National Institute on Drug Abuse

RESEARCH

MONOGRAPH SERIES

Methamphetamine

Abuse:

Epidemiologic

Issues and

Implications

U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health

115
Methamphetamine

Abuse: Epidemiologic

Issues and Implications

Editors:

Marissa A. Miller, D.V.M., M.P.H.

Nicholas J. Kozel, M.S.

Research Monograph 115

1991

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

Alcohol, Drug Abuse, and Mental Health Administration

National Institute on Drug Abuse

5600 Fishers Lane

Rockville, MD 20857
ACKNOWLEDGMENT

This monograph is based on the papers and discussion from a technical

review on “Methamphetamine Abuse: Epidemiologic Issues and Implications”

held on August 28-29, 1990, in Bethesda, MD. The review meeting was

sponsored by the National Institute on Drug Abuse.

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Citation of the source is appreciated.

Opinions expressed in this volume are those of the authors and do not

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

product or company. Trade, proprietary, or company names appearing in this

publication are used only because they are considered essential in the context

of the studies reported herein,

NIDA Research Monographs are indexed in the Index Medicus. They are

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Information Service, Chemical Abstracts, Current Contents, Psychological

Abstracts, and Psychopharmacology Abstracts.

DHHS publication number (ADM)91-1836

Printed 1991

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ISBN 0-16-035810-8
Contents

Page

Introduction and Overview 1

Marissa A. Miller and Nicholas J. Kozel

Pyrolytic Characteristics, Pharmacokinetics, and

Bioavailability of Smoked Heroin, Cocaine, Phencyclidine,

and Methamphetamine 6

C. Edgar Cook

Neurotoxicity of Methamphetamine: Mechanisms of

Action and Issues Related to Aging 24

Lewis S. Seiden

The Environmental Impact and Adverse Health Effects

of the Clandestine Manufacture of Methamphetamine 33

Gary D. Irvine and Ling Chin

Heavy Metal and Organic Contaminants Associated

With Illicit Methamphetamine Production 47

Brent T. Burton

Methamphetamine Abuse in California 60

Bruce Heischober and Marissa A. Miller

Trends and Patterns of Methamphetamine Smoking

in Hawaii 72

Marissa A. Miller

iii
Methamphetamine Abuse in Japan 84

Hiroshi Suwaki

Trends and Patterns of Methamphetamine Abuse in the

Republic of Korea 99

Byung In Cho

Community Networks for Response to Abuse Outbreaks

of Methamphetamine and Its Analogs 109

James N. Hall and Pauline M. Broderick

List of NIDA Research Monographs 121

iv
Introduction and Overview

Marissa A. Miller and Nicholas J. Kozel

The category of drugs known as stimulants has been used and abused for

centuries. Within this general category, abuse of amphetamine and

methamphetamine can be traced to the time that they first appeared on the

licit market during the 1930s. The international nature of abuse of these

substances was chronicled during the Second World War. There is evidence

that shows epidemic patterns of methamphetamine abuse in several Asian

countries. A resurgence in methamphetamine abuse in the United States also

has been documented during the 1980s. The National Institute on Drug Abuse

(NIDA) has been monitoring this resurgence of methamphetamine abuse

through its surveillance mechanisms and systems.

A convergence of information from the Drug Abuse Warning Network, a

drug abuse morbidity and mortality surveillance system reflecting an

increasing trend in deaths and nonfatal emergency department episodes

related to methamphetamine use, and from the Community Epidemiology

Work Group (CEWG) members, a network of State and local drug abuse

experts representing 20 cities and metropolitan areas across the United States,

indicated that methamphetamine use was on the rise during the 1980s in

several U.S. cities. This information prompted NIDA to sponsor a field study

in 1988 that added further evidence that methamphetamine abuse was

becoming increasingly problematic. In December 1988 methamphetamine

smoking was identified as an emerging problem in Hawaii, and NIDA was

requested to assist the State of Hawaii Department of Health in investigating

and characterizing the nature and extent of the problem.

While these studies were being initiated, it also became apparent that little

was known about methamphetamine as a drug of abuse or the implications

and consequences from the relatively new route of administration by smoking.

To understand more fully the contributing factors to the reemergence of

methamphetamine, a technical review was held by NIDA on August 28 and 29,

1990. Trends of drug abuse are influenced by many factors, including physical

and biochemical properties of the drug and its neuropharmacologic effects,

characteristics of the abusing population and other epidemiologic influences,

1
and broader factors related to drug manufacturing, marketing, and distribution

throughout the world. This monograph attempts to address many of these

issues, to describe patterns and trends of the recent resurgence of

methamphetamine abuse, and to provide an overview of contributing factors

and consequences of that abuse.

C. Edgar Cook’s chapter discusses the bioavailability and pharmacokinetics

of smoked drugs, revealing that smoking methamphetamine is a highly

efficient route of administration. Methamphetamine hydrochloride is readily

volatilized and recovered at temperatures compatible with the common

methods of smoking. The method of smoking “ice” in a glass pipe was shown

to be an efficient smoking delivery system. Smoking results in rapid onset of

effect, similar to intravenous use, with large amounts of drug delivered to the

brain, The rapid and intense psychoactive effect is desirable to users and

serves to reinforce use. This, combined with a long plateau effect and relatively

lengthy half-life, suggests serious health consequences, including addiction, to

repetitive smoking of methamphetamine.

Lewis S. Seiden’s chapter presents evidence that methamphetamine causes

damage to dopamine- and serotonin-containing neurons in the brain. This

damage occurs in several species of animals, is long-lasting, and is probably

irreversible. These methamphetamine-related effects may have implications

related to loss of dopamine neurons during the human aging process.

Methamphetamine abuse, especially at high levels, may accelerate this aging

with subsequent physiologic and pathologic consequences. Seiden points out

that more research is needed to explain further the neurotoxicity and delayed

consequences of methamphetamine abuse.

Violence as a consequence of methamphetamine abuse was discussed at the

technical review by Everett H. Ellinwood. Chronic, moderate- to high-dose

methamphetamine abuse often results in assaultive behavior and other forms of

violent action. The interaction of methamphetamine’s behavioral and

psychological effects, including hyperactivity, agitation, lability of emotion, and

paranoid delusional thinking, combined with personality factors and the social

context, contribute to the occurrence of violence.

Factors contributing to drug abuse related to drug manufacture, distribution, and

marketing were discussed at the technical review by Joan Zolac of the Drug

Enforcement Administration. In the unique case of ice, production was traced to

Korea, Taiwan, and the Philippines, and importation and marketing was traced

to organized criminal groups. These factors have combined with others to

result in a sharp increase in availability and use in Hawaii during the late 1980s.

2
Domestic laboratories have replicated the process for synthesizing ice, although

only a limited number of ice laboratory seizures have occurred. An indicator of

methamphetamine abuse domestically is the number of methamphetamine

laboratory seizures that have increased dramatically thoughout the 1980s most

of them in California, Texas, and Oregon,

Gary D. Irvine and Ling Chin’s chapter discusses the environmental impact

and adverse health effects related to the sharp increase in domestic

methamphetamine laboratories. The illicit manufacture of methamphetamine

is a relatively simple chemical process. However, illicit producers may not

possess the knowledge or the skill to carry out the synthesis properly. Many of

the precursor chemicals are corrosive, irritating, and flammable; the process

can result in explosions and toxic fumes: and the final product can be

contaminated with metals, unreacted precursors, and unintended by-products—

all presenting medical and public health concerns. Special consideration must

be given to the environmental cleanup of the methamphetamine laboratory

sites and to the protection of exposed populations during this process.

Brent T. Burton’s chapter discusses health consequences resulting from illicitly

produced methamphetamine contaminated with reagents, solvents, and

unintended reaction by-products. Two case reports of human toxicity due to

lead contamination of methamphetamine are presented from the scientific

literature, as are the problems involved in documenting the extent of

contaminant-induced illness from methamphetamine.

The trends, patterns, and characteristics of current methamphetamine abuse in

California are discussed by Bruce Heischober and Marissa A. Miller in their

chapter. Methamphetamine abuse on the U.S. mainland is primarily a west

coast phenomenon, and methamphetamine abuse in California is influenced

geographically and is location specific, occurring predominantly in the San

Diego and San Francisco areas. Increases in methamphetamine abuse have

been reported in adolescent, minority, and gay populations, with increasing

numbers of abusers entering treatment and experiencing traumatic

consequences.

Findings from the NIDA outbreak investigation and followup field study into ice

smoking in Hawaii are presented in the chapter by Marissa A. Miller. The

retrospective analysis of treatment records revealed ice smoking to have a

lengthy history among certain ethnic groups; however, the widespread smoking

of ice is a recent trend cutting across racial and ethnic lines. The study

revealed a peak of first use in 1988, resulting in clients entering treatment 1 to 2

years later. These data suggest a decreasing trend in 1990 of users entering

treatment, and more current information obtained from Hawaiian treatment

3
facilities confirms this trend. Adverse health and social consequences and risk

factors related to the smoking of ice also are presented.

A perspective on the international character of methamphetamine abuse is

provided by two chapters, Hiroshl Suwaki’s chapter describes Japan’s second

epidemic of methamphetamine abuse, which differs significantly from the first.

The first occurred during the post-World War II (1945-1956) era largely as a

result of wartime use and the postwar release of large pharmaceutical

stockpiles of methamphetamine to the general public. With the passage of the

Stimulants Control Law (1951) and a vigorous enforcement policy combined

with information and education campaigns, the abuse of methamphetamine

abated. However, a different situation exists today. Control efforts have been

unable to significantly decrease methamphetamine abuse, which has plateaued

at a high level.

The chapter by Byung In Cho chronicles Korean association with the

methamphetamine trade and market since the Second World War and factors

influencing the growth of that association, including changes in laws and

regulations such as the stiffening of drug control policies in Japan. Indicators of

methamphetamine abuse in the Republic of Korea showed increases

throughout the 1980s but appeared to be decreasing in 1989. This decrease

appeared to be the result of a nationwide drug control strategy, including

increased law enforcement activities directed at abusers and suppliers and

increased seizures of raw materials and final product, in Korea

methamphetamine is abused primarily by males through multiple daily

intravenous injections. Abuse has been noted throughout Korea but is localized

primarily in and around the city of Pusan.

The final chapter by James N. Hall and Pauline M. Broderick presents

community networks as a response to outbreaks of methamphetamine abuse

and abuse of related analog drugs. Due to the localized nature of the

methamphetamine problem in the United States, community-based strategies

are appropriate and effective in assessing and addressing this type of drug

problem. Community networks utilize a multidisciplinary approach and facilitate

and enhance cooperation and coordination of strategy among participating

organizations. Networks are essential as a method to gather drug abuse data,

to monitor existing data systems, and to identify specific needs such as

treatment, prevention, or public policy redirection. Community networks

frequently are sensitive to changes in drug usage and may detect the

emergence of a new drug or drug abuse trend. This drug surveillance function

of networks is demonstrated by the CEWG, which detected the reemergence of

methamphetamine as cited at the beginning of this chapter.

4
We are grateful to the participants and authors for their valuable contribution to

the technical review meeting and to this monograph. It is our hope that this

monograph will serve to inform public health officials, clinicians,

epidemiologists, and researchers concerning some of the basic issues of

methamphetamine abuse. We anticipate that this monograph will stimulate

further directed research into the mechanism, consequences, and patterns of

methamphetamine use and abuse.

AUTHORS

Marissa A. Miller, D.V.M., M.P.H.

Epidemiologist

Nicholas J. Kozel, M.S.

Chief

Epidemiology Studies and Surveillance Branch

Division of Epidemiology and Prevention Research

National Institute on Drug Abuse

Rockwall II, Room 815

5600 Fishers Lane

Rockville, MD 20857

5
Pyrolytic Characteristics,

Pharmacokinetics, and Bioavailability

of Smoked Heroin, Cocaine,

Phencyclidine, and Methamphetamine

C. Edgar Cook

INTRODUCTION

Smoke from plant material containing psychoactive drugs has long been used

as a means of self-administration. This route of administration is simple (one

merely burns the plant material). It is also highly effective; the major route of

blood circulation through the lungs and heart to the brain results in rapid

delivery of inhaled substances to the central nervous system. The volatilization

of the material can be assisted by codistillation or steam distillation as air is

drawn through the burning plant material.

In 450 B.C., Herodotus (translated 1942) described the inhalation of smoke

from marijuana by the Scythians. Tobacco was being smoked by the American

Indians well before the arrival of the Europeans (Corti 1932), and opium has

been smoked for centuries in the Middle and Far East (Masood 1979; Meyers et

al. 1972). Tetrahydrocannabinol THC) from marijuana, nicotine from

tobacco, and morphine-the major psychoactive component of opium-have

volatility properties that facilitate the smoking method of administration. In view

of these precedents, it is not surprising that as newer psychoactive drugs were

found, attempts were made to smoke these drugs also, either alone or in a

mixture with such plant material as tobacco, marijuana, and herbs.

Smoking drugs presents added hazards to the drug user. Since the rate of

chemical reactions generally increases with temperature, a variety of new

compounds can be produced as a result of smoking. The drug can undergo

unimolecular fragmentations. It can react with itself or with other constituents of

the smoked mixture in a bimolecular fashion. The combination of oxygen and

heat can be expected to lead to oxidized products. The chemical reactivity of

the compound, the temperature of smoking and of volatilization, and the

6
presence of coreactants all can have a significant influence on the product

mixture that is inhaled. Thus, there is considerable potential for formation and

inhalation of toxic substances. Smoking gives a rapid onset of effect of the

drug, comparable in many ways to that from intravenous (IV) administration.

The rapid reinforcement also enhances the addicting power of the drug. In

combination with the now well-advertised health hazards of IV injection of drugs

(particularly human immunodeficiency virus infection), these factors are likely to

lead to a further increase in smoking as a route of administration.

Within the past few years, considerable information has been accumulated

regarding pyrolysis and smoking of various drugs of abuse (Cook and Jeffcoat

1990). This chapter summarizes work with four of these drugs-heroin,

cocaine, phencyclidine, and methamphetamine-and attempts to compare and

contrast their pyrolytic properties and the factors that affect their bioavailability.

HEROIN

Around the beginning of this century, heroin was introduced into China and

began to replace opium as a narcotic. Since opium generally was smoked, it

was natural that heroin was used in the same way (Huizer 1987). The earliest

scientific study of the bioavailability of heroin by this route was reported in 1937

(Ito 1937). MO and Way (1968) found that 14 percent of the dose of heroin

smoked on cigarettes could be recovered in urine as morphine (conjugated and

free), whereas a 25-percent morphine recovery was achieved in urine for

“dragon chasing” (inhaling the vapors of heroin heated on foil). Compared with

the recovery of 68 percent of an IV dose of heroin as morphine, this would give

bioavailabilities of 21 percent for smoking on cigarettes and 37 percent for

dragon chasing.

Significant amounts of the drug are decomposed on heating. Cook and

Brine (1985) studied the pyrolysis products of both heroin and heroin

hydrochloride by a combination of proton and 13-carbon nuclear magnetic

resonance, mass spectrometry, and comparison with authentic materials.

They identified heroin and three major pyrolysis products in the 250°C

pyrolysate of heroin hydrochloride. The products were 6-0-acetylmorphine,

N,6-0-diacetylnormorphine, and N,3-0,6-0-triacetylnormorphine. In addition,

a minor component was suggested to be 3,4-diacetoxyphenanthrene on the

basis of high-resolution mass spectrometric analysis. Formation of this

compound illustrates the extensive breakdown that can occur under pyrolytic

conditions. HPLC analysis showed many other ultraviolet-absorbing peaks

present in minor amounts, some of which were tentatively identified (figure 1)

(Cook and Jeffcoat 1990). Similar pyrolysis products were apparently present

upon pyrolysis of heroin.

7
FIGURE 1. Pyrolytic products of heroin

NOTE: Solid arrows lead to identified products; broken arrows lead to other

tentative products.

Huizer (1987) followed this work by studying the volatilization of heroin under a

variety of conditions, particularly in the presence of various diluents often used

in the smoking process. A common means of smoking heroin is by dragon

chasing. Heroin for smoking often is diluted with a barbiturate or caffeine and

sometimes small amounts of strychnine.

When heroin hydrochloride was heated on aluminum foil (Huizer 1987) the

aforementioned major products reported by Cook and Brine (1985) were found

in the residue. The amounts of these products increased with increasing

temperature. Heroin base gave smaller amounts of pyrolysis products, with

6-0-acetylmorphine predominating. Caffeine enhanced the volatilization and

changed the ratio of products to favor 6-0-acetylmorphine. Thus, caffeine has a

very strong positive effect on the volatilization of heroin hydrochloride, as does

barbital (Mo and Way 1966), whereas ascorbic acid markedly reduced the

amount of the drug in the smoke. Recoveries of heroin in the fumes from

heating on aluminum foil ranged from nearly 80 percent for the freebase mixed

with caffeine to about 1 percent when ascorbic acid was used as the diluent

(Huizer 1987). Thus, the amount of heroin inhaled by smoking is strongly

8
dependent on the presence of diluents, and these also may influence the ratio

of pyrolysis products obtained.

COCAINE

In the case of basic compounds that are heated as their acid salts, pyrolytic

degradation may be facilitated by hydrogen ion catalysis. Furthermore, the

generally higher melting point and lower volatility of the hydrochloride salts also

favor pyrolytic breakdown and reduce the amount of drug available for

inhalation. Both these factors are probably operative in the case of cocaine.

The freebase melts at 98°C is volatile above 90°C, and boils at 187-188°C and

0.1 mm pressure. In contrast, cocaine hydrochloride melts at around 195°C

(Windholz et al. 1983). Studies in the author’s laboratory have shown that only

1 percent of the cocaine can be recovered after heating cocaine hydrochloride

to 800°C, whereas 16 percent of the freebase is recovered at that high

temperature. When cocaine freebase was heated in a glass pipe at 265°C

under simulated smoking conditions, about 44 percent of the drug was

recovered in the smoke (Perez-Reyes et al. 1982; Jeffcoat et al. 1989).

When the freebase was smoked in a tobacco cigarette, only 6 percent of the

cocaine could be recovered in the smoke. It appears that the cocaine interacts

with constituents in the plant material to reduce the amount that can be

obtained on smoking. The concentration of cocaine in coca leaves is relatively

low as well—Rivier (1981) indicates less than 1 percent of dry weight in

cocaine. Thus, in contrast to marijuana and THC, smoking coca leaves has

not been used as a method of cocaine administration (Carroll 1982). It was not

until drug users and suppliers began to convert cocaine hydrochloride to the

neutral form (either freebase or, more recently, “crack” cocaine) that the

popularity of smoked cocaine began to grow.

A variety of reaction pathways are available to cocaine upon pyrolysis (figure 2),

and the products obtained appear to depend strongly on the precise conditions

used. In experiments in which cocaine was pyrolyzed in the presence of a

stream of air that swept the volatile pyrolysis products into a collection trap, the

formation of methyl ecgonidine and two isomers was observed. These

compounds could be separated by capillary gas chromatography but had

essentially identical mass spectra. These products could result from benzoic

acid elimination followed by isomerization of the double bond to the position

as well as internal ring opening (Cook et al. 1985; Cook and Jeffcoat 1990).

Four other components with similar retention times and mass spectra appeared

to be double-bond isomers of methyl cycloheptatrienecarboxylate. The

presence of these materials can be explained by further internal eliminations

leading eventually to loss of methylamine from the tropane structure. Benzoic

9
FIGURE 2. Reported pyrolysis products of cocaine

acid also was observed as well as methyl benzoate and N-methylbenzamide.

All these products are chemically reasonable, and straightforward mechanisms

can be drawn to explain their occurrence.

Novak and Salemink (1989) heated cocaine at 600°C in a nitrogen atmosphere

and identified 15 products. They found only a trace of amethylcycloheptatrienecarboxylate but identified three isomeric methyl toluate compounds as well as

methyl phenyl acetate, all of which were suggested to arise via a methyl

cycloheptatrienecarboxylate intermediate. Under these conditions, a major

pyrolysis product (7 percent of total) was methyl-4-(3-pyridyl)butanoate. This

compound and an isomer were suggested to be derived by a combination of

elimination, rearrangement, and aromatization. Methyl nicotinate and its 2- and

6-methyl homologs also were observed and were presumably the result of a

combination of elimination, N-demethylation, and aromatization. At 400°C

under these conditions, cocaine essentially was unchanged, with only methyl

ecgonidine identified as a pyrolytic product.

Sisti and Fowler (1989) subjected cocaine to flash vacuum thermolysis in

an oven at 500 to 550°C. The conditions used were such as to favor

unimolecular reactions. They observed the formation of N-methylpyrrole and

10
methyl 3-butenoate in addition to benzoic acid. Martin and colleagues (1989)

vaporized cocaine in a glass pipe heated in a furnace at 260°C in a stream of

air and recovered benzoic acid and methyl ecgonidine as the major

decomposition products.

For studies in which pure cocaine is delivered by inhalation, Hatsukami and

colleagues (1990) have reported the use of a device in which the drug is

deposited on a wire (Nichrome). The wire is heated electrically, and the heating

mechanism is activated when the subject begins to inhale. Excellent

reproducibility of delivery is reported by use of this device.

A smoked drug may be delivered to the lungs as a true vapor or as an aerosol.

In the case of an aerosol, particle size is important for efficient delivery to the

alveolar region, with 3 μm particles having the greatest alveolar deposition from

mouth breathing (Hinds 1982). Recently, Snyder and colleagues (1988)

reported that smoking crack cocaine in a pipe resulted in only 6 percent vapor,

with 94 percent of the drug being delivered as particles with an average size of

2.3 μm.

All the factors involved make the bioavailability of smoked cocaine quite

variable. In a study in which cocaine was smoked by human subjects, the

calculated bioavailability based only on the amount of material inhaled (which

was about 80 percent of the amount of drug placed in the pipe) ranged from 32

to 77 percent, with an average of 57 percent. Since simulated smoking studies

indicated that an average of 56 percent of the drug was decomposed under

these conditions, the true bioavailability of the cocaine that reached the body is

probably nearly 100 percent. Smoked cocaine results in rapidly attained peak

plasma levels (average 6 minutes after beginning smoking). Apparent terminal

elimination rates of cocaine after smoking (58 minutes) were similar to those

after IV (78 minutes) or intranasal (80 minutes) administration (Jeffcoat et al.

1989).

PHENCYCLIDINE

The thermal elimination of an amine to yield an olefin appears to be a

particularly facile reaction in the case of phencyclidine (PCP), yielding as initial

products (figure 3) 1-phenylcyclohexene (Freeman and Martin 1981; Cook et al.

1961) and piperidine (Cook et al. 1981). The hydrochloride of PCP is 95

percent decomposed on heating at 300°C for 5 minutes (Cook et al. 1981).

However, simulated smoking studies with the hydrochloride on parsley

cigarettes in conjunction with human smoking studies showed that, on a molar

basis, 39 percent of the PCP was in the mainstream smoke together with 30

percent of phenylcyclohexene. Fifteen percent of the material remained in the

butt, and 16 percent was lost in sidestream smoke (Cook et al. 1983).

11
FIGURE 3. Products of phencyclidine from pyrolysis and smoking on

marijuana cigarettes

In another simulated smoking study involving PCP on marijuana cigarettes,

1-phenylcyciohexene (47 percent), PCP (40 percent), piperidine (15 percent),

and N-acetylpiperidine (9 percent) were found in trapped mainstream smoke

(Lue et al. 1986). Thus, the piperidine formed undergoes reaction with other

constituents of the plant material. Under stringent pyrolysis conditions, PCP

can yield a variety of aromatic and polynuclear aromatic compounds (Beaver

and Jones 1984), but these were not found in the simulated smoking studies.

As with cocaine, the bioavaiiability of smoked PCP is not easy to determine

precisely but has been estimated by Cook and colleagues (1982a) to be about

100 percent, if based on the PCP inhaled. The terminal elimination rate for

PCP when it was smoked (24 hr) was similar to that observed when it was

taken orally (27 hr) or intravenously (16 hr) (Cook et al. 1982b).

METHAMPHETAMINE

One would expect, based on their relative molecular weights, the volatility of

methamphetamine to be similar to that of nicotine and considerably greater than

that of PCP. Also, as a secondary amine, methamphetamine should be less

likely than PCP to undergo thermal elimination to an olefin. it is not surprising

then to find that, when methamphetamine is placed in a pyrolysis tube that then

is put into a heated furnace, the methamphetamine volatilizes, and at

temperatures of 200 to 400°C more than 98 percent of it can be recovered

intact. Recovery falls to 88 percent at 600°C and 62 percent at 800°C. At

these temperatures, small amounts of amphetamine (0.7 and 1.5 percent) are

formed (K.H. Davis, personal communication, July 1990).

Hydrochloride salts of simple amines are also volatile, and 91 percent of

methamphetamine hydrochloride is recovered unchanged after volatilization at

12
300°C in a tube furnace (compared with 5 percent of PCP hydrochloride).

Recovery from the hydrochloride drops to 81 percent at 400°C, 62 percent

at 600°C, and 38 percent at 800°C. The salt form is more subject to Ndealkylation due to the presence of a protonated nitrogen and a chloride

nucleophile, so that even at 400°, 5 percent of amphetamine is formed by

N-demethylation (10 percent at 600°C and 9 percent at 800°C) (K.H. Davis,

personal communication, July 1990). Significant amounts of at least four other

pyrolysis products were observed but not identified.

The availability of methamphetamine is much reduced by smoking it in a

mixture with tobacco. Thus, Sekine and Nakahara (1987) found that from 6 to

17 percent (depending on amount and smoking conditions) of the

methamphetamine hydrochloride added to tobacco was recovered from the

mainstream smoke of cigarettes. This was confirmed by Davis and colleagues

(personal communication, July 1990) who recovered 4.7±1.1 (SD) percent of

added methamphetamine hydrochloride in mainstream smoke when cigarettes

were smoked in the puff mode and 12.7±2.9 percent when a constant draft

mode of smoking was used. Results were essentially the same in the latter

study when the freebase was used (4.8±0.6 percent/puff mode and 15.6±1.3

percent/draft mode), again in confirmation of the report of Sekine and Nakahara

(1987).

Seven significant pyrolysis products (figure 4) were rigorously identified in the

tar from methamphetamine/tobacco cigarettes-amphetamine, phenylacetone,

dimethylamphetamine, and N-formyl, N-acetyl, N-propionyl, and N-cyanomethyl

methamphetamine (Sekine and Nakahara 1987), with the N-cyanomethyl

compound predominating. In a later study, phenylacetone was the predominant

product, and trans-ß-methylstyrene also was found. It was shown that

formation of the N-cyanomethyl compound required both heat and air and that

other amines formed N-cyanomethyl products when smoked with tobacco

(Sekine and Nakahara 1990).

The hydrochloride salt of S-(+)-methamphetamine is the form that is smoked as

“ice” (Cho 1990). Reports from Hawaii indicate a common method of

administration of “ice” is to smoke it in a glass pipe. Interest in studying this

phenomenon led to the initiation of human studies using this material smoked in

a glass pipe (Cook et al. 1991; Perez-Reyes et al. 1991).

Six informed, healthy, male, paid volunteers familiar with the use of

amphetamines were the subjects. Cardiovascular effects of the drug were

monitored during the experiment. Heart rate and blood pressure were

measured. Other cardiovascular parameters were measured by computeraveraged impedance cardiogram. The subjects gave a subjective rating of drug

13
FlGURE 4. Products of methamphetamine hydrochloride from pyrolysis and

smoking on tobacco cigarettes

effect during the study on a scale of 0-100, with 100 representing the most

affected they had ever been after taking amphetamines (Perez-Reyes et al.

1991).

Smethamphetamine hydrochloride was placed in a glass pipe. The pipe was

inserted in a heated aluminum block, and the subjects inhaled the vapor at

1-minute intervals for approximately 4 minutes (Perez-Reyes et al. 1991),

Plasma samples were collected at intervals and analyzed for methamphetamine

and amphetamine by the procedure shown in figure 5.

Preliminary experiments with the glass pipe were carried out by partially

immersing it in a silicone oil bath, making use of a large-volume syringe to

simulate the smoker’s lungs and pulling the vapors through a series of acid

traps. When methamphetamine hydrochloride was placed in the pipe and the

pipe was lowered into an oil bath at 268°C, roughly 9 to 11 mg of the

methamphetamine hydrochloride was recovered from the pipe, with the balance

being drawn into the traps. The residue remaining in the pipe appeared to be

more a function of the area of cooler surface on which it can condense than of

the absolute amount placed in the pipe and remained relatively constant with

increasing doses placed in the pipe.

