Ecstasy, MDMA information
MDMA (3,4-methylenedioxymethamphetamine), most commonly known today by the street name ecstasy, is a synthetic entactogen of the phenethylamine family whose primary effect is to stimulate the secretion of large amounts of serotonin as well as dopamine and noradrenaline in the brain, causing a general sense of openness, empathy, energy, euphoria, and well-being. Tactile sensations are enhanced for some users, making general physical contact with others more pleasurable, but contrary to popular mythology, it generally does not have aphrodisiac effects. Its ability to facilitate self-examination with reduced fear has proven useful in some therapeutic settings, leading to its 2001 approval by the United States FDA for testing in patients with post-traumatic stress disorder.
There have been several fatal overdoses of MDMA, resulting in hyperthermia and serotonin syndrome. Acute dehydration is a risk among users who are highly physically active and forget to drink water, as the drug may mask one's normal sense of exhaustion and thirst. Also the opposite, "water intoxication" resulting in acute hyponatremia has been reported. By far the biggest danger comes from the fact that other, more dangerous chemicals (such as PMA, DXM or methamphetamine) are either added to ecstasy tablets, or more often simply sold as ecstasy. Long-term effects in humans are largely unknown and the subject of much controversy —particularly with regard to the risks of severe long-term depression as a result of a reduction in the natural production of serotonin.
MDMA is also known by many other street names, including Adam, Beans, Disco Biscuits, E, Eccies, Googs, MaDMAn, M&Ms, Mollies, Pills, Rolls, Scoobies, Smarties, Tabs, Vitamin E, Vitamin X, X, XTC and Yokes.
MDMA was first patented on Christmas eve 1914 by the German pharmaceutical company Merck, two years after its first synthesis. At the time, Merck was systematically synthesizing and patenting a wide variety of chemically related compounds which could be potentially used in human health, and MDMA remained largely forgotten for many years.
Contrary to many rumours, the drug was never used as an appetite suppressant or as a stimulant for armed forces during wartime. The U.S. Army did, however, do lethal dose studies of it and several other compounds in the mid-1950's. It was given the name EA-1475, with the EA standing for Edgewood Arsenal. The results of these studies were not declassified until 1969. MDMA was first brought to public attention through Dr. Alexander Shulgin in the 1960s who recommended it for use in certain therapy sessions, naming the drug 'window' (he discovered it while searching for compounds that might have a similar psychoactive effect as other compounds contained in nutmeg). It was widely used therapeutically by US psychotherapists (especially on the West Coast) because of its empathogenic effects until its criminalization in the late 1980s. The drug was hailed as a miracle by therapists and counselors who claimed couples could have six months worth of progress in one use of the drug, and soldiers returning from the Vietnam war could overcome their PTSD sometimes more effectively than talk or group therapy. A small number of therapists continue to use it in their practices today. (See below for 2001 FDA approval and DEA licensing for use in patients with post-traumatic stress disorder.)
Until the mid 1980s, MDMA was not illegal in the United States. Recreationally, it first came into prominence in certain trendy yuppie bars in the Dallas area, then in gay dance clubs. From there, use spread to rave clubs, and then to mainstream society. During the 1990s, along with the growing popularity of the rave subculture, MDMA use became increasingly popular among young adults in universities and later in high schools. It rapidly became one of the four most widely used illegal drugs in the US, along with cocaine, heroin and marijuana.
MDMA is synthesized from MDP2P through a chemical reaction known as reductive amination.
Ecstasy as a recreational drug
The primary effects of MDMA include openness, euphoria, empathy, love, and heightened self-awareness. Its initial adoption by the dance club sub-culture is probably due to the enhancement of the overall social and musical experience. Taking MDMA or Ecstasy is commonly referred to as rolling, popping, dropping, flipping, or dosing.
MDMA use has increased markedly since the late 1980s and spread beyond its original sub-cultures to mainstream use. Prices have also fallen since its introduction, with an evening's drug use often costing less than an equivalent evening drinking alcohol, although street price can vary between as little as $8 to as much as $40 per tablet. This depends on the drug being bought beforehand or on the place of use (which drastically increases price). In countries in which distribution is more extensive, such as in the Netherlands, prices can sometimes be as low as $1 per tablet. In Britain, a usual price is around $4 for a pill, and $80 for a gram of pure mdma powder.
Supply and administration
MDMA is usually ingested in pill form. Pills come in a variety of "brands", usually identified by the icons stamped on the pills. The brands never consistently designate the actual active compound within the pill, as anyone can make their own pills which copy the features of a well-known brand.
