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This is something I have given one of you all privately. I posted it in psychoactives, but it also shoudl go here to in my opinion. Anyway, it is a california report on estacy. Drug Abuse Information California Department of and Monitoring Project Alcohol and Drug Programs Chauncey L. Veatch III, Director DRUG ABUSE SERIES MDMA Health and Welfare Agency State of California Clifford L. Allenby, Secretary George Deukmejian, Governor The Monograph Series which is issued by the Drug Abuse Information and Monitoring Project is prepared for and funded by the State of California Department of Alcohol and Drug Program under contracts # D-0053-5 and # D-0001-7. The primary purpose of this series is to provide information to the drug abuse treatment community and to the general public on the epidemiology and treatment of drug abuse. The material herein does not necessarily reflect the opinions, official policy, or position of the Department of Alcohol and Drug Program of the State of California. The views of this study are solely those of the authors. All material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from DAIMP or ADP or the authors. Citation of the source is appreciated. MDMA By Jerome E. Beck School of Public Health Berkeley, CA Institute for Scientific Analysis April 1987 Edited by Elizabeth Piper Deschenes PREFACE In September 1986, the California Department of Alcohol and Drug Programs (ADP) formally sponsored initiation of the Drug Abuse Information and Monitoring Project (DAIMP). One of the primary objectives of this project is to conduct ethnographic and epidemiological research in order to provide information on the new and changing conditions in drug abuse. Another key objective of the project is to provide an assessment of state needs and resources to deal with the treatment and prevention of drug abuse. As a third objective, DAIMP will produce a series of monographs focusing on specific issues in drug abuse that are useful to California's drug program network. The continuing problem of drug abuse has been recently compounded by several developments. These include the increasing amounts of illicit drugs (e.g., heroin and cocaine) being imported into the U.S., by an increasing number of routes, and the appearance of new and different drugs. The abuse potential of these newer drugs has not yet been ascertained. California is especially affected by these developments. The use of drugs such as MDMA has increased since their introduction on the street in the early 1970's. Only due to recent mass media interest has the public become aware of these drugs. While some therapists have portrayed the drug MDMA as a therapeutic tool, those in the drug treatment network are concerned about its abuse potential. Thus, there is a polarization of opinion regarding MDMA and similar drugs. Much of the current knowledge about MDMA is limited as it relies upon anecdotal sources. As part of the DAIMP series, this first monograph presents information about MDMA. It is intended to inform the public and those in the field who must learn about these newer drugs and their unique effects. As part of continuing research on drug abuse the current monograph represents an important contribution to the understanding of a much publicized drug and its potential for abuse. Chauncey L. Veatch III, Director California Department of Alcohol and Drug Programs UCLA Drug Abuse Research Group (M. Douglas Anlgin, PhD, Director) i UCLA Drug Abuse Research Group (M. Douglas Anlgin, PhD, Director) i TABLE OF CONTENTS Preface.........................................................i Fact Sheet.....................................................iv Executive Summary.............................................iii I. Introduction...............................................1 II. Origins and Distribution...................................2 III. Epidemiology...............................................4 IV. Psychopharmacology.........................................5 V. Related Problems/Health Risks..............................7 VI. Conclusion................................................12 VII. Resources.................................................13 VIII...................................................References 14 UCLA Drug Abuse Research Group (M. Douglas Anlgin, PhD, Director) ii FACT SHEET WHAT IS MDMA? MDMA (3,4-methylenedioxymethamphetamine) is the N-methyl analog of MDA, and shares similarities to both mescaline, a hallucinogen, and amphetamines, a family of stimulants. Although often referred to itself as a hallucinogen, this association is somewhat erroneous. The effects of MDMA dramatically differ from those of LSD and other psychedelics, with a notable lack of the perceptual distortions usually associated with these substances. WHO IS USING MDMA? MDMA appears to be most often used in urban areas, particularly certain college towns (e.g. UC Berkeley, UCLA, UC Santa Barbara, and UC Santa Cruz). In the past, some psychotherapists have employed it, under carefully supervised conditions, for a wide variety of purposes, ranging from improving couple communication to dealing with rape trauma. Illicit use has been most commonly associated with college students, gays and "yuppies." HOW IS MDMA MOST COMMONLY USED? MDMA is most often ingested orally, although inhalation and injection have been infrequently reported. The usual dose ranges from 100 to 150 mg and costs between $10 and $20. Although analyzed samples have been fairly pure in the past, this may change due to increased popularity and newly illicit status. WHY ARE PEOPLE USING MDMA? iii iii UCLA Drug Abuse Research Group (M. Douglas Anlgin, PhD, Director) Many users of MDMA are probably attracted to the drug for the same reasons as some psychotherapists. They feel that MDMA has the ability to increase empathy and self-insight. Reportedly, the advantages of MDMA over traditional psychedelics are less distortion of sensory perception and fewer unpleasant emotional reactions. In addition, many individuals describe strong euphoric and/or sensual effects associated with MDMA. DESCRIBE A 'TYPICAL' MDMA EXPERIENCE Effects generally appear within 20-60 minutes, when the user often experiences a brief "rush" of energy, usually described as mild but euphoric. After this rush, the high levels off to a plateau which lasts 2-3 hours and is followed by a gradual "coming down" sensation, culminating in a feeling of fatigue. MDMA exerts amphetamine-like effects which include dilated pupils, dry mouth and throat, tension in the lower jaw, grinding of the teeth, and overall stimulation. These side effects are dose dependent and will vary depending on the health of the individual user. In addition, MDMA exerts a strong paradoxical effect of relaxation which often causes many users to be unaware of the stimulant side effects. Most users cite a dramatic drop in defense mechanisms and increased empathy towards others. Combined with the stimulant effect, this generally produces an increase in intimate communication. WHAT IS KNOWN ABOUT THE TOXICITY OF MDMA? iv iv UCLA Drug Abuse Research Group (M. Douglas Anlgin, PhD, Director) Unfortunately, very little. So far, MDMA has been associated with few overdoses or deaths. However, studies in rats have indicated that large intravenous doses of MDMA in rats are associated with suspected degeneration of serotonergic nerve terminals in certain areas of the brain. Also, there may be some suppression of the immune system. Further research is needed to determine the significance of this damage, and to what extent it may occur in humans. WHAT IS MDMA'S ABUSE POTENTIAL? The euphoric effects of MDMA, combined with its street reputation, would suggest a significant abuse potential. To date, however, there appear to be relatively few cases of what might be considered serious abuse of MDMA. Excessive use is probably self limiting in that the frequent use of MDMA almost invariably produces a strong dysphoric (unpleasant) reaction, that is only exacerbated with continued use. In addition, frequent use produces an almost total loss of the desired actions with a greater rapidity and intensity than with other more commonly abused substances. v v UCLA Drug Abuse Research Group (M. Douglas Anlgin, PhD, Director) 11/14/86 epd Rev. 12/31/86 epd Rev. 3/24/87 vi vi UCLA Drug Abuse Research Group (M. Douglas Anlgin, PhD, Director) EXECUTIVE SUMMARY The 1980's have witnessed the emergence and popularization of a rather unique psychoactive substance -- MDMA, (3,4- methylenedioxy-methamphetamine), also known as "Adam," "Ecstasy," or "XTC". Extensive media coverage recently highlighted what appears to be a dramatic increase in both therapeutic and recreational use. A controversy has since ensued providing very different perspectives on the substance. Some psychotherapists view MDMA as a therapeutic aid which, when combined with psychological treatment, has benefits that outweigh potential health consequences and see minimal harm associated with carefully monitored use. Some drug treatment counselors and drug enforcement officials, on the other hand, see it as a potentially dangerous substance possessing harmful actions, and increasingly being abused outside of therapeutic circumstances. Unfortunately, research has only just begun to address many of the questions and concerns that have arisen. Consequently, it can be anticipated that much of the following information will become dated as more formal studies are completed. Research examining patterns of MDMA use has been minimal. Most of the information available regarding street use of MDMA is based on anecdotal accounts given to the media, therapists and substance abuse professionals. Beck has conducted preliminary research over the last ten years interviewing hundreds of individuals in the San Francisco Bay Area and at the University of Oregon in Eugene. Zinberg (1976) has published the only v naturalistic study of 23 users of MDA. Greer (1983) administered MDMA to 29 subjects in a therapeutic setting. Downing (1985) studied the effects of a single exposure to MDMA among 21 individuals. Siegel (1985) and Seymour (1986) have ongoing studies at UCLA and the Haight Ashbury Free Clinic, respectively. Much of the information for this paper is based upon these studies, testimony at federal hearings, and personal communications. MDMA, which is essentially the successor to MDA, first appeared on the street in the early 1970's. Use remained very limited until the end of the decade. On July 1, 1985 the Drug Enforcement Administration (DEA) used its emergency scheduling power to temporarily place MDMA in Schedule I of the Controlled Substances Act. The DEA's actions were challenged by some therapists and researchers who argued that a Schedule I status would severely hinder research into what they regarded as MDMA's therapeutic potential. Based on testimony from federal hearings, the administrative law judge recommended that MDMA be placed in Schedule III -- a category for drugs with accepted medical use and only a low to moderate abuse potential. However, the DEA administrator rejected his recommendation and MDMA was permanently placed in Schedule I effective November 13, 1986. The scheduling process and ensuing reaction by therapists using the drug in their practices brought MDMA to national attention via mass media features which often sensationalized the reputed euphoric and therapeutic qualities of MDMA. The increase in vi publicity was accompanied by an escalation in street demand from an estimated 10,000 doses distributed in all of 1976 to 30,000 doses distributed per month in 1985 (Siegel, 1986). The DEA found evidence of use in a majority of states. MDMA appears to be most often used in urban areas, particularly certain college towns. Its use has been most commonly associated with college students, gays and "yuppies". The usual dose ranges from 100 to 150 mg. and costs between $10 and $20. MDMA is most often ingested orally, although inhalation and injection have also been infrequently reported. Drug effects generally appear within 20-60 minutes after ingestion, when the user often experiences a brief "rush" of energy, usually described as mild but euphoric. After this rush, the high levels off to a plateau which lasts 2-3 hours and is followed by a gradual "coming down" sensation, culminating in a feeling of fatigue. MDMA exerts amphetamine-like side effects on the body, including dilated pupils, dry mouth and throat, tension in the lower jaw, grinding of the teeth, and overall stimulation. These effects vary depending on dose. In addition, MDMA exerts a strong paradoxical effect of relaxation, which often causes many users to be unaware of the stimulant side effects. Most users cite a dramatic drop in defense mechanisms and increased empathy towards others. Combined with the stimulant effect, this generally produces an increase in intimate communication. Psychotherapeutic Effects vii It appears that well over one hundred psychiatrists and other therapists have employed MDMA as a therapeutic adjunct. At the federal hearings several psychiatrists praised MDMA's ability to increase both empathy and self-insight. They felt that a major advantage of MDMA over the traditional psychedelics was that it produced far less distortion of sensory perception and fewer unpleasant emotional reactions. Although some preliminary research suggested that MDMA has significant therapeutic potential, the notable absence of well-controlled, double-blind studies seriously limits any conclusions concerning the possible efficacy or risk associated with the use of MDMA in therapy. Health Risks Although some research has assessed toxic and lethal doses in animals, little is known about MDMA's potential toxicity for humans. A few deaths have been associated with the use of MDMA, but its role as a causative factor in each case remains uncertain. As of April, 1986 20 emergency room incidents for MDMA had been listed in the federal government's Drug Abuse Warning Network (DAWN). Ignorance of the substance undoubtedly contributes to underreporting. However, the number of mentions still appears to be rather low when compared with the suspected extent of use described by Siegel and the DEA. MDMA has been associated with relatively few overdoses or deaths. However, it's neurotoxic potential is cause for concern. Acute and chronic problems are most often associated with the repeated use of high dosages. Generally, the side effects of viii MDMA are similar to those of amphetamine. MDMA also appears to exert an adverse action on the immunological response of some individuals, particularly with heavy use. Long-term users often describe increasingly uncomfortable and prolonged "burn-out" periods, sometimes lasting two or more days. Many individuals have also reported an increased susceptibility to various ailments, particularly sore throats, colds, flus, and herpes outbreaks. It should be noted that these reactions appear to be rare in novice users and individuals in good physical and mental health. Based on the limited information available, researchers have identified the following medical conditions as possible contraindications to MDMA use: diabetes, diminished liver function, epilepsy, glaucoma, heart disease, hypertension, hypoglycemia, hyperthyroidism and pregnancy. Infrequent psychological problems have been associated with the use of MDMA. Rare episodes of hyperventilation have been noted, but this phase is transitory. In addition, problems occur for some individuals who, in attempts at self-therapy, run the risk of exacerbating their emotional problems with unsupervised episodes. Among individuals who have tried both MDMA and cocaine, Beck found that the majority usually express a strong preference for MDMA which would suggest a high abuse potential. However, in sharp contrast to cocaine, there appear to be relatively few cases of what might be considered serious abuse of MDMA. ix Excessive use is probably self limiting in that frequent use of MDMA always produces a strong dysphoric (unpleasant) reaction, that is only increased with continued use. In addition, frequent use produces an almost total loss of the desired actions with a greater rapidity and intensity than with other more commonly abused substances. Conclusion Media accounts and substance abuse professionals often dismiss MDMA as a short-term fad. However, the perceived therapeutic and/or euphoric effects combined with the ease with which MDMA is usually experienced can be expected to attract new users. The danger in this regard is the uncertain potential for abuse. In addition, there are potentially severe health risks associated with MDMA and probable contraindications. This is particularly true with repeated use of high dosages which may lead to acute or chronic medical and psychological problems. Unfortunately, our current knowledge regarding nearly every aspect of MDMA is extremely limited and based almost exclusively on anecdotal data. Research is obviously needed to better determine the potential risks of a substance which is rapidly establishing itself in our drug culture. 