14
FIGURE 5. Analytical procedure for methamphetamine and amphetamine in

plasma

For human experiments, the pipe was inserted into an aluminum block heated

to 302-308°C on a hot plate. Approximately 30-mg doses of methamphetamine

hydrochloride were placed in the pipe. Analysis of pipe residue showed that an

average of 7.8±1.0 (SD) mg of methamphetamine hydrochloride remained in

the pipe and pipe stem after the experiments with the volunteers were

complete. Thus, the apparent dose of the methamphetamine hydrochloride was

approximately 20 to 21 mg, assuming that, as in the in vitro studies, little

decomposition occurred during the smoking process.

In the analytical procedure (figure 5), methamphetamine recoveries through the

extraction process were monitored by use of radiolabeled compounds and

averaged 69 to 73 percent. The trifluoroacetamide derivatives were

chromatographed on a DB-5 gas chromatography column. The standard curve

was linear over a range of 1 to 225 ng of methamphetamine. Similar standard

curves were obtained for 1 to 15 ng for amphetamine. Control samples showed

15
an average difference from nominal values of 3.5 to 6.4 percent, with a relative

standard deviation of 1.9 to 4.5 percent at values from 5.4 to 8 ng/mL for

methamphetamine. At 2 ng/mL, the values were 15 percent and 10 percent for

methamphetamine and 10 percent and 4 percent for amphetamine.

Analysis of plasma samples from the subjects who smoked the

methamphetamine hydrochloride gave the results shown in figure 6. Although

the initial plasma concentrations of methamphetamine rose rapidly after the

start of smoking, they did not decline rapidly. In fact, there was essentially a

plateau over the first 3 to 4 hours of the experiment, after which plasma levels

began to decline. It was therefore not possible to fit a standard one- or twocompartment pharmacokinetic model with an absorption phase to these data.

However, by use of a noncompartmental approach, it was possible to determine

an elimination half-life with an average value of 11.7±3.3 (SD) hours and a

range of 8 to 17 hours.

FIGURE 6. Comparison of plasma concentrations of methamphetamine after

oral administration (•) and smoking Only the time points

through 8 hours are shown. The oral dose was 0.250 mg/kg, and

the smoking dose was slightly higher (about 21 mg/subject).

Means of six subjects±SEM are shown.

16
In another study (Cook et al. 1990), a 10-mg daily oral dose of a slow-release

form of S-(+)-methamphetamine hydrochloride (Gradumet) was administered to

volunteers over a 13-day period. On the day preceding and the day after this

continuous dosage, oral S-(+)-d3-methamphetamine hydrochloride was

administered at doses of 0.125 mg/kg or 0.250 mg/kg. The deuterium label was

present on the terminal methyl group of the compound, a position that does not

appear to be involved with the primary metabolism of methamphetamine. The

subjects again were monitored medically and psychologically. Urine, blood, and

saliva were collected. Urine and saliva pH were measured but not controlled.

Plasma, urine, and saliva were analyzed for the quantlties of d3- and d0-

methamphetamine and amphetamine present. Analysis was by gas

chromatography and mass spectrometry of the pentafluorobenzoylchloride

derivative, and internal standards were penta-deuteromethamphetamine and

hexadeuteroamphetamine. Chromatography was carried out on a 30 m DB-1

column, and analysis was positive methane Cl [M+H]+.

A one-compartment pharmacokinetic model with a first-order absorption phase

could be fit to plasma concentrations of each subject at the high dose and five

out of six subjects at the low dose by means of a computer curve-fitting program

(SAS NLIN) (Cook et al. 1990). A better fit for all subjects was achieved by

introducing a lag time into the model. Area under the plasma concentration

time curve also was determined by a model independent method (trapezoidal

rule). Maximum concentration and time to achieve it were determined from the

model and from individual data points. Statistical comparisons were made to

determine whether there were any significant differences before and after the

13-day daily treatment with methamphetamine hydrochloride or whether there

was any evidence of differences between the two doses.

There was no evidence of dose-dependent pharmacokinetics when the 0.125

mg/kg and 0.250 mg/kg doses were compared for the various parameters.

Comparisons between day 1 and day 15 indicated that the maximum

concentration was slightly (about 14 percent) but significantly (paired t-test)

greater on day 15 than on day 1. None of the other parameters measured

showed any statistically significant differences. In view of this, the values of

various parameters were averaged. Analysis of the data showed a lag time of

approximately 30 minutes, an absorption half-life thereafter of 38 minutes, and a

terminal elimination half-life of 10 hours (figure 7). The maximum concentration

was reached at approximately 3 hours. The maximum plasma concentration

averaged about 35 to 38 ng/mL after an oral dose of approximately 18 mg

(0.250 mg/kg) (figure 6). This does not differ markedly from the plateau plasma

concentrations of methamphetamine (40 to 44 ng/mL) after a 30-mg dose was

smoked. In spite of this, the maximum subjective effects were quite modest (10

to 16 percent) when compared with the subjective effects of 38 percent for

smoked methamphetamine (Perez-Reyes et al. 1991).

17
Parameter Mean

Lag time

Absorption t1/2

Elimination t1/2

tmax

Clap

Cmax(0.125 mg/kg)

Cmax(0.250 mg/kg)

0.524 h

0.640 h

10.2 h

3.1 h

496.0 mL/min

20.2 ng/mL

39.8 ng/mL

FIGURE 7. Average pharmacokinetic parameters for oral 1,1,1-

trideuteromethyl-S-methamphetamine hydrochloride

NOTE: These average values do not show trends with dose or time. Clap is the

apparent clearance, assuming complete absorption of the dose.

Since the dose of methamphetamine inhaled was approximately 20 to 21 mg

(analogous to the oral dose) and the maximum plasma concentrations were

similar, the difference in subjective effects between the oral dose and the

smoked dose may have to be explained on the basis of the rate of change in

concentration (figure 8).

Figure 8 shows a comparison of plasma levels of cocaine after smoking cocaine

freebase with those of methamphetamine after smoking methamphetamine

hydrochloride. There is a strong contrast between the two drugs. Cocaine

levels after smoking cocaine freebase rapidly peak and, with some minor

deviations, also rapidly decline with a terminal half-life of about 56 minutes. As

pointed out previously, the methamphetamine levels, although they rapidly

approach peak concentrations, remain high for a considerable period before

declining with a half-life of about 11 to 12 hours. A somewhat similar

phenomenon, with a secondary maximum, also was observed in the inhalation

of smoked PCP (Cook et al. 1982a).

One possible explanation for these differences is that the vaporization of

methamphetamine hydrochloride physically presents a much different picture

than that of cocaine freebase. In the case of cocaine freebase, relatively little

visible condensation appears on the pipe, although a considerable amount of

18
FIGURE 8. Comparison of plasma levels of methamphetamine and cocaine

after smoking S-methamphetamine HCl or cocaine

NOTE: Data points from 8 to 48 hr are not shown.

the cocaine is lost by pyrolysis. On the other hand, although the

methamphetamine hydrochloride was volatilized at temperatures only slightly

above those for cocaine, it condensed readily to a crystalline solid on the cooler

portions of the pipe. Similar condensation may be occurring in the mouth and

throat of the subject who subsequently swallows or absorbs the

methamphetamine through mucous membranes. Thus, some of the

methamphetamine presumably reaches the lung, but another portion of it may

undergo oral or buccal absorption resulting in an apparent sustained release of

the drug to the systemic circulation. Another explanation for this finding is

based on the observation that several lipophilic amines are known to

accumulate and persist in rat and rabbit lungs (Wilson et al. 1979).

Regardless of the explanation for this phenomenon, this long plateau effect and

the much longer half-life of methamphetamine vs. cocaine suggests

considerable dangers in repeated smoking of methamphetamine since

markedly higher plasma concentrations could be expected to occur if the dose

is repeated, even at fairly long intervals.

19
CONCLUSIONS

Smoking of psychoactive drugs in plant material has a long history, and this

technique has been transferred to newer drugs. The volatility and stability of

the drug have great bearing on the efficiency of the smoking process, as does

the presence of other substances that can codistill, enhance stability, or react

with the drug being smoked. Of the four drugs discussed—heroin, PCP,

cocaine, and S-methamphetamine hydrochloride (ice)—the last one is most

efficiently delivered when the substances are heated in a glass pipe. This

factor, combined with the addictive properties of the compound and with the

justifiable fears about use of IV injection, is likely to lead to an increase in this

mode of administration unless educational efforts on the hazards of ice and

research efforts to find the bases of drug addiction and treatment methods are

successful.

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cocaine and phencyclidine. In: Barnett, G., and Chiang, C.N., eds.

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J.A.; White, W.R.; and McDonald, S. Pharmacokinetics of oral d3-Smethamphetamine in humans before and after 13 days of oral dosing with Smethamphetamine hydrochloride. Eur J Pharmacol 183:456-457, 1990.

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Huber, M. A method for delivery of precise doses of smoked cocaine base to

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cocaine. Tetrahedron 45(13):4287-4292, 1989.

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Free-base cocaine smoking. Clin Pharmacol Ther 32:459-465, 1982.

Perez-Reyes, M.; White, R.; McDonald, S.; Hill, J.; Jeffcoat, R.; and Cook, C.E.

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DC: Supt. of Docs., US. Govt. Print. Off., 1991. pp. 575-577.

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characterization of alkaline substances used during coca chewing.

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tobacco: I. Inhalation efficiency and pyrolysis products of

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Sekine, H., and Nakahara, Y. Abuse of smoking methamphetamine mixed with

tobacco: II. The formation mechanism of pyrolysis products. J Forensic Sci

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Tetrahedron Lett 30(44):5977-5980, 1989.

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smoke” is a respirable aerosol of cocaine base. Pharmacol Biochem Behav

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Index. 10th ed. Rahway, NJ: Merck & Co., Inc., 1983. p. 348, #2411.

ACKNOWLEDGMENT

Work reviewed here from Research Triangle Institute and the University of

North Carolina was supported by National Institute on Drug Abuse contracts

22
271-87-8128 and 271-80-3705. Dr. Mario Perez-Reyes of the University of

North Carolina carried out the clinical portions of our collaborative work. The

contributions of my colleagues at Research Triangle Institute are indicated by

the various references listed.

AUTHOR

C. Edgar Cook, Ph.D.

Vice President

Chemistry and Life Sciences

Research Triangle Institute

P.O. Box 12194

Research Triangle Park, NC 27709-2194

23
Neurotoxicity of Methamphetamine:

Mechanisms of Action and Issues

Related to Aging

Lewis S. Seiden

INTRODUCTION

Historically, the use of mood-altering drugs has increased or decreased in

cycles similar to those observed with bacterial or viral epidemics. Increases in

the abuse of psychomotor stimulants such as cocaine and methamphetamine

have occurred in different countries at different times (Seiden and Ricaurte

1987). Cocaine and methamphetamine are similar in their discriminative

stimulus properties, and both cocaine and methamphetamine compounds are

self-administered by humans as well as nonhuman animals. The patterns of

social problems engendered by cocaine or methamphetamine abuse indicate

similarities in behavior, and similarities in their neuropharmacological actions

strongly suggest that cocaine and methamphetamine may continue to be

problematic drugs in society. In recent years, cocaine has been abused to a far

greater extent than methamphetamine, although the converse was true in the

1950s through 1970s in Japan, Great Britain, Sweden, and the United States

(Kramer et al. 1967; lnghe 1969; Brill and Hirose 1969). Cocaine continues to

be a frequently abused psychomotor stimulant (Wish 1990), but there are some

indications that methamphetamine abuse has increased because of

marketplace pressures as well as differences in the duration of action between

methamphetamine and cocaine, with methamphetamine having about 1 O-fold

longer duration of action in humans. Accurate data on the frequency and

prevalence of illicit drug abuse is difficult to obtain, but there are some

indications that the prevalence of methamphetamine use in Hawaii and

California is sizeable enough to warrant concern (Miller, this volume;

Heischober and Miller, this volume). The estimates of prevalence are based on

the number of seizures of illicit manufacturers of methamphetamine and the

number of hospital admissions that are believed to be related to

methamphetamine ingestion.

24
The crystalline form of methamphetamine hydrochloride, known as “ice,” is

volatile at low temperatures, and the pharmacological effects can be achieved

by inhaling vapors. The inhaled route of administration delivers a bolus of

methamphetamine to the brain. Similar effects can be achieved with

intravenous (IV) injection, but smoking omits dangers inherent in IV drug

administration such as contracting blood-borne diseases. In this way it is

similar to “crack” cocaine, which is smoked and inhaled. Health officials, law

enforcement agencies, and the public have perceived cocaine and

methamphetamine as damaging to an individual’s ability to serve a useful role in

society. Based on animal studies, there is evidence that methamphetamine

causes long-lasting changes in the central nervous system (CNS), indicating

that methamphetamine is neurotoxic, especially at high doses. Although CNS

effects on humans due to methamphetamine or cocaine have not been

determined, data from animal studies suggest that caution be exercised.

This chapter presents evidence that methamphetamine causes damage to

dopamine and serotonin (5-hydroxytryptamine [5HT])-containing neurons in the

brain and that this damage occurs in several species of animals, is long lasting,

and probably is irreversible. Data and theory are presented that suggest a

mechanism by which methamphetamine may engender toxicity to dopamine

and 5HT neurons. Finally, the implications of these data are discussed in terms

of changes in humans as a function of age.

METHAMPHETAMINE ENGENDERS NEUROTOXICITY

Early findings revealed that high and repeated doses of methamphetamine in

the rhesus monkey and the rat caused long-lasting depletion of dopamine and

decreased the activity of tyrosine hydroxylase (TH) in the brain (Seiden et al.

1976; Koda and Gibb 1973). In the Seiden and colleagues study, rhesus

monkeys received IV injections eight times per day in escalating doses that

reached a final cumulative dose of between 9 and 15 mg/kg/day. Monkeys

injected with high doses of methamphetamine for 3 to 6 months were sacrificed

3 or 6 months after the last injection of methamphetamine. The most

remarkable finding in this study was a large depletion of caudate dopamine from

the monkeys treated with methamphetamine. An indirect replication of this

experiment used similar doses of IV methamphetamine for 2 weeks, with a 2-

week interval between the last injection and assay for brain catecholamines;

this shorter injection regimen also caused large depletions of caudate

dopamine. Koda and Gibb (1973) injected rats with five large doses of

methamphetamine over a 24-hour period and found that TH was decreased for

7 days after the last injection.

25
It seemed unlikely that methamphetamine would remain in the brain or other

tissues for 3 to 6 months, and since methamphetamine does not inhibit TH, the

drug remaining in the system even after the shorter interval would not be likely

to affect the enzyme directly. The results of these early experiments suggested

that repeated and high doses of methamphetamine lead to long-lasting

depletions of dopamine in the caudate and a reduction in the amount of enzyme

available for the rate-limiting synthetic step. These results suggested that

methamphetamine is neurotoxic to these cells.

Neurotoxicity in a dopamine-containing cell occurs when (1) there is a longlasting effect on dopamine levels that persist after the withdrawl of the drug, and

the total activity of the rate-limiting enzyme is decreased; (2) the number of

dopamine high-affinity-uptake sites is reduced; and (3) there is morphological

evidence for degeneration.

Methamphetamine has been shown to engender long-lasting transmitter

depletion on the dopamine and 5HT systems in rhesus monkeys, rats, mice,

guinea pigs, and cats (Seiden et al. 1976; Wagner et al. 1979, 1980, 1983;

Levine et al. 1980; Steranka and Sanders-Bush 1980). The generality of this

effect is important because it implies that the effects of methamphetamine on

dopamine and 5HT levels extends to humans. In all species that have been

examined, the methamphetamine dose that causes the neurotoxic effects on

dopamine cells is between 20-fold and 30-fold greater than the dose required

for engendering behavioral effects such as increased locomotion, decreases in

food intake, or stereotypic behavior (Seiden and Dykstra 1977). Humans who

use methamphetamine or amphetamine for controlling food intake or

counteracting narcolepsy or fatigue take approximately 0.2 to 0.4 mg/kg,

whereas humans using the drug for its mood-altering effects use as much as 10

to 20 mg/kg over a 24-hour period (Gilman et al. 1985). Comparing doses in

humans used for altering mood with doses that engender toxic responses in

other animals suggests that it is reasonable to be concerned that humans using

methamphetamine in large doses will be susceptible to the same neurotoxicity

observed in other species.

The same doses of methamphetamine that reduce dopamine levels and TH

activity in brain also cause prolonged reductions of 5HT levels and the activity

of the rate-limiting enzyme in 5HT synthesis, tryptophan hydroxylase (Ricaurte

et al. 1980; Bakhit et al. 1981; Hotchkiss and Gibb 1980). These results

suggest that high and repeated dosing with methamphetamine can lead to longlasting reductions of dopamine and 5HT levels as well as the enzymes that are

rate limiting in their synthesis, suggesting that methamphetamine produces

neurotoxicity to these systems. It is of interest that methamphetamine is not

neurotoxic to norepinephrine, gamma-amino-butyric-acid, glutamic acid, or the

26
acetylcholine system, and increases in levels of peptides have been observed

following methamphetamine treatment (Seiden and Ricaurte 1987). The

neurotoxlcity engendered by methamphetamine is long lasting if not permanent,

and depletions of dopamine and 5HT have been observed in rhesus monkeys

as long as 3 years after the cessation of methamphetamine administration

(Woolverton et al. 1989).

Methamphetamine-induced degeneration of neurons has been detected using

silver-staining techniques. It has been possible to demonstrate that about 24

hours after methamphetamine there are cells in the caudate that are

argyrophillic (Ricaurte et al. 1982, 1984). These silver-stained cells are

apparent in the caudate nucleus, where there are dopamine and 5HT cells. It is

not possible, however, to use silver techniques to determine the transmitter in

the damaged cell. Therefore, one must infer that the same damaged cells

contain the transmitter that is measured with the chemical assays. The main

factor that favors this interpretation is that the pattern of positive argyrophylllc

cells is similar to terminal field loss for dopamine and 5HT.

In summary, three factors indicate that methamphetamine is neurotoxic to

dopamine and 5HT cells. First, methamphetamine produces a long-lasting

change in the levels of dopamine and 5HT as well as the quantity of enzyme

catalyzing the rate-limiting step in their synthesis. Second, the number of highaffinity-uptake sites is reduced, indicating that a fraction of nerve endings are

destroyed. Third, neuronal degeneration is indicated by the number of cells that

take up silver after methamphetamine administration.

MECHANISM OF ACTION IS RELATED TO OXIDATIVE STRESS

The molecular mechanism by which methamphetamine produces long-lasting

and irreversible damage to dopamine-containing and 5HT-containing neurons in

the CNS is not completely understood, but some interesting data and theory

exist.

A number of observations are consistent with a mechanism by which

methamphetamine engenders the release and conversion of dopamine to a

toxic metabolite, 6-hydroxydopamine (6-OHDA). First, it was shown that

inhibition of dopamine synthesis by alpha-methyl-tyrosine protects against the

toxic effects of methamphetamine (Wagner et al. 1983). Blockade of synthesis

suggests that dopamine is important in mediating methamphetamineengendered neurotoxicity. Furthermore, pretreatment of rats with reserpine

potentiates methamphetamine neurotoxicity. At first, it would seem that the

protection from the neurotoxicity by alpha-methyl-tyrosine is inconsistent with

the potentiation of neurotoxicity caused by reserpine, but alpha-methyl-tyrosine

27
depletes dopamine from the newly synthesized dopamine pool that is bound to

the cytoplasm, while reserplne depletes dopamine from the vesicular bound

pool and therefore causes a shift in the equilibrium between cytoplasmlc and

vesicular pools that increases the cytoplasmically bound pool. Amphetamine

and probably methamphetamine engender dopamine release from the

cytoplasmically bound pool (Ralteri et al. 1979); therefore, methamphetamineinduced release of dopamine is retarded under conditions in which the

cytoplasmically bound pool decreases and can be enhanced when the pool is

increased. Alpha-methyl-tyrosine decreases and reserpine increases the

cytoplasmically bound pool, thus diminishing or enhancing methamphetamineinduced toxicity, respectively.

The formation of an endogenous neurotoxln is based on the observation that

the catecholamine neurotoxin 6-OHDA has been found in the urine of humans

and that dopamine can be metabolized to 6-OHDA through a Fenton-type

reaction in which a hydroxy radical is formed from hydrogen peroxide in the

presence of ferrous iron according to the reaction system below:

Fe2+-EDTA+H202—>Fe3+-EDTA+OH-+OH’

2Fe3+-EDTA+(H2)-ascorbate—>Fe2+-EDTA-dehydroascorbate+2H+

2Fe2+-EDTA+2H+

+02—>Fe3+-EDTA+H202

02

-

+2H++Fe2+-EDTA—>H202+Fe3+-EDTA

02

-

+Fe3+-EDTA—>02+Fe2+-EDTA

02

-

+H202—>02+OH-+OH’

Ferrous iron, hydrogen peroxide, and ascorbic acid are all present in the brain,

and although ethylenediaminetetraacetlc acid (EDTA) is an important factor of

the in viva Fenton reaction, there are other electrophylic molecules in brain that

could serve as intermediates in place of EDTA. Furthermore, Slivka and Cohen

(1985) have found that dopamine reacts in a Fenton-type system to yield

trihydroxyphenethylamine derivatives, of which 6-OHDA is one, and therefore it

seemed possible that the dopamine released by methamphetamine into the

synapse could be converted to 6-OHDA; once formed, 6-OHDA could be

actively transferred into the dopamine terminal by the high-affinity-uptake pump,

and once inside the dopamine cell, 6-OHDA is toxic. Seiden and Vosmer

(1984) detected small amounts of 6-OHDA in the caudate nucleus after a large

single injection of methamphetamine that is sufficient to cause long-lasting

dopamine depletions. Furthermore, the formation of 6-OHDA engendered by

treatment with methamphetamine can be blocked by pretreating rats with amethyl-p-tyrosine (AMPT) (Axt et al. 1990). Pretreatment with AMPT attenuates

many of the behavioral and physiological consequences of methamphetamine

28
and further indicates that methamphetamine-induced release is from the

cytoplasmically bound pool rather than a vesicular bound pool. Similar

experimental procedures have revealed methamphetamine-induced formation

of 5,6-dihydroxytryptamine (5,6-DHT, a neurotoxln to the 5HT system) after a

neurotoxlc dose of methamphetamine (Commlns et al. 1987). It is possible that

the formation of neurotoxlns from endogenous amines that are released by

methamphetamine may mediate methamphetamine neurotoxiclty.

Aside from observation of 6-OHDA and 5,6-DHT, there are also indirect

observations that support these data and theory. Ascorbic acid attenuates

methamphetamine neurotoxicity (Wagner et al. 1985). According to a Fenton

type of reaction system, an excess of ascorbate should protect against 6-OHDA

formation. Conversely, if one deprives guinea pigs of ascorbic acid in the diet,

then one can make them more susceptible to methamphetamine-induced

neurotoxlcity (Matsuda et al. 1987). lnhibition of catylase leads to increased

hydrogen peroxide and increases neurotoxlclty in rats (Axt 1988). In summary,

there is direct and indirect evidence that the formation of neurotoxic substances

from dopamine and 5HT are responslble for the toxicity of methamphetamine to

dopamine and 5HT nerve endings.

There are findings, however, that are either inconsistent with the data

and theory or findings that apparently do not reinforce the data. Rollema

and coworkers (1986) have not been able to detect 6-OHDA after

methamphetamine administration using the technique of in viva dialysis.

Other investigators who have attempted direct replication of these results

have seen either variable results or not seen the 6-OHDA at all (J.W. Gibb

and G. Cohen, personal communication, 1990). Seiden and Vosmer (1984)

reported the number of rats in which the endogenous formation of the toxin

was observed as well as the number of rats examined. The formation of

neurotoxins was not detected in every animal. Attempts to replicate the

experiment also have been variable. In some experiments, no 6-OHDA in

tissue was observed, but in other experiments six of eight rats were seen to

form 6-OHDA. Formation of 6-OHDA was seen in hooded rats and in guinea

pigs.

Sonsalla and colleagues (1989) have found that the N-methyl-d-aspartate

(NMDA) receptor antagonist MK801 can antagonize the neurotoxic effects of

methamphetamine on the dopamine and 5HT systems. This finding suggests

that the release of glutamate may be an important factor in the mediation of

methamphetamine-induced neurotoxicity. Although these data are not

inconsistent with the idea that methamphetamine exerts its toxicity because of

an oxidative stress response, it is not clear how the glutamate and the oxidative

stress are related to one another. NMDA receptors are localized in part on

29
dopamine cell bodies, but the damage engendered by methamphetamine

occurs at the nerve ending.

Oxldative stress reactions seem to occur more frequently in older mammals,

and the hypothesis has been advanced that the progressive loss of dopamine

neurons in humans as a result of aging may be a result of oxidation reactions,

and this finding has implications for Parkinson’s disease. Humans lose

dopamine neurons with advancing age (Hornykiewicz 1989), and insofar as

Parkinson’s disease is related to dopamine and aging, this dopamine loss might

account for the onset of the symptoms. It is possible that this process could

be accelerated in humans taklng large amounts of methamphetamine. Both

dopamine and 5HT have been related to feeding and affective disorders, and

5HT has been related to depression, transmission of pain, sleep, and

sexuality. Since both 5HT and dopamine are depleted by a high dose of

methamphetamine, systematic work to determine the relationship between

methamphetamine abuse and subsequent symptoms is needed. One of the

chief difficulties is that the effects of a large dose of methamphetamine may

deplete dopamine and 5HT enough to cause minimal or no effects shortly after

drug ingestion, but es the amine loss with aging occurs, the loss may become

more apparent; however, it may be difficult to obtain accurate drug histories at

the time such symptoms begin to occur. One of the challenges in this area is to

be able to track toxic changes in the brain with consequences only apparent a

decade or two later.

REFERENCES

Axt, K.J. “Characterization of the Formation of Endogenous Neurotoxins in the

Rat Brain Following Administration of Neurotoxic Amphetamines.” Ph.D.

dissertation, University of Chicago, 1988.

Axt, K.J.; Commins, D.L.; Vosmer, G.; and Seiden, L.S. A-methyl-p-tyroslne

pretreatment partially prevents methamphetamine-induced endogenous

neurotoxln formation. Brain Res 515:269-276, 1990.

Bakhit, C.; Morgan, M.A.; Peat, M.A.; and Gibb, J.W. Long-term effects of

methamphetamine on the synthesis and metabolism of 5-hydroxytryptamine

in various regions of the rat brain. Neuropharmacology 20:1135-1140, 1981.

Brill, H., and Hirose, T. The rise and fail of a methamphetamine epidemic:

Japan 1945-55. Semin Psychiatry 1:179-194, 1969.

Commins, D.L.; Axt, K.J.; Vosmer, G.; and Seiden, L.S. 5,6-

Dihydroxytryptamine, a serotonerglc neurotoxln is formed endogenously in

the rat brain. Brain Res 403:7-14, 1987.

Gilman, A.G.; Goodman, L.S.; Rall, T.W.; and Murad, F. The Pharmacological

Basis of Therapeutics. 7th ed. New York: MacMillan, 1985.

30
Hornykiewicz, O. Ageing and neurotoxlns are causative factors in idiopathic

Parkinson’s disease: A critical analysis of the neurochemical evidence. Prog

Neuropsychcpharmacol Biol Psychiatry 13:319-328,1989.

Hotchkiss, A.J., and Gibb, J.W. Blockade of methamphetamine-induced

depression of tyrosine hydroxylase by GABA transaminase inhibitors. Eur J

Pharmacol 66:204-205, 1980.

Inghe, G. The present state of abuse and addiction to stimulant drugs in

Sweden. In: Sjoqvist, F., and Tottie, M., eds. Abuse of Central Stimulants.

Stockholm: Almqvist and Wiksell, 1969. pp. 187-219.

Koda, L.Y., and Gibb, J.W. Adrenal and striatal tyroslne hydroxylase activity

after methamphetamine. J Pharmacol Exp Ther 185:42-48, 1973.

Kramer, J.C.; Fischman, VS.; and Littlefield, D.C. Amphetamine abuse.

Pattern and effects of high doses taken intravenously. JAMA 201:305-309,

1967.

Levine, M.S.; Hull, C.D.; Garcia-Rill, E.; Erinoff, L.; Buchwald, A.; and Heller, A.

Long-term decreases in spontaneous firing of caudate neurons induced by

methamphetamine in cats, Brain Res 194:263-268, 1980.

Matsuda, L.A.; Schmidt, C.J.; Gibb, J.W.; and Hanson, G.R. Ascorbic aciddeficient condition alters central effects of methamphetamine. Brain Res

400:176-180, 1987.

