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Modern humans must learn how to relate to psychoactives
responsibly, treating them with respect and awareness,
working to minimize harms and maximize benefits, and
integrating use into a healthy, enjoyable, and productive life.
E for Ecstasy
by Nicholas Saunders


[ Appendix 4 sec. 6 ] [ Index ] [ Appendix 4 sec 8 ]

Appendix 4: Bibliography Clinical studies

Beck, J. The Public Health Implications of MDMA Use. The Clinical, Pharmacological and Neurotoxicological Effects of the Drug MDMA. Kluwer, New York. (1990) Ed: S.J. Peroutka.

This sociological paper brings together the street acceptance of, and the public health rejection of, MDMA as a tool for therapy and a vehicle of simple intoxication. The part that this drug has played in each of these roles is carefully defined.

Beck, J., Harlow, D., McDonnell, D., Morgan, P.A., Rosenbaum, M. and Watson, L. Exploring Ecstasy: A Description of MDMA Users. Report to NIDA, September 15, 1989. Grantee: Institute for Scientific Analysis, San Francisco, CA.

This is a 253 page report of a research project that conducted a broad and thorough analysis, through interview, of over 100 MDMA users. A fascinating picture emerges of the pros and cons of MDMA usage. This is the only analysis of this depth and candidness that has ever been done, and it is an essential reference volume for all social researchers in this area.

Buffum, J. and Moser, C. MDMA and Human Sexual Function. J. Psychoactive Drugs 18 355-359 (1986).

A survey of some 300 MDMA users produced a response of 25%. An analysis of the presented data is offered, organized as to types of activity and performance. There was a significant increase in intimacy, and a decrease (especially for males) in performance.

Downing, J. The Psychological and Physiological Effects of MDMA on Normal Volunteers. J. Psychoactive Drugs 18 335-340.

This is certainly the most complete clinical study on the effects of MDMA on the normal human subject. A total of 21 normal volunteers were administered known amounts of MDMA, orally. The entire group had analyses of blood chemistry, timed and frequent physiological measures, including pulse and blood pressure (for all) and as well as neurological and electrocardiographic tests (for some). The neurological and electrocardiogram evaluations were continued for 24 hours.

Physiologically, all subjects experienced an elevation in blood pressure and pulse rate, with a peaking on the average at about one hour. At the sixth hour, most subjects were at or below their pre-dose levels, and at 24 hours all were within their normal ranges. Eye dilation was seen in all subjects, more than half had jaw clench and an increased jaw reflex, which persisted in one subject to the 24 hour point. Some neurological reflexes were enhanced (deep tendon) or equivocal (planter reflex), and there were signs of incoordination (finger-nose testing, gait) in some subjects, giving a strong warning against motor vehicle operation. One subject was nauseous, with vomiting, but there were no difficulties with either urination or defecation, and there were neither headaches nor insomnia. Appetite was suppressed in all subjects to varying degrees.

At the psychological level, all subjects reported a heightened sensual awareness, and three reported sexual arousal. It is concluded that MDMA produces remarkably consistent psychological effects that are transient, and is free of clinically apparent major toxicity.

Greer, G. MDMA: A New Psychotropic Compound and its Effects in Humans. Privately Published, 333 Rosario Hill, Sante Fe, NM 87501. Copyright 1983. 15 pages.

The most complete study of the effects of MDMA published as of this date, describing the results of administration of MDMA to 29 human subjects (none with serious psychiatric problems) in a therapeutic setting. It is concluded that the best uses of MDMA are: facilitation of communication and intimacy between people involved in emotional relationships; as an adjunct to insight-oriented psychotherapy; and in the treatment of alcohol and drug abuse. It is explained why MDMA does not lend itself to over-use, since its most desirable effects diminish with frequency of use.

Greer, G. Recommended Protocol for MDMA Sessions. Privately Published. 333 Rosario Hill, Sante Fe, NM 87501. Copyright 1985. 6 pages.

This is a generalized protocol designed to cover the clinical use of MDMA. It reviews the issues of law, of safety, and of efficacy.

Greer, G. Using MDMA in Psychotherapy. Advances, 2 57-57 (1985).

A conference was held at Esalen March 10-15 1985, to discuss the potential of MDMA for therapy, and to evaluate its differences from earlier therapeutic tools such as LSD. A total of 13 subjects, with the supervision of several experienced psychiatrists, participated in a experiment designed to familiarize the potential clinician with the actions of MDMA. Most of the attendees had already known of the drug in a therapeutic context, and their collected comments are presented and discussed.

Greer, G. Ecstasy and the Dance of Death. British Med. J. 305 775 (1992).

A defence of MDMA is presented, in answer to published conclusions that no clinical benefits have been observed. There is a tallying of the benefits seen amongst the author's patients, in earlier clinical studies.

Greer, G. and Tolbert, R. Subjective Reports of the Effects of MDMA in a Clinical Setting. J. Psychoactive Drugs 18 319-327 (1986).