11/14/86 epd Rev. 12/31/86 epd, 9/15/87 jh x 1 I. INTRODUCTION The last decade witnessed the emergence and popularization of the "drug of the 80's"--MDMA. Also known as "Adam," "Ecstasy," or "XTC," extensive media coverage recently highlighted what appears to be a dramatic increase in both therapeutic and recreational use. A controversy has since ensued providing very different perspectives on the substance. Some psychotherapists view MDMA as a therapeutic aid, which, when combined with psychological treatment, has benefits that outweigh potential health consequences and see minimal harm associated with carefully monitored use (Greer, 1985, Grinspoon, 1985, Lynch, 1985, Wolfson, 1985). Some drug treatment counselors and drug enforcement officials, on the other hand, see it as a potentially dangerous substance possessing harmful actions, and increasingly being abused outside the therapeutic community (United States Department of Justice, 1985, Sapienza, 1985, Sapienza, 1986). As pharmacologist Alexander Shulgin describes it: MDMA has been thrust upon the public awareness as a largely unknown drug which to some is a medical miracle and to others a social devil. ... There have been the born-again protagonists who say that once you have tried it you will see the light and will defend it against any attack, and there have been the staunch antagonists who say this is nothing but LSD revisited and it will certainly destroy our youth. There are many voices to be heard presenting the modest inventory of facts that are known, but there is no one who will answer questions in a way that can be heard by both camps. (1985, p. 3) UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 2 While no formal survey has been conducted to determine the exact extent of MDMA use, nonmedical use appears to be increasing. Still, MDMA remains largely unknown to much of American society, including frequent users of other psychoactive drugs. There are signs, however, that this is changing. Research has only just begun to address many of the questions and concerns that have arisen. Consequently, it can be anticipated that much of the following information will become dated as more formal studies are completed.1 The uniqueness of MDMA (3,4-methylenedioxymethamphetamine) can be seen in the controversy over the proper terminology used to describe it (Beck, 1986, Seymour, 1986). As the N-methyl analogue of MDA, it is related to both mescaline and the amphetamines. Although often referred to as a hallucinogen, this association is somewhat erroneous. The effects of MDMA dramatically differ from those of LSD and other psychedelics, with a notable lack of the perceptual distortions usually associated with these substances. The label, "designer drugs" has often been applied to MDMA. Designer drugs have been described as "substances wherein the psychoactive properties of a scheduled drug have been retained, but the molecular structure has been altered in order to avoid prosecution under the Controlled Substances Act" (Smith and Seymour, 1985: 1). Whether MDMA is actually a designer drug is debatable since it was first synthesized and patented in 1914 ____________________ 1 Much of the following discussion is excerpted from articles by Beck (1986) and Beck and Morgan (1986). UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 3 long before the Controlled Substances Act (1970) came into being. Nevertheless, the media has occasionally confused MDMA with the other designer drugs (Beck and Morgan, 1986; Seymour, 1986). Most often these substances are synthetic opiates employed as heroin substitutes and which, because of their potency, are considerably more dangerous. Among these are MPTP (capable of causing Parkinson's disease) and the fentanyl analogues (responsible for a large number of fatal overdoses).2 Therefore, it is important for substance abuse professionals to be extremely cautious in learning about the different designer drugs and the unique effects of each. II. ORIGINS AND DISTRIBUTION In terms of popular use, MDMA is essentially the successor to MDA, the counterculture "love drug" of the late 1960s and early 1970s. MDA first appeared on the streets in 1967 and became known as a drug which produced a sensual, easily managed psychedelic high (Meyers, Rose, & Smith, 1967/68). After MDA was placed in Schedule I of the Controlled Substances Act in 1970, its use seemed to level off and gradually decline. While MDMA first appeared on the street in the early 1970s, use remained very limited until the end of the decade. MDMA was a legal substance until July 1985 when the Drug Enforcement ____________________ 2 This reached the point of absurdity in the portrayal of MDMA on NBC's "Another World," a daytime soap. MDMA appears to have been confused with "synthetic heroin so potent that addicts prefer it to the real stuff" (New York Post, June 20, 1985, p. 80). A good discussion of other problems associated with media coverage of MDMA and similar compounds is provided by Reidlinger and Reidlinger (1985). UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 4 Administration (DEA) used its emergency scheduling power to temporarily place MDMA in Schedule I of the Controlled Substances Act (Federal Register, May 31, 1985). This schedule is reserved for those drugs designated as possessing no medical use and having a high potential for abuse (e.g., heroin, LSD). The DEA's actions were challenged by some therapists and researchers who argued that a Schedule I status would severely hinder research into what they regarded as MDMA's therapeutic potential. According to most reports (Beck, 1986, Seymour, 1986), psychotherapists who had been using the drug as part of therapeutic programs since the mid- to late 1970s found its benefits to outweigh any potential health risks for patients under their care. In response to these challenges, three federal administrative hearings were held to help determine the final scheduling of MDMA. Based on testimony from the hearings, the administrative law judge concurred with the proponent therapists in recommending that MDMA be placed in Schedule III -- a category for drugs with accepted medical use and only a low to moderate abuse potential (Young, 1986). However, the DEA administrator rejected this recommendation and MDMA was permanently placed in Schedule I effective November 13, 1986 (Federal Register, October 14, 1986).3 The scheduling process and ensuing reaction by therapists soon brought MDMA to national attention. Nearly all the major ____________________ 3 For a more thorough policy discussion, the reader is referred to Beck (1986) and Seymour (1986). UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 