Raiteri, M.; Cerrito, F.; Cervoni, A.M.; and Levi, G. Dopamine can be released

by two mechanisms differentially affected by the dopamine transport inhibitor

nomifensine. J Pharmacol Exp Ther 208:195-202, 1979.

Ricaurte, G.A.; Guillery, R.W.; Seiden, L.S.; and Schuster, C.R. Selective

neurodegenerative changes in the somatosensory cortex following treatment

with methylamphetamine, p-chloroamphetamine but not 6-HDA. Soc

Neurosci 6(259.7):764, 1980.

Ricaurte, G.A.; Guillery, R.W.; Seiden, L.S.; and Schuster, C.R. Nerve terminal

degeneration after a single injection of d-amphetamine in iprindole-treated

rats: Relation to selective long-lasting dopamine depletion. Brain Res

291:378-382, 1984.

Ricaurte, G.A.; Guillery, R.W.; Seiden, L.S.; Schuster, C.R.; and Moore, R.Y.

Dopamine nerve terminal degeneration produced by high doses of

methylamphetamine in the rat brain. Brain Res 235:93-103, 1982.

Rollema, H.; DeVries, J.B.; Westerink, B.H.C.; VanPutten, F.M.S.; and Horn,

A.S. Failure to detect 6-hydroxydopamine in rat striatum after the dopamine

releasing drugs dexamphetamine, methylamphetamine and MPTP. Eur J

Pharmacol 132:65-69, 1986.

Seiden, L.S., and Dykstra, L.A. Psychopharmacology: A Biochemical and

Behavioral Approach. New York: Van Nostrand Reinhold Company, 1977.

Seiden, L.S.; Fischman, M.W.; and Schuster, C.R. Long-term

methamphetamine-induced changes in brain catecholamines in tolerant

rhesus monkeys. Drug Alcohol Depend 3:215-219, 1976.

31
Seiden, L.S., and Ricaurte, G.A. Neurotoxicity of methamphetamine and

related drugs. In: Meltzer, H., ed. Psychopharmacology: The Third

Generation of Progress. New York: Raven Press, 1987. pp. 359-366.

Seiden, L.S., and Vosmer, G. Formation of 6-hydroxydopamine in caudate

nucleus of the rat brain after a single large dose of methylamphetamine.

Pharmacol Biochem Behav 21:29-31, 1984.

Slivka, A., and Cohen, G. Hydroxyl radical attack on dopamine. J Biol Chem

260:15466-15472, 1985.

Sonsalla, P.K.; Nicklas, W.J.; and Heikkila, R.A. Role for excitatory amino acids

in methamphetamine-induced nigrostiagal dopaminergic toxicity. Science

243:398-400, 1989.

Steranka, L.R., and Sanders-Bush, E. Long-term effects of continuous

exposure to amphetamine in brain dopamine concentration and

synaptosomal uptake in mice. Eur J Pharmacol 65:439-443, 1980.

Wagner, G.C.; Carelli, R.M.; and Jarvis, M.F. Pretreatment with ascorbic acid

attenuates the neurotoxic effects of methamphetamine in rats. Res Commun

Chem Pathol Pharmacol 47:221-228, 1985.

Wagner, G.C.; Lucot, J.B.; Schuster, C.R.; and Seiden, L.S. Alphamethyltyrosine attenuates and reserpine increases methamphetamineinduced neuronal changes. Brain Res 270:285-288, 1983.

Wagner, G.C.; Ricaurte, G.A.; Johanson, C.E.; Schuster, C.R.; and Seiden, L.S.

Amphetamine induces caudate dopamine depletion. Neurology 30:547-550,

1980.

Wagner, G.C.; Schuster, C.R.; and Seiden, L.S. Methamphetamine induced

changes in brain catecholamines in rats and guinea pigs. Drug Alcohol

Depend 4:435-438, 1979.

Wish, E.D. U.S. drug policy in the 1990s: Insight from new data from

arrestees. Int J Addict 25(3A):377-409, 1990.

Woolverton, W.L.; Ricaurte, G.A.; Forno, L.S.; and Seiden, L.S. Long-term

effects of chronic methamphetamine administration in rhesus monkeys,

Brain Res 486:73-78, 1989.

AUTHOR

Lewis S. Seiden, Ph.D.

Professor

Department of Pharmacology and Physiological Sciences

University of Chicago

947 East 58th Street

Chicago, IL 60637

32
The Environmental Impact and

Adverse Health Effects of the

Clandestine Manufacture of

Methamphetamine

Gary D. Irvine and Ling Chin

INTRODUCTION

Seizures of clandestine methamphetamine drug laboratories are becoming

increasingly common. In the 1980s the number of methamphetamine drug

laboratory seizures had risen dramatically, from 88 seizures in 1981 to 652 in

1989, an increase of more than 600 percent (figure 1). Since 1987 more than

over 80 percent of all clandestine laboratories seized have been involved with

the synthesis of methamphetamine (unpublished data, Office of Intelligence,

Drug Enforcement Administration 1990). Although these drug laboratories can

be found throughout the United States, three states accounted for 76.5 percent

of all laboratories seized in 1988: California (50.1 percent), Texas (13.4

percent), and Oregon (13.0 percent) (U.S. Department of Justice 1989) (figure

2). States with the next highest number of seizures were New Mexico (3.5

percent) and Washington (3.2 percent).

The illicit manufacture of methamphetamine was dominated historically by

outlaw biker gangs. These bikers were known to purchase the precursor

chemicals in cities and produce the methamphetamine in remote country areas

where the telltale fumes were vented more easily. Other groups have now

become involved with the illicit manufacture of methamphetamine and are quite

versatile in where they place their laboratories, which have been found in

private residences, rental homes, motel rooms, garages, campgrounds,

moving vans, storage facilities, horse trailers, houseboats, and commercial

establishments. These makeshift laboratories have increased the mobility of

the individuals involved: it is not uncommon for them to cook up a batch, make

a sale, discard the equipment and chemical residues onsite, and move on to

continue the process at another location.

33
FIGURE 1. U.S. clandestine laboratory seizures, 1988

SOURCE: US. Department of Justice 1989

METHAMPHETAMINE SYNTHESIS

The illicit manufacture of methamphetamine is a relatively simple process and

can be carried out by individuals without special knowledge or expertise in

chemistry. “Cookers” have produced methamphetamine batches by following

cookbook-style recipes (which may have been obtained while they were in jail).

Therefore, methods of methamphetamine production and the final product can

vary from laboratory to laboratory.

The two predominant methods of methamphetamine production are the

amalgam and ephedrine methods (Oregon Department of Human Resources

1988).

The amalgam method uses phenyl-2-propanone (P2P) and methylamine

as the primary precursors. Hydrochloric acid, mercury, and aluminumcontaining reagents also are used. In forensic chemistry reports on 190

methamphetamine laboratories seized by the Drug Enforcement Administration

(DEA) during the 45-month period ending in September 1981, three methods of

synthesis predominated (Frank 1983). The most common method of synthesis

(employed by more than 50 percent of laboratories) uses P2P, methylamine,

mercuric chloride, and aluminum metal in alcohol; the second most common

34
FIGURE 2. Clandestine methamphetamine laboratory seizures in the United States, 1988

SOURCE: U.S. Department of Justice 1989
method (<10 percent) uses acetaldehyde, methylamine, and benzylmagnesium

chloride. The third (<10 percent) uses a Leuckart reaction, utilizing P2P,

methylamine, formic acid or N-methylformamide, and hydrochloric acid.

The ephedrine method is a newer and cleaner method employing ephedrine as

the primary precursor. The most common ephedrine process known involves

the use of red phosphorus. Whatever the process used to manufacture

methamphetamine, the inclusion of by-products and contaminants in the final

product is inevitable.

In February 1980, P2P became a Schedule II controlled substance, and the

popularity of the P2P method of making methamphetamine waned as a result.

Some illicit manufacturers began making their own P2P. The most frequently

used method (>75 percent) of making P2P used phenylacetic acid and acetic

anhydride, with sodium acetate or pyridine.

The ephedrine method of synthesizing methamphetamines gained popularity

after P2P became a controlled substance. The use of ephedrine and pyridine

with hydrogen iodide and red phosphorus was observed for the first time

in 1981 (Frank 1983). The use of the ephedrine method in clandestine

laboratories first began in southern California, spreading north to other

California cities, and then to other cities along the west coast.

DEA data from 1989 showed a total of 652 methamphetamine laboratories

seized, with a breakdown on method of synthesis used for 416 of these

laboratories; 219 (53 percent) laboratories were using the ephedrine method,

whereas 197 (47 percent) laboratories were using the P2P method

(unpublished data, Office of Intelligence 1990).

ADVERSE EFFECTS

Although the production of methamphetamine is a relatively simple process,

it can have dangerous consequences and can place several groups of people

at risk of exposure to toxic chemicals and its subsequent effects. Those most

likely to be exposed include the drug manufacturers; law enforcement officers:

local health, fire, and police personnel: residents near laboratory sites; and

future occupants of discarded laboratory sites. The chemicals used in the

manufacturing process can be corrosive, explosive, flammable, toxic, and,

possibly, radioactive. There is also a potential for infectious disease from

exposure to drug paraphernalia such as used needles left onsite by

manufacturers who may be users. Exposure can occur via skin absorption,

inhalation, ingestion, or injection. Inhalation and/or skin absorption are the

most likely routes of exposure for those exposed directly to the laboratory

environment.

36
Environmental Effects

The underlying problem with the illicit production of methamphetamine is that for

the most part the producers possess neither the knowledge nor the skill to carry

out the synthesis appropriately. They often do not use the correct proportion of

precursors, reagents, solvents, or catalysts, and they may not follow instructions

for the synthetic process exactly as stated. They may not be able to eliminate

undesirable by-products or contaminants; thus, end products are of variable

purity and quality. Also, they may operate under suboptimal conditions with

poor ventilation and temperature control systems. When the final product is

obtained, leftover equipment and chemicals often are neither stored nor

disposed of appropriately. All these factors create a highly dangerous

environment where the potential for chemical spills, fire, explosion, and

environmental contamination could have significant impact on the public’s

health.

Several of the chemicals used in the production of methamphetamine are

highly flammable and/or explosive. Typical chemicals in a clandestine

methamphetamine laboratory, such as methylamine, petroleum ether,

phosphine, benzene, ethanol, and lithium aluminum hydride, are highly or

extremely flammable (Joint Federal Task Force 1990). Other chemicals, such

as sodium, magnesium, and potassium metals, are extremely reactive with air

and water and can ignite or explode. There is always potential for a fire or

explosion at one of these clandestine laboratories. In fact, approximately 30

percent of drug laboratories found by police in Oregon are found secondary to

mysterious explosions (VanDyk 1989). The lack of proper ventilation and

temperature controls at these laboratories further compound this problem of fire,

explosion, and human exposure.

Chemical spills are another potentially serious problem. In a large chemical

spill, ambient air concentrations could be great enough to cause symptoms from

the inhalation of solvents, corrosives, or cyanide.

Another serious problem with wider public health implications is the

indiscriminate contamination of the environment with hazardous chemicals.

Residual chemicals and other chemical by-products are usually not stored or

disposed of according to regulations governing hazardous wastes, Solvent

chemicals may be dumped into the ground or into sewers or septic systems,

thus contaminating surface water, ground water, and wells, requiring extensive

cleanup efforts.

Traces of chemicals can permeate the walls, drapes, carpets, and furniture of a

laboratory site and can leave a lingering odor that is not easily dissipated.

37
Phenylacetic acid produces a disagreeable odor, characteristically described as

“cat urine” smell, which is a giveaway sign of methamphetamine production.

Other toxic vapors also can permeate building walls or be vented outside.

Clandestine operators are often afraid that these vapors may alert law enforcers

to the laboratory and purposely seal all potential outlets to prevent the vapors

from escaping. Since these vapors are potentially toxic, the operators may

suffer fatal consequences from overexposure.

Methamphetamine producers also are known to install booby traps to prevent

entry by unwanted individuals and to destroy the evidence should the facility be

discovered. These booby traps are designed to cause serious injury. When

chemical booby traps are used, there is significant potential for serious chemical

exposure to intruders and/or law enforcement personnel.

Acute Health Effects

The most significant health risk related to the production of methamphetamine

is the acute injury secondary to massive chemical exposure. Primary routes of

exposure occur via inhalation and contact to the skin and eyes.

Acute health effects from exposure to any combination of corrosive chemicals

include irritation to the skin, eyes, nose, throat, and lungs causing symptoms

such as burning of the skin and eyes, lacrimation, coughing, chest pain, and

shortness of breath. Conjunctivitis and corneal injury may result from the

exposure. Pulmonary edema and hemoptysis may occur in severe cases.

Other symptoms of inhalation of chemical vapors include nausea, dizziness,

headache, anxiety, and lethargy (Oregon Department of Human Resources

1988).

When hydrogen cyanide gas is present, inhalation may result in rapid

progression of symptoms to coma, respiratory failure, and death. Freon spilled

onto the skin may cause a freezing injury to the skin. Inhalation of solvent

vapors at low concentrations causes mild eye, nose, and throat irritation, At

higher concentrations, drowsiness and incoordination may occur. High doses of

exposure to solvent chemicals also could lead to liver and kidney impairment

(Oregon Department of Human Resources 1988).

Other substances that may be present in the laboratories include various metals

and salts. These substances are usually stable solids but in the presence of

moisture may become extremely corrosive and/or reactive. When heated,

some of these substances could be present in the air as dust or fumes and may

be inhaled, with subsequent health effects (Oregon Department of Human

Resources 1988). (See Appendix 1 for a list of possible chemicals used in the

38
synthesis of methamphetamine. See Appendix 2 for a list of exposure routes

and health effects by type of chemical involved.)

Chronic Health Effects

Little is known about the chronic health effects of exposure to clandestine drug

laboratories. There is some data from animal and human toxicology studies

that indicate that some of the chemicals used in the manufacture of

methamphetamine may cause cancer, brain damage, liver and kidney

problems, and birth defects and reproductive problems. There is no current

scientific evidence that human health risk continues once the site is properly

decontaminated (Oregon Department of Human Resources 1988).

Health Effects Due to Product Contamination

The presence of contaminants in the final product of clandestine

methamphetamine synthesis presents other health problems. Illicit

methamphetamine is not produced under good manufacturing practices. For

example, lead acetate used as a reagent in the manufacture of P2P, a

precursor for methamphetamine production using the amalgam method, can

result in significant quantities of lead being present in the methamphetamine

thus produced. ln 1987 two cases of acute lead poisoning were repported in

intravenous users of illicitly produced methamphetamine in Oregon (Allcott et al.

1987). In 1988, also in Oregon, a cluster of lead poisoning cases was

discovered among intravenous methamphetamine drug users (Centers for

Disease Control 1990). Patients commonly presented with symptoms such as

abdominal pain, nausea, vomiting, body pains, Weakness, weight loss, and

anorexia. Testing of a sample of illicitly produced methamphetamine provided

by one of these cases revealed the presence of 60 percent lead by weight.

Another potential contaminant found in illicitly produced methamphetamine is

mercury. The “mercury method” uses P2P and methylamine, which undergo

condensation in the presence of aluminum foil and mercuric chloride.

Inadequate purification produces a final product contaminated with mercury,

residues of which have been found in varying amounts ranging from zero to

1,300 ppm, in methamphetamine samples from 25 clandestine

methamphetamine laboratories Seized by DEA (Davidson 1983). However, a

literature search did not reveal any cases of mercury poisoning in

methamphetamine users in the United States.

Impurities found in the final product of some of these clandestine drug

laboratories have resulted in severe and permanent neurologic disability to the

drug user. One dramatic example, although not related to methamphetamine,

39
is the observance of parkinsonlsm in drug users exposed to meperidine analogs

contaminated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin8e

(Ballard et al. 1985; Ruttenber et al. 1986).

Economic Effects

A deserted clandestine methamphetamine laboratory poses significant risks to

the health of the public in nearby vicinities, and proper decontamination of such

sites must be carried out. A typical cleanup of a property that has been used as

a methamphetamine drug laboratory may cost more than $5,000. If it is a rental

property, the owner may be burdened with the costs and responsibility of the

cleanup. The DEA uses asset forfeiture funds to finance the cleanup of

clandestine laboratories and advises the States to develop and implement their

own asset forfeiture programs. ln some instances, proper decontamination for

reuse may not be feasible, and the property may have to be totally destroyed.

The cleanup process may involve all the following:

Removal of surface material layers

Use of encapsulants and fixative sealers

Neutralization of corrosives

Steam cleaning with light-duty equipment

Use of industrial steam and pressure washers

Use of detergent washes

Use of chemical neutralizers/coverups

“Bake-out” of a property

CONCLUSION

Use of methamphetamine is endemic in certain parts of the United States, and

according to the Drug Abuse Warning Network of the National Institute on Drug

Abuse, increases were observed in indicators of methamphetamine use during

the 1980s in several west coast cities. In keeping with this trend is the problem

of the proliferation of clandestine methamphetamine drug laboratories as

evidenced by the greater than 600-percent increase in number of such

laboratories seized from 1981 to 1989 (National Institute on Drug Abuse 1990).

This proliferation of clandestine drug laboratories poses a serious problem

because it places innocent bystanders, public officers, and individuals who are

manufacturing the drug at risk of exposure to hazardous chemicals. It also

should be of public health concern because the potential for a larger segment of

the population to be affected is significant via the inappropriate dumping of

hazardous chemicals into the environment, thereby causing contamination of

both ground and surface water.

40
Several significant steps have been taken in recent years to address this

emerging problem, including the formation of state clandestine drug laboratories

committees, passage of State precursor laws, development of guidelines on

how to respond to methamphetamine drug laboratory complaints, and adoption

of local regulations that deal with the health and safety hazards associated with

methamphetamine drug laboratories.

Precursor control legislation has been passed in the States of California,

Oregon, Washington, and Texas during 1987 and 1988 (U.S. Department of

Justice 1999). For example, California requires a 21-day waiting period and full

identification of the purchaser before dispensing any one of 17 specified

chemicals, among which are ephedrine and pseudoephedrine. Oregon requires

transactions involving the transfer of precursor substances to be reported to the

State Police. Texas requires records to be kept of identifying information on

purchasers of chemicals, a copy of which goes to the Department of Public

Safety, Narcotics Service.

However, much more needs to be done to curtail the demand for

methamphetamine and the production of methamphetamine by illicit drug

laboratories. Some recommendations for a future strategy to combat this

problem include:

Establish comprehensive drug programs to decrease the problem of drug

abuse.

Increase public awareness of the clandestine drug laboratory problem.

Conduct further research on the health effects, especially chronic health

effects, of exposure to hazardous chemicals used in the manufacture of

methamphetamines.

Conduct further research to determine the safe levels for reoccupation of a

property that had been used as a drug laboratory.

Consider national strategies to impose stricter controls on the availability of

precursor chemicals for methamphetamine production.

REFERENCES

Allcott, J.V.; Barnhart, R.A.; and Mooney, L.A. Acute lead poisoning in two

users of illicit methamphetamine. JAMA 258(4):510-511, 1987.

Ballard, P.A.; Tetrud, J.W.; and Langston, J.W. Permanent parkinsonism in

humans due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): A

41
report of seven moderate-to-severely affected cases. Neurology 35:949-956,

1965.

Centers for Disease Control. Lead poisoning associated with intravenousmethamphetamine use—Oregon, 1988. JAMA 263(6):797-798, 1990.

Davidson, A. Mercury residues in illicit methamphetamine. Microgram

16(9):142-146, 1983.

Frank, R.S. The clandestine drug laboratory situation in the United States.

J Forensic Sci 28(1):18-31, 1983.

Joint Federal Task Force: Drug Enforcement Administration, Environmental

Protection Agency, U.S. Coast Guard. Guidelines for the Cleanup of

Clandestine Drug Laboratories. Washington, DC: U.S. Department of

Justice, Drug Enforcement Administration, March 1990.

National Institute on Drug Abuse. Semiannual Report. Data from the Drug

Abuse Warning Network. DHHS Pub. No. (ADM)90-1664. Washington, DC:

Supt. of Docs., U.S. Govt. Print. Off., 1990.

Oregon Department of Human Resources. Hazardous Chemicals: Guidelines

for Local Law Enforcement Personnel: (Substances Found in

Methamphetamine Menufactories). 4th ed. Portland, OR: Department of

Human Resources, Health Division, June 1988.

Ruttenber, A.J.; Garbe, P.L.; Kalter, H.D.; Castro, K.G.; Tetrud, J.W.; Porter, P.;

Irwin, I.; and Langston, J.W. Meperidine analog exposure in California

narcotics abusers: Initial epidemiologic findings. In: Markey, S.P.;

Castagnoli, N.; Trevor, A.J.; Kopin, I.J., eds. MPTP: A Neurotoxin Producing

a Parkinsonian Syndrome. Orlando, FL: Academic Press, 1986. pp. 339-

353.

U.S. Department of Justice. Clandestine Laboratory Seizures in the United

States: Calendar Year 7988. Washington, DC: U.S. Department of Justice,

Drug Enforcement Administration, Office of Intelligence, August 1989.

VanDyk, J. Drug labs require special ecology attention, Baseline 8(5):4, 1989.

AUTHORS

Gary Irvine, B.S., R.S.

Environmental Health Supervisor

Seattle-King County Department of Public Health

Suite 101

1404 Central Avenue South

Kent, WA 98032

42
Ling Chin, M.D., M.P.H.

Epidemiologist

Division of Epidemiology and Prevention Research

National institute on Drug Abuse

Rockwall II, Suite 815

5800 Fishers Lane

Rockville, MD 20857

APPENDIX 1

Chemicals Associated With Illicit Methamphetamino Manufacture

METAL/SALT REAGENTS SOLVENTS

Aiuminum foll

Iodine

Lead acetate

Lithium aluminum hydride

Magnesium

Mercuric chloride

Palladium

Red phosphorus

Sodium

Sodium cyanide

Thicnyl chloride

Acetone

Benzene

Chloroform

Ethyl ether

Freon

Hexane

lsopropanol

Methanol

Pyrldine

PRECURSORS ACID-BASE REAGENTS

Acetaldehyde

Benzyl chloride

Ephedrine

Methytamine

Phenylacetic acid

P2P

Acetic acid

Acetic anydride

Ammonla

Hydrochloric acid

Hydrogen peroxide

Hydrlodic acid

Sodlum hydroxide

Sulfuric acid

By-Products and Contamlnants Associated With the Manufacture of

Methamphetamine

P2P AMALGAM METHOD

Dibenzyl ketone

Enol acetate of P2P

Lead oxides

Aluminum oxides

Aluminum hydroxlde

Mercury

Acetic acid

-benzyl-N-methylphenethylamine

N,N-dimethytamphetamine

Amphetamine

Di-(1-phenyllaopropyl) amine

Di-(1-phenylleopropyl) methylamine

Tri-(1-phenyllsopropyl) amine

Benzyl methyl ketone phenyllsopropyllmine

Benzyl methyl ketone benzyllmine

2,4-dihydrozy-1.5-diphenyl-4-methylpentone

43
EPHEDRINE METHOD

Iodine

Chloropseudoephedrine

Phosphine (produced from overheating)

Yellow phosphorus (produced from overheating)

SOURCE: Oregon Department of Human Resources 1988

APPENDIX 2

Chemical Toxicity and Routes of Exposure (Skln and Respiratory)

CYANIDE

Substance Form Exposure

Sodium cyanide Solid Skin, eyes

Potassium cyanide Solid Skin, eyes

Benzyl cyanide Liquid Skin, eyes, inhalation

Hydrogen cyanide Gas lnhalation

Health effects: Highly toxic substances. If solid salt forms are mixed with acid, hydrogen

cyanide gas will be released. lnhalation of hydrogen cyanide may result in rapid progression of

symptoms to coma, respiratory failure, and death.

CORROSIVES AND IRRITANTS

Substance Form Exposure

Acetic acid

Acetic anhydride

Benzyl chloride

Hydrlodic acid

Methylamine

Perchloric acid

Phosphine

Sodium metal

Sodium hydroxide

Thlonyl chloride

Liquid

Liquid

Liquid

Liquid

Gas, liquid, solid

Liquid

Gas

Solid

Liquid, solid

Liquid

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Eyes, inhalation

Skin, eyes

Skin, eyes

Skin, eyes

Health effects: Vapors of volatile corrosives may cause eye irritation, lacrimation,

conjunctivitie, and corneal injury. lnhalation may cause irritation of mucous membranes of the

nose and throat and lung irritation resulting in cough, chest pain, shortness of breath.

Pulmonary edema and hemoptysis may occur in severe cases. High concentrations of vapor

may cause skin irritation. Additional symptoms of vapor inhalation may include headache,

nausea, dizziness, and anxiety. Direct contact with corrosives may result in severe eye or skin

burns.

44
SOLVENTS

Solvents Form Exposure

Acetone

Benzene

Benzyichloride

Chloroform

Ethanol

Ethyl ether

Freon

Hexane

Isopropanol

Methanol

Petroleum ether

Pyridine

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Skin, eyes, inhalation

Health effects: inhatation of vapors at low ccncentrations may result in mild eye, nose, and

throat irritation. Symptoms of intoxication (drowsiness and incoordination) or loss of

consciousness may occur at high concentrations. Liver and kidney impairment also may occur

at high doses. Freon spilled onto the skin may result in freezing injury to the skin.

METALS/SALTS

Substance Form Exposure

Abuminum

Magnesium

Palladium

Red phosphorous

lodine

Mercuric chloride

Lead acetate

Lithium aluminum hydride

Sodium acetate

Sodium hydroxide

Sodium metal

Potassium metal

Thorium

Solid

Solid

Solid

Solid

Solid

Solid

Solid

Solid

Solid

Solid

Solid in kerosene

Solid in kerosene

Solid

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Skin, eyes

Health effects: Most metals and salts are stable solids with minimal potential for exposure

unless ingested or unless the metal is present in the air as dust or fumes, if heated. Sodium

and potassium metal and sodium hydroxide are extremely corroeive in the presence of

moisture. Lithium aluminum hydride is extremely reactive. Thorium is an alpha-emitting

radioactive material.

PRECURSORS

Substance Form Exposure

Phenylacetic acid

Solid, with characteristic

foul odor. Used in fragrances,

flavorings. May produce

irritation upon direct contact.

Solid Skin, eyes

45
P2P

Spacific toxiclty data

lacking. Simllar compounds

used in fragrances and

phamaceuticals.

Liquid Skin, eyes

Methylamine

Ammonia odor present at

very low levels. See

also irritants, corrosives.

Gas Skin, eyes, inhalation

Liquid Skin, eyes inhalation

Solid Skin, eyes

SOURCE: Oregon Department of Human Resources 1988

46
Heavy Metal and Organic

Contaminants Associated With Illicit

Methamphetamine Production

Brent T. Burton

INTRODUCTION

Methamphetamine is a powerful stimulant drug commonly known on the street

as “crank” or “speed.” It is currently the most popular and widespread

amphetamine that is iiiegaiiy manufactured, distributed, and abused.

Illicit methamphetamine is produced in clandestine laboratories that are

widespread in the United States. The profit motive for the clandestine chemist

is enormous, with some laboratories producing in excess of $800,000 per week

in street value. Although several other illicit drugs of abuse are occasionally

manufactured in clandestine laboratories, methamphetamine accounts for

almost 95 percent of all clandestine laboratory seizures. The frequency of

laboratory seizures has been increasing nationwide over the past decade (Anon

1988). The States of California, Texas, Oregon, and Washington have shown

the greatest increase in clandestine laboratory activity.

Adverse health effects to the abuser are not limited to toxic effects of the drug.

Illicit drugs produced in clandestine laboratories by unskilled chemists are likely

to contain potentially toxic contaminants due to unintended reaction by-products

and reagent residuals. Process errors in the production of clandestine drugs

previously have resulted in severe health effects, including acute Parkinson’s

disease from attempted production of 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP) and acute lead poisoning from injection of methamphetamine

(Aiicott et al. 1987; Ballard et al. 1985; Norton et al. 1989).

The average concentration of methamphetamine street samples is

approximately 40 to 50 percent (Hall et al. 1988). Most contaminants found in

illicit drugs are intentionally added by the distributor to dilute or “cut” the product

to increase profits. Such substances include lactose, mannitoi, iidocaine,

procaine, caffeine, quinine, and sodium bicarbonate and may account for as

47
much as 94 percent of the finished product (Grinspoon and Bakalar 1985). In

the case of drugs produced by the clandestine chemist, additional contaminants

may be introduced by the production process. One can predict such potential

contaminants due to unreacted substances or unintended reaction products

from known production methods available to the clandestine chemist. Though

unintended contaminants may be introduced into the finished drug by the

clandestine chemist, the extent and types of substances as a result of the

production process have not yet been adequately studied.

