143-144, 149-

150, 201-202

massive pulmonary, 175

medical examiners, 153-154

medical history

related to cocaine deaths,

161-162, 177

medicinal uses (see also therapeutic uses), 139, 193

mental performance

creativity, 103

mepivacaine, 169

mescaline, 73

metabolic pathways of cocaine

in man (see also behavioral

actions of cocaine metatolites in animals), 50, 57,

114, 155

methadone, 143, 162

methamphetamine, 127

methaqualone, 169

methyldopa, 195

methylphenidate, 83

micropsia, 130

mining, 36, 41

modeling of animal behavior.

119-150, 132

mood, 128 (see also cocaineinduced depression)

in normals, 103

in depressed, 12, 103, 148

crash (post coke depression),

103

morphine, 26, 66, 72, 81, 161-

162, 166-167, 173, 175, 177

mortality (see also death), 12

muscle strength, 101

mydriasis, 129

nalorphine, 169

naltrexone, 66

Narcotic Drugs Import and Export Act, 30

nasal insufflation (see intranasal administration)

nasal problems, 129, 131, 197

nasal septum, 106, 141, 175

n-butyl chloride, 169

nerve block anesthesia, 193,

198

neurotransmitters, 50, 52, 66,

124,

non-drug reinforcers, 78

norbenzoylecgonine, 50-52

norcocaine, 50, 67

norepinephrine, 195

nutritional value (see also

vitamins), 120

occupation

related to cocaine deaths,

161

olfactory hallucinations, 131

operant behavior. 69

opiates, 25, 28-29-139, 176-

177, 201, 203

opthalmology, 24, 113, 193-

otolaryngology, 113, 198

paranoia, 128, 143-144

pargyline, 80

patent medicine, 27-29, 31

pathologists, 153, 179

patterns of use, 126-129, 138-

139

pentobarbital, 70, 81-83

perforated nasal septum, 106,

141, 175

peridural anesthesia, 193

perphenazine, 80

Peru, 18, 36, 38-39, 47, 52,

119-120, 139

pharmaceutical use of cocaine,

47

218
pharmacology, 67, 113, 137, racial characteristics (cont'd)

193-194 of cocaine users, 202

phencyclidine, 147 recreational use, 1, 119, 153-

phenmetrazine, 81 154

phenobarbital, 81 radioimmunoassay, 169

pheochromocytoma, 195 reinforcing properties, 69-72,

phenytoin, 66 74-76, 120

Physiology, 193 religious significance, 18, 35

physical dependence (see reported effects of cocaine

also addiction), 13, 145 controlled -- man, 101-106

physical performance, 104 clinical, 101-106

physiological effects, 64, 128 laboratory -- man, 101-106

pimozide, 80 animal, 101-106

plasma concentrations, 170, 194 single case, 101-106

plasma cholinesterase, 173 street, 101-106

poisoning from cocaine, 154 unverifiable, 101-106

polyopia, 130

post-mortem cases, 153-190

reserpine, 66, 80, 195

respiratory failure, 154, 196

procaine, 176 respiratory rate, 101

propranolol, 81-82, 195, 197 respiratory tract, 193

pseudocholinesterase, 195 resuscitation, 144

pseudohallucinations, 130-131, rhinitis (see also nasal prob133 lems, 131

psychoactive effect, 120, 128, route of administration, 64,

132 74-75, 82, 84, 125, 138, 142

psychological dependence (see run (see dose)

dependence) rush, 142-144

psychological intoxication, 119

psychopharmacologic effect,

132-133 SKF-525A, 81, 169

psychosis (see cocaine psycho- sample of users, 123

sis) San Francisco Polydrug Project,

procaine as a substitute for 138

cocaine, 52 schedules of cocaine reinforcepsychoactive effect, 120-121 ment, 76-78

psychological effects, 13 secobarbital, 83

pulmonary edema, 175 skin (see tactile hallucinations)

pupillary size, 101

Pure Food and Drug Act of 1906,

slang terms for cocaine, 137

sleep

30 disorder, 144

purity of street preparations, rapid eye movement, 103

52, 124-125, 127 total, 103

smoking cocaine, 75, 125-126,

130

snorting (see intranasal adminqualitative analysis, 53-55, istration)

57 social effects

quantitative analysis, 53, 55, sexual performance and

57, 169 libido, 104, 121, 128, 144

quinine as an adultersnt, 53 crime, 104

aggression, 104

social-recreational use, 119-

racial characteristics 133, 137-150

related to cocaine deaths, sodium fluoride, 169, 177

161 solvent extraction, 177

219
sources of cocaine, 47 ultraviolet spectrophotometry,

sources of information re: co- 167, 169

caine effects, 97-115

South America, 17, 20, 52, 57

unconditioned behavior, 63-64,

72

Spanish, 19-20, 35, 39, 41 Uniform Controlled Substances

speedballs (see also heroin),

142, 147

Act, 30

Uniform Narcotic Drug Act, 30

spinal anesthesia, 193

spoons (see also dose) 35, 52,

125-126

Valium(R) (see diazepam)

statistical analysis, 159

vasoconstrictor, 113, 193-195,

198

stereochemical characteristics, ventricular arrhythmias, 195-

5 0

stereotypy 65 69 79

197

visceral congestion, 175

stimulant qualities, 67, 112, 128, vitamins in coca leaves, 42,

132, 139, 143-145, 154 120

street preparations of cocaine,

52

street preparations zoopsia, 130

purity of, 52

structure of cocaine, 48-51

substitutes for cocaine, 52

surety of information re: cocaine effects, 97-115

sympathomimetic, 114

synthesis of cocaine, 48

systemic effects, 101, 113, 196

THC (see tetrahydrocannabinol)