5 newspapers and magazines devoted features to the substance, sensationalizing the reputed euphoric and therapeutic qualities of MDMA (Life, 1985, Newsweek, 1985, Time, 1985). The increase in publicity was accompanied by an increased street demand. University of California, Los Angeles (UCLA) psychopharmacologist Ronald Siegel (1985:2) stated that street use "escalated from an estimated 10,000 doses distributed in all of 1976 to 30,000 doses distributed per month in 1985." The DEA found evidence of use in a majority of states and estimated that "30,000 dosage units are distributed each month in one Texas city" (1985:2). These estimates (made just before MDMA became illegal) must be considered highly speculative and it is unknown what changes in use have occurred since then. III. EPIDEMIOLOGY Although research examining recreational use patterns of MDMA has been minimal, the drug appears to be most popular in urban areas, especially college towns (Beck, 1986, Renfroe, 1986).4 Many users belong to groups who have traditionally been associated with MDA use. Prominent among these are gays and college students. Newsweek noted that MDMA "has become popular over the last two years on college campuses, where it is ____________________ 4 Most of the information available regarding street use of MDMA is based on anecdotal accounts given to the media, therapists, and substance abuse professionals, as well as preliminary research conducted by Jerome Beck (1986). Through his capacity as a drug educator and counselor at the University of Oregon and in the San Francisco Bay Area, Beck has been able to interview hundreds of individuals who reportedly used MDMA over the past 10 years. UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 6 considered an aphrodisiac" (Newsweek, 1985, p.96). This reputation explains why MDMA seems to be increasing in popularity even among groups such as college fraternities, which are not traditional psychedelic users (Beck, 1986). One of the first media accounts of MDMA described it as a "yuppie psychedelic" whose popularity was spreading rapidly among educated professionals in their 30s and 40s. The article stated that "in contrast to the mind-bending hallucinogens of the '60s, Adam is reported to leave one's faculties fairly clear," (Mandel, 1984, p.A2). The same article quoted a drug abuse program director as noting that "some of these people haven't touched a psychedelic for 10 or 15 years, but cocaine is really scaring folks these days. They are turning elsewhere" (Mandel, 1984, p.A2). Many individuals describe using MDMA on occasion while claiming to rarely or never use other more commonly available illegal drugs or even alcohol (Beck, 1986, Seymour, 1986). As the author of a recent article titled "Drugless in L.A." stated, "For veterans of the '60s it is interesting to note that the major new drug of the '80s, Ecstasy, has been hyped as a drug that is not really a drug" (Kaye, 1986, p.34). MDMA's cost has ranged from $50 to $120 a gram, yielding 5 to 15 doses per gram. The price has increased slowly since MDMA became illegal. The oral route is by far the most common method of ingestion, although some individuals occasionally inhale the drug. Intravenous (IV) use seems to be rare. At times a small quantity of MDMA will be swallowed or inhaled as a "booster" UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 7 after the initial oral dose begins to wear off. A continuous use of boosters, however, generally leads to great fatigue the next day. Although MDMA has been described occasionally as a "party drug," that is not its most common use pattern. Most individuals describe taking it with a small intimate group or another person, usually a close friend, spouse, or lover. A major exception was certain bars in the Dallas, Texas, area, where tablets were purchased at the door or counter, and where, according to the DEA, 30,000 dosage units of MDMA a month were sold by one local dealer alone, right up until the scheduling ban (United States Department of Justice, 1985). IV. PSYCHOPHARMACOLOGY A. Effects The MDMA dosage range between effectiveness and toxicity is fairly narrow. It is reported that toxic effects begin to increase sharply over the 200 mg dose level. Effects generally appear within 20 to 60 minutes, when the user experiences a "rush" usually described as mild but euphoric. The "rush" may last from a few minutes to half an hour or not occur at all, depending on the user's mental set and the environment, the dose ingested, and the MDMA's quality. Zinberg (1976) described a similar pattern with MDA in an early field study. After the rush, the high levels off to a plateau, usually lasting from two to three hours, followed by a gradual "coming down" sensation, ending with a feeling of fatigue. Insomnia, however, may persist UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 8 long after the fatigue stage, depending on the dosage and the user. MDMA, although milder and shorter-lasting than MDA, still exerts amphetamine-like effects on the body, including dilated pupils, dry mouth and throat, tension in the lower jaw, grinding of the teeth, and overall stimulation. These effects vary depending on dose. In addition, MDMA exerts a strong paradoxical effect of relaxation, which often causes many users to be unaware of the stimulant side effects (Beck, 1986). Most users cite a dramatic drop in defense mechanisms and increased empathy towards others. Combined with the stimulant effect, this generally produces an increase in intimate communication. Although both MDA and MDMA have been labeled "aphrodisiacs," users most often describe a more sensual, rather than sexual, experience. B. Psychotherapeutic Effects Research evaluating MDA as a psychotherapeutic tool preceded that of MDMA. Studies were conducted by Naranjo et al. (1967), Naranjo (1973), Turek et al. (1974), and Yensen et al. (1976). The studies described similar outcomes and unanimously supported