HISTORY

Methamphetamine was developed in 1919 as an amphetamine derivative by A.

Ogata, a Japanese pharmacologist. However, it was not until the 1930s that

the pharmacologic properties of amphetamines became known, The

sympathomimetic properties of amphetamines initially made them useful as

vasoconstrictor agents, and they were first introduced into the marketplace in

1932 as Benzedrine, an inhaler designed for relief of nasal congestion. Users

of these nonprescription inhalers soon noted that the amphetamine contents

were powerful central nervous system stimulants, This property subsequently

made amphetamines useful drugs in the treatment of narcolepsy and some

forms of depression but also made them desirable as drugs of abuse.

The abuse of amphetamine began almost as soon as it was available as an

over-the-counter medication. Shortly after the Benzedrine nasal inhaler

became available in 1931, abusers were taking apart the spray bottle to retrieve

the paper inside containing 250 mg of amphetamine. These strips of paper

then were consumed in chewing gum or stirred into a beverage for its

stimulating and euphoric effect (Grinspoon and Hedblom 1975).

By 1962 the legal production of amphetamines was estimated by the Food and

Drug Administration to be more than 8 billion tablets per year, with output

increasing every year. Much of the amphetamine abuse of the 1950s and

1960s occurred as a result of prescription abuse by individual patients obtaining

drugs from their private physician, many of whom knowingly were writing

prescriptions for profit.

The drug culture of the 1960s brought a dangerous new route of administration

for amphetamines. An injectable form of pharmaceutical methamphetamine

rapidly became responsible for the amphetamine abuse lifestyle known as the

“speed freak.” The dangerously addictive nature of injectable amphetamines

became obvious with the advent of the amphetamine-tolerant freak who would

inject as much as 15 g of amphetamine during a single day (Grinspoon and

Hedblom 1975).

48
Until the 1970s most amphetamines were obtained from pharmaceutical

sources that were diverted into the black market. It has been estimated that as

much as 50 percent of legitimate amphetamine production was diverted by

shipments to unauthorized persons, thefts, or prescription forgeries (Morgan

1981).

Due to the abuse of amphetamines and other drugs in the United States,

the Controlled Substance Act (CSA) was passed in 1970, which designated

control schedules for drugs according to their abuse potential. This act

dramatically changed the availability of pharmaceutical amphetamines by

requiring special procedures for manufacturers to register shipments and

provide detailed accounting of transactions involving controlled substances.

Predictions that strict controls would result in a shift to clandestine production

of methamphetamine did not materialize at that time. However, the increased

availability and use of cocaine in the 1970s may have temporarily reduced

market demand for methamphetamine.

As amphetamines became more difficult to obtain, purity of street samples

began to decline. During the mid-1970s many street samples sold as

amphetamine contained little or none of it, and a variety of drugs began to show

up that were being sold as amphetamine. Samples of street amphetamines in

1973, after the effect of the CSA was apparent, contained only about 10 percent

amphetamine on average (Morgan 1981). Most often, over-the-counter drugs

with stimulant properties such as caffeine, ephedrine, and phenylpropanolamine

were substituted and sold as amphetamine. This practice eventually led to the

drug “look-alike” business, a thriving mail-order enterprise offering these legal

over-the-counter drugs packaged and promoted with names, tablet shapes, and

colors designed to mimic amphetamines.

Since the mid-1980s there has been a reemergence of the illicit use of

methamphetamine. One such indicator is the rapid increases that have been

documented in numbers of clandestine laboratories seized by law enforcement

agencies. Most recently, media reports have focused on the increasing

popularity of “ice,” a smokable form of methamphetamine (Lerner 1969). The

use of this crystalline form of methamphetamine has been prevalent especially

in Hawaii, where it is imported from Pacific rim countries. As this form of

methamphetamine becomes more widely available in the United States, it is

possible that stimulant users once again will shift to methamphetamine.

CLANDESTINE SYNTHESIS OF METHAMPHETAMINE

Illicit manufacture of methamphetamine is a simple process that does not

require special knowledge or expertise in chemistry. Most methamphetamine is

49
produced by relatively uneducated persons who synthesize the drug from

published or handwritten recipes, The drug subculture provides abundant

opportunities for the potential clandestine chemist to obtain recipes, or even

attend cooking classes, for methamphetamine. Many recipes in circulation are

handwritten instructions that describe how to procure the needed chemicals,

glassware, and supplies. These instructions often include detailed sketches

and descriptions of the procedure so the novice can produce methamphetamine

without prior trainlng. Some underground recipes even describe the legal status

of various chemicals and methods to avoid detection by law enforcement

officials.

Several publications, available in bookstores or by mail order, describe the

methods of drug manufacture. One such publication, Psychedelic Chemistry,

describes detailed recipes for the production of several drugs. In addition,

information is provided about how to obtain chemicals and laboratory equipment

without prompting the attention of law enforcement officials (Smith 1981).

The clandestine chemist need not resort to handwritten underground recipes or

try to locate the proper reference text in a bookstore. Numerous scientific

journals provide a wealth of information regarding drug synthesis, including

alternate procedures for a variety of processes, that the chemist may select

depending on chemical availability. The educational level of persons utilizing

such references must be more sophisticated than that of the typical clandestine

chemist due to the highly technical nature of the journals. An example of such

an article is a description of a currently unused but proposed method of

production, authored by chemists of the U.S. Drug Enforcement Administration

(DEA) (Cason et al. 1984). These references usually are torn or cut out of

library journals, presumably to reduce competition from other would-be

clandestine chemists.

Because the clandestine chemist usually lacks skill and training in chemistry,

there are multiple opportunities for errors or misunderstanding of proper

procedure. Attempts at shortcuts, inadequate filtering, salt washing, or solvent

extraction could result in serious contamination with reagents. At least one

clandestine chemist apparently completely misunderstood the proper procedure

and produced a finished product that contained 60 percent lead with phenyl-2-

propanone (P2P) but no methamphetamine (Norton et al. 1989).

Numerous chemicals associated with the illicit production of methamphetamine

are listed below. Although only a few chemicals may be required for production,

there are multiple reagents and precursors that can be substituted for those that

are difficult to obtain legally. Thus, there may be many chemicals that

potentially can contaminate the finished product.

50
SOLVENTS REAGENTS

Acetone

Benzene

Chloroform

Ethyl ether

Ethanol

Freon

Hexane

lsopropanol

Methanol

Pyridine

Toluene

PRECURSORS

Acetaidehyde

Acetic anhydride

Allyl benzene

Benzyl cyanide

Benzylchloride

Diethylmalonate

Dimethylformamide

Ephedrine

Ethanol

Ethyl acetate

Formic acid

Hydrogen gas

Hydrogen peroxide

Methylamine

N-methylformamide

Nitroethane

Phenyl-2-propanone

Phenylacetic acid

Phenylacetylchloride

Metals

Aluminum

Barium sulfate

Calcium chloride

Copper chloride

ron

Lead acetate

Lithium aluminum hydride

Magnesium

Magnesium sulfate

Manganese oxide

Mercuric oxide

Mercuric chloride

Palladium

Palladium chloride

Potassium cyanide

Sodium acetate

Sodium ethoxide

Sodium cyanide

Sodium

Cyanotrlhydroborate

Sodium

Thorium oxide

Nonmetals

Butylamine

Iodine

Phosphorous

Phosphorouapentachoride

Thionyl chloride

Acids

Acetic acid

Hydrochloric acid

Hydroiodic acid

Perchloric acid

Phosphoric acid

Sulfuric acid

Bases

Ammonia

Sodium hydroxide

Sodium carbonate

51
PRODUCTION PROCESSES

P2P is the primary precursor most often used by the clandestine chemist. The

amalgam and Leukart processes are the most popular (figure 1), accounting for

about 90 percent of clandestine methamphetamine production (Frank 1983).

Processes involving P2P as the precursor often utilize methylamine to provide

the amine group and thus formulate methamphetamine in a simple single-step

reaction procedure. The amalgam method utilizes a combination of mercuric

chloride and aluminum foil as catalysts (figure 1). These and all reactions

require a variety of acids and solvents for extraction and purification of the

finished product.

FIGURE 1. Synthesis of methamphetamine utilizing the amalgam method

catalyzed by mercuric chloride and aluminum foil

The clandestine manufacturing and purification procedure is represented by the

following instructions paraphrased from a recipe obtained from a clandestine

chemist (Dallosta 1985): The process is initiated by adding mercuric chloride,

aluminum foil, isopropanol, and sodium hydroxide to a reaction vessel and

heating. When the solution comes to a boil, the P2P and methylamine are

added to the mixture and heated for 4 hours. The reaction material then is

passed through filter paper to remove contaminants. Excess methylamine is

removed by the application of heat to the reaction product. The remaining

mixture containing “freebase amine” is purified with a salt wash to “kill the

poisonous mercuric chloride.” The product then is acidified to adjust the pH,

crystallized, purified with solvent in a separatory funnel, and then recrystallized

and packaged for distribution.

Unavailability of P2P and legal controls of other precursors have resulted in the

increasingly popular use of ephedrine as a primary precursor. Ephedrine is a

52
common over-the-counter decongestant cold remedy that differs in molecular

structure from methamphetamine only by the presence of a hydroxyl group

at the p-carbon. A single-step hydrogenation reaction of ephedrine, which

can be accomplished by several methods, will produce a high yield of

methamphetamine. This reaction has the advantage of considerably less

noticeable odor than reactions utilizing P2P (the unpleasant, lingering odor of

P2P and another precursor, phenylacetic acid, has frequently been a clue to

the operation of a clandestine laboratory). To escape detection and also utilize

easily available chemicals, clandestine chemists may resort to using

hydrogenation methods of ephedrine using red phosphorous as a catalyst with

hydroiodic acid. In some cases clandestine chemists are fabricating highpressure reaction vessels to react ephedrine with hydrogen gas. If ephedrine

or P2P are not available, the chemist may resort to industrial chemicals, such

as benzyl chloride, as the precursor.

PRECURSOR SYNTHESIS

Clandestine manufacture of methamphetamine became more complicated in

1980 when P2P was classified as a Schedule II controlled substance by DEA.

In addition, States with clandestine drug laboratory problems, that is, California,

Oregon, and Washington, have passed laws requiring that any person who

purchases listed chemicals that may be used in methamphetamine production

be reported to the State police. These legal restrictions on P2P, intended to

curb the growth of clandestine methamphetamine, spurred the development of

clandestine laboratories specializing in the production of P2P from phenylacetic

acid. Legitimate P2P sells commercially for less than $100 per liter, but the

same amount will net more than $4,000 for the clandestine chemist. Synthesis

of P2P usually is accomplished by utilizing lead acetate as the primary reagent

in a process that requires a distillation procedure (figure 2). In the hands of the

unskilled or careless clandestine chemist, these processes may result in the

introduction of contamination from lead and other reagents used in the

production process.

In the absence of phenylacetic acid there are several alternative reactions the

clandestine chemist may choose to produce methamphetamine, utilizing easily

available chemicals but requiring more complex and often more dangerous

reactions. For example, phenylacetic acid may be synthesized from industrial

chemicals such as benzylchloride, toluene, or benzene. In a possible endless

source of potential reaction pathways, the chemist may resort to manufacturing

many precursors from uncontrolled chemicals. For example, ephedrine may be

synthesized from propiophenone, or methylamine may be produced in a

reaction with ammonia and methanol. The increasing complexity of the reaction

sequence and the substantial numbers of chemicals required in the production

53
FIGURE 2. Synthesis of the precursor P2P from phenylacetic acid and lead

acetate

process increase the risk of errors and the probability of toxic contamination in

the final product.

TOXICITY OF DRUG CONTAMINANTS

Although drug contamination may result in potentially serious adverse health

effects for the drug user, the difficulty in studying such a group of subjects has

made it problematic to document the extent of drug Contaminant-induced illness

from methamphetamine. For this reason most reports of drug contaminant

illness have been anecdotal cases. Epidemiological investigation into this

problem has not yet been accomplished.

There have been reports of contaminated drugs produced in clandestine

laboratories that have resulted in disastrous health effects in the unsuspecting

user. One such major outbreak of serious illness from contaminated drugs

occurred in 1982 when an attempt was made by a clandestine chemist to

produce the meperidine congener, MPPP. Instead, due to a relatively minor

aberration in the reaction process, highly toxic 1-methyl-4-phenyl-1,2,5,6-

tetrahydropyridine (MPTP) was synthesized and distributed on the street. Drug

users unlucky enough to inject MPTP developed severe and permanent

Parkinson’s disease. Only by a series of coincidences was the cause of the

Parkinson’s disease traced to the contaminated drug (Ballard et al. 1985). It is

not known how many other toxic substances may be created by the clandestine

chemist attempting to make other illegal drugs, including methamphetamine.

Two case reports have documented human toxicity due to methamphetamine

contamination. In both instances illness was caused by heavy contamination of

lead. In 1987 two patients in Oregon were reported to have developed lead

toxicity as a result of the injection of methamphetamine. Both patients

54
developed illnesses consistent with lead intoxication and presented with

symptoms of nausea, vomiting, constipation, numbness and tingling,

weakness, and headache. Laboratory data revealed elevation of liver

enzymes, suggesting a diagnosis of infectious hepatitis. However, in view of

the nonspecific clinical presentation, the possibility of lead poisoning apparently

was not considered until basophilic stippling was found on the blood smear,

which prompted an investigation for lead toxicity. A blood lead level of

204 μg/dL was measured in one of the patients (<40 μg/dL is normal). A blood

lead level was not reported for the second patient, although a free erythrocyte

protoporphyrln was elevated at 68 μg/L (<50 μg/L is normal). Both patients

required chelation therapy with disodium calcium edetate. A sample of

methamphetamine obtained later from one of the victims was shown to contain

899 ppm of lead. This would result in the injection of approximately 0.1 mg of

lead per dose of drug (Allcott et al. 1987).

The second outbreak of lead poisoning was reported in 1988 and involved 12

methamphetamine abusers in a three-county area in Oregon. All cases came

to medical attention between April 18 and September 15, 1988. The mean age

of these patients was 27 years (range 24 to 36 years), nine males and three

females. The most common complaints were gastrointestinal, that is, nausea,

vomiting, abdominal pain, and constipation. Although lead poisoning typically is

associated with neurological findings, only one patient complained of

paresthesias. The physical examinations were remarkable for abdominal

tenderness, but evidence of encephalopathy or neuropathy was not present.

Anemia was common with a mean hematocrit of 29.8 percent (range 20 to 44

percent). Basophilic stippling was present in 10 cases. Elevation of liver

enzymes was consistent with chemical hepatitis. The most severely poisoned

patient also developed a clinical pancreatitis. The mean blood lead level was

146 μg/dL, with a range from 49 μg/dL to 513 μg/dL, the latter being the highest

level yet reported in a living person. Seven patients underwent chelation

treatment. Although followup was not possible for all patients, it appeared that

all improved with treatment. It was presumed that this outbreak resulted from

perhaps a single source because of the close proximity of the cases. Although

the source or the responsible clandestine chemist could not be identified, one of

the victims supplied a sample of the drug he had allegedly injected. Analysis of

this drug revealed that the sample contained 80 percent lead (Norton et al.

1989). This concentration of lead would result in a dose of more than 50 mg of

lead per injection.

The cases described above involved relatively large doses of lead that

resulted in severe acute poisoning. Although smaller doses of lead in

methamphetamine may result in illness, the effects may not be readily apparent

to the clinician, particularly in view of the nonspecific symptoms frequently seen

in lead poisoning. It is not known if methamphetamine abusers, as a group,

55
may be at risk of unrecognized chronic lead toxicity due to chronic low-level

exposure to lead; chronic accumulation may not result in illness until large body

burdens of lead have been attained.

It has been suspected, but not yet documented, that drug abusers may be at

risk of developing poisonlng from other reagents used in the manufacturing

process. Although mercury has been considered as a possible contaminant

with significant health impact, there have not yet been any confirmed cases of

mercury poisoning. However, it must be recognized that this may be due to the

lack of case recognition in patients that have complications that are consistent

with drug abuse such as hepatitis and nephritis. In an attempt to document

excessive mercury exposure, hair samples of 12 methamphetamine abusers

were measured for mercury. None of the samples showed a significant

increase in mercury concentrations compared with nonuser controls (French

1985). However, this exploratory study could not overcome the difficulty of selfselection of patients and the inherent technical problems associated with

collection and interpretation of hair sampling for mercury. Blood or urine levels

were not measured, and drug samples were not assayed to determine if the

drug users had been exposed to methamphetamine contaminated with mercury.

Injection of mercuric chloride probably would produce severe burning pain at

the injection site and the development of thrombophlebitis. Hepatitis and

nephritis likely would occur following systemic absorption.

In addition to heavy metal contamination from reagents, the clandestine

production process also may result in the formation of a variety of possible

organic contaminants. One study revealed that contamination by organic

products to be as high as 10 to 39 percent of the sample (LeBelle et al. 1973).

Of the few studies that have attempted to characterize the contamination of illicit

methamphetamine, most have attempted to identify drug contaminants as

intermediates or markers of a particular process for evidentiary purposes (Kram

et al. 1976; Sottolano 1988). It has been noted by forensic chemists that gas

chromatographic analysis of illicit methamphetamine has demonstrated a

variety of substances, including several contaminants that, thus far, have not

been identified and have unknown toxicity. These contaminants are most often

due to incomplete reactions, inadequate purification procedures, or unintended

reactions. Attempts to identify some of these substances have required

synthesis of expected contaminants to use as standards for confirmation of

chemical structure. Noggle and colleagues (1985), utilizing liquid

chromatographic procedure, noted that a-benzylphenethylamine derivatives

were the most common contaminants. These derivatives were shown to have

greater potency to induce seizures in mice than methamphetamine. Organic

contaminants found in illicit methamphetamine are summarized in table 1.

56
TABLE 1. Organic contaminants of illicit methamphetamine

Substance Reference

N,N-dimethylamphetamine

N-formylamphetamine

N-formylmethamphetamine

Dibenzylketone

a-benzylphenethylamine

a-benzyl-N-methylphenethylamine

a,a’-dimethyldiphenethylamine

N-methyldiphenylethylamine

N,a,a’-trimethyldiphenethylamine

Kram et al. 1976

Kram et al. 1976

LeBelle et al. 1973

Kram et al. 1976

Noggle et al. 1985

Barron et al. 1974

Kram et al. 1976

Kram et al. 1976

Barron et al. 1974

CONCLUSION

The clandestine production of methamphetamine is performed by unskilled

chemists utilizing an array of potentially toxic chemicals. Residual reagents,

solvents, and unintended reaction by-products may remain as contaminants in

the finished product. Fourteen cases of acute lead poisoning have been

reported in the medical literature as result of methamphetamine contamination.

It is unknown if lead poisoning from methamphetamine is episodic, due to poor

technique, or is more widespread but at a lower level of toxicity. Further

investigation into the prevalence of lead toxicity is currently under way.

Toxicity due to other reagents and organic by-products remains a distinct

possibility, although known cases have not been reported. Further research is

needed to examine the extent of contaminants in illicit methamphetamine and to

determine their adverse health implications.

REFERENCES

Allcott, J.V.; Barnhart, R.A.; and Mooney, L.A. Acute lead poisoning in two

users of illicit methamphetamine. JAMA 258:510-511, 1987.

Anon. Clandestine Laboratory Seizures in the United States, 1988 and 1987.

Washington, DC: U.S. Drug Enforcement Administration, 1988.

Ballard, P.A.; Tetrud, J.W.; and Langston, J.W. Permanent human

parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Neurology 35:949-956, 1985.

Barron, R.P.; Kruegel, A.V.; Moore, J.M.; and Kram, T.C. Identification of

impurities in illicit methamphetamine samples. J Assoc Off Anal Chem

57:1147-1158, 1974.

57
Cason, T.A.; Angelos, S.A.; and Raney, J.K. A clandestine approach to the

synthesis of phenyl-2-propanone from phenylpropenes. J Forensic Sci

29:1187-1208, 1984.

Dallosta, K.L. Clandestine Laboratory Manual, Sacramento, CA: Western

States Information Network, 1985.

Frank, R.S. The clandestine drug laboratory situation in the United States.

J Forensic Sci 28:18-31, 1983.

French, J.F. Methamphetamine and Mercury Ingestion. New Jersey:

Department of Health, Division of Alcohol, Narcotics, and Drug Abuse, 1985.

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

New York: Basic Books, 1985.

Grinspoon, L., and Hedblom, P. The Speed Culture: Amphetamine Use and

Abuse in America. Cambridge, MA: Harvard University Press, 1975.

Hall, J.N.; Uchman, R.S.; and Dominguez, R. Trends and Patterns of

Methamphetamine Abuse in the United States. National Institute on Drug

Abuse. Miami, FL, 1988.

Kram, T.C.; Kram, B.S.; and Kruegel, A.V. The identification of impurities in

illicit methamphetamine exhibits by gas chromatography/mass spectrometry

and nuclear magnetic resonance spectroscopy. J Forensic Sci 22:40-52,

1978.

LeBelle, M.; Sileikam, M.; and Romach, M. Identification of a major impurity in

methamphetamine. J Pharm Sci 62:862, 1973.

Lerner, M.A. The fire of ice. Newsweek, November 27, 1989. pp. 37-40.

Morgan, J.P. Amphetamine. In: Lowlnson, J.H., and Ruiz, P., eds. Substance

Abuse: Clinical Problems and Perspectives, Baltimore: Williams & Wilkins,

1981.

Noggle, F.T.; Clark, C.R.; and Davenport, T.W. Synthesis, identification, and

acute toxicity of a-benzylphenethylamine and a-benzyl-Nmethylphenethylamine. Contamlnants in clandestine preparation of

amphetamine and methamphetamine. J Assoc Off Anal Chem 88:1213-

1222, 1985.

Norton, R.L.; Kauffman, K.W.; Chandler, D.B.; Burton, B.T.; Gordon, J.; and

Foster, L.R. Intravenous lead poisoning associated with methamphetamine

use. (Abstract.) Vet Human Tox 31:379, 1989.

Smith, V.S. Psychedelic Chemistry. Port Townsend, WA: Loompanics

Unlimited, 1981.

Sottolano, SM. The quantitation of phenyl-2-propanone using highperformance liquid chromatography. J Forensic Sci 33:1415-1420, 1988.

58
AUTHOR

Brent T. Burton, M.D.

Medical Director

Oregon Poison Center

Associate Professor of Emergency Medicine

Oregon Health Sciences University

3181 Southwest Sam Jackson Park Road

Portland, OR 97201

59
Methamphetamine Abuse in California

Bruce Heischober and Marissa A. Miller

INTRODUCTION

Methamphetamine is a drug that historically has been abused and continues

to be abused among Californians. There is no reliable estimate of exact

prevalence of methamphetamine abuse in the State of California, and there

also is a general paucity of epidemiologic and clinical data in the scientific

literature describing the current problem, which developed during the 1980s.

Historical information from previous epidemics of methamphetamine abuse in

the United States reveals that during the 1950s and 1980s methamphetamine

and amphetamines were diverted pharmaceutical products most commonly

taken orally by truck drivers, students, and housewives as insomniac agents

and anorectics (Lukas 1985). Later, intravenous (IV) use became popular

among white, young adults, particularly in the Haight-Ashbury district of San

Francisco (Smith 1972). Over the past several years the demographics of the

amphetamine abuser have been changing to include more ethnic minorities,

adolescents, and women. Today, alternate methods of administration, such as

intranasal, smoking in pipes, inhaling vapors from methamphetamine heated on

aluminum foil (known as “chasing the dragon”), and mixing in soft drinks are

becoming more common. In addition, there clearly have been major changes

in production and distribution patterns in recent years.

NOMENCLATURE

Amphetamines and methamphetamine fall within the phenylethylamine class

of stimulants. Methamphetamine typically is referred to and marketed as

‘speed,” “crystal,” “crank,” “go,” and, most recently, “ice.” At this time in

California virtually all the chemicals offered as amphetamine or by the other

terms listed above have been shown by laboratory analysis to contain

d-methamphetamine or a mixture of d- and d/l-methamphetamine (Puder et al.

1988). During the early 1980s when other chemicals such as cocaine,

phenylpropanolamine hydrochloride (PPA), d-amphetamine, ephedrine, and

pseudoephedrine were mixed with or substituted for methamphetamine, street

60
products being marketed as methamphetamine did not always contain the drug

(Heischober and Derlet 1989).

In 1980 the majority of drugs sold on the street as methamphetamine or speed

were a combination of ephedrine, PPA, and caffeine (Lake and Quirk 1984).

This combination came to be termed “look-alike” speed because the powder

or capsules looked identical to the real thing. Research has shown that this

combination can mimic the central nervous system (CNS) discriminative cue

for amphetamine. However, a major difference is noted in the area of

stimulation of alpha and beta receptors vs. cortical stimulation. The PPA and

ephedrine molecules are structurally configured to result in decreased potency

as central stimulants with retained peripheral activity. Users of look-alike speed

attempting to achieve the same level of cortical stimulation may overadminister

the drug and risk overstimulation of the cardiovascular system. An increased

risk and incidence of stroke has been noted in abusers of PPA (Kase et al.

1987).

The term “ice” most often refers to a pure form of d-methamphetamine HCl

that is marketed in a large crystalline form. Ice typically is smoked or ground

up and injected or snorted. Public Law 101-647, passed on November 29,

1990, refers to smokable crystal methamphetamine, and the guidelines

subsequently released in the Federal Register further define ice as a mixture

or substance containing d-methamphetamine HCl of at least 80-percent purity

(Federal Register 1991).

Geographic variations on street drug names exist within California. Crystal

commonly refers to methamphetamine in southern California, while in other

areas of the State it can mean heroin, The street name in San Diego for the

mixture of methamphetamine and cocaine is “croak.” Another example of the

variations seen in street terminology is the term “night owl.” In a recent

interview with Heischober, a patient described night owl as a marijuana

cigarette dipped in phencyclidine and sprinkled with a mixture of crack cocaine

and methamphetamine.

PATTERNS OF METHAMPHETAMINE PRODUCTION

Methamphetamine is relatively simple to synthesize in a laboratory from

precursor chemicals (Allen and Cantrell 1989). Traditionally, production

was controlled by white motorcycle gangs, which continue to produce

methamphetamine in clandestine laboratories, but there has been a change

toward two other types of production and distribution patterns. First, there

has been an increase in the number of individuals who alone or with a few

others buy precursors and attempt to produce moderate amounts of

61
methamphetamine and distribute it independently. It has been suggested

that the relative simplicity of production and profit associated with

methamphetamine production and sale may underlie this recent development.

A second development reported by law enforcement agencies has been the

apprehension of illegal aliens hired by organized groups of criminals to produce

methamphetamine and initiate distribution. This has suggested interest and

involvement on the part of groups involved with sale and distribution of drugs

such as heroin, cocaine, and marijuana.

California also has experienced a shift in the method used to produce illicit

methamphetamine. The two primary methods for the synthesis of

methamphetamine are the amalgam method and the ephedrine reduction

method. Historically, methamphetamine in California was produced by the

amalgam method using phenyl-2-propanone (P2P) as the primary precursor.

In 1980 P2P was reclassified nationally as a Schedule II controlled substance,

which reduced the availability of this precursor for illicit methamphetamine

synthesis. At least partially as a result of the change in the availability of

P2P, in the past several years ephedrine reduction laboratories have become

more prevalent, first in southern California, then in areas to the north. The

ephedrine reduction process is responsible for more than 90 percent of the

methamphetamine currently produced in southern California (Derlet and

Heischober 1990). This is a significant shift because the resulting product is

d-methamphetamine rather than the racemic mixture of d/l-methamphetamine

resulting from the P2P method. D-methamphetamine is 2 to 10 times as

physiologically active as l-methamphetamine (Taylor and Snyder 1970). This

increased potency translates into increased CNS stimulation and the potential

for increased neurotoxicity.

TRENDS OF METHAMPHETAMINE ABUSE IN CALIFORNIA

Although methamphetamine abuse has increased in the 1980s little has

been written on current trends and consequences of abuse. A paper in the

American Journal of Drug and Alcohol Abuse states, “The previous image of

methamphetamine used intravenously by ‘speedfreaks’ and members of

motorcycle gangs has never been entirely accurate” (Puder et al. 1988).