This article summarizes and gives additional detail on the collection of 29 therapeutic trials discussed earlier. The protocol of drug administration, a review of both the benefits and the undesirable effects, and an outlining of the changes seen in the patients, are presented. There is a considerable body of retrospective evaluation.

Greer, G. and Tolbert, R. The Therapeutic Use of MDMA. The Clinical, Pharmacological and Neurotoxicological Effects of the Drug MDMA. Kluwer, New York. (1990) Ed: S.J. Peroutka.

A structure is provided in detail for the clinical use of MDMA in a therapeutic setting. A number of the preferred procedured are illustrated with specific case examples.

Grob, C., Bravo, G., McQuade, J. and Doblin, R. Analgesic Efficacy of 3,4-Methylenedioxymethamphetamine (MDMA) in Modification of Pain and Distress of End-stage Cancer. Proposal submitted to the FDA for clinical approval, August 4, 1991.

A proposal has been submitted to the FDA for the evaluation of MDMA as an analgesic against clinical pain in advanced cancer patients.

Grob, C., Bravo, G., and Walsh, R., Second Thoughts on 3,4-Methylenedioxymethamphetamine (MDMA) Neurotoxicity. Arch. Gen. Psychiatry 47 288 (1990).

A letter to the editor presents a critique of studies done on alleged MDMA users in search for evidence of serotonin nerve damage (Price et al., Arch. Gen. Psychiatry 46 20-22 (1989). The fact that all nerve toxicity is based on animal studies, and that the long-used drug Fenfluramine is considerably more potent a neurotoxin than MDMA, might argue that studies into the potential therapy use should be encouraged.

Grob, C.S., Bravo, G.L., Walsh, R.N. and Liester, M.B. Commentary: The MDMA-Neurotoxicity Controversy: Implications for Clinical Research with Novel Psychoactive Drugs. J. Nerv. Ment. Dis. 180 355-356 (1992).

The points raised by Kosten and Price, in criticism to the retrospective interview paper, are answered.

Hastings, A. Some Observations on MDMA Experiences Induced Through Posthypnotic Suggestion. J. Psycho. Drugs 26 77-83 (1994).

A study is reported with subjects who were familiar with MDMA action. The techniques of hypnosis were employed toreinstitute MDMA-like effects, and the potential for post-hypnotic suggestion in therapy is explored.

Kosten, T.R. and Price, L.H. Commentary: Phenomenology and Sequelae of 3,4-Methylenedioxymethamphetamine Use. J. Nerv. Ment. Dis. 180 353-354 (1992).

The retrospective interview by Liester et al. is critically analysed, and found to be faulted both methodologically and as to the conclusions reached.

Liester, M.B., Grob, C.S., Bravo, G.L. and Walsh, R.N. A Study of MDMA Use Among Psychiatrists. Poster #NR-62, New Research Poster Session, American Psychiatric Association, San Francisco, CA May 8, 1989.

A survey was conducted among 20 psychiatrists who had previously taken MDMA, and a tally of the various responses made. There was a discussion of both the methodological problems and the ethical considerations of this type of study.

Liester, M.B., Grob, C.S., Bravo, G.L. and Walsh, R.N. Phenomenology and Sequelae of 3,4-Methylenedioxymethamphetamine Use. J. Nerv. Ment. Dis. 180 345-352 (1992).

Twenty psychiatrists experienced with MDMA were retrospectively interviewed as to side effects, insight gained, pleasure experienced, and intensity of effects.

McCann, U.D. and Ricaurte, G.A. MDMA ("Ecstasy") and Panic Disorder: Induction by a Single Dose. Biol. Psychiatry 32 950-953 (1992).

A patient is described with a lasting panic disorder syndrome that started during the course of an alledged MDMA experience. Alprazolam improved his condition, but it was reprecipitated by OTC cold remedies, suggesting that some catecholamine function had been disturbed.in the patient.

McCann, U.D. and Ricaurte, G.A. Reinforcing Subjective Effects of (+/-) 3,4-Methylenedioxymethamphetamine ("Ecstasy") May Be Separable from its Neurotoxic Actions: Clinical Evidence. J. Clin. Psychopharmacol. 13 214-217 (1993).

Four subjects who had voluntarily, and anecdotaly, exposed themselves to MDMA, report that pretreatment with Fluoxetine found some increased somatic distress, but no attenuation of the expected responses to the drug, including enhanced awareness and ease of communication. It is implied that a pretreatment with a serotonin uptake inhibitor attenuates the neurotoxic effects of the drug MDMA, but the thrust of the report might well be to suggest that there is a neurotoxic effect in man that can indeed be attenuated.

McCann, U.D., Ridenour, A., Shaham, Y. and Ricaurte, G.A. Serotonin Neurotoxicity After (+/-)3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy"): A Controlled Study in Humans. Neuropsychopharmacology 10 129-138 (1994).

A group of 30 MDMA users and 28 matched controls with no history of MDMA use were studied. The MDMA subjects had lower levels of 5-hydroxyindoleacetic acid in their cerebrospinal fluid, indicating some serotonin depletion. At the psychological level, the MDMA users showed a decreased impulsivity and hostility, and increased harm avoidance and constraint.