Pills sold illegally on the street don't always have MDMA as the only active ingredient. Black market pills have been found to contain analogues such as MDEA, MDA and MDBD, and occasionally other unrelated psychoactive additives such as amphetamines (speed), DXM, ephedrine, PMA, caffeine, ketamine (Special K), and others.
Ecstacy commonly appears in a tablet form, usually imprinted with a monogram.While overdose from MDMA itself is rare, many more toxic substances are often sold as ecstasy, and overdose or other adverse reaction to adulterants is not uncommon. MDMA appears to be one of the most commonly adulterated drugs. However, it is less likely that it is mixed, or "cut", with another substance than that it has simply been replaced by another substance which is sold as MDMA.
Many legal pills such as aspirin, paracetamol (acetaminophen), or even canine heartworm tablets have had the letter E scratched into them and been sold as ecstasy, for enormous profit. (This is a minor plot device in the movie Go.) Such false labeling can have deadly results, as a significant number of people are allergic to aspirin. Paracetamol is fairly hepatotoxic and can cause significant liver damage or death if taken in large doses, as might happen to a person taking four or five tablets in quick succession, thinking the tablets to be ecstasy.
Although full and proper characterization of ecstasy pills requires advanced lab facilities such as GCMS, it is also possible to use a less accurate presumptive alkaloid test known as the Marquis reagent. DanceSafe sells testing kits, and includes an extensive database of photographs of different pills, along with the results of a laboratory analysis of their contents.
Serotonin is one of the chemicals responsible for mood and pleasure. MDMA's main action is believed to cause serotonin stores in the brain to release abnormally large quantities of serotonin into the synapses during the 4 to 6 hour high, which is responsible for the primary subjective effects. MDMA also raises dopamine and norepinephrine levels and promotes the release of the hormone prolactin. These effects are primarily due to MDMA's action on the monoamine transporters, SERT (serotonin transporter), DAT (dopamine transporter) and NET (norepinephrine transporter).
Other short-term effects
Apart from the dangers from impurities, the primary acute risks of taking MDMA are allergic reaction, which is extremely rare, and dehydration. Like many amphetamines, MDMA can mask the body's normal thirst and exhaustion responses, particularly if a user is dancing or is otherwise physically active for long periods of time without hydration. MDMA is known to temporarily reduce the body's ability to regulate its core temperature, and in high-temperature surroundings (e.g. clubs) combined with physical exertion this may lead to hyperpyrexia if precautions are not taken to remain cool. In sedentary therapeutic use, incidence of dehydration is not statistically significant. Experts do warn regular users of the drug in more physically active social settings to be cognizant of water intake. While dehydration is undesirable, there also have been a very small number of users overly concerned about hydration drinking excessive water and suffering from water intoxication and associated hyponatremia (dilution of the blood that can cause swelling of the brain). This is what caused the death of British teen Leah Betts, which may be the world's most widely-publicised MDMA-related fatality.
Some users also report decreased libido or impotence, although studies in this area have provided conflicting results  (http://www.idmu.co.uk/esex.htm).
Long-term effects are still unknown and heavily debated among scientists.
There are several reports of Hallucinogen Persisting Perception Disorder being induced by MDMA. In some cases, the disorder appears to be permanent. The disorder seems to occur in only a small percentage of users, and its mechanism of causation is unknown.
The central criticism of MDMA is the "what goes up must come down" theory, which deals with MDMA's artificial boosting of serotonin levels as causing the inverse effect of diminishing of the brain's natural production of serotonin — producing symptoms of acute or chronic depression. However while mood and serotonin levels are known to be related, its not yet clear by what chain of mechanisms serotonin causes changes in mood, and in turn, which effects can be linked to MDMA.
Some experiments indicate that continuous use at very high doses may lead to the synaptic terminals of serotonin neurons being damaged. The precise mechanism of this action is unknown, but recent evidence (Jones 2004; Miller 1997; Monks et al. 2004) suggests that the metabolic breakdown of MDMA includes the formation of reactive oxygen species (ROS), chemicals known to cause oxidative cell damage when taken up into the serotonin neurons.
This effect has been observed in the brains of rats, where the serotonin terminals of animals who are given extremely high doses of MDMA over a prolonged period of time (usually one to two orders of magnitude greater than a typical human dose) become withered and useless. This hypothesis is supported by the fact that the administration of selective serotonin reuptake inhibitors ("SSRIs", which bind to the serotonin cell's reuptake transporters and thus block ROS from entering the serotonin cells) along with or immediately following MDMA seems to completely block neuron damage in rats given MDMA.
For this reason many users self-administer an SSRI while, or shortly after taking MDMA, in an attempt to prevent possible neurotoxicity. These SSRIs are typically antidepressants such as Prozac or Zoloft. It should be noted, however, that MDMA use in conjunction with a different class of antidepressants, namely Monoamine oxidase inhibitors, is strongly contra-indicated due to danger of serotonin syndrome.