National drug use surveillance systems such as the Drug Abuse Warning

Network (DAWN), a national system for tracking morbidity and mortality

consequences of drug abuse, shows methamphetamine abuse as a regional

phenomenon primarily localized in west coast cities such as Seattle, San

Francisco, Los Angeles, and San Diego (National Institute on Drug Abuse

1990). Other cities and localities have experienced sporadic outbreaks of

methamphetamine abuse (e.g., Phoenix and Dallas) and ice abuse (e.g.

Hawaii) (Miller and Tomas 1989).

82
A National Institute on Drug Abuse (NIDA) publication describing trends and

patterns of methamphetamine abuse in the United States noted that the typical

methamphetamine abuser in treatment was white, low to middle income, high

school educated, and from 20 to 35 years old (National Institute on Drug Abuse

1989). Clients interviewed for this study ranged from 18 to 44 years of age; 89

percent of the clients were white, and 11 percent were black. Average age for

flrst use of methamphetamines was 20.6 years old, and the IV route was

preferred by 82 percent of the participants, The NIDA study was limited to small

numbers of methamphetamine abusers in selected treatment programs in San

Diego, CA, Portland, OR, and Dallas, TX. Although the NIDA study generally

describes typical methamphetamine abusers in the United States, some

differences are appearing in California since the NIDA study.

Stimulant abuse does not appear to be a major problem throughout the State of

California. However, in certain counties and subpopulations methamphetamine

abuse is a significant problem. An examination of 1988 and 1990 data from the

National Household Survey on Drug Abuse estimates that a total of 2.3 percent

of Californians used stimulants in the year before the interview. The highest

prevalence of use was seen in the 18- to 25-year-old age group at 8.4 percent,

higher than that seen for the same age group in the coterminous United States

(4.9 percent) (unpublished data). This reflects use of methamphetamine

predominantly but also includes amphetamines and other illicit and licit products

(but not cocaine). Although the total numbers are small, the California Drug

Abuse Data System (CAL-DADS) shows an increase in methamphetamine use

among whites (140 percent), American Indians (342 percent), and Hispanics

(185 percent) in publicly supported treatment programs in California between

1982-83 and 1987-88 (figure 1).

The localized nature of methamphetamine abuse is reflected in treatment data

from San Diego and San Francisco. In San Diego County, located in the

extreme southwestern corner of California, methamphetamine is the most

commonly abused drug among the treatment population (Haight 1990). From

January 1988 to October 1990 methamphetamine was the most frequent

primary drug problem at admission to drug treatment programs. In 1989

methamphetamine accounted for 39 percent of all admissions. From these

CAL-DADS statistics the typical profile of a methamphetamine abuser entering

treatment was a white (79 percent) female (54 percent), age 21 to 30 (82

percent). The primary route of administration reported was inhalation (88

percent), with 27 percent injecting the drug. In a questionnaire administered

through crisis intervention, diversion, and early intervention services, clients

listed methamphetamine as the primary drug problem for each program

category from January 1988 to October 1990.

63
FIGURE 1. Number of methamphetamine users in rreatmenr by ethnic group

In contrast, in the five counties of the San Francisco standard metropolitan

statistical area (SMSA) (San Francisco, Marin, Contra Costa, Alameda, and

San Mateo) methamphetamine ranked third behind heroin and cocaine for drug

treatment admissions (Newmeyer 1990). California Department of Alcohol and

Drug Programs admissions data show a steady increase in the number of

primary amphetamine-type admissions from 1988 through the first half of 1990

(Newmeyer 1990). The profile of recent treatment admittees is overwhelmingly

white (about 84 percent) and male (73 percent). Overall, amphetamine-type

admissions only accounted for approximately 4 percent of all drug admissions in

the SMSA. Gays (homosexual men) in their 20s and 30s accounted for a

predominant number of methamphetamine abusers in this area.

National and State data are not comprehensive in describing the local

demographics and trends of drug abuse. Certain treatment communities are

experiencing an increase in acceptance and abuse among adolescents in the

middle and upper socioeconomic classes. Retrospective review of 275

consecutive admissions between 1988 and 1988 to the Redlands Community

Hospital inpatient adolescent drug treatment program indicated that 80 percent

64
of the 12- to 20-year-olds admitted reported methamphetamine as their drug

of choice (unpublished data). The majority of these patients were polydrug

abusers who also used tobacco, marijuana, and alcohol. The majority of

adolescents who preferred methamphetamine also indicated they would not

use cocaine even if methamphetamine were not available. Reasons given for

the methamphetamine preference were longer duration of effect, availability,

and the rather subjective but commonly stated reason that “speed gets me

more wired.”

In areas of endemic methamphetamine abuse there are certain beliefs held

by adolescents that put them at risk for early initiation of methamphetamine

abuse. In these areas methamphetamine may act as a gateway drug (initial

use leads to subsequent use of other drugs) (DuPont 1984). Several

characteristics of methamphetamine abuse support this theory, including the

use of methamphetamine as a performance enhancer and as an anorectic

agent and the perception by many adolescents that methamphetamine is safer

than cocaine (Mandell 1979; Laties and Seiss 1981). Adolescent athletes

become aware of the use of legal stimulants for performance enhancement

through advertisements in body-building magazines and learn that these are

pharmacologically similar to methamphetamine. Methamphetamine also is

used by teens to stay awake for late-night studying or to have endurance

after sleep deprivation. The majority of adolescent patients in the Redlands

Community Hospital program who reported methamphetamine as their drug of

choice also reported that they perceived methamphetamine as being safer than

cocaine when they began abusing it.

An interesting demographic pattern of clinical significance is noted in the

Los Angeles County area, which is experiencing a significant increase in

treatment admissions over the past 2 years due to methamphetamine abuse

as reported through CAL-DADS (McAllister et al. 1990). In general, indicators

of methamphetamine abuse in Los Angeles County are low, and the

predominant stimulant of abuse is cocaine. However, in the West Hollywood

area there is a much higher prevalence of methamphetamine abuse. This is

also an area with a predominantly gay population. In conversations with

physicians and substance abuse counselors in this area and in the Bay area

of San Francisco, Heischober learned that methamphetamine is preferred by

gays because it allegedly has the ability to enhance and prolong sexual

performance. As opposed to the use of opiate or sedative classes of drugs,

there are consistent reports of binge use focusing around sexual activity and of

decreased caution in general with methamphetamine abuse. Stimulant abuse

and compulsive sex behavior is well described (Washton 1989). Unsafe sexual

practices put the individual at high risk of contracting human immunodeficiency

virus and other sexually transmitted diseases.

65
Metharnphetamine is ideally suited to the current trend in smoking drugs of

abuse (Wesson and Washburn 1990) since it is readily volatilized and passes

into mainstream smoke (combustion gases that are taken directly into the lung

when a product is smoked) at temperatures compatible with smoking in a pipe

or chasing the dragon (Chiang and Hawks 1989). Smoking is a method of drug

administration that is generally acceptable, easy, and perceived as safe.

Smoking methamphetamine is similar to IV use in that the drug gets to the brain

in a matter of seconds and produces a rapid and intense effect. The CALDADS data show that in 1982-83 there were essentially no reports of smoking

methamphetamine by drug abusers entering treatment. By 1987-88 the number

smoking and inhaling methamphetamine had increased significantly (figure 2).

Clinical practice confirms this gradual increase in the practice of smoking

methamphetamine. Of 30 successive patients with a recent history of

methamphetamine abuse admitted to an inpatient drug treatment program in

Riverside County, 100 percent reported either smoking methamphetamine at

least occasionally or knowing someone who did. These individuals also were

FIGURE 2. Number of methamphetamine abusers in treatment by route of

administration

66
aware that, unlike cocaine, methamphetamine in powder or crystalline form is

immediately smokable.

CONSEQUENCES OF USE

Trauma

Traumatic incidents frequently are associated with alcohol and other drug

abuse and can be used as indicators of drug abuse in a population. The

etiologic role of alcohol in trauma is well documented and has been shown

to be a contributing factor in 65 to 70 percent of fatal highway accidents

(Lindenbaum and Carroll 1989). Although accepted as an etiologic factor,

many trauma centers still do not routinely screen for drugs of abuse.

Drug-associated trauma data are not uniformly available; however, an areaspecific pattern emerges where these data are available. Data from the trauma

registry at a level-one (tertiary, the highest level of care) trauma facility in San

Bernardino County show that in the 15- to 24-year-old age group nearly five

times as many patients tested positive for methamphetamine compared with

cocaine. Also, in 1989, of 675 18- to 24-year-olds who were admitted to the

University of California at Davis trauma service, 7 percent tested positive for

methamphetamine and 4 percent for cocaine.

Methamphetamine abusers are less likely to interface with emergency care and

medical facilities as a result of the acute medical problems (cerebrovascular

accidents, acute cardiac ischemia and failure, hyperthermia, seizures) that

bring cocaine abusers to these facilities. In a retrospective study of 127 cases

of amphetamine (including methamphetamine) toxicity in an emergency

department, the major presenting symptom was altered mental status (57

percent); 10 percent were found unresponsive, and the remainder exhibited

such physiologic complaints as chest pain, weakness, palpitations, and seizures

(Derlet et al. 1989). The CNS symptoms most commonly encountered in the

Derlet study included agitation, confusion, delusions, hallucinations, and

suicidal ideation.

It has been suggested that the infrequent occurrence of acute medical problems

in methamphetamine abusers is a result of the rapid development of tolerance

to methamphetamine (Ellenhorn and Barceloux 1988). Tolerance develops to

some of the central effect of amphetamines such as its euphorigenic, anorectic,

hyperthermic, and lethal actions; however, tolerance does not develop to

certain toxic CNS effects (Jaffe 1985). Chronic abusers exhibit limited

sympathomimetic effects, with blood pressure not unduly elevated, but

frequently suffer from paranoid psychosis and other mental status alterations

(Ellinwood 1971).

67
Trauma and death as a consequence of methamphetamine abuse is

increasing in localized areas of California. San Bernardino County Coroner’s

data consisting of all traffic deaths, homicides, suicides, and unknown causes

of death for the past 5 years were reviewed (unpublished data). Although

methamphetamine and cocaine positives were approximately equal through

1985, there has been a gradual increase in methamphetamine cases, with

methamphetamine present two to three times as frequently as cocaine in 1989.

In a retrospective analysis of drug-related homicides and accidental overdoses

(Bailey and Shaw 1989), it was reported that cocaine or methamphetamine or

both were involved in approximately one-third of all homicides in San Diego

County in 1987. The profile for a methamphetamine decedent from the Bailey

study is a 32-year-old white male who had used at least one other drug, usually

ethanol, codeine, or morphine. The San Diego Sheriffs Crime Laboratory

reports that, in cases in 1988, methamphetamine was the most common illicit

substance (Rasmussen et al. 1989). Drug-related mortality reported through

DAWN shows that methamphetamine was involved in approximately 4 percent

of the drug-related deaths in Los Angeles, 18 percent in San Diego, and 17

percent in San Francisco from January through June 1990.

CONCLUSION

It is difficult to generalize when discussing methamphetamine abuse in

California. Observation reflects a phenomenon that is geographically

influenced and location specific. In some respects, trends and characteristics

of methamphetamine abusers in California mimic what is known of the national

profile. In general the composite national methamphetamine abuser is

predominantly white, male, and with low to middle income. What appears to

be emerging in California is a broadening of abuse of methamphetamine in all

socioeconomic classes and among women, diversification of use among ethnic

minorities, and an increase in special populations using methamphetamine,

including adolescents and gays. There is the suggestion of a shift in use from

cocaine to methamphetamine in some populations in some areas. California

also is experiencing new patterns of drug administration. Based on national

data, the typical abuser injects, whereas in California, inhalation, smoking, and

ingestion are common (National Institute on Drug Abuse 1989, 1990).

The trend in California has been toward the production of a more

neuropharmacologically potent product in a form that has high purity and is

easily administered. Consequences of these changes are being reflected in

an increase in methamphetamine abusers entering treatment centers and

trauma facilities and interfacing throughout the law enforcement and medical

care community.

68
The trends of methamphetamine abuse in California need to be more

thoroughly documented and understood. The problem of methamphetarnine

abuse must be described and quantified before prevention, treatment, and

rehabilitation programs can be developed and before resources can be

allocated to address the problem. As the drug abuse research community in

California begins to understand how methamphetamine is produced and

marketed, how the drug is used and abused, and the extent and nature of

consequences of abuse, others can benefit from the resultant insight

concerning this insidious drug that refuses to fade away.

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methamphetamine labs. J forensic Sci 42:183-199, 1989.

Bailey, D.N., and Shaw, R.F. Cocaine and methamphetamine-related deaths in

San Diego County (1987): Homicides and accidental overdoses. J Forensic

Sci 34:407-422, 1989.

Chiang, C.N., and Hawks, R.L. Introduction and overview. In: Chiang, C.N.,

and Hawks, R.L. Research Findings on Smoking of Abused Substances.

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center patients. J Trauma 29:1654-1658, 1989.

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synthesis, and availability. Am J Drug Alcohol Abuse 14:463-473, 1988.

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Sex December: 32-39, 1989.

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Smoking of Abused Substances. National Institute on Drug Abuse Research

Monograph 99. DHHS Pub. No. (ADM)90-1690. Washington, DC: Supt. of

Docs., U.S. Govt. Print. Off., 1990. pp. 5-11.

AUTHORS

Bruce Heischober, M.D.

Assistant Professor of Adolescent and Emergency Medicine

Department of Emergency and Adolescent Medicine

Loma Linda University Medical Center School of Medicine

11234 Anderson Street

Loma Linda, CA 92350

Marissa A. Miller, D.V.M., M.P.H.

Epidemiologist

Epidemiology Studies and Surveillance Branch

Division of Epidemiology and Prevention Research

National Institute on Drug Abuse

Rockwall II, Suite 815

5600 Fishers Lane

Rockville, MD 20857

71
Trends and Patterns of

Methamphetamine Smoking in Hawaii

Marissa A. Miller

INTRODUCTION

A sharp increase in law enforcement actions related to smoking of dmethamphetamine HCl, known as “ice,” was observed and reported by the

U.S. Attorney for Hawaii during the last half of 1988. This report was

confirmed by Hawaii treatment personnel who observed increasing numbers

of clients entering treatment as a result of methamphetamine smoking. At the

request of the Hawaii Department of Health, Alcohol and Drug Abuse Branch,

a field studies team from the National Institute on Drug Abuse (NIDA)

conducted an outbreak investigation during February and March 1989 to

characterize the epidemic as to person, place, and time and to document the

extent and trend of the problem. A followup data collection was initiated

during February 1990.

METHODS

Information was abstracted from treatment records and State treatment

admission and discharge summary forms. In addition, a group of

methamphetamine smokers currently in treatment were interviewed about their

symptomatology and patterns and preferences of drug use. Methamphetamine

smokers admitted to treatment between October 1985 and February 1990 in

two large treatment programs, the Young Men’s Christian Association (YMCA)

and Salvation Army (SA), were identified. Methamphetamine smoking was first

detected by treatment centers in Hawaii in the summer of 1986 with wider

recognition of the problem coming later. YMCA Outreach Services provides

community outreach and counseling to individuals younger than 21 primarily in

the areas surrounding and including Honolulu. SA offers inpatient, outpatient,

and women’s drug and alcohol programs and administers services throughout

Oahu, including court referral cases.

72
RESULTS

Treatment and State Admission Data

A total of 172 methamphetamine smoking cases were identified, with 66 (38

percent) from YMCA and 106 (62 percent) from SA (table 1). These

methamphetamine smokers at date of admission to treatment ranged in age

from 12 to 44 years with a mean of 20.5 years (median 17 years). The age

distribution has two peaks, a sharp one at 15 and a more gradual one at 26.5

years. As a whole, 50 percent of the group was younger than age 17, but due

to the composition of the treatment population, the YMCA clients tended to be

younger. Men comprised 58 percent of the total group (68 percent men in SA

and 41 percent men in YMCA). Women tended to be younger than men, with

the average age of women being 18.2 years and men 22.2 years. Seventy-five

percent of women were younger than 20 years old compared with 50 percent of

men. There was no difference between genders for time of admission to

treatment, with men and women being admitted throughout the period.

The clients reflected a range of ethnic backgrounds, including 35 percent

Hawaiian/part Hawaiian (defined as having at least half Hawaiian ethnicity), 23

percent Filipino, 13 percent Japanese, 10 percent Caucasian, 7 percent Other

Asian (including Chinese, Korean, Okinawan, Samoan, and unspecified Asian),

5 percent mixed (defined as three or more ethnicities with none being

predominant), 4 percent unknown, 2 percent Hispanic, and 1 percent black.

The two treatment programs had different ethnic distributions: YMCA was

predominantly Filipino (35 percent) and Hawaiian/part Hawaiian (30 percent),

whereas SA was predominantly Hawaiian/part Hawaiian (41 percent), with a

broader representation of other groups (11 percent Filipino, 14 percent

Japanese, and 11 percent Caucasian). Female clients were primarily of Filipino

(32 percent) and Hawaiian/part Hawaiian (30 percent) ethnicity, whereas males

were predominantly Hawaiian/part Hawaiian (39 percent) and a variety of other

ethnic backgrounds, including Filipino (17 percent), Japanese (13 percent), and

Caucasian (9 percent). This ethnic distribution differs from the general

population on Oahu, with a higher percentage of Hawaiian/part Hawaiians and

Filipinos and a lower percentage of Caucasians and Japanese (table 1).

The epidemiologic curve of treatment admissions shows single cases beginning

in October 1985 and continuing sporadically through July 1987 (not depicted in

figure 1). The curve shows two peaks: The first begins in September 1988 and

runs through April 1989; the second larger peak is centered around October

1989. The admissions for YMCA peak during October 1989, whereas the SA

admissions peak slightly earlier in September 1989. Males and females are

73
TABLE 1. Demographic characteristics of methamphetamine smokers

entering treatment (1986-90) and the general population in Hawaii

(1984)

N

Ice Smokers General Population

172 803,135

Mean age 20.5 29.6

Age range 12-44 -

Percent younger than 20 years of age 59 30

Percent male 58 51

Ethnic distribution (percent)

Filipino

Hawaiian/part Hawaiian

Japanese

Mixed

Caucasian

Chinese

Hispanicb

Black

Korean

OtherC

Missing

23

35

13

5

10

2

2

1

1

4

4

Census 1980a

12.6

10.7

24.9

-

34.4

6.9

7.2

2.3

2.2

6.0

-

a

In the census, persons of mixed origin were classified by self-identification or

origin of the mother. In the outbreak investigation, persons of mixed origin

were classified by predominant ethnicity as recorded in clinical records or

classified as “mixed” if they had three or more ethnicities and no predominance

of any ethnic group.

bHispanic persons may be of any race.

c

“Other” includes Eskimo, Aleutian, American Indian, Vietnamese, Guamanian,

Samoan, Other Asian/Pacific islander, and not elsewhere classified. All these

categories represented 2 percent or less of the total population individually.

distributed throughout as are YMCA and SA admissions. The two earliest

admissions in October 1985 and September 1986 (not pictured in figure 2) are

Japanese men ages 19 and 13, respectively. Following these admissions, the

curve is dominated by young females during the period October 1986 through

May 1988. Also, during this period 11 of 18 admissions (61 percent) are

women, with 5 and 4 admissions of Filipino and Hawaiian/part Hawaiian

74
FIGURE 1. Ice admissions epidemic curve by facility

ethnicity, respectively. The average age at admission of these nine women was

15.3 years. In the remainder of the curve from July 1988 through February

1990, the first half is dominated by Hawaiian/part Hawaiians (July 1988 through

April 1989), and the latter half is dominated by Filipinos (September 1989

through February 1990). Japanese and Caucasians are scattered throughout.

The earliest reported date of methamphetamine smoking of a client in treatment

was 1968, and sporadic single cases continued until 1985 (figure 3). Reported

first use began increasing in 1985 and steadily increased until peaking in 1988

followed by a steady decline in 1989 and 1990. Of the 13 sporadic early cases

(1968, 1969, 1970, 1972, 1974, 1975, 1978, 1979, 1982, 1983, and 1984), all

but two were male, and all but two were older than 25 years at time of

admission. The ethnicities of these early cases include Japanese, Caucasian,

Hawaiian/part Hawaiian, and Filipino (figure 4). The remainder of the curve

(1985 to 1990) comprises all age groups and ethnicities. All the predominant

ethnic groups—Filipino, Japanese, Hawaiian/part Hawaiian and Caucasian—

peak in 1988. The majority of females reported first use after 1984. The early

flat portion of the curve represents clients admitted to treatment at older ages

who started using ice at early ages. When the popularity of ice increased

75
FIGURE 2. Ice admissions epidemic curve by ethnicity

during the mid-1980s, the clients admitted to treatment were younger, had

started using ice later, and had used for a shorter duration of time before

entering treatment programs in comparison with older users. This suggests a

change in the epidemiology of ice use from use by a few older persons to a

“cultural” or “peer-pressure” spread to younger users and others in the

population.

There was a short lag between first use and seeking treatment for these data.

Lag between first use and admission to treatment was estimated by subtracting

calendar year of first use from calendar year of admission to treatment. This

information was available from 91 percent of the records. The mean lag time

was 2.1 years (median=1), ranging from 0 to 20 years. There was a difference

between the two treatment centers: Clients from YMCA had a shorter lag time

(mean=.9, median=1 , range=0 to 3) than clients from SA (mean=3.2, median=1,

range=0 to 20). There also were differences by gender and age group. Males

76
FIGURE 3. First year of use epidemic curve by gender

tended to have longer lag times (mean=3, median=1 , range=0 to 20) than

females (mean=1, median=1 , range=0 to 3). Increasing age groups exhibited

increasing time between first use and seeking treatment. The youngest age

group (less than 15 years) had a mean of 1 year progressing to an 8-year mean

for the oldest age group (older than 35). Filipinos and Hawaiian/part Hawaiians

had among the shortest lag times (1.5 and 1.4 years, respectively), and

Japanese and Caucasians had the longest lag times (2.7 and 3.8 years,

respectively).

Sixty percent of the clients reported methamphetamine to be their primary drug

of abuse. There were small differences in the number of clients in each of the

treatment groups reporting methamphetamine to be their primary drug of abuse

(55 percent in YMCA and 65 percent in SA). The same was true for both

genders (58 percent for males and 62 percent for females). Users younger than

age 15 were least likely to report methamphetamine as the primary or

secondary drug of abuse (50 percent and 22 percent, respectively). Japanese

and Caucasians were the ethnic groups least likely to report methamphetamine

as a primary drug problem (47 percent and 55 percent, respectively).

77
FIGURE 4. First year of use epidemic curve by ethnicity

Interview Data

To augment these data, informal interviews were conducted with 35 users in

treatment between February 1989 and February 1990, and discussions were

held with treatment counselors and law enforcement personnel. These

discussions revealed that methamphetamine, a synthetic stimulant, is referred

to as “crystal” in and around Honolulu, ice in Waianae and on the leeward and

rural parts of Oahu, and “Batu” by the Filipino community. It is a large, usually

clear, crystal of high purity (usually greater than 90 percent) in the

psychoactively potent d-methamphetamine form that is smoked in a glass pipe.

Sixty-six percent of those interviewed had knowledge of ice by age 20 and

began using shortly afterward. Most users (84 percent) reported binge use or

repeated administration of methamphetamine, which typically would entail

continuous use for an average of 5 days, during which time they would forego

both food and sleep. Between binges, users reported extensive sleeping or

78
what they called “crashing out.” The time between binges was reported to be

approximately 3 to 4 days for most users interviewed. Recent use of ice (in the

last 30 days before treatment) was heavy, with 74 percent using ice on 15 or

more days and 63 percent using 2 or more grams during the month prior to

treatment. All but one client preferred to smoke and usually did smoke ice. All

those interviewed had previously used at least one drug other than ice, with all

having tried alcohol, more than 90 percent having used cocaine and marijuana,

and 83 percent having used tobacco. The duration of use of these other drugs

was considerable considering the age limitations of the clients, averaging more

than 9 years for tobacco, alcohol, and marijuana and more than 5 years for

cocaine.

Methamphetamine smokers in treatment self-reported physical symptoms

associated with the smoking of methamphetamine, including weight loss,

tachycardia, tachypnea, hyperthermia, insomnia, muscular tremors, and, less

frequently, blurred vision. The behavioral and psychiatric symptoms most

commonly reported included repetitive activity, memory problems, paranoia,

stereotypic behavior, delusions of reference, auditory hallucinations, and

confusion/fright. Other manifestations of paranoid ideation (e.g., delusions of

persecution, visual hallucinations) also were reported. Less common but also

reported were olfactory and tactile hallucinations and the feeling that bugs or

parasites were crawling over their body or on their skin (formication).

Approximately one-third of the clients interviewed reported entering treatment

within 12 months of initiating use of methamphetamine, and more than 60

percent entered treatment within 2 years of first use. The majority of clients

reported negative effects on their family life (85 percent), social life (79 percent),

and work or school performance (73 percent). Other consequences of ice use

included injuring others (65 percent), being injured (53 percent), and inflicting

injuries on themselves (45 percent). The majority of clients also reported

carrying a weapon (74 percent) and dealing drugs (72 percent).

DISCUSSION

The characteristics of the users identified in this field investigation differ from

other drug users in treatment in Hawaii and overall in the United States

(National Institute on Drug Abuse and National Institute on Alcohol Abuse and

Alcoholism 1989). The Hawaii drug treatment population in 1987 was 72

percent male, 29 percent age 20 or younger, and 48 percent Caucasian

(n=536). As a whole, according to Hawaii State drug abuse experts and

treatment counselors, drug users in treatment in Hawaii tend to be in their mid20s and older, male, Caucasian or Hawaiian/part Hawaiian, and polydrug users.

The total U.S. population in treatment for drug abuse the same year was 67

percent male, 57 percent Caucasian, and 22 percent age 20 or younger. The

79
ice users in thls study were younger, with a higher representation of women and

a larger proportion of Hawaiian/part Hawaiian than the ‘typical” Hawaiian or

average U.S. drug user.

There appear to be two distinct population peaks in the data collected: (1)

females, predominantly younger than 20 years of age and Filipino, with

methamphetamine predominating as their primary drug of abuses, and (2)

males, most often older than 20 years of age and most often Hawaiian/part

Hawaiian, Filipino, or Japanese, with methamphetamine being more often their

second or third drug of abuse. Filipinos in this study were shown to rank ice as

a more severe problem (82 percent listed ice as their primary drug problem)

compared with Hawaiian/part Hawaiians, 47 percent of whom listed ice as their

primary problem. The drug-related problems of Filipinos appeared to be

predominantly from ice use, whereas the Hawaiian/part Hawaiians seemed

more often to have a polydrug abuse problem. Young female Filipinos

appeared to be especially vulnerable to the adverse effects of ice, causing them

to seek treatment within 1 year of first use.

Anecdotally, young Filipino females were reported to be targets of

methamphetamine dealers because of their reliability as customers. Also,

females reportedly used ice to lose or control body weight. The presence of

young Filipino female users within the early epidemic curve was demonstrated

in these data. Older polydrug users had a long lag time before entering

treatment, possibly reflecting an ability to use drugs and still function outside of

treatment. Japanese users exhibited a long lag time to enter treatment as well,

which may reflect a cultural tendency to handle problems within the home or

community rather than seeking outside assistance.

There is a dearth of baseline data on the Hawaiian drug-abusing population.

From 1988 through 1989 the proportion and total number of ice users increased

for YMCA and SA. The proportions increased from 13 to 17 percent and 9 to

19 percent for YMCA and SA, respectively. The data from this study suggest

that admissions to treatment due to methamphetamine smoking has peaked or

may peak shortly. The frequency curve of methamphetamine admissions by

half-year (figure 5) shows a peak during the second half of 1989 and a decline

for the first 2 months of 1990 (indicated as “H1 1990” in figure 5). Extrapolation

of the same rate of admissions for the first 2 months of 1990 over the

hypothesized first 6 months is depicted in figure 5 as “*H1 1990,” which shows

an overall decreasing trend. In addition, the curve for users first trying ice

peaked in 1988, and the data indicate a 1- to 2-year lag time between first use

and entering treatment, which corresponds with the peak and decline described

in the admissions curve.

80
FIGURE 5. Frequency of methamphetamine admissions by half-year

*Extrapolated rate of admissions for the first 6 months of 1990 based on actual

admissions for the first 2 months of 1990 (depicted as H1 1990)

Surveillance systems monitoring trends of drug use show methamphetamine

use to be static across the United States but increasing during the last part of

the 1980s in certain cities, particularly on the west coast. The Drug Abuse

Warning Network (DAWN) shows statistically significant increases in

emergency room mentions of methamphetamine in the San Francisco and

Seattle metropolitan areas during the period January 1987 through December

1989 (National Institute on Drug Abuse 1990). However, first quarter 1990 data

show a decrease in mentions for San Diego, San Francisco, Los Angeles, and

Seattle. The total DAWN system showed no statistical change in

methamphetamine use for first quarter 1987 through fourth quarter 1989, but

first quarter 1990 results suggest a decreasing trend. San Diego, San

Francisco, and Seattle metropolitan areas all showed increases in the

proportion of smoked methamphetamine mentions between second quarter

1989 through first quarter 1990 compared with the same period 1 year earlier.

