MDMA
Ecstasy and Club Drugs: Established and Possible DangersBy David M. McDowell, MD, Medical Director, Assistant Clinical Professor of Psychiatry Columbia University/ The New York State Psychiatric Institute
Abstract
In recent years, so called "club drugs" have become a regular part of many young people 's social life. MDMA, better known as "Ecstasy," is a synthetic amphetamine derivative, with some unique physiological properties. MDMA can induce negative side effects such as depression. A serious concern is the potential that MDMA may cause long lasting, or even permanent, damage to a sensitive portion of the central nervous system, the serotonin system. There is mounting evidence that MDMA causes the destruction of a portion of the serotonin cell, and that this has a functional impact. Furthermore, the extent of this damage may not be apparent for many years. There are a number of other "club drugs," such as Ketamine" as well as GHB-gamma hydroxybuterate, which has been implicated in numerous deaths by overdose. Awareness of these particular substances, as well as their dangers, is an important step in order to implement more effective legal, therapeutic, and educational strategies.
Introduction
Much has been written about substance abuse within the youth culture. Some recent evidence indicates that the rates of such substances are rising. There are some illicit substances that are especially popular among young people. Methylenedioxymethamphetamine (MDMA), Ketamine, and Gamma Hydroxybutyrate (GHB) are unique compounds, differing in terms of their pharmacological properties and their phenomenological effects. They are particularly popular among young people who are part of the "rave" culture, but are used extensively by a wide variety of different people. Because of their use at various nightclubs, raves and other social events, they are widely known as "club drugs."
In recent years, the popularity of "club drugs" has been inextricably linked with the rise of the rave phenomenon. Raves first became popular in England during the late 1980s and have since spread to the United States and the rest of the world. In the early 1990s, raves were considered "the next big thing," a rising trend. Although their popularity has not grown dramatically, it has remained relatively constant. These events remain part of the popular youth culture, and are encountered in numerous venues. A mainstream example of this is "Groove," a movie about the rave culture, which opened commercially last week and was chosen as an official selection of the Sundance Film Festival.
At raves, groups of young people (typically in their teens) dance to rapid electronically synthesized music with no lyrics (techno). These events take place in unregulated and unlicensed locations such as stadiums, abandoned warehouses, and other surreptitious arenas. Since the early nineties, the venues have become increasingly mainstream. These drugs, along with marijuana and LSD, are extremely popular at these events. At some of these events, as many as 70% of rave participants are using Ecstasy, Ketamine, or GHB, along with other drugs such as marijuana and LSD.
Another event where these drugs are commonly used are at "circuit parties." Circuit parties are large-scale social events, which have become increasingly popular over the last decade. At these events, several thousand people, mostly (but not exclusively) young gay men, congregate in a dance club setting. Recently, they have become much larger, and spawned a worldwide industry, including a magazine called Circuit Noize, which is dedicated to issues related to circuit parties.
MDMA
MDMA has unique subjective and biochemical properties. Recreational use of MDMA h as been illegal since it was made a Schedule I drug on July 1, 1985. Prior to that time, because it was not mentioned in the controlled substances act of 1970, its use was unregulated and therefore legal. In spite of its present illegal status, the popularity of MDMA has skyrocketed in the past several years. In the past several months it has become readily apparent that the trafficking of the drug, and its use, is far more widespread than once believed. This rise in usage has been particularly marked among adolescents, where MDMA usage is prevalent at raves, and other nightlife settings.
Research in mammals and non-human primates has shown that MDMA damages brain serotonin axons. These species share many characteristics with their human counterparts. The weight of scientific evidence indicates that Ecstasy does the same in humans. Research with MDMA in humans is logistically and scientifically difficult to accomplish, thus the evidence that MDMA is neurotoxic in humans comes indirectly from these studies. A number of recent research articles have demonstrated that individuals who use ecstasy, compared to matched controls who have not used MDMA, have decreased amounts of serotonin metabolites in their spinal fluid, and decreased serotonin activity as measured by brain imaging and cognitive deficits. The direct implication is that using MDMA does indeed damage neurons. This is particularly germane for individuals who may be prone to mental illness, because it is known that lower serotonin metabolite levels correspond with depression, impulsiveness, and suicide.
MDMA's appeal rests primarily on its psychological effect. It causes a dramatic and consistent feeling of attachment and connection. This feeling of connection is not necessarily to another individual, but rather, people who use the drug alone may feel "connected to" the larger world. Ecstasy is perhaps a misnomer; the LA dealer who coined the term wanted to call the drug "Empathy", but asked, "Who would know what that means?"
History
MDMA is not a new drug. Merck in Darmstadt, Germany first patented it in 1914. MDMA was probably first created as so many compounds were at that time, to serve for subsequent research. Except for a minor chemical modification in a patent in 1919, there is no other known historical record of MDMA until the 1950's. At that time, the United States Army experimented with MDMA, as well as with numerous other compounds. The resulting informational material was declassified and became available to the general public in the early 1970s. MDMA was apparently not used on humans at that time.
MDMA was probably first used by humans in the late 1960s. It was lionized as a recreational drug by free thinkers and "New Age Seekers," people who liked its property to induce feelings of well-being and connection. