Subject: A Medscape Article on MDMA Date: Sun, 26 Sep 1999 00:43:44 -0500 From: "Serotonin" Organization: Deconstruction, Inc. Newsgroups: alt.drugs.chemistry,alt.drugs.culture,rec.drugs.chemistry,rec.drugs.smart I thought the following information may be of general interest: The author, Jeffrey T. Kirchner, DO, Department of Family and Community Medicine, Lancaster General Hospital, has compiled an *extensive* list of references, including the Ricaurte studies and one citation of *somebody* by the name of A. Shulgin :-) (Shulgin AT. The background and chemistry of MDMA. J Psychoactive Drugs 1986;18:291-304. ) If anybody would like the whole list, let me know. (serotonin1 at hushmail.com) History of MDMA The first preparation and description of MDMA was through a patent issued by the E. Merck Pharmaceutical firm in Darmstadt, Germany, in 1912. The drug was developed as an appetite suppressant but never became commercially successful. It resurfaced in the 1950s as a method of lowering inhibitions in patients undergoing psychoanalysis.[1] Patients using the drug found it gave them a sense of closeness with others around them. They believed it let down barriers or filters to free communication and aided in the introspective analysis of one's psyche. In 1983 a study performed on 29 volunteers (primarily academics and medical professionals), MDMA was found to be an adjunct to insight-oriented psychotherapy and to facilitate intimacy and communication between people involved in intimate relationships.[2,3] Despite some of these reported benefits of MDMA, in July 1985 the Food and Drug Administration (FDA) placed the drug into the schedule 1 category, which greatly restricted its availability.[1] Since that time its use as an adjunct to psychoanalytical therapy has greatly diminished, but its illicit use has become more common, perhaps in response to all of the attention given to MDMA by the lay press during the hearings that led to its schedule 1 classification. Recreational use of MDMA began to surface in the early to mid 1980s. Reports from Ireland and college campuses in the United States showed its use was growing noticeably. Cases of ingestion reported by the Irish Poison Information Center increased 130 percent from January 1991 to June 1992.[4] Recreational use by college students surveyed at a private southern university increased from 8 percent in 1986 to 24 percent in 1991.[5] In addition, reports of adolescent knowledge of MDMA in England showed a dramatic increase in awareness of MDMA in the past 5 years.[6] Currently most MDMA use occurs during "raves" -- large (sometimes numbering thousands of participants) dance parties held in abandoned warehouses or other similar structures. Apart from techno-pop music and "smart drinks" (drinks laced with amino acid mixtures), MDMA seems to be an integral component of the rave scene. Preparation of MDMA At least six methods of making MDMA are described in the scientific literature. Several recipes can be located easily on the World Wide Web. Some specialized equipment is required as well as some expertise in organic chemical synthesis. Most expert black-market manufacturers recommend 1 to 2 years of undergraduate chemistry experience, including organic and analytic chemistry courses that have laboratory components. Problems with impure or incorrect synthesis can result in some rather potent and toxic contaminants, however, which could be the reason for toxic ingestions noted in the literature. Pharmacology In vivo and in vitro animal studies have shown that MDMA affects the serotonergic (and to a lesser extent dopaminergic) neurons of the brain. The compound seems to cause a calcium-independent flood of serotonergic neuron release into the synaptic cleft while inhibiting serotonin reuptake. This response results in the euphoria and stimulus effect of MDMA. Toxicology and Neurotoxicology Concerns about MDMA have arisen as a result of studies showing both reversible and possible irreversible damage to serotonergic neurons.[7-15] These studies involved rats, rabbits, and nonhuman primates. Human studies of the effect of MDMA, which have been limited to indirect analysis through assays of cerebrospinal fluid obtained from patients, have shown conflicting results. Some studies have found a reduction in serotonin metabolites in the cerebrospinal fluid, suggesting a general depression or loss of serotonin from the brain.[16] Another study showed no such loss of the serotonin metabolites.[17] Because these studies were uncontrolled, the results are difficult to interpret. Ongoing controlled trials in Europe, as well as positron emission tomography (PET) scanning, could aid in further answering the question of neurotoxicity in humans.[18] The lethal dose (LD50) of MDMA has been studied in various animal models and by various routes of administration. Studies in rats have shown an LD50 of 49 mg/kg (parenterally) and 325 mg/kg orally.[1] Nonhuman primate studies have shown an LD50 of 22 mg/kg.[13] While no LD50 studies in humans have been done, serum levels assayed on patients with toxic MDMA ingestions have approached or in some cases exceeded the primate LD50 dose. Recreational Use in Popular Culture Information concerning the use and synthesis of MDMA is available through the Internet. Many sites on the World Wide Web discuss dosage methods for safe usage. These instructions are supported by literature from academics who have spent time studying the effects of and analyzing MDMA.[1,2,43] Their recommended dosage is 2 mg/kg as an initial dose with a booster dose after 3 to 4 hours of 0.5 to 1 mg/kg. It is also recommended that the user stay well-hydrated and refrain from vigorous physical activity to reduce the risk of serious hyperthermia and dehydration. Another important safety tip is having a trip guide to protect the user from risky behavior.[48] The current street price of MDMA is $10 to $30 per dose. The drug can be ingested orally, injected, smoked, or snorted. The onset of action is directly related to the route of administration, and for an oral dose onset usually occurs in 30 to 45 minutes. Psychologic effects of MDMA include enactogenesis (touching within) or a sensation that all is right with the world; empathogenesis, which is a feeling of emotional closeness to others coupled with a breakdown of personal communication barriers; and enhancement of the senses of touch, taste, vision, smell, and proprioception. These effects last approximately 4 to 6 hours, but a noticeable decrease in effect occurs within 2 to 3 hours. Known side effects of MDMA include trismus and bruxism for which gum chewing is recommended. The drug is contraindicated in persons taking monoamine oxidase inhibitors because it can cause malignant hyperthermic reactions.[1] MDMA should also be avoided by persons who have a history of hypertension or cardiac, peripheral vascular, or renal disease because of its propensity to increase blood pressure. Final Comment Ecstasy, or MDMA, is a substance that has become popular with a subset of today's young adults. It has been associated with numerous fatal outcomes when used in improper situations or to excess. Because of the illicit nature of its production, impurities and toxic by-products are an additional hazard. The family physician should be aware that this drug, as well as many other so-called designer drugs, are being used in the community. The clinician should also be prepared to deal with the consequences of MDMA ingestion in patients who have a constellation of symptoms described in the patient above. Further research is needed (and currently underway) to define better the pharmacologic effects of MDMA and determine whether it might be of therapeutic benefit to the medical and psychiatric communities.