81
The San Diego smoking cases accounted for 8 percent of the total

methamphetamine cases in San Diego during the period between April 1, 1989,

and March 30, 1990 (unpublished data). Overall, the smoking route accounted

for less than 1 percent (0.5 percent) of the national methamphetamine mentions

during this same 12-month period. Intravenous injection remains the most

popular and common route of administering methamphetamine in the United

States.

The dangers involved with methamphetamine use include both acute and

chronic sequellae (Preston et al. 1985; Jaffe 1985; Kramer 1970; Sato 1986).

Acute toxicity is similar to that caused by cocaine, and there are studies

suggesting permanent neural toxicity from methamphetamine use (see Seiden,

this volume). Chronic use typically results in serious psychological

consequences. There are also social and behavioral consequences such as

loss of friends, alienation of family, job and school failure, and violence that

have been associated with chronic methamphetamine use (Kalant and Kalant

1978; Smith 1970; Ellinwood 1971; Asnis and Smith 1978; Beezley et al. 1987).

CONCLUSIONS

At this time the widespread smoking of methamphetamine appears to be unique

to Hawaii. However, the widespread use of other forms of methamphetamine

and other routes of administration within the continental United States raises

concern about the transference of this highly pure and potent form of

methamphetamine and the smoking pattern of use. As with cocaine, the

smoking route of administration can lead to additional serious adverse health

and social consequences. To date, the NIDA drug use surveillance systems

have not shown the ice phenomenon to have spread extensively. However,

given the lag times between initiation of use of ice and the need to seek

treatment, as indicated by the subjects in this investigation, it may be that the

drug is being used, but not yet to the threshold necessary for detection by

NIDA’s national surveillance systems. For these reasons continued vigilance in

conducting surveillance is indicated.

REFERENCES

Asnis, S.F., and Smith, R.C. Amphetamine abuse and violence. J Psychedelic

Drugs 10:371-377, 1978.

Beezley, D.A.; Gantner, A.B.; Bailey, D.S.; and Taylor, S.P. Amphetamines and

human physical aggression. J Res Personality 21:52-60, 1987.

Ellinwood, E.H., Jr. Assault and homicide associated with amphetamine abuse.

Am J Psychiatry 127:1170-1175, 1971.

82
Jaffe, J.H. Drug addiction and drug abuse, CNS sympathomimetics:

Amphetamine, cocaine, and related drugs. In: Gilman, A.G.; Goodman,

L.S.; Rall, T.W.; and Murad, F., eds. The Pharmacological Basis of

Therapeutics. New York: McMillan, 1985. pp. 550-554.

Kalant, H., and Kalant, O.J. Death in amphetamine users: Causes and rates.

In: Smith, D.E.; Wesson, D.R.; Buxton M.E.; Seymour, R.B.; Vugerleider,

J.T.; Morgan, J.P.; Mandell, A.J.; and Jara, G. Amphetamine Use, Misuse,

and Abuse: Proceedings of the National Amphetamine Conference. San

Francisco: University of California, 1978, pp. 169-189.

Kramer, J.C. Introduction to amphetamine abuse. In: Ellinwood, E.H., and

Cohen, S., eds. Current Concepts on Amphetamine Abuse. National

Institute of Mental Health. DHEW Pub. No. (HSM)72-9085. Washington,

DC: Supt. of Docs., U.S. Govt. Print. Off., 1970. pp. 177-184.

National Institute on Drug Abuse. Statistical Series. Data from the Drug Abuse

Warning Network (DAWN). Semiannual Report, Series G, Number 24.

DHHS Pub. No. (ADM)90-1664. Washington, DC: Supt. of Docs., U.S.

Govt. Print. Off., 1990.

National Institute on Drug Abuse and National Institute on Alcohol Abuse and

Alcoholism. National Drug and Alcoholism Unit Survey (NDATUS), 1987

Final Report. Washington, DC: Supt. of Docs., U.S. Govt. Print. Off., 1989.

Preston, K.L.; Wagner, G.C.; Schuster, C.R.; and Seiden, L.S. Long-term

effects of repeated methylamphetamine administration on monoamine

neurons in the rhesus monkey brain. Brain Res 338:243-248, 1985.

Sato, M. Psychotoxic manifestations in amphetamine abuse.

Psychopharmacol Bull 22:751-756, 1986.

Smith, R.C. Compulsive methamphetamine abuse and violence in the HaightAshbury district. In: Ellinwood, E.H., and Cohen, S., eds. Current Concepts

on Amphetamine Abuse. National Institute of Mental Health. DHEW Pub.

No. (HSM)72-9085. Washington, DC: Supt. of Docs., U.S. Govt. Print. Off.,

1970. pp. 205-216.

AUTHOR

Marissa A. Miller, D.V.M., M.P.H.

Epidemiologist

Epidemiology Studies and Surveillance Branch

Division of Epidemiology and Prevention Research

National Institute on Drug Abuse

Rockwall II, Room 615

5600 Fishers Lane

Rockville, MD 20857

83
Methamphetamine Abuse in Japan

Hiroshi Suwaki

INTRODUCTION

The history of methamphetamine abuse in Japan, where it has been the

dominant stimulant of abuse since the end of World War II, is instructive

because it shows the emergence of two entirely different patterns of and

motivations for substance abuse. Furthermore, it demonstrates the utility and

limitation of preventive and educational approaches to the problem.

This chapter first summarizes general trends in substance abuse in Japan to

place methamphetamine problems in a historical context and then discusses

specific problems in methamphetamine abuse, focusing on its epidemiologic

and social problems. Finally, the chapter presents a recent study (Suwaki

et al. 1990) of a longitudinal pattern of substance abuse, including

methamphetamine. (A person often shifts from one substance of abuse to

another or abuses several substances simultaneously).

HISTORICAL TRENDS IN SUBSTANCE ABUSE

Before 1945 substance abuse was not a substantial problem in Japan, with the

exception of alcoholism, but from 1945 to 1956 Japan suffered from the new

problem of stimulant abuse (methamphetamine is the dominant drug in this

category) (figure 1). This problem quickly spread throughout Japan because

there were no laws prohibiting the use or sale of this substance. With the

passage of the Stimulants Control Law (1951) and its amendments in 1954

and 1955 together with a vigorous policy of enforcement, the abuse of

methamphetamine rapidly abated. This epidemic served to awaken the

Japanese Government and medical community from its naivete about

substance abuse (Suwaki and Bjorksten 1983). Interestingly, cocaine was

not included in the Stimulants Control Law but was included in the Narcotics

Control Law (1953). Amphetamine and methylphenidate, which along with

methamphetamine are the main drugs targeted by the Stimulants Control Law,

rarely have been abused in Japan.

84
FIGURE 1. Arrests for drug statue violations except alcohol

SOURCE: National Police Agency, Division of Prevention of Crimes,

Department for Countermeasures of Drugs, 1989

With the success of efforts to control the methamphetamine epidemic, attention

turned to the control of heroin abuse, which also had increased dramatically

after 1945. The period of increased heroin use lasted from 1957 to 1963

(Ministry of Health and Welfare 1985). Coordinated Government action

began in 1962 with the organization of the Ministers’ Council for Narcotics

Countermeasures and in 1963 with amendments to the Narcotics Control Law

that increased penalties for narcotics violations. Figure 1 demonstrates that

these measures, combined with vigorous enforcement, were successful.

However, in the author’s view, illegal drug traffickers in “Bohryokudan” (a

criminal organization similar to the Mafia) then must have begun dealing in

methamphetamine instead of heroin, because figure 1 shows that, instead of

opiates violations declining, methamphetamine violations again sharply

increased in the early 1970s.

The period from 1964 to 1969 often has been referred to as one of “declining

drug abuse” (Ministry of Health and Welfare 1985); however, it may be

more appropriate to call it the “quiet before the storm.” At that time,

methamphetamine abuse seemed to stabilize, although at a higher level

than in 1959, and narcotics abuse was declining.

85
However, two important aspects in this period should not be overlooked. First,

300 to 800 methamphetamine-related arrests still were made each year, which

suggests “veterans” of methamphetamine abuse survived through this period

and eventually sparked the second epidemic. Second, a new phenomenon of

drug abuse emerged among teenage delinquents who chose hypnotics and

analgesics, which at that time they could buy quite freely in drugstores. This

new trend of substance abuse by teenagers was succeeded by the abuse of

volatile solvents that are cheaper, easier to obtain, more potent, and quicker to

produce a dreamy hallucinatory trip. Volatile solvents abuse among delinquents

and school dropouts spread throughout Japan at a high rate from 1967 to 1970

(Suwaki 1982).

The recurrence of methamphetamine abuse began in 1970 and again led to

tougher legislation when the Stimulants Control Law was amended in 1973.

However, this time the success of the legislative method of control was shortlived. Although this legislation seemed to decrease methamphetamine abuse

by about 30 percent, by 1975 levels again had reached that of 1973 and

continued to increase despite the law. In the first epidemic, the rapid spread of

methamphetamine abuse was due partially to naivete and partially to lack of

legislation to control it. The striking success at control during that time seemed

to be because any measures could be employed to combat substance abuse.

Public education and the passage of legislation worked well. However, the

revival of methamphetamine abuse and the increase of solvents sniffing in spite

of legal and educational efforts seem to indicate a different attitude toward

substance abuse today, one that may be more troublesome and require a

different approach.

Since 1980 the numbers of solvents- and methamphetamine-related arrests

shown in figure 1 (stimulants category) stabilized at high levels. Arrests for

cannabis and opiates violations also show similar tendencies, although these

remain at relatively low levels. This recent phenomenon of an apparently stable

equilibrium in substance abuse seems to be inherently unstable. Any new

substance of abuse or a change in the social situation may upset this

equilibrium.

METHAMPHETAMINE ABUSE-EPIDEMIOLOGIC AND SOCIAL

PROBLEMS

At the end of the World War II, most Japanese were ignorant about the

hazardous properties of methamphetamine, and no laws controlling its sale

or distribution existed. Many soldiers and workers in the military had used

methamphetamine during the war to remain awake at night and did not think of

its use in terms of potential harm or drug dependence. Methamphetamine

86
became available from those military sources and pharmaceutical companies

after the war and could be purchased in drugstores. Thus, at that time

the availability of methamphetamine was essentially unlimited and usage

dramatically increased until 1955.

Because abuse was believed to be related not only to availability but also to

naivete, the Stimulants Control Law passed in 1951 was aimed at both these

issues, with the result that abuse rapidly decreased; by 1959 it was below 1950

levels. This is an example of the remarkable effectiveness of legal and

educational measures in a population that was ignorant of the hazards of drug

abuse and was willing to change its behavior. During the 1945 to 1959

epidemic, people abused methamphetamine in the form of pills as well as by

injection.

Figure 1 also shows that after a 10-year lull from 1960 to 1970

methamphetamine abuse (stimulants category) once again rose sharply and

has continued to remain at high levels until today, shaping a plateau curve

recently. It appears that the current epidemic has an entirely different character

from that of the immediate postwar period. Because legal stimulant distribution

is tightly controlled today, the sources of methamphetamine are almost

entirely illegal. Thus, one factor contributing to the increase in abuse is the

availability of methamphetamine from criminal sources, and the high rates of

methamphetamine abuse continue in spite of sustained legal and education

efforts, suggesting a more malignant motivation than in the previous epidemic.

It seems that legal and educational measures can be remarkably effective in

controlling drug abuse as it occurs in naive populations, but those measures are

less effective in informed ones that consciously choose this pattern of behavior.

In Japan today, almost all methamphetamine is imported, and importation

appears to be accomplished by organized crime, which derives a large

profit from this source. Table 1 shows that the seaports where illegal

methamphetamine arrived are scattered throughout Japan from Hokkaido to

Yakushima Island. Figure 2 shows that Taiwan and South Korea are the major

countries from which illicit methamphetamine is imported. The location of high

abuse areas in Japan can be seen from figures 3 and 4, which show that there

was a dramatic spread of abuse into central and northern Japan from 1970 to

1980.

Figure 5 demonstrates that stimulant abusers are Bohryokudan members,

unemployed people, and construction workers. One of the greatest concerns

is that this abuse pattern may change and spread to other subpopulations.

This concern is genuine, as can be seen from figure 6, which shows that the

prevalence of abuse in homemakers in 1980 was 7 times that in 1972, though

87
TABLE 1. Number and sites of illegally imported methamphetamine seizures

(>1 kg)

Sites

Airports

Haneda

Narita

1987 1988

1

1

Seaports

Tomakomai 1

Tokyo 1 1

Kawasaki 1

Nagoya 1

Osaka 2

Sakai 1

Kobe 1 1

Shimonoseki 4

Yakushima 1

SOURCE: National Police Agency, Division of Prevention of Crimes,

Department for Countermeasures of Drugs, 1989

in 1988 the number of homemakers arrested remained at 415, almost the same

level or a slightly less than in 1980. The number of students arrested for

methamphetamine-related violations (158) is also small, only 0.8 percent of total

arrests. These data suggest that methamphetamine abusers in Japan are still

confined to rather distinct subpopulations and are not evenly distributed

throughout the general population.

Table 2 shows the distribution of psychiatric inpatients by diagnosis, age, and

sex. The survey was conducted by the Ministry of Health and Welfare on June

30, 1987 (Ministry of Health and Welfare 1987). The number of inpatients who

abused methamphetamine was 678; of these, 124 (18.3 percent) were female

and 34 (5.0 percent) were younger than 20 years of age. In 1981 the Ministry

of Health and Welfare issued an unusual policy statement that urged hospitals

to accept more methamphetamine abusers (Ministry of Health and Welfare

1987). Still, the number of inpatients who abused methamphetamine was far

less than those who abused alcohol (table 2). Even medical professionals tend

to view drug-seeking behavior as more criminal than medical, and the condition

on which methamphetamine abusers are accepted into mental hospitals is that

they exhibit psychotic symptoms such as hallucinations or confusion.

88
FIGURE 2. Countries from which a large amount of illicit methamphetamine

(>1 kg) was exported

SOURCE: National Police Agency, Division of Prevention of Crimes,

Department for Countermeasures of Drugs, 1989

Methamphetamine abuse is closely associated with criminal activity, and

prisons contain 10 times more methamphetamine abusers than do hospitals,

although many of them are casual users. According to a survey of Kochi

Prefectural Prison in 1983 (Suwaki et al. 1985), 105 of 405 prisoners (26.1

percent) were convicted under Stimulants Control Law violations, whereas 222

prisoners (55.1 percent) admitted using methamphetamine. In addition,

prisoners generally were younger than hospital patients; 61.9 percent were 20

to 29 years old, and 25.2 percent were 30 to 39 years old.

Fukui and colleagues (1988) conducted a survey of substance abuse in

psychiatric hospitals and clinics throughout Japan in 1987. There were 776

hospitals and clinics (48.9 percent) that responded to the survey; of these, 310

(39.9 percent) treated substance abusers in the 2-month survey period.

Substance abusers totaled 881; of these, 345 (39.2 percent) were on

methamphetamine, and 301 (34.2 percent) were on volatile solvents (table 3).

Figure 7 shows the age distribution of these substance abusers; many abusers

of volatile solvents and cough syrups are in younger age groups, and abusers

89
FIGURE 3. Geographic distribution of methamphetamine-related arrests,

1970 and 1980

SOURCE: National Police Agency, Division of Prevention of Crimes, 1981

of antianxiety drugs, hypnotics, and analgesics tend to be older. Ages of

methamphetamine abusers vary from those in their twenties to those in their

fifties. Surprisingly, 13.9 percent of them are in the 50 to 59 age group,

although the peak group are those ages 30 to 39. This suggests that many

chronic, older patients who abuse methamphetamine are relegated to treatment

in mental hospitals due to its effects.

A 55-year-old methamphetamine abuser today would have been a teenager in

the previous epidemic. This raises speculation as to how many of today’s

abusers are holdovers from that period. It is clear that previous efforts at

control did not eradicate abuse because abuse levels between 1960 and 1970

still were considerable. It is possible that those “veterans” may have helped

spark the present epidemic by continuing to be a ready market for

methamphetamine from 1960 to 1970.

90
FIGURE 4. Geographic distribution of methamphetamine-related arrests,

1988

SOURCE: National Police Agency, Division of Prevention of Crimes,

Department for Countermeasures of Drugs, 1989

91
FIGURE 5. Distribution of occupations of persons arrested for stimulant

violations (total n=20,716)

SOURCE: National Police Agency, Division of Prevention of Crimes,

Department for Countermeasures of Drugs, 1989

FIGURE 6. Prevalence of amphetamine abuse among homemakers by year

SOURCE: National Police Agency, Division of Prevention of Crimes, 1981

92
TABLE 2. Distrubution of psychiatric inpatient diagnoses by age and sex
LONGITUDINAL PATTERN OF SUBSTANCE ABUSE

Finally, the author presents a recent study (Suwaki et al. 1990) of longitudinal

patterns of substance abuse, including methamphetamine. Substance abusers

often are viewed as abusing only one main substance, and other substances of

abuse are likely to be disregarded even when they are abused at the same

time. Once a patient is diagnosed with alcoholism or methamphetamine

dependence, physicians tend to focus on that diagnosis. Data from hospitals

and police offices, to which the author referred in this chapter, also were

classified on such identification of each substance of abuse.

However, in our clinic, we often treat young patients who change their drug of

abuse from organic solvents to methamphetamine and middle-age

methamphetamine abusers who simultaneously consume a large quantity of

alcohol. in considering such a situation, it was intended to make clear the

pattern of substance abuse, including alcohol, in an individual, covering every

substance of abuse and other addictive behaviors such as pathological

gambling. Subjects in this study were 225 patients with substance abuse who

visited psychiatric hospitals and clinics from December 1987 to December

1988.

In Type 1 alcoholism, alcohol is consumed for a long period as a single

substance of abuse. Many Type 1 abusers also had a cigarette smoking habit,

but cigarette smoking is not used as a criterion for deciding pattern of abuse,

because in the preliminary study of 57 patients, 53 (93.0 percent) had a

smoking habit. Type 1b abusers consumed tranquilizers, hypnotics, or

analgesics in later stages. Many of them initiated their use by physicians’

prescription when they visited hospitals or clinics.

Type 2 abuse is initiated at younger ages and usually involves organic solvents.

This type is further subdivided into Type 2a, exclusively solvents; 2b, solvents

with alcohol, hypnotics, or analgesics; and 2c, solvents with methamphetamine.

The latter two types involve many substances of abuse and constitute a core

group of multiple substance abusers in Japan. Type 2c is considered the most

vicious pattern of substance abuse in youth.

Type 3 is the pattern of methamphetamine abuse without use of any organic

solvents and is subdivided into 3a, without alcohol, and 3b, with alcohol. Most

Type 3b patients used alcohol and methamphetamine at the same time.

Type 4 abuse does not include alcohol, organic solvents, or methamphetamine.

94
TABLE 3. Disrtibution of substances of abuse in psychiatric patients with

substance use disorder

Substance of Abuse

Number of Patients

(N=881) Percent

Methamphetamine 345 39.2

Volatile solvents 301 34.2

Hypnotics 85 9.8

Analgesics 84 9.5

Cough syrup 30 3.4

Antianxiety drugs 21 2.4

Others 13 1.5

Unknown 2 0.2

SOURCE: Fukui et al. 1988

FIGURE 7. Age distribution of psychiatric patients with substance use

disorder

SOURCE: Fukui et al. 1988

Table 4 shows the longitudinal patterns of substance abuse from the analyses

of 225 cases. They were categorized into four types and seven subtypes,

based on the longitudinal pattern of abuse, that is, the initial substance of abuse

and its continuation, shift to, or combination with other substances.

95
TABLE 4. Pattern of substance abuse in psychiatric patients in Japan

Number of Patients

Type Subtype (N=225)

1. Alcohol 1a.

1b.

2. Solvents initiated 2a.

2b.

2c.

3. Amphetamine 3a.

3b.

4. Other type

Alcohol alone

Alcohol with tranquilizers,

analgesice

Solvents alone

Solvents with alcohol, tranquilizers,

and analgesics

Solvents with amphetamines

(alcohol, tranquilizers, analgesics)

Amphetamines alone or with

tranquilizers and analgesics

Amphetamines with alcohol

(tranquilizers, analgesics)

Not including alcohol, solvents,

or amphetamines

91

52

7

19

28

7

21

2

SOURCE: Suwaki et al. 1990

Table 5 shows the age of onset in three types of substance abuse: Type 1,

alcohol; Type 2, solvents; Type 3, amphetamines. The youngest case began

his abuse of organic solvents at age 12, and most of the Type 2 cases began

their abuse before age 20. Most of the Type 3 cases began their abuse before

30 years of age. Type 1 cases also initiated their abuse relatively younger than

expected, between 20 and 39 years of age. These three types of abuse are

relatively distinct from each other in terms of age of onset.

Table 8 shows the present diagnoses of 225 cases of substance abuse. In

Types 2b and 2c, the percentage of cases with the diagnosis of solvents abuse

decreased to 68.4 percent and 23.1 percent, respectively. On the other hand,

38.8 percent of Type 2b cases were diagnosed with alcohol abuse, and 73.1

percent of Type 2c cases were diagnosed with methamphetamine abuse. This

suggests that many solvents abusers shifted the substance of abuse to alcohol

or methamphetamine. in Type 3b cases, 80 to 70 percent of them were

diagnosed with alcohol and methamphetamine abuse, which suggests that

many of them use methamphetamine and alcohol simultaneously. Physical

illnesses often were observed in alcohol-related patterns such as Types 1, 2b,

2c, and 3b. in Type 1b (alcohol with hypnotics, tranquilizers, and analgesics),

relatively few cases were diagnosed as hypnotics or analgesics abuse.

However, the cases that consumed these prescribed drugs on a regular basis

were included in the 1b category.

96
TABLE 5. Distribution of the age of onset in substance abuse (n= 192)

1. Alcohol 2. Solvents 3. Amphetamine

Age of Onset Number of Patients Number of Patients Number of Patients

<14 0 13 0

15 to 19 11 29 9

20 to 29 59 2 8

30 to 39 34 0 1

40 to 49 19 0 0

50 to 59 5 0 0

>60 0 0 0

SOURCE: Suwaki et al. 1990

CONCLUSION

Japan has experienced two epidemics of methamphetamine abuse that are

quite different in their backgrounds, Substance abuse problems in a society or

substance use behaviors in an individual should be understood in an overall

dynamic context that involves the movements and availabilities of other

substances of abuse. Japan has reached a plateau in substance abuse for the

10 years in which problems of methamphetamine and volatile solvents abuse

stabilized at high levels and those of cannabis and opiates at low levels.

Equilibrium among substances of abuse on this plateau is inherently unstable

and might be upset by a new epidemic or social conditions.

TABLE 6. Present diagnoses of substance abuse patients

97
REFERENCES

Fukui, S.; Watanabe, N.; lyo, M.; Konuma, K.; Kurisu, E.; Wada, K.; and

Toyama, G. An epidemiologic survey of drug dependence. In: 1987 Report

of Studies on Etiological Factors and Pathological Conditions of Drug

Dependence. Tokyo: Ministry of Health and Welfare, 1988. pp. 169-182.

Ministry of Health and Welfare. A Brief Account of Drug Abuse and

Countermeasures in Japan. Tokyo: Ministry of Health and Welfare, 1985.

Ministry of Health and Welfare, Division of Mental Health. Mental Health in

Japan. Tokyo: Ministry of Health and Welfare, 1987.

National Police Agency, Division of Prevention of Crimes. Actual Situations of

the Violations Against Stimulants and Narcotics Control Laws and Their

Controls in 1980. Tokyo: National Police Agency, 1981.

National Police Agency, Division of Prevention of Crimes, Department for

Countermeasures of Drugs. Statistics of the Violations Against Stimulants

and Other Drug-Related Laws in 1988. Tokyo: National Police Agency,

1989.

Suwaki, H. Solvents and stimulants abuses. Jpn J Clin Psychiat 11(8):955-

963,1982.

Suwaki, H., and Bjorksten, O.J.W. Substance abuse trends in Japan. Public

Health Rev 11(3):199-222, 1983.

Suwaki, H.; Horii, S.; Fujimoto, A.; Akita, I.; Yamasaki, M.; Kazunaga, H.; and

Shigenari, N. A study of substance abuse pattern with special reference to

multiple use problems in Japan. In: 1989 Report of Studies on Etiological

Factors and Pathological Conditions of Drug Dependence. Tokyo: Ministry

of Health and Welfare, 1990. pp. 153-161.

Suwaki, H.; Yoshida, T.; and Ohara, H. A survey of stimulant abusers in prison,

probation office, and mental hospitals in Kochi Prefecture. Jpn J Social

Psychiat 8(2):144-150, 1985.

AUTHOR

Hiroshi Suwaki, M.D.

Professor of Psychology

Kagawa Medical School

1750-1 Mikicho

Kagawa 761-07

JAPAN

96
Trends and Patterns of

Methamphetamine Abuse in the

Republic of Korea

Byung In Cho

OVERVIEW

Methamphetamine was first synthesized in the Republic of Korea by individuals

who returned home from civilian service for the Japanese Government during

World War II and who probably learned the manufacturing process while they

were working at chemical plants or substance-producing companies in Japan

(Min 1989). It is uncertain when methamphetamine was first introduced or

manufactured for illegal business purposes in Korea. Most researchers agree

that methamphetamine manufacturing increased in Korea in the early 1970s

because at that time Japanese drug control policies stiffened the punishment

for illegal substance manufacturers and traffickers in that country (Min 1989).

As the Japanese Government prosecuted illegal methamphetamine

manufacturers with heavier sentences and stricter enforcement, the Japanese

suppliers, presumably the key personnel of major underworld criminal

organizations, visited Korea and contacted skilled technicians, resulting in the

acceleration of illegal methamphetamine production in Korea.

Since methamphetamine was produced on a contractual basis between

Japanese buyers and Korean suppliers, the methamphetamine problem in

Korea was thought to be restricted to illegal manufacturing and smuggling.

Until the middle 1970s the number arrested for methamphetamine abuse was

estimated to be less than 100 per year. By the late 1970s however, Korea

and Japan actively blocked methamphetamine smuggling by strengthening

border interdiction after the Korean producers also became professional

methamphetamine pushers, securing domestic customers and preying on them.

In 1970 the Korean Government began controlling activities involving

methamphetamine production and abuse by authority of the Habit-Forming

Medicine Control Act. Although that act was replaced by the Psychotropic

Medicine Control Act (PMCA) in December 1979, it was not until 1987 that

99
the annual total of methamphetamine-related arrests exceeded 1,000.

Methamphetamine arrestees exceeded 3,300 in 1988, accounting for 84.3

percent of the year’s total of accused drug offenders (3,939).

For some time it was believed that the methamphetamine epidemic was a

phenomenon unique to the harbor city of Pusan, which previously had been

used as a shipping venue by professional methamphetamine smugglers,

However, in recent years, PMCA violators have been arrested in almost every

part of the nation, indicating that there is no methamphetamine-free area in

Korea. Until early 1980 the methamphetamine-abusing population consisted

almost exclusively of street gangsters, public entertainers, prostitutes, and truck

drivers. However, recent data indicate that college students, homemakers,

factory workers, and the unemployed make up the methamphetamine-abusing

population throughout Korea.

DATA SOURCE

This chapter summarizes what is known about methamphetamine abuse in

Korea in terms of (1) trends in arrested abusers, (2) general characteristics of

Korea’s methamphetamine problem, (3) characteristics of methamphetamine

abusers based on the official documents provided by the Supreme Public

Prosecutor’s Office, and (4) research findings obtained from a prison survey by

the Korean Institute of Criminology (KIC) (1989).

Information on trends in abuse arrests, geographical distribution, and

demographic characteristics of methamphetamine offenders were obtained from

official documents on PMCA violators compiled by the Supreme Public

Prosecutor’s Office. These data cover 1980 through the first quarter of 1990.

Data on distribution of methamphetamine offenders by sex, age, and

occupation were obtained by examining the prosecution records and court

decisions of 817 convicted methamphetamine offenders arrested during 1988

and charged with violation of the PMCA.