the therapeutic potential of MDA. Subjects described an intensification of feelings, facilitation of self-insight, and heightened empathy as qualitative characteristics of MDA. Zinberg (1976) carried out what is still the only published field study of either MDA or MDMA. He interviewed 23 experienced MDA users while they were high in their "natural" settings, either individually or in groups. None of the users reported any UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 9 past negative experiences. Zinberg observed no panic reactions or hallucinatory episodes. The most complete study of MDMA's effects published to date was conducted by Greer (1983) who administered the drug to 29 subjects (none with severe mental disorders) in a therapeutic setting. Most of the subjects were given an oral dose of 75-150 mg of MDMA. After about two hours, they were offered a second dose of 50-75 mg. Greer reported that all the subjects experienced some benefits. Each described feeling closer and more intimate with the others present, and almost all reported positive changes in their feelings and attitudes. Moreover, 17 subjects reported some cognitive benefit (e.g., an expanded mental perspective and insight into personal patterns or problems). Follow-up questionnaires were given at a median time of about nine months after the last session, and the majority of subjects reported positive changes in work, relationships, mood, and attitude. Half reported decreased use of mood-altering drugs, often mentioning that these substances seemed less appealing after experiencing MDMA. According to Greer, "The ability not only to feel free of conflict--which can be provided by many drugs of abuse--but to learn how to prevent conflicts in everyday life seems unique to MDMA as a therapeutic adjunct" (Greer, 1983, p.12). It appears that well over one hundred psychiatrists and other therapists have employed MDMA as a therapeutic adjunct. Several psychiatrists testified on behalf of MDMA at the federal UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 10 administrative hearings concerning permanent scheduling. Wolfson (1985) cited optimistic results in the treatment of a few psychotic patients. He concluded that "MDMA provides a positive alternative to the dark and negative experiences of people experiencing psychotic states" (p.9). In general, therapists attending the hearings believed that a major advantage of MDMA (less so with MDA) over the traditional psychedelics is that it produces far less distortion of sensory perception and fewer unpleasant emotional reactions. The experience is generally seen as both personal and familiar and seems to differ only in its degree of intensity from that of everyday experience. This is in sharp contrast to the effects of most other psychedelics, where the experience is often perceived as unfamiliar and transpersonal. As Grinspoon asserted, "MDMA appears to have some of the advantages of LSD-like drugs without most of the corresponding disadvantages" (Grinspoon, 1985, p.3). Although some preliminary research suggested that MDMA has significant therapeutic potential, the notable absence of well- controlled, double-blind studies limits conclusions about the possible efficacy or risks associated with the use of MDMA in therapy. As Siegel recently noted, "MDMA has been promoted as a cure for everything from personal depression to alienation to cocaine addiction. . . . It's got a lot of notoriety, but the clinical claims made for its efficacy are totally unsupported at this time" (Siegel, 1985, p.14). Researchers and therapists are UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 11 aware that only formal, well-controlled research will adequately assess the true therapeutic value of MDMA. V. RELATED PROBLEMS/HEALTH RISKS A. Physiological Problems. Although little is known about the potential toxicity for humans of MDA, MDMA, or any of the other amphetamine psychedelics, some research has assessed toxic and lethal doses in animals (Hardman, Haavik, & Seevers, 1973, Davis, & Borne, 1984). Assuming the results of the data on animals can be generalized to humans, indications are that a lethal IV dose for 50% (LD-50) of 150-pound individuals would be about 1100 to 1780 mg. The dangers of such extrapolation are well known, but these figures would seem to indicate that a lethal dose for injected MDMA may be a little over 10 times the usual 100-150 mg amount. A recent study suggested a much higher LD-50 for MDMA when ingested orally. The single-dose oral LD-50 for rats was found to be approximately 325 mg/kg, with death associated with kidney and liver damage (Goad 1985). This dose corresponds to over 150 times the human therapeutic level (1.5-2.0 mg/kg). Street use of MDA has been connected to a number of deaths, although not clearly, because other drugs were also involved (Reed, Cravey, & Sedgwick, 1972). Some deaths reported in 1972 and 1973 to be a result of MDA toxicity are now known to have occurred as a result of ingesting another amphetamine derivative: PMA (paramethoxyamphetamine) (Inaba, Way, & Blum, 1978). The PMA UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 12 compound, frequently passed off as MDA, often caused a dangerous rise in blood pressure at effective doses. Fortunately, PMA appears to have been totally withdrawn from circulation (Stafford, 1983). A few deaths have been associated with the use of MDMA, but its role as a causative factor in these deaths remains uncertain (Shulgin, 1985). As of April, 1986, 20 emergency room incidents for MDMA had been listed in the federal government's Drug Abuse Warning Network (DAWN) (Newmeyer, 1986). Ignorance of the substance undoubtedly contributes to underreporting. However, the number of mentions still appears to be rather low when compared with the suspected extent of use described by Siegel (1985) and the DEA (Sapienza, 1985). While associated with relatively few overdoses or deaths, MDMA's neurotoxic potential