Because MDMA's neurotoxicity is known to be highly dependant on its metabolic disposition (Jones 2004; de la Torre & Farré 2004), it is not known whether experiments in rats and monkeys have any direct bearing on human users.
Considerable research has been done into possible cognitive-behavioral deficits among ecstasy users but data have been largely inconclusive. At least two meta-analyses of these studies have been completed (Morgan 2000; Sumnall & Cole 2005). Morgan's analysis of 17 studies showed that ecstasy users had a slight tendency to be more impulsive and depressed than controls. Sumnall and Cole's analysis showed a slight increase in the prevalence of depressive symptoms in ecstasy users over controls. Of course, in retrospective studies like these we are always faced with a chicken-or-egg question: did these impulsive and depressed people use ecstasy to self-medicate or did otherwise normal people become depressed and impulsive after using ecstasy? This question has not been answered. Moreover, such research is problematic as ecstasy users are much more likely than control subjects to have taken other drugs in addition to ecstasy, or even abused various chemicals. This makes it difficult for researchers to establish a direct causal relationship.
Although some experimental evidence exists indicating that long-term ecstasy users experience memory difficulties, a large study in 2002 (Strote et al.) showed that ecstasy users in 4-year colleges have GPAs which do not differ significantly from those of non-users.
Other effects include:
Pupil dilation with attendant photosensitivity and color perception
Jaw clenching or bruxism ("gurning" or "grinding")
Juddery vision (nystagmus)
Loss of appetite/taste sensation
Lack of focus / concentration
Ecstasy and Parkinson's
Research at the University of Manchester indicates that ecstasy dramatically reduces tremors in patients receiving L-DOPA treatment for Parkinson's Disease.
A research team led by Dr. George A. Ricaurte at Johns Hopkins University implicated MDMA as a cause of Parkinson's-like brain abnormalities in monkeys. In a now-retracted study, they suggested that a single use of MDMA caused permanent and serious brain damage. These claims were hotly disputed by physicians, therapists, and other experts, including a team of scientists at New York University. Criticisms of the study included its use of injection rather than oral administration; that this type and scale of damage (>20% mortality) would translate to hundreds of thousands or millions of deaths which had not materialized in the real world amidst extremely broad global MDMA usage; and, perhaps most important, that other research teams could not duplicate the study's findings. It was later discovered that the chemical in question, which had caused severe Parkinson's in a group of heroin users, was actually MPTP.
On September 6, 2003, Dr. George A. Ricaurte and his team announced that they were retracting all results of their commonly cited and controversial study. The researchers said that the labels on the drugs had been somehow switched, and they had inadvertently injected their experimental monkeys and baboons with methamphetamine instead of MDMA. The chemical supplier, Research Triangle Institute, has publicly claimed that the proper drug was supplied, and Ricaurte has yet to pursue them for their alleged error.
Ricaurte had also come under fire for supplying PET scans to the U.S. Office of National Drug Control Policy that were used in anti-drug literature (Plain Brain/Brain After Ecstasy) that seemed to suggest MDMA created holes in human brains, an implication that critics called misleading. Ricaurte later asked the Agency to change the literature, citing the "poor quality" of the images.
Ecstasy and the law
Use, supply and trafficking of ecstasy are currently illegal in most countries. In the United States, MDMA was legal and unregulated until the 31st of May 1985, at which time it was added to DEA Schedule I, for drugs deemed to have no medical uses and a high potential for abuse. During DEA hearings to criminalize MDMA, most experts recommended DEA Schedule III prescription status for the drug, due to its beneficial usage in psychotherapy. The judge overseeing the hearings, Francis Young, also made this recommendation. Nonetheless, DEA classified it as Schedule I.
That same year, the World Health Organization's Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the Convention on Psychotropic Substances. Unlike the Controlled Substances Act, the Convention has a provision (in Article 7(a) (http://www.incb.org/e/conv/1971/articles.htm#7)) that allows use of Schedule I drugs for "scientific and very limited medical purposes". The Committee's report stated (http://www.ecstasy.org/books/e4x/e4x.ap.01/e4x.ap.01.015.html):
It should be noted that the Expert Committee held extensive discussions concerning therapeutic usefulness of 3,4 Methylenedioxymethamphetamine. While the Expert Committee found the reports intriguing, it felt that the studies lacked the appropriate methodological design necessary to ascertain the reliability of the observations. There was, however, sufficient interest expressed to recommend that investigations be encouraged to follow up these preliminary findings. To that end, the Expert Committee urged countries to use the provisions of article 7 of the Convention on Psychotropic Substances to facilitate research on this interesting substance.