Information on the characteristics of methamphetamine abusers was obtained

from a prison survey that used questionnaires and interviews with the convicted

offenders. Questionnaires were filled out by 260 convicted methamphetamine

abusers selected from three major prisons, and 10 offenders were interviewed.

The research findings are reported in a special KIC publication (Korean Institute

of Criminology 1989).

100
RECENT TRENDS

Except for 1983 and 1984, the number of arrested methamphetamine offenders

has increased steadily. Table 1 shows that arrests increased by 63.9 percent

and 67.7 percent in 1986 and 1987, respectively. Furthermore, the rate more

than doubled in 1988 compared with 1987; total cases reached 3,320 in 1988.

In 1989 arrest figures declined by 39.9 percent. If this trend continues the

methamphetamine epidemic could be curtailed in the near future. The newly

established Drug Division of the Supreme Public Prosecutor’s Office has made

a strong effort to eradicate drug abuse in general and methamphetamine abuse

in particular throughout the nation. Nationwide drug control strategies, ted by

prosecution authorities and the police, severely restricted the activities of

syndicated raw material suppliers and several highly sophisticated underground

methamphetamine networks. Leading individuals in methamphetamine supply

and sales are serving their terms in prisons or are appealing their convictions.

It is assumed that the concentrated and successive drug investigations reduced

the total methamphetamine supply on one hand and caused a rapid rise in the

drug’s price on the other. Thus, the sudden decrease in arrests of

methamphetamine abusers probably was caused by decreasing supply and

high prices.

As for the methamphetamine and raw materials seized, the amount confiscated

in 1989 is calculated to be 821.619 kg (1,814 pounds), which is 2.7 times more

than the total amount confiscated during the previous 5 years. Table 2 shows

amounts of methamphetamine and raw materials for methamphetamine

production seized from 1984 to 1990. Table 3 shows the number of raided

clandestine methamphetamine laboratories and the total amount of

methamphetamine and raw materials seized in those same years. Table 4

TABLE 1. Number of people arrested for methamphetamine-related offenses,

1980 to 1990

Year 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990a

Number of 78 216 501 420 417 501 821 1,377 3,320 1,994 301

arreetees

Percent - +177 +132 -16.2 -0.7 +20.1 +63.9 +67.7 +141 -39.9 -

Increase

The figures for 1990 represent the arrestees during the first quarter of the year.

SOURCE: Supreme Public Prosecutor’s Office

101
TABLE 2. Amounts (kg/lbs) of methamphetamine and raw materials seized,

1984-90

Year Methamphetamine Raw Material

1984 47.892 (105.72) -

1985 24.349 (53.75) -

1986 34.157 (75.40) -

1987 120.761 (266.58) .500 (1)

1988 73.538 (162.33) -

1989 131.619 (290.54) 690.060 (1,523)

1990a

7.372 (16.27) 164.000 (362)

Total 439.688 (970.61) 854.500 (1,686)

a

The figures for 1990 represent amounts seized during the first quarter of the

year.

SOURCE: Supreme Public Prosecutor’s Office

TABLE 3. Methamphetamine laboratories raided and the total amounts (kg/

lbs) of methamphetamine and raw materials seized through raids,

1984-90

Year Laboratories Raided Total Amounts Seized

1984

1985

1986

1987

1988

1989

1990a

3

1

4

7

4

9

2

Total 30 991.49 (2,188.71)

2.60 (6.16)

11.20 (24.72)

23.75 (52.42)

29.80 (65.78)

115.45 (254.85)

637.07 (1,406.33)

171.42 (376.42)

a

The figures for 1990 represent the cases and the amounts seized during the

first quarter of the year.

SOURCE: Supreme Public Prosecutor’s Office

102
TABLE 4. Methamphetamine pricesa

 at various levels of trade

Price City

1988

(Oct.)

1989 1990

(Oct.) (Jan.)

1990

(Apr.)

Producer’s price/kg Seoul

Pusan

Wholesale price/100g Seoul

Pusan

Retail price/g Seoul

Pusan

injection price/0.03g Seoul 7-14 14-21 28

Pusan 14 43 70

5,000

4,300

700

1,400

70

140

6,400 7,000 11,000

5,700 14,000 21,000-29,000

1,000

2,900

140

280

1,400

5,700

210

430

4,300

7,000-14,000

700

700-1,400

70

70-140

a

The price at each trade level was converted into U.S. dollars in accordance with the

foreign exchange rate as of June 19, 1990.

SOURCE: Supreme Public Prosecutor’s Office

shows the changes in the price of methamphetamine at various levels of trade

from October 1988 to April 1990. The price per injection increased by a factor

of 10 during that period in Seoul.

Despite these apparently favorable trends, few predictions of future drug

use are optimistic. Most experts on drug use in Korea are aware that the use

of marijuana and opiate derivatives abruptly increased while the use of

methamphetamine decreased. Figure 1 compares the arrests by type of drug

abused. It is widely assumed that many methamphetamine abusers gradually

began using marijuana or opiate derivatives instead.

It is anticipated that methamphetamine abuse will increase steadily whenever

control efforts decline and the supply increases, resulting in price reduction.

Some investigators warn of the possibility that the cheaper, foreign-made

methamphetamine, possibly from Taiwan or Thailand, would be smuggled into

Korea if the price stays high for a prolonged period.

103
FIGURE 1. Number of drug arrests and types of drugs involved, 1980-1989

GENERAL CHARACTERISTICS

Geographic Distribution

Geographic distribution of methamphetamine offenders can be ascertained by

reviewing the arrest data compiled by the Supreme Public Prosecutor’s Office.

Although the figures have fluctuated slightly, about half the arrests for

methamphetamine-related offenses were made in the city of Pusan and

adjacent districts.

Data presented in table 5 confirm that methamphetamine is being used in every

part of Korea. Methamphetamine arrests are increasing rapidly in Kyungki

Province, which includes Seoul, rising from 23.4 percent of nationwide drug

arrests in 1986 to 34.1 percent in 1989. Kyungbuk Province, including the city

of Taegu, also has been identified as a potential area in which the

methamphetamine epidemic may rapidly expand.

104
TABLE 5. Geographical distribution of methamphetamine offenders

1986 1987 1988 1989

Province N % N % N % N %

Kyungki 202 (23.4) 467

Kyungnam 462 (53.5) 744

Kyungbuk 123 (14.2) 153

Cheonnam 4 (0.5) 28

Cheonbuk 6 (0.8) 15

Kangwon 13 (1.5) 10

Choongnam 40 (4.6) 34

Choongbuk 4 (0.5) 8

Cheju 8 (1.0) -

(32.0)

(51.0)

(10.5)

(1.9)

(1.0)

(0.7)

(2.3)

(0.6)

-

624 (18.8) 680 (34.1)

2,261

295

(68.1) 826 (41.4)

(8.9)

(0.8)

363 (18.2)

27 51 (2.6)

7 (0.2) 20 (1.0)

27 (0.8) 6 (0.3)

46 (1.4) 36 (1.8)

13 (0.4) 6 (0.3)

20 (0.6) 6 (0.3)

Total 862 1,459

SOURCE: Supreme Public Prosecutor’s Office

3,320 1,994

Distribution by Sex, Age, and Occupation

Chronological data on the demographic character of methamphetamine

offenders are not available at this time. However, based on the demographic

data on those arrested in 1988, a nationwide picture can be projected.

According to table 6, in Korea, as in many other countries of the world, males

constitute the majority of methamphetamine offenders. The ratio of male to

female offenders is 84.7 percent vs. 15.3 percent. As for age distribution, 51.2

percent were between 21 and 30 years of age; the majority of female offenders

were disproportionately concentrated under 25 years of age, while the male

offenders are relatively evenly distributed across ail ages.

Table 7 shows distribution by occupation of those arrested in 1988. About half

those arrested were unemployed. A disproportionate number of female

offenders come from the service or entertainment industry (e.g., prostitutes, bar

girls), while the occupations of male offenders vary.

ABUSE PATTERNS

Motivations

The KIC survey revealed that 70 percent of the respondents first used

methamphetamine between the ages of 16 and 30. The average age of first

experience was 28.7 for males and 22.7 for females. As for preliminary

105
TABLE 6. Distribution of accused methamphetamine offenders by sex and

age, 1988

Age

Male Female Total

N % N % N %

Younger than 20 264 (9.4) 104 (20.4) 368 (11.1)

21-25 631 (22.4) 208 (40.9) 839 (25.3)

26-30 773 (27.5) 87 (17.2) 860 (25.9)

31-40 803 (28.6) 80 (15.1) 883 (26.6)

41-50 165 (5.8) 21 (4.1) 186 (5.6)

Older than 51 32 (1.2) 6 (1-2) 38 (1.2)

Unknown 142 (5.1) 2 (0.5) 144 (4.3)

Total 2,810 (84.7) 408 (15.3) 3,318

SOURCE: Korean Institute of Criminology 1989

TABLE 7. Distribution of methamphetamine offenders by occupation

arrested, 1988

Occupation

Male Female Total

N % N % N %

Unemployed 1,438

Service workera

301

Factory worker 226

Sales clerk 201

Farmer 62

Office clerk 57

Technician 51

College student 33

Homemaker -

Others 441

Total 2,810 (84.7) 508 (15.3) 3,318 (100.0)

(51.2)

(10.7)

(8.0)

(1.2)

(2.2)

(1.8)

(1.8)

(1.2)

-

(15.7)

236

232

7

10

1

3

18

(46.5)

(45.7)

(1.4)

(2.0)

(0.2)

(0.6)

(3.5)

1,674 (50.5)

553 (16.1)

226 (6.8)

208 (6.3)

62 (1.9)

56 (1.7)

56 (1.7)

34 (1.1)

3 (0.1)

459 (13.6)

a

In Korea, “service” occupations include such jobs as waiters, pimps, bell boys

(males); and waitresses, prostitutes, coffee shop madams (females).

SOURCE: Korean institute of Criminology 1989

106
knowledge of methamphetamine at the time of first use, 56.6 percent reported

that they thought of methamphetamine as a substance for getting high; 32.2

percent thought of it as an excellent remedy for tiredness; and 26.2 percent

tried it to enhance sexual pleasure. From these findings, it appears that

most methamphetamine abusers began using because of myths and false

information. Approximately 90 percent of the respondents reported that they

began methamphetamine use due to peer influence.

Methods and Locations

Eighty-one percent of the respondents reported that they first used

methamphetamine by intravenous injection, while 15 percent drank it with soft

drinks, and 4 percent snorted it. After they became addicts, however, 97

percent used intravenous injection almost exclusively; the abusers agreed that

injection is the best method to get high within seconds.

Asked where they used methamphetamine, about 55 percent said they used it

in hotels, while bars, cars, and recreation facilities also were used frequently.

The KIC research also revealed that 92.6 percent of respondents abused

methamphetamine with peers, lovers, or wives rather than alone.

Frequency, Dosage, and Duration

Frequency, dosage, and duration were investigated by inquiring into abuse

habits for a month before arrest: 42.8 percent reported that they injected more

than once a day; 18.8 percent injected once a day; 14.3 percent injected once

every 2 or 3 days; and 8 percent injected once a week. More than 60 percent

of respondents used methamphetamine once or more a day.

As for dosage, it has been known that abusers generally use 0.03 g (0.001

ounce) of methamphetamine per injection. However, the KIC research revealed

that only 33.8 percent of the respondents administered less than 0.03 g per

injection; 28.4 percent of the respondents reported a dosage of 0.1 g (0.03

ounce) or more per injection.

As for duration, 37.4 percent reported that they had used methamphetamine

longer than 3 years, while 39.9 percent had used it for 1 to 3 years; only 10.4

percent of respondents reported using methamphetamine less than 6 months.

Methamphetamine Abusers and Other Drugs

The KIC research discovered that 54.3 percent of the respondents also had

used at least one other drug prior or subsequent to methamphetamine use:

83.3 percent smoked marijuana; 19.4 percent snorted inhalants (e.g., glue,

107
butane gas); 18.5 percent used tranquilizers; and 6.3 percent used heroin or

cocaine. Respondents reported smoking marijuana or using inhalants prior to

methamphetamine use and using heroin or cocaine after an experience with

methamphetamine. From these findings, it is hypothesized that the drug

addiction process starts with marijuana and inhalants and progresses to use of

methamphetamine and other drugs.

CONCLUSION

in general, the drug epidemic in Korea is not serious in number of drug users

and the impact on and cost of drug use to society compared with the drug

situation in the more industrialized Western countries, Even so, the Korean

Government is well aware that drug abuse, particularly methamphetamine

abuse, will become uncontrollable unless treated at the beginning stages.

As is the case with other nations, the drug policy of Korea has taken two

directions: (1) suppressing the supply of raw materials and the final products of

illegal drugs and (2) providing self-reported abusers and addicts with treatment

opportunities free of charge and with immunity from criminal punishment.

Whereas the drug control policies focus on border interdiction to prevent illegal

trade of methamphetamine and raw materials between nations, the government

considers education and prevention as the final solution to the problem. The

National Drug Addicts Treatment Center under construction near Pusan is

intended as the cornerstone of a more advanced drug policy in the Republic of

Korea.

REFERENCES

Korean institute of Criminology. A Study on Methamphetamine Abuse and

Countermeasures. Seoul: Korean institute of Criminology, 1969.

Min, B.H. Present Situation of Drug Offenders and the Countermeasures.

Research Report 20. Seoul: Legal Research and Training Institute,

Department of Justice, 1989.

AUTHOR

Byung In Cho, Ph.D.

Senior Researcher

Korean institute of Criminology

1103 Teacher’s Welfare Building

142 Woomyun-Dong

Sucho-gu, Seoul 135-140

REPUBLIC OF KOREA

106
Community Networks for Response to

Abuse Outbreaks of Methamphetamine

and Its Analogs

James N. Hall and Pauline M. Broderick

INTRODUCTION

The most recent drug abuse prevalence surveys as well as morbidity and

mortality indicators demonstrate that the Nation’s cocaine epidemic has started

to decline. In assessing potential drug problems for the 1990s, it is important to

recognize the increased significance of local and regional drug issues.

Previously, drug problems have been associated with major urban centers,

particularly on the east and west coasts. In recent years, all communities are at

risk of drug abuse outbreaks. Several factors contribute to this trend. The

increased domestic production of marijuana and synthetic drugs from

clandestine laboratories means that even isolated rural areas may be centers of

illicit drug production and trafficking. The rapid distribution of crack cocaine via

the US. interstate highway system demonstrates that more aggressive drug

marketing strategies place all communities at risk.

Community-based networks are a vital resource for countering the problems

of alcohol and other drug abuse. Indeed, such organizations represent the

“homefront” of the “war on drugs.” The impact of these networks is

particularly appropriate for addressing the spread of domestically produced

methamphetamine (speed, crank, crystal, or ice) and its analog MDMA (XTC

or ecstasy). The localized nature of methamphetamine abuse has been a

unique aspect of its epidemics.

A 1989 National Institute on Drug Abuse (NIDA) study concluded that the most

important factor in determining a community’s risk for methamphetamine abuse

is the presence of local clandestine laboratories that produce the drug (National

Institute on Drug Abuse 1989a). Patterns of the drug’s abuse tend to be

concentrated in selected cities and regions. However, locations of such drug

outbreaks have shifted over the past 30 years. Since 1960, areas affected by

abuse of synthetic stimulants have moved from coast to coast as well as to the

Midwest and, more recently, to the South.

109
In the early 1960s pharmaceutical stimulants were prescribed widely as appetite

suppressants for the treatment of obesity. Diversion of these legally prescribed

products became rampant and ultimately led to stricter government regulations

and more cautious prescribing for medical use. Later in that decade, “street

speed” from clandestine laboratories was introduced by motorcycle gangs,

which quickly gained control of the manufacture and distribution of illicit

amphetamine products. The mobility of these laboratories and their affiliation

with biker groups in different regions of the country Contributed to the changing

geography of the methamphetamine problem. Today, methamphetamine

producers and sellers still include biker gangs but also have expanded to

include large and small independent criminal enterprise groups.

San Francisco and the Pacific Northwest were the center of amphetamine

abuse in the late 1960s and early 1970s. Trafficking spread to the Midwest

throughout the 1970s and by the early 1980s Philadelphia and Minneapolis led

the Nation in consequences of methamphetamine problems. In 1987 San

Diego surpassed all other U.S. cities in the consequences of methamphetamine

abuse (National Institute on Drug Abuse 1989a).

Table 1 tracks methamphetamine-related emergency room (ER) mentions

reported to NIDA’s Drug Abuse Warning Network (DAWN) from 1985 to 1989.

Such mentions increased from 1,370 in 1985 to 2,439 in 1988 and then

decreased slightly to 2,135 in 1989. It should be noted that these totals are

from only those hospitals that have consistently reported to DAWN during the 5-

year period covered and represent only a sample of the national total. Of the

1989 mentions, 77 percent were from only five cities-San Diego (25 percent),

San Francisco (22 percent), Dallas (11 percent), Phoenix (11 percent), and Los

Angeles (8 percent). Likewise, table 2 reveals that 74 percent of the 180

methamphetamine-related deaths reported by medical examiners (MEs) to

DAWN in 1989 were from the three California cities of San Diego (36 percent),

San Francisco (24 percent), and Los Angeles (14 percent).

Demographic profiles of abusers from various sources reflect a similar at-risk

group. The National Institute on Drug Abuse (1989b) reported that abusing

populations are predominantly white, lower middle-income, high schooleducated (or less), young adults ranging in age from 20 to 35 years. Table 3

reflects a similar demographic pattern of 1988 DAWN emergency room

mentions and ME-reported deaths for methamphetamine. More recently,

adolescent use appears to be on the rise (Adams et al. 1990). Although most

drug abuse monitoring systems focus on major metropolitan areas, anecdotal

surveillance and reports from State epidemiology work groups indicate that

methamphetamine is spreading rapidly to rural communities in the West,

Midwest, and South (Westrate 1989).

110
TABLE 1. Methamphetamine-related ER mentions, 1985-1989

Total DAWN System and

Metropolitan Areas 1985 1986 1987 1966 1989

Total ER Mentions 1,370 1,472 2,062 2,439 2,135

San Diego 112 218 528 778 524

San Francisco 360 240 218 256 461

Dallas 72 230 284 308 243

Phoenix 51 85 208 345 234

Los Angeles 65 87 117 176 166

Seattle 30 32 58 86 121

Denver 65 102 84 71 97

Philadelphia 285 161 206 102 79

SOURCE: NIDA Drug Abuse Warning Network, March 1990 data file for ERs

and April 1990 data file for MEs

TABLE 2. Methamphetamine-related deaths, 1985-1989

Total DAWN System and

Metropolitan Areas 1985 1986 1987 1988 1989

Total ME Mentions 65 116 141 163 180

(excludes New York)

San Diego 9 27 39 52 64

San Francisco 13 37 51 53 44

Los Angeles 3 23 18 18 25

Philadelphia 34 23 14 15 13

Oklahoma City 0 2 6 0 8

Phoenix 0 0 3 7 8

SOURCE: NIDA Drug Abuse Warning Network, March 1990 data file for ERs

and April 1990 data file for MEs

The inhalation (“smoking”) of melted d-methamphetamine hydrochloride (ice)

reached epidemic proportions in Hawaii between 1987 and 1990 (Cave 1990).

This highly pure, recrystalized methamphetamine product is believed to be

manufactured in Korea and trafficked by Filipino crime groups. Abuse of ice in

the United States still appears to be isolated to Hawaii according to Federal

drug use tracking systems (Drug Enforcement Administration 1990). Scattered

111
TABLE 3. Demographics of methamphetamine-related ER patients and ME

decedents, 1988, by percent

Category White Male Number (Age Range)

ER Patients 76 62

Decedents 75 83

51 (20-29 years old)

43 (30-39 years old)

SOURCE: NIDA Drug Abuse Warning Network Statistical Series, 1-8 Annual

Data, 1988, 1989a

reports of ice use along the west coast and in the South generally have referred

to abuse of a less pure form of methamphetamine than that being abused in

Hawaii and Asia. Yet the potential for a mainland US. ice epidemic exists if

supplies of the drug become available. It is believed that crack users might be

attracted to the economy offered by the long duration (4 to 6 hours) of the

drug’s stimulant effects.

The abuse of the methamphetamine analog MDMA has not been adequately

tracked. Newmeyer (1986) has identified the problems of applying traditional

drug abuse epidemiology systems in monitoring patterns of MDMA abuse. The

general perception is that the drug is widely used, particularly among college

Students in the West and South. However, as Fuller (1989) notes, there are few

hard data regarding the geographic distribution of MDMA use or its patterns of

abuse. Consequently, community networks may be able to identify local

outbreaks of MDMA abuse years before national drug abuse surveillance

systems, such as DAWN and Federal prevalence surveys, may report it.

COMMUNITY-BASED STRATEGIES

It is increasingly apparent that Comprehensive, community-based strategies

represent a strong deterrent in the prevention of drug abuse. Recognizing that

problems associated with drug abuse are multifaceted indicates that a variety of

solutions from many different disciplines are appropriate. Even more important

is the need to coordinate these solutions into a comprehensive approach. Such

strategies are formulated by networks that may exist among Federal, State, and

local agencies within the same field (e.g., law enforcement) or from crossdisciplinary alliances, including health and human services, criminal justice,

education, and environmental agencies. Some of these types of networks

include:

Private-sector drug prevention coalitions

Local drug epidemiology networks

112
Alcohol and other drug abuse and mental health agencies

Criminal justice interagency networks

Private-Sector Coalitions

Private-sector drug prevention coalitions have been formed in at least 35 US.

cities during the past few years (personal communication, M. Culp, August

1990). These groups have proven effective in organizing and promoting public

policy requiring comprehensive approaches and interagency cooperation,

although their organizational structures and foci may vary from city to city. One

of the most important functions performed by these coalitions is community

consensus development. Consequently, it is important that they develop

formats based on community needs. It is also vital that community coalitions

establish as broad a membership base as possible, drawing from every sector

of the community. Many of these local coalitions grew out of parent action

groups, which recognized the need to expand family-oriented antidrug efforts to

comprehensive community strategies.

Local Drug Epidemiology Networks

A local drug epidemiology network (DEN) is a committee comprising

representatives from health, criminal justice, and other community agencies

affected by drug abuse. The DEN gathers, monitors, and analyzes drug abuse

indicator data from these various community institutions. The DEN tracks drugrelated medical emergencies and deaths reported by hospital ER facilities and

ME departments and reviews addiction treatment admissions data for

substance abuse patterns and client demographic information. Criminal justice

data may include information on arrestees, drug-related crime, and price and

purity statistics from drug seizure. Local drug abuse research from academic

institutions helps complete a comprehensive profile of community substance

abuse patterns. Local trends may be tracked from semiannual or quarterly

reports generated by the DEN.

Local epidemiology may reveal an emerging drug problem, such as

methamphetamine abuse, much sooner than it would be detected from national

data or surveys. Local drug epidemiology assists public policy planners by

identifying where to provide services. Community epidemiology networks also

provide a vital communication link for health, criminal justice, and education

professionals. Traditionally, these groups have worked independently and

missed the benefits of comprehensive strategies derived from interagency

cooperation.

113
Alcohol and Other Drug Abuse and Mental Health Agencies

Networks of alcohol and other drug abuse and mental health organizations

include community councils of treatment and prevention service provider

agencies. Local substance abuse planning boards are responsible for

identifying community needs and preparing recommendations on resource

allocations and budgets for addiction treatment. Community addiction services

boards may administer central intake units that offer diagnosis and assessment

services independent of the treatment program where therapy is provided.

Independent assessment centers provide efficient Utilization of a community’s

limited addiction therapy resources.

Criminal Justice Networks

Interagency law enforcement networks promote cooperation among Federal,

State, and local agencies. Networks linking enforcement, courts, corrections,

and probation help coordinate the various local service components of the

criminal justice system. It is important that each part of the justice system be

aware of the needs and limitations of the other components. Local networks

provide that opportunity.

ROLE OF NETWORKS

Community networks may assume various roles in countering drug abuse

outbreaks of methamphetamine and its analogs. These roles include:

Conducting surveillance

Planning and implementing prevention programs

Developing intervention Strategies

Adapting addiction treatment

Enforcing legal sanctions

Surveillance

The earliest detection of local methamphetamine problems often begins from

anecdotal mentions from school personnel, drug hotlines, or treatment

admissions counseiors. Yet it is important that there be a recognized reporting

center for such information, Professionals may hesitate to contact police solely

on the basis of unconfirmed reports. Consequently, local DENS are ideal

forums to receive such information. Once the DEN is alerted, it may further

investigate the availability of methamphetamine products through its multiindicator system.

114
Surveillance includes identification of sources for precursor chemicals and

laboratory equipment. Below are lists of popular chemicals used as precursors,

solvents, and metal/salt or acid-based reagents in the illicit manufacture of

methamphetamine (Oregon Department of Human Resources 1988). These

substances have many industrial applications; therefore, monitoring their

distribution is often more appropriate than outlawing their sale. Indeed,

legitimate chemical supply houses should be included in the surveillance

process. Law enforcement officers should be alerted to these chemicals in the

event of their discovery during routine property searches. Laboratory analysis

of seized methamphetamine will help identtfy precursor chemicals being used

locally.

Metal/Salt Reagents Solvents

Aluminum foil

Magnesium

Palladium

Mercuric chloride

Sodium cyanide

Red phosphorous

Thionyl chloride

Lead acetate

Iodine

Lithium alumlnum hydride

Sodium

Freon

Chloroform

Methanol

lsopropanol

Ethyl ether

Acetone

Pyridine

Hexane

Benzene

Precursors Acid-Based Reagents

Phenylacetic acid

Phenyl-2-propanone

Methylamine

Ephedrine

Benzyl chloride

Acetaldehyde

Hydrochloric acid

Acetic anhydride

Sodium hydroxide

Hydriodic acid

Acetic acid

Hydrogen peroxide

Sulfuric acid

Ammonia

The detection of clandestine laboratories may be facilitated by distinct odors

emanating from such operations. Information campaigns may alert the public to

signs of clandestine laboratory operations and may solicit reporting of

suspected activity to law enforcement agencies. Such campaigns should

emphasize the health and safety hazards associated with the presence of illicit

drug laboratories. Public electrical utilities may help identify an unusually large

115
consumption of energy indicating the possible location of a methamphetamine

laboratory. Recently, this type of assistance led to the seizure of a

methamphetamine laboratory in Racine, WI.

Surveillance for methamphetamine requires an understanding of how the drug

is trafficked both from local laboratories and nationally via interstate highways.

The recent spread of methamphetamine from Southern California eastward

parallels movement along interstate Highways 10 and 44. In the North, a

similar pattern may be observed along Interstate 90. It is important that law

enforcement agencies share information about general trafficking patterns with

community networks. This type of intelligence need not include specific facts

nor jeopardize ongoing investigations.

Communities at risk for methamphetamine abuse should monitor all available

drug prevalence surveys for changes in patterns of stimulant use. Morbidity

and mortality indicators also may alert local networks to the arrival or spread of

methamphetamine abuse. These data sources include ME departments,

hospital ERs, and addiction treatment programs. Patterns first may be reported

as secondary or tertiary drug problems, particularly among cocaine clients.

Methamphetamine use may be reported by arrestees for drug and nondrug

offenses. The National Institute of Justice’s Drug Utilization Forecast (DUF)

system is an excellent example of drug abuse surveillance methods among the

criminal justice population. The DUF program interviews and conducts urine

drug screens among arrestees on a voluntary, anonymous basis. Early

detection of methamphetamine and its analogs, as Well as other new street

drugs, is more likely to be revealed first in the DUF interviews rather than in the

toxicology test results.

A special problem related to the surveillance of methamphetamine involves

the many different street names by which the drug is known Users rarely

refer to the drug by its five-syllable chemical name. Street names for

methamphetamine include crank, crystal, speed, crystal meth, glass, peanut

butter speed, ice, go-fast, zip, chris, cristy, go, or meth. Some of these names

are more popular in one community than in others. In San Diego the drug

usually is called crystal; in Portland, OR, the name crank is used most often;

in Dallas it is known as speed. Because of the variety of terms used, it is likely

that data collection and reporting of methamphetamine abuse may not always

properly classify the substance described. Consequently, it is important that

ER staff, treatment counselors, educators, and law enforcement personnel be

familiar with the various street names,

116
Prevention Requirements

Prevention of methamphetamine abuse requires a comprehensive

understanding of the drug’s desired and adverse effects, its unique patterns of

abuse, the at-risk populations most likely to be using it, and its special risks

related to transmission of the human immunodeficiency virus. Recovering

methamphetamine addicts interviewed in a 1988 study (National Institute on

Drug Abuse 1989b) identified the need for methamphetamine-specific

prevention strategies. They reported seeing national antidrug messages about

cocaine, crack, alcohol, and marijuana on television, billboards, and in

newspapers but never hearing about methamphetamine. Consequently, they

naively assumed that the drug must not be dangerous.