Moody, C.P. Facsimile letter to C.S. Grob concerning FDA approval of human Phase I study application. November 4, 1992.

This is an official statement from the Pilot Drug Evaluation Section of the Food and Drug Administration, that the Phase I study submitted by Dr. Grob, has been approved.

Peroutka, S.J. Recreational Use of MDMA, Ecstasy: The Clinical, Pharmacological and Neurotoxicological Effects of the Drug MDMA. Kluwer, New York. (1990) Ed: S.J. Peroutka.

There is a distillation from some 300 users of MDMA as to their experiences on the drug, both as to subjective mental effects, and as to physical difficulties. Although the reports are largely favourable, there is a mention of both panic attacks and of a lethal event, and several popular myths are itemized. It is concluded that recreational use should be avoided.

Peroutka, S.J., Newman, H. and Harris, H. Subjective Effects of 3,4-Methylenedioxymethamphetamine in Recreational Users. Neuropsychopharmacol. 1 273-277 (1988).

A survey has been made of about a hundred admitted MDMA users and has been organized into reports of subjective feelings such as "closeness" (the most often reported) to "blurred vision" (the least often reported). A brief review of the toxicological history is presented, and no unequivocal evidence of human toxicity could be concluded from this study.

Price, L.H., Krystal, J.H., Heninger, G.R. and Ricaurte, G.A., In Reply. Arch. Gen. Psychiatry 47 289 (1990).

The critique of Grob et al. is responded to. The self-claimed MDMA users had been assayed by urine EMIT screening for recent drug use prior to the experiments reported (Price et al., Arch. Gen. Psychiatry 46 20-22 (1989). The justification for continued Fenfluramine use was that it had no record of abuse (as contrasted to MDMA use), and that the claims for drugs serving as psychotherapeutic adjuncts have been made for many compound for many years, and have not bourn fruit. The recommendation is strongly made that clinical studies are inappropriate at this time.

Shulgin, A.T. and Nichols, D.E. Characterization of Three New Psychotomimetics, The Psychopharmacology of Hallucinogens, Eds. R.C. Stillman and R.E. Willette, Pergamon Press, New York. (1978).

The psychopharmacological properties of MDMA are presented, in company with two new compounds, para-DOT (2,5-dimethoxy-4-methylthioamphetamine) and alpha,O-DMS (5-methoxy-alpha-methyltryptamine). It is described as evoking an easily controlled altered state of consciousness with emotional and sensual overtones. It appears to be with little hallucinatory component. This is the first clinical report of the effects of MDMA in man.

Siegel, R.K. MDMA: Nonmedical Use and Intoxication. J. Psychoactive Drugs 18 349-354 (1986).

From a group of 415 acknowledged MDMA users, a sub-group of 44 were chosen for examinations and tests. They were interviewed, physically examined, and tested by several of a large battery of psychological evaluation procedures. From this, patterns of use and the nature of the intoxicating effects were deduced.

The author has concluded that the visual effects of MDMA intoxication were typical of the intoxications from the classical hallucinogens such as mescaline with imagery characteristic of drug-induced hallucinations, as well as those induced by isolation and stress. These are mollified when attention is directed towards external events. There were, nonetheless, no abnormal profiles on the psychological tests. It is felt that the MDMA intoxication is neither uniformly controllable nor uniformly predictable.

Tatar, A. and Naranjo, C. MDMA in der Gruppenpsychotherapie. Symposion "Uber den derzeitigen Stand der Forschung auf dem Gebiet der psychoaktiven Substanzen." Nov. 29 - Dec. 12, 1985, in Hirschhorn/Neckar, Germany.

Two independent reports of clinical utility are presented. Both investigators report MDMA use in group settings. The groups consisted mainly of psychosomatic patients involving problems such as allergies, eczema, sexual dysfunction, troublesome urination, cardiac irregularities, and cancer. There were some positive changes reported, and in some cases there were no improvements. No details are presented.

Watson, L. and Beck, J. New Age Seekers: MDMA Use as an Adjunct to Spiritual Pursuit. J. Psychoactive Drugs 23 261-270 (1991).

In an analysis of a sociological investigation into the lay use of MDMA, the quality of MDMA experiences with a sub-set of "New Age" oriented users. As there appears to be a wide variety of motivations for MDMA use, care must be paid to the social context in evaluating drug-using behaviour.

Widmer, S. Ins Herz der Dinge Lauschen, vom Erwachen der Liebe. Nachtschatten Verlag, Solothurn, Switzerland, 1989.

This reference book of just over 300 pages, is a thorough collection of ideas, comments, and illustrations, of the use of MDMA and/or LSD in psychotherapy. It is in German.

Wolfson, P.E. Meetings at the Edge with Adam: A Man for All Seasons. J. Psychoactive Drugs 18 329-333 (1986).

An extensive discussion is presented listing the potential virtues and hazards of MDMA use in the psychotherapeutic setting. The roles of drugs currently used, and those of MDMA-like action that might some day be available, are reviewed. A case report of the use of MDMA in a family problem situation is presented in considerable detail.