TLC (see Thin Layer Chromatography)

tactile hallucinations, 11, 122,

131

tachycardia, 196

tetracaine, 52, 146

tetrahydrocanna binol (THC)

(see also cannabis and marihuana), 73

therapeutic uses of cocaine,

25-26

Thin Layer Chromatography (TLC),

54, 56, 67

tonics, 27

toxicity, 145, 194

toxicological analysis, 153,

155

treatment of cocaine abuse, 12

203

Trendlenberg position, 196-197

tricyclic antidepressant, 145,

195

trihexyphenidyl, 169

trifluorperazine, 80

220

monograph series

Monographs can be ordered from either the U.S. Government Printing

Office (GPO) or from the National Technical Information Service (NTIS)

at the addresses below. NTIS prices given are for papercopy. Microfiche copies at $2.25 are also available from NTIS.

GPO NTIS

Superintendent of Documents National Tech. Info. Service

U.S. Government Printing Office U.S. Department of Commerce

Washington, D. C. 20402 Springfield, Virginia 22161

1 FINDINGS OF DRUG ABUSE RESEARCH. An annotated bibliography of

NIMH and NIDA-supported extramural grant research, 1967-74.

Volume 1, pp. 384; Volume 2, pp. 377 Not available from NTIS

Vol.1: GPO Stock #017-024-0467 $7.00; Vo1.2: #017-024-0466-9 $5.05

2 OPERATIONAL DEFINITIONS IN SOCIO-BEHAVIORAL DRUG USE RESEARCH 1975.

Editors: Jack Elinson, Ph.D. and David Nurco, Ph.D. Task Force

articles proposing consensual definitions of concepts and terms used

in psychosocial research to achieve operational comparability. pp. 167

GPO Stock #017-024-0048-4-7 $2.50 NTIS PB #246 338 $6.75

3 AMINERGIC HYPOTHESES OF BEHAVIOR: REALITY OR CLICHE? Editor:

Bruce J. Bernard, Ph.D. Articles examining the relation of the brain

monoamines to a range of animal and human behaviors. pp. 149

GPO Stock #017-024-0048-6-3 $2.25 NTIS PB #246 687 $6.25

4 NARCOTIC ANTAGONISTS: THE SEARCH FOR LONG-ACTING PREPARATIONS

Editor: Robert Willette, Ph.D. Articles reporting current alternative

inserted sustained-release or long-acting drug devices.

GPO Stock #017-024-00488-0 $1.10 NTIS PB #247 096 $4.00

5 YOUNG MEN AND DRUGS: A NATIONWIDE SURVEY. Authors: John A.

O'Donnell, Ph.D. et al. Report of a national survey of drug use by

men 20-30 years in 1974-5. pp. 144

GPO Stock #017-024-00511-8 $2.25 NTIS PB #247 446 $6.75

6 EFFECTS OF LABELING THE "DRUG-ABUSER" - AN INQUIRY. Author: Jay R.

Williams, Ph.D. Analysis and review of the literature examining

effects of drug use apprehension or arrest on the adolescent. pp. 39

GPO Stock #017-024-00512-6 $1.05 NTIS PB #249 092 $4.00

222
7 CANNABINOID ASSAYS IN HUMANS. Editor: Robert Willette, Ph.D.

Articles describing current developments in methods for measuring

cannabinoid levels in the human body by immunoassay, liquid and

dual column chromatography and mass spectroscopy techniques. pp. 120

GPO Stock #017-024-00510-0 $1.95 NTIS PB #251 905 $6.00

6 Rx 3 TIMES/WK LAAM - METHADONE ALTERNATIVE. Editors: Jack

Blaine, M.D. and Pierre Renault, M.D. Comprehensive summary of

development of LAAM (Levo-alpha-acetyl methodol), a new drug for

treatment of narcotic addiction. pp. 127

Not available from GPO NTIS PB #253 763 $6.00

9 NARCOTIC ANTAGONISTS: NALTREXONE. Editors: Demetrios

Julius, M.D. and Pierre Renault, M.D. Progress report of development, pre-clinical and clinical studies of nultrexone, a new drug

for treatment of narcotic addiction.

GPO Stock #017-024-00521-5 $2.55

pp. 182

NTIS PB #255 833 $7.50

10 EPIDEMIOLOGY OF DRUG ABUSE: CURRENT ISSUES. Editors: Louise G.

Richards, Ph.D. and Louise B. Blevens. Conference Proceedings.

Examination of methodological problems in surveys and data

collection. In Press.

11 DRUGS AND DRIVING. Editor: Robert Willette, Ph.D. State-ofthe-art review of current research on the effects of different

drugs on performance impairment, partcularly on driving. In Press.

12 PSYCHODYNAMICS OF DRUG DEPENDENCE. Editors: Jack D. Blaine M.D.

and Demetrios A. Julius, M.D. A pioneering collection of papersto

discover the part played by individual psychodynamics in drug

dependence. In Press.

13 COCAINE: 1977. Editors: Robert C. Petersen, Ph.D. and

Richard C. Stillman, M.D. A series of reports developing a picture of current knowledge (and its limits) of the drug, its use

and misuse. In Press.

223

U.S. GOVERNMENT PRINTING OFFICE: 1977 O–233–879