The localized nature of methamphetamine epidemics emphasizes the need

for creative prevention strategies created by community-based networks.

Such groups are in the best position to determine the most appropriate way

of marketing and disseminating drug prevention messages. An example of a

local prevention effort focused on MDMA is the “Agony of Ecstasy” campaign

created by the “I Care” program of the East Baton Rouge Parish School

Board in Louisiana. Local networks also are ideal groups for evaluating the

effectiveness of prevention campaigns.

lntervention Strategies

Intervention for methamphetamine abuse involves identification of users and

addicts as well as development of effective communications and options

available to help them change their behavior. Local drug abuse networks may

help community groups identify the specific signs and symptoms of

methamphetamine abuse most likely to be observed by various institutions such

as health and human service agencies, the criminal justice system, employers,

and families and other social organizations, An understanding of the drug’s

unique abuse patterns will assist in developing such guidelines. Once

identified, methamphetamine abusers need to be educated about the hazards

of continued use in terms relevant to their own experiences and their

observations of other users. A well-formulated continuum of care based on

availability of local services should include resources for private counseling,

self-help groups, and inpatient and outpatient addiction therapy. These

services provide options for helping individuals change drug-using behavior. An

example of a community network’s intervention training program is Project First

Aid for Addiction, developed by the Miami, FL, Coalition for a Drug-Free

Community. Project First Aid for Addiction is a 3-evening educational series

designed to teach the nature of addiction and how family members and friends

may intervene with an addict.

117
Networks of addiction treatment programs and health departments may

anticipate and allocate therapy resources at the onset of a methamphetamine

abuse outbreak. Gawin and Ellinwood (1988) have reported that stimulant

abuse produces some unique problems such as anhedonia (lack of pleasure in

acts that are normally pleasurable) and anergia (inactivity, lack of energy).

Kleber and Gawin (1984) have indicated that many substance abuse treatment

programs are patterned after therapy for alcohol or opiate addiction and applied

without adaptation for stimulant abuse. Experience with treating cocaine

addiction will prove helpful. Nevertheless, an important role of local networks is

to provide specialized training for stimulant addiction treatment to counselors in

communities affected by methamphetamine abuse.

Adaptlng Addiction Treatment

Gawin and Ellinwood (1988) report that stimulant abuse treatments are being

developed and applied, including adaptations of most major types of

psychotherapy as well as pharmacotherapy. They also indicate that outpatient

treatment is often successful, although early relapse is a strong possibility, and

brief, episodically evoked craving recurs after withdrawal. Although it gradually

diminishes in frequency, such craving can reemerge months or years after

cessation of stimulant use. Such craving emerges as a crucial component of

strategies for relapse prevention for stimulant abuse, which otherwise

resembles the postwithdrawal treatment for other addictions.

Legal Sanctions

Community networks may assist law enforcement officers by promoting

communication about methamphetamine problems among drug abuse

professionals from various disciplines. Sharing information is an important

source of intelligence for law enforcement activities. Networks may identify key

resource persons and provide training for police about typical user profiles,

trafficking patterns, and clandestine laboratory operations. Westrate (1989) has

identified outlaw motorcycle gangs as the largest organized group involved with

methamphetamine trafficking. In some areas, they control the market, whereas

elsewhere they share the market with other types of traffickers. Motorcycle

gangs appear to be strongest in areas that are not influenced by traditional

organized crime groups or other ethnic criminal organizations. Generally, the

most productive methamphetamine laboratories have been sited in secluded,

rural areas away from the metropolitan distribution areas that these laboratories

service.

Clandestine laboratory seizure requires specialized training in detection and

safety precautions as well as hazardous waste cleanup and disposal. Federal

118
networks have been most helpful in conducting laboratory enforcement schools.

The Drug Enforcement Administration has sponsored more than 23 such

schools instructing more than 800 enforcement personnel from Federal, State,

and local agencies. In addition, the Bureau of Justice Assistance has trained

more than 230 State and local personnel. Community networks may help

identify local experts to provide similar training programs. State epidemiology

networks provide an excellent central reporting mechanism for tracking

methamphetamine seizures and arrests. Two recent ice seizures in Florida

were first reported to the State’s Epidemiology Work Group by local law

enforcement agencies in two rural counties.

Drug abuse problems frequently have been viewed as a national crisis requiring

Federal solutions. This perception is particularly understandable with drugs of

foreign origin such as cocaine or heroin, However, domestically produced

drugs tend to have more regional patterns of abuse. Consequently, local

strategies may more rapidly identify, prevent, intervene in, and stop expansion

of the problem. Local networks encourage communication and cooperation

among key professionals from various disciplines and develop comprehensive

strategies. NIDA’s drug abuse telecommunication network promotes

exchanges among local networks in various parts of the country. A vital role for

Federal institutions is to stimulate, train, and assist with the implementation of

local initiatives for solving community drug problems. This approach is of

particular significance for problems related to drugs of domestic origin such as

methamphetamine and its analogs.

REFERENCES

Adams, E.H.; Blanken, A.J.; Ferguson, L.D.; and Kopstein, A. “Overview of

Selected Drug Trends.” Unpublished paper. Division of Epidemiology and

Prevention Research, National Institute on Drug Abuse, 1990.

Cave, L.J., ed. NIDA monitors Hawaiian “ice” epidemic, NIDA Notes. Vol. 5,

No. 2. National Institute on Drug Abuse. DHHS Pub. No. (ADM)90-1488.

Washington, DC: Supt. of Docs., US. Govt. Print. Off., 1990. pp. 22-23.

Drug Enforcement Administration, A special report on “ice” (dmethamphetamine hydrochloride).” In: Epidemiologic Trends in Drug

Abuse, Proceedings of the Community Epidemiology Work Group, December

1989. National Institute on Drug Abuse. DHHS Pub. No. 90-721-75720058.

Washington, DC: Supt. of Docs., U.S. Govt. Print. Off., 1990. pp. Ill-69-lll83.

Fuller, R.W. Recommendations for future research on amphetamines and

related designer drugs. In: Asghar, K., and De Souza, E., eds.

Pharmacology and Toxicology of Amphetamine and Related Designer Drugs.

National Institute on Drug Abuse Research Monograph 94. DHHS Pub. No.

119
(ADM)89-1640. Washington, DC: Supt. of Docs., U.S. Govt. Print, Off.,

1989. pp. 341-357.

Gawin, F.H., and Ellinwood, E.H., Jr. Cocaine and other stimulants: Actions,

abuse, and treatment. N Engl J Med 318:1173-1182, 1988.

Kleber, H.D., and Gawin, F.H. Cocaine abuse: A review of current and

experimental treatments. In: Grabowski, J., ed. Cocaine: Pharmacology,

Effects, and Treatment of Abuse. National Institute on Drug Abuse Research

Monograph 50. DHHS Pub. No. (ADM)87-1326. Washington, DC: Supt. of

Docs., U.S. Govt. Print. Off., 1984. pp. 111-129.

National Institute on Drug Abuse. Methamphetamine Abuse in the United

States. DHHS Pub. No. (ADM)89-1608. Washington, DC: Supt. of Docs.,

U.S. Govt. Print. Off., 1989b.

National Institute on Drug Abuse. Statistical Series 1-8, Annual Data, 1988.

DHHS Pub. No. (ADM)89-1634. Washington, DC: Supt. of Docs., U.S.

Govt. Print. Off., 1989a.

Newmeyer, J.A. Some considerations on the prevalence of MDMA use.

J Psychoactive Drugs 18:361-362, 1986.

Oregon Department of Human Resources, Health Division. Clandestine Drug

Lab Committee, Final Report. Portland, OR, 1988.

Westrate, D.L. “Methamphetamine Trafficking and Abuse.” Statement to the

Select Committee on Narcotics Abuse and Control, US. House of

Representatives, October 24, 1989.

AUTHORS

James N. Hall, B.A.

Executive Director

Pauline M. Broderick, B.P.S.

Director of Research

Up Front Drug Information Center

Suite 602

5701 Bisoayne Boulevard

Miami, FL 33137

120
National

Institute on

While limited supplies last, single copies of the monographs may be obtained

free of charge from the National Clearinghouse for Alcohol and Drug

Information (NCADI). Please contact NCADI also for information about

availability of coming issues and other publications of the National Institute on

Drug Abuse relevant to drug abuse research.

Additional copies may be purchased from the U.S. Government Printing Office

(GPO) and/or the National Technical Information Service (NTIS) as indicated.

NTIS prices are for paper copy; add $3 handling charge for each order.

Microfiche copies are also available from NTIS. Prices from either source are

subject to change.

Addresses are:

NCADI

National Clearinghouse for Alcohol and Drug Information

P.O. Box 2345

Rockville, MD 20852

(301) 468-2600

(800) 729-6686

GPO

Superintendent of Documents

U.S. Government Printing Office

Washington, DC 20402

(202) 275-2981

NTIS

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U.S. Department of Commerce

Springfield, VA 22161

(703) 487-4650

For information on availability of NIDA Research Monographs 1 through 24

(1975-1979) and others not listed, write to NIDA, Community and Professional

Education Branch, Room 10A-54, 5600 Fishers Lane, Rockville, MD 20857.

121
25 BEHAVIORAL ANALYSIS AND TREATMENT OF SUBSTANCE ABUSE.

Norman A. Krasnegor, Ph.D., ed.

GPO out of stock NCADI out of stock

NTIS PB #80-112428/AS $31

26 THE BEHAVIORAL ASPECTS OF SMOKING. Norman A. Krasnegor,

Ph.D., ed. (reprint from 1979 Surgeon General’s Report on Smoking and

Health)

GPO out of stock NTIS PB #80-118755/AS $23

30 THEORIES ON DRUG ABUSE: SELECTED CONTEMPORARY

PERSPECTIVES. Dan J. Lettieri, Ph.D.; Mollie Sayers; and Helen W. Pearson,

eds.

GPO out of stock NCADI out of stock

Not available from NTIS

31 MARIJUANA RESEARCH FINDINGS: 1980. Robert C. Petersen, Ph.D.,

ed.

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32 GC/MS ASSAYS FOR ABUSED DRUGS IN BODY FLUIDS. Rodger L.

Foltz, Ph.D.; Allison F. Fentiman, Jr., Ph.D.; and Ruth B. Foltz, eds.

GPO out of stock NCADI out of stock

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36 NEW APPROACHES TO TREATMENT OF CHRONIC PAIN: A REVIEW

OF MULTIDISCIPLINARY PAIN CLINICS AND PAIN CENTERS. Lorenz K.Y.

Ng, M.D., ed.

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37 BEHAVIORAL PHARMACOLOGY OF HUMAN DRUG DEPENDENCE.

Travis Thompson, Ph.D., and Chris E. Johanson, Ph.D., eds.

GPO out of stock NCADI out of stock

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38 DRUG ABUSE AND THE AMERICAN ADOLESCENT. Dan J. Lettieri,

Ph.D., and Jacqueline P. Ludford, M.S., eds. A RAUS Review Report.

GPO out of stock NCADI out of stock

NTIS PB #62-148198/AS $23

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40 ADOLESCENT MARIJUANA ABUSERS AND THEIR FAMILIES. Herbert

Hendin, M.D; Ann Pollinger, Ph.D.; Richard Ulman, Ph.D.; and Arthur Carr,

Ph.D., eds.

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42 THE ANALYSIS OF CANNABINOIDS IN BIOLOGICAL FLUIDS. Richard

L. Hawks, Ph.D., ed.

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44 MARIJUANA EFFECTS ON THE ENDOCRINE AND REPRODUCTIVE

SYSTEMS. Monique C. Braude, Ph.D., and Jacqueline P. Ludford, M.S., eds.

A RAUS Review Report.

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45 CONTEMPORARY RESEARCH IN PAIN AND ANALGESIA, 1983. Roger

M. Brown, Ph.D.; Theodore M. Pinkert, M.D., J.D.; and Jacqueline P. Ludford,

M.S. eds. A RAUS Review Report.

GPO out of stock NCADI out of stock

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46 BEHAVIORAL INTERVENTION TECHNIQUES IN DRUG ABUSE

TREATMENT. John Grabowski, Ph.D.; Maxine L. Stitzer, Ph.D.: and Jack E.

Henningfield, Ph.D., eds.

GPO out of stock NCADI out of stock

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47 PREVENTING ADOLESCENT DRUG ABUSE: INTERVENTION

STRATEGIES. Thomas J. Glynn, Ph.D.; Carl G. Leukefeld, D.S.W.; and

Jacqueline P. Ludford, M.S., eds. A RAUS Review Report.

GPO out of stock NCADI out of stock

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48 MEASUREMENT IN THE ANALYSIS AND TREATMENT OF SMOKING

BEHAVIOR. John Grabowski, Ph.D., and Catherine Bell, M.S., eds.

GPO out of stock NCADI out of stock

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50 COCAINE: PHARMACOLOGY, EFFECTS, AND TREATMENT OF

ABUSE. John Grabowski, Ph.D., ed.

GPO Stock #017-024-01214-9 $4 NTIS PB #85-150381/AS $23

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51 DRUG ABUSE TREATMENT EVALUATION: STRATEGIES, PROGRESS,

AND PROSPECTS. Frank M. Tims, Ph.D., ed.

GPO out of stock NTIS PB #85-150365/AS $23

52 TESTING DRUGS FOR PHYSICAL DEPENDENCE POTENTIAL AND

ABUSE LIABILITY. Joseph V. Brady, Ph.D., and Scott E. Lukas, Ph.D., eds.

GPO out of stock NTIS PB #85-150373/AS $23

53 PHARMACOLOGICAL ADJUNCTS IN SMOKING CESSATION. John

Grabowski, Ph.D., and Sharon M. Hall, Ph.D., eds.

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54 MECHANISMS OF TOLERANCE AND DEPENDENCE. Charles Wm.

Sharp, Ph.D., ed.

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55 PROBLEMS OF DRUG DEPENDENCE, 1984: PROCEEDINGS OF THE

46TH ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

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56 ETIOLOGY OF DRUG ABUSE: IMPLICATIONS FOR PREVENTION.

Coryl LaRue Jones, Ph.D., and Robert J. Battjes, D.S.W., eds.

GPO Stock #017-024-01250-5 $6.50 NTIS PB #89-123160/AS $31

57 SELF-REPORT METHODS OF ESTIMATING DRUG USE: MEETING

CURRENT CHALLENGES TO VALIDITY. Beatrice A. Rouse, Ph.D.; Nicholas

J. Kozel, M.S.; and Louise G. Richards, Ph.D., eds.

GPO out of stock NTIS PB #88-248083/AS $23

58 PROGRESS IN THE DEVELOPMENT OF COST-EFFECTIVE

TREATMENT FOR DRUG ABUSERS. Rebecca S. Ashery, D.S.W., ed.

GPO out of stock NTIS PB #89-125017/AS $23

59 CURRENT RESEARCH ON THE CONSEQUENCES OF MATERNAL

DRUG ABUSE. Theodore M. Pinkert, M.D., J.D., ed.

GPO out of stock NTIS PB #89-125025/AS $23

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68 PRENATAL DRUG EXPOSURE: KINETICS AND DYNAMICS. C. Nora

Chiang, Ph.D., and Charles C. Lee, Ph.D., eds.

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61 COCAINE USE IN AMERICA: EPIDEMIOLOGIC AND CLINICAL

PERSPECTIVES. Nicholas J. Kozel, M.S., and Edgar H. Adams, M.S., eds.

GPO out of stock NTIS PB #89-131866/AS $31

62 NEUROSCIENCE METHODS IN DRUG ABUSE RESEARCH. Roger M.

Brown, Ph.D.; David P. Friedman, Ph.D.; and Yuth Nimit, Ph.D., eds.

GPO out of stock NCADI out of stock

NTIS PB #89-130660/AS $23

63 PREVENTION RESEARCH: DETERRING DRUG ABUSE AMONG

CHILDREN AND ADOLESCENTS, Catherine S. Bell, M.S., and Robert Battjes,

D.S.W., eds.

GPO out of stock NTIS PB #89-103287/AS $31

84 PHENCYCLIDINE: AN UPDATE. Doris H. Clouet, Ph.D., ed.

GPO out of stock NTIS PB #89-131858/AS $31

65 WOMEN AND DRUGS: A NEW ERA FOR RESEARCH. Barbara A. Ray,

Ph.D., and Monique C. Braude, Ph.D., eds.

GPO Stock #017-024-01283-1 $3.50 NTIS PB #89-130637/AS $23

66 GENETIC AND BIOLOGICAL MARKERS IN DRUG ABUSE AND

ALCOHOLISM. Monique C. Braude, Ph.D., and Helen M. Chao, Ph.D., eds.

GPO out of stock NCADI out of stock

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68 STRATEGIES FOR RESEARCH ON THE INTERACTIONS OF DRUGS

OF ABUSE. Monique C. Braude, Ph.D., and Harold M. Ginzburg, M.D., J.D.,

M.P.H., eds.

GPO out of stock NCADI out of stock

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89 OPIOID PEPTIDES: MEDICINAL CHEMISTRY. Rao S. Rapaka, Ph.D.;

Gene Barnett, Ph.D.; and Richard L. Hawks, Ph.D., eds.

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70 OPIOID PEPTIDES: MOLECULAR PHARMACOLOGY, BIOSYNTHESIS,

AND ANALYSIS. Rao S. Rapaka, Ph.D., and Richard L. Hawks, Ph.D., eds.

GPO out of stock NTIS PB #89-158430/AS $45

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71 OPIATE RECEPTOR SUBTYPES AND BRAIN FUNCTION. Roger M.

Brown, Ph.D.; Doris H. Clouet, Ph.D.; and David P. Friedman, Ph.D., eds.

GPO out of stock NTIS PB #89-151955/AS $31

72 RELAPSE AND RECOVERY IN DRUG ABUSE. Frank M. Tims, Ph.D.,

and Cari G. Leukefeid, D.S.W., eds.

GPO Stock #017-024-01302-1 $6 NTIS PB #89-151963/AS $31

73 URINE TESTING FOR DRUGS OF ABUSE. Richard L. Hawks, Ph.D., and

C. Nora Chiang, Ph.D., eds.

GPO Stock #017-024-01313-7 83.75 NTIS PB #89-151971/AS $23

74 NEUROBIOLOGY OF BEHAVIORAL CONTROL IN DRUG ABUSE.

Stephen I. Szara, M.D., DSc., ed.

GPO Stock #017-024-01314-5 83.75 NTIS PB #89-151989/AS $23

75 PROGRESS IN OPIOID RESEARCH. PROCEEDINGS OF THE 1988

INTERNATIONAL NARCOTICS RESEARCH CONFERENCE. John W.

Holaday, Ph.D.; Ping-Yee Law, Ph.D.; and Albert Herr, M.D., eds.

GPO out of stock NCADI out of stock

Not available from NTIS

78 PROBLEMS OF DRUG DEPENDENCE, 1988: PROCEEDINGS OF THE

48TH ANNUAL SCIENTIFIC MEETING, THE COMMlTTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO out of stock NCADI out of stock

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77 ADOLESCENT DRUG ABUSE: ANALYSES OF TREATMENT

RESEARCH. Elizabeth R. Rahdert, Ph.D., and John Grabowski, Ph.D., eds.

GPO Stock #017-024-01348-0 $4 NCADI out of stock

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78 THE ROLE OF NEUROPLASTICITY IN THE RESPONSE TO DRUGS.

David P. Friedman, Ph.D., and Doris H. Clouet, Ph.D., eds.

GPO out of stock NTIS PB #88-245683/AS $31

79 STRUCTURE-ACTIVITY RELATIONSHIPS OF THE CANNABINOIDS.

Rao S. Rapaka, Ph.D., and Alexandros Makriyannis, Ph.D., eds.

GPO out of stock NTIS PB #89-109201/AS $31

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80 NEEDLE SHARING AMONG INTRAVENOUS DRUG ABUSERS:

NATIONAL AND INTERNATIONAL PERSPECTIVES. Robert J. Battjes,

D.S.W., and Roy W. Pickens, Ph.D., eds.

GPO out of stock NTIS PB #88-236138/AS $31

81 PROBLEMS OF DRUG DEPENDENCE, 1987: PROCEEDINGS OF THE

49TH ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01354-4 $17 NTIS PB #89-109227/AS

Contact NTIS for price

82 OPIOIDS IN THE HIPPOCAMPUS. Jacqueline F. McGinty, Ph.D., and

David P. Friedman, Ph.D., eds.

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83 HEALTH HAZARDS OF NITRITE INHALANTS. Harry W. Haverkos, M.D.,

and John A. Dougherty, Ph.D., eds.

GPO out of stock NTIS PB #89-125496/AS $23

84 LEARNING FACTORS IN SUBSTANCE ABUSE. Barbara A. Ray, Ph.D.,

ed.

GPO Stock #017-024-01353-6 $6 NTIS PB #89-125504/AS $31

85 EPIDEMIOLOGY OF INHALANT ABUSE: AN UPDATE. Raquel A. Crider,

Ph.D., and Beatrice A. Rouse, Ph.D., eds.

GPO Stock #017-024-01360-9 $5.50 NTIS PB #89-123178/AS $31

86 COMPULSORY TREATMENT OF DRUG ABUSE: RESEARCH AND

CLINICAL PRACTICE. Carl G. Leukefeid, D.S.W., and Frank M. Tims, Ph.D.,

eds.

GPO Stock #017-024-01352-8 $7.50 NTIS PB #89-151997/AS $31

87 OPIOID PEPTIDES: AN UPDATE. Rao S. Rapaka, Ph.D., and Bhoia N.

Dhawan, M.D., eds.

GPO Stock #017-024-01366-6 $7 NTIS PB #89-158430/AS $45

88 MECHANISMS OF COCAINE ABUSE AND TOXICITY. Doris H. Clouet,

Ph.D.; Khursheed Asghar, Ph.D.; and Roger M. Brown, Ph.D., eds.

GPO Stock #017-024-01359-5 $11 NTIS PB #89-125512/AS $39

89 BIOLOGICAL VULNERABILTY TO DRUG ABUSE. Roy W. Pickens,

Ph.D., and Dace S. Svikis, B.A., eds.

GPO Stock #017-022-01054-2 $5 NTIS PB #89-125520/AS $23

127
90 PROBLEMS OF DRUG DEPENDENCE, 1988: PROCEEDINGS OF THE

50TH ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01362-5 $17

91 DRUGS IN THE WORKPLACE: RESEARCH AND EVALUATION DATA.

Steven W. Gust, Ph.D., and J. Michael Walsh, Ph.D., eds.

GPO Stock #017-024-01384-6 $10 NTIS PB #90-147257/AS $39

92 TESTING FOR ABUSE LIABILITY OF DRUGS IN HUMANS. Marian W.

Fischman, Ph.D., and Nancy K. Mello, Ph.D., eds.

GPO Stock #017-024-01379-0 $12 NTIS PB #90-148933/AS $45

93 AIDS AND INTRAVENOUS DRUG USE: FUTURE DIRECTIONS FOR

COMMUNITY-BASED PREVENTION RESEARCH. C.G. Leukefeid, D.S.W.;

R.J. Battjes, D.S.W.; and Z. Amsel, D.Sc., eds.

GPO Stock #017-024-01388-9 $10 NTIS PB #90-148941/AS $39

94 PHARMACOLOGY AND TOXICOLOGY OF AMPHETAMINE AND

RELATED DESIGNER DRUGS. Khursheed Asghar, Ph.D., and Errol De

Souza, Ph.D., eds.

GPO Stock #017-024-01386-2 $11 NTIS PB #90-148956/AS $39

95 PROBLEMS OF DRUG DEPENDENCE, 1989: PROCEEDINGS OF THE

51ST ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01399-4 $21 NTIS PB #90-237660/AS $67

96 DRUGS OF ABUSE: CHEMISTRY, PHARMACOLOGY, IMMUNOLOGY,

AND AIDS. Phuong Thi Kim Pham, Ph.D., and Kenner Rice, Ph.D., eds.

GPO Stock #017-024-01403-6 $8 NTIS PB #90-237678/AS $31

97 NEUROBIOLOGY OF DRUG ABUSE: LEARNING AND MEMORY. Lynda

Erinoff, Ph.D., ed.

GPO Stock #017-024-01404-4 $8 NTIS PB #90-237886/AS $31

98 THE COLLECTION AND INTERPRETATION OF DATA FROM HIDDEN

POPULATIONS. Elizabeth Y. Lambert, M.S., ed.

GPO Stock #017-024-01407-9 84.75 NTIS PB #90-237694/AS $23

99 RESEARCH FINDINGS ON SMOKING OF ABUSED SUBSTANCES,

C. Nora Chiang, Ph.D., and Richard L. Hawks, Ph.D., eds.

GPO Stock #017-024-01412-5 $5 NTIS PB #91-141119 $23

128
100 DRUGS IN THE WORKPLACE: RESEARCH AND EVALUATION DATA.

VOL. Il. Steven W. Gust, Ph.D., and J. Michael Walsh, Ph.D., eds.

101 RESIDUAL EFFECTS OF ABUSED DRUGS ON BEHAVIOR. John W.

Spencer, Ph.D., and John J. Boren, Ph.D., eds.

GPO Stock #017-024-01426-7 $6 NTIS PB #91-172858/AS $31

102 ANABOLIC STEROID ABUSE. Geraline C. Lin, Ph.D., and Lynda Erinoff,

Ph.D., eds.

GPO Stock #017-024-01425-7 $6 NTIS PB #91-172866/AS $31

103 DRUGS AND VIOLENCE: CAUSES, CORRELATES, AND

CONSEQUENCES. Mario De La Rosa, Ph.D.; Elizabeth Y. Lambert, M.S.;

and Bernard Gropper, Ph.D., eds.

GPO Stock #017-024-01427-3 $9 NTIS PB #91-172841/AS $31

104 PSYCHOTHERAPY AND COUNSELING IN THE TREATMENT OF

DRUG ABUSE. Lisa Simon Onken, Ph.D., and Jack D. Blaine, M.D., eds.

GPO Stock #017-024-01429-0 $4 NTIS PB #91-172674/AS $23

105 PROBLEMS OF DRUG DEPENDENCE, 1990: PROCEEDINGS OF THE

52ND ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01435-4 $22

106 IMPROVING DRUG ABUSE TREATMENT. Roy W. Pickens, Ph.D.; Carl

G. Leukefeld, D.S.W.; and Charles R. Schuster, Ph.D., eds.

GPO Stock #017-024-01439-7 $12

107 DRUG ABUSE PREVENTION INTERVENTION RESEARCH:

METHODOLOGICAL ISSUES. Carl G. Leukefeld, D.S.W., and William J.

Bukoski, Ph.D., eds.

GPO Stock #017-024-01441-9 $9

108 CARDIOVASCULAR TOXICITY OF COCAINE: UNDERLYING

MECHANISMS. Pushpa V. Thadani, Ph.D., ed.

GPO Stock #017-024-01446-0

109 LONGITUDINAL STUDIES OF HIV INFECTION IN INTRAVENOUS

DRUG USERS: METHODOLOGICAL ISSUES IN NATURAL HISTORY

RESEARCH. Peter Hartsock, Dr.P.H., and Sander G. Genser, M.D., M.P.H.,

eds.

GPO Stock #017-024-01445-1

129
110 THE EPIDEMIOLOGY OF COCAINE USE AND ABUSE. Susan Schober,

Ph.D., and Charles Schade, M.D., M.P.H., eds.

111 MOLECULAR APPROACHES TO DRUG ABUSE RESEARCH:

VOLUME I. Theresa N.H. Lee, Ph.D., ed.

112 EMERGING TECHNOLOGIES AND NEW DIRECTIONS IN DRUG

ABUSE RESEARCH. Rao S. Rapaka, Ph.D.; Aiexandros Makriyannis, Ph.D.:

and Michael J. Kuhar, Ph.D., eds.

113 ECONOMIC COSTS, COST-EFFECTIVENESS, FINANCING, AND

COMMUNITY-BASED DRUG TREATMENT. William S. Cartwright, Ph.D.,

and James M. Kaple, Ph.D., eds.

114 METHODOLOGICAL ISSUES IN CONTROLLED STUDIES ON

EFFECTS OF PRENATAL EXPOSURE TO DRUGS OF ABUSE.

M. Mariyne Kiibey, Ph.D., and Khursheed Asshar, Ph.D., eds.

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DHHS Publication No. (ADM) 91-1836

Alcohol, Drug Abuse, and Mental Health Administration

Printed 1991