is cause for concern. Studies in rats conducted at the University of Chicago indicate that large intravenous doses of MDA and MDMA in rats are associated with suspected degeneration of serotonergic ("chemical messenger") nerve terminals in certain areas of the brain (Ricaurte, 1986, Ricaurte, Bryan, Strauss, Seiden, & Schuster, 1985). Also, there may be some suppression of the immune system. Serotonin is a neurotransmitter that apparently plays an important role in regulating sleep, mood, sexual activity, and sensitivity to stimuli (Schuster, 1986). However, the University of Chicago researchers acknowledged that "because of the differences in species, dose, frequency, and route of administration, as well as UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 13 differences in the way in which rats and humans metabolize amphetamine, it would be premature to extrapolate our findings to humans" (Ricaurte, et al., 1985, p.988). In addition, our overall lack of knowledge concerning serotonin makes it difficult to interpret the significance of these findings. Research is now being conducted at Stanford and other institutions to determine the potential significance of this damage, whether it occurs in humans, and if so, at what dosage level (both orally and intravenously). A number of acute and chronic problems have been identified. for example, MDMA may exert an adverse action on the immunological response of some individuals. This effect is most often associated with repeated high dosages, particularly in individuals who have used the drug over a long period of time. Long-term users often describe increasingly uncomfortable and prolonged "burn-out" periods, sometimes lasting two or more days. Many individuals have also reported an increased susceptibility to various ailments, particularly sore throats, colds, flus, and herpes outbreaks (Beck, 1986). These reactions appear to be rare in novice users and individuals in good physical and mental health. Generally, many of the side effects of MDMA are similar to those of amphetamine and, as Weil (1976) noted with MDA, are very much dose-related. One of the most common annoying effects is a tension of the jaw muscles, often progressing to involuntary grinding of the teeth, an effect noted with MDMA and amphetamine- UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 14 like drugs in general. Nausea and dizziness are occasionally reported, most often during the initial onset of the high. Individuals become dehydrated and should be drinking water or juice throughout the experience. Unfortunately, some choose to drink alcoholic beverages, which increase dehydration. As with other stimulants, individuals under the influence of MDMA are often capable of ingesting large quantities of alcohol with few discernible effects until a short time later. Thus, overdose of alcohol likely plays a significant role in the next day's hangover (Beck, 1986). The potentially toxic interaction between MDMA and alcohol merits further investigation. One research project studied the effects of a single exposure to MDMA among 21 healthy individuals. All these subjects had used MDMA on previous occasions. Using blood chemistry, physiological measures, and neurological examinations, the researchers concluded that: This experimental situation produced no observed or reported psychological or physiological damage, either during the twenty-four hour study period, or during the three month follow-up period. From the information presented here one can say only that MDMA, at the doses tested, has remarkably consistent and predictable physiological effects which are transient and free of clinically apparent major toxicity (Downing, 1985, p.5-6). The research design of this experiment was heavily criticized by an FDA pharmacologist at the administrative hearings (Tocus, 1985). He agreed with the study's conclusion UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 15 that "there is insufficient evidence to judge accurately either harm or benefit" (Downing, 1985, p.6). Based on the limited information available, researchers have identified the following medical conditions as possible contraindications to MDMA use: diabetes, diminished liver function, epilepsy, glaucoma, heart disease, hypertension, hypoglycemia, hyperthyroidism and pregnancy (Beck, 1986, Seymour, 1986; Greer, 1983). B. Psychological Problems. The most frequent use of MDMA usually occurs during the first months following the initial experience. After first exposure, some individuals will attempt to continually reexperience the positive aspects of the drug. However, this abusive cycle tends to be brief. Within a short time, the frequent use of MDMA almost invariably produces a strong dysphoric reaction, which is only exacerbated with continued use. The increasing number of unpleasant side effects coupled with an almost total loss of desired effects occurs with greater rapidity and intensity than they do with other more commonly abused substances (Beck, 1986; Seymour, 1986; Greer, 1983; Strassman, 1985). However, since the popularity of MDMA is fairly recent, more time is needed to see how use patterns develop among new user groups introduced to the drug (e.g., adolescents, i.v. users). The strong euphoria associated with MDMA points towards a high abuse potential. Although Seymour (1986) states that MDMA UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 16 doesn't seem to pack a "euphoric punch" or "rush" comparable to other drugs, Beck (1986) finds just the opposite to be true. Among individuals who have tried both MDMA and cocaine, the majority usually express a strong preference for the longer, smoother euphoria provided by MDMA. As one individual interviewed by the NIDA-funded Cocaine Cessation Project described it: Cocaine usually gives me an up-and-down jagged feeling that lasts for only a short time. I alternately like it and hate it, though for some reason it has very seductive qualities. "Ecstasy," on the other hand, is just as the name implies. It's "state of the art." It puts me in a place of total bliss for 3 or 4 hours. Whereas coke often makes me feel jittery, MDMA is very smooth. I know it has amphetamine in it, but I feel so relaxed . . . (Murphy, 1986). Recent studies at Johns Hopkins found that primates will self-administer MDMA at regular intervals (although not quite as frequently as cocaine) (Sapienza, 1986). In sharp contrast to cocaine, however, there appear to be relatively few cases of what might be considered heavy abuse of MDMA (Beck, 1986; Seymour, 1986; Siegel, 1985; Greer, 1983). In an ongoing study of MDMA users, Siegel (1985) cited that the most common patterns of use are "experimental" (ten times or less in lifetime) or "social- recreational" (one to four times per month). He also said that "compulsive patterns marked by escalating dose and frequency of use have not been reported with MDMA users" (Siegel, 1985, p.2- 3). UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 17 Occasional psychological problems have been reported with MDMA use, but appear to be quite rare. Episodes of hyperventilation have been noted (Beck, 1986; Seymour, 1986; Siegel, 1985), but these almost always occur during the onset of the experience as part of a generalized panic reaction. Reassurance that the phase is transitory generally lessens this problem. In 1985, the Haight Ashbury Free Medical Clinic reported that each month three to four individuals sought treatment for problems related to MDA, MDMA, or related drugs (Seymour, 1986). Some clients present acute symptoms that include anxiety, rapid pulse, and in advanced cases, paranoia. As Seymour notes: "With MDMA and the methoxylated amphetamines, as is the case with most stimulants and psychedelics, the acute toxicity symptoms that are usually seen in treatment are similar and result from taking too much of the drug. These dose related symptoms usually dissipate as the drug wears off, and the patient can be discharged within a few hours" (1986: 54-55). Seymour also goes on to state that "More severe reactions to what users believed to be MDMA have been reported, including prolonged psychotic reactions, but we haven't seen them" (1986: 55). Treatment is usually symptomatic and of relatively short duration. From the Haight Ashbury data, it appears that the highly unpleasant aftereffects associated with heavy use of MDMA serve to temper the appetite of all but a few users. UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 18 Some additional psychological problems have recently been noted in an ongoing study conducted by Mim Landry of the Haight Ashbury Training and Education Project. A "delayed anxiety disorder" has been observed in a few individuals. This problem typically occurs among novice users of MDMA, and the manifestations "range from a mild anxiety or concentration difficulties to a full-blown disorder such as a panic attack with hyperventilation and tachycardia, phobic disorders, parathesias, or other anxiety states" (Seymour, 1986, p.56). These initial findings underscore a growing danger of unsuccessful attempts at "self-therapy" by individuals who run the risk of exacerbating their emotional problems with unsupervised episodes. Up to this point, the Haight Ashbury research provides some of the only significant data on the potential problems associated with MDMA abuse. VI. CONCLUSION Media accounts and substance abuse professionals often dismiss MDMA as a short-term fad. However, the perceived therapeutic and/or euphoric effects combined with the ease with which MDMA is usually experienced can be expected to attract new users. A danger in this regard is the uncertain potential for abuse. In addition, there are potentially severe health risks associated with MDMA and probable contraindications. This is particularly true with repeated use of high dosages which may lead to acute or chronic medical and psychological problems. Unfortunately, our current knowledge regarding nearly every UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 19 aspect of MDMA is extremely limited and based almost exclusively on anecdotal data. Research is obviously needed to better determine the potential risks of a substance which is rapidly establishing itself in our drug culture. VII. RESOURCES Dr. Jerome E. Beck Institute for Scientific Analysis 2410 Lombard St. San Francisco, CA 94123 (415) 921-4987 Dr. Mim Landry Haight-Ashbury Free Medical Clinics 529 Clayton Street San Francisco, CA 94117 Dr. John Newmeyer Haight-Ashbury Free Medical Clinics 529 Clayton Street San Francisco, CA 94117 (415) 864-6090 Dr. George Ricuarte Department of Neurology Stanford University Medical Center Palo Alto, CA 94305 Dr. Frank Sapienza Drug Enforcement Administration 1405 Eye Streeet, NW Washington, D.C. 20537 Dr. Richard Seymour Haight-Ashbury Free Medical Clinics 529 Clayton Street San Francisco, CA 94117 UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 20 11-13-1986 MD Rev. 12/31/86 epd Rev. 4/6/87 epd, 9/15/87 jh UCLA Drug Abuse Research Group (M. Douglas Anglin, PhD, Director) 14 REFERENCES Beck, J. The Popularization and Resultant Implications of a Recently Controlled Psychoactive Substance. Contemporary Drug Problems, 13: 1, 1986. Beck, J. & P. Morgan. Designer Drug Confusion: A Focus on MDMA. Journal of Drug Education, 16(3): 267-282, 1986. Davis W. M., & R. F. Borne. Pharmacologic Investigation of Compounds Related to 3,4-Methylenedioxyamphetamine (MDA). Substance and Alcohol Actions/Misuse, 5: 105-110, 1984. Downing, J. J. MDMA Pilot Study: Physiological, Psychological, and Sociological Summary, Unpublished manuscript, 1985. Federal Register, May 31, 1985: 50:106. Federal Register, Oct. 14, 1986: 51:198 36552-36560. Greer, G. MDMA: A New Psychotropic Compound and Its Effects in Humans, Self-published (333 Rosario Hill, Sante Fe, New Mexico 87501), 1983. Greer, G. Written Testimony Submitted on Behalf of Drs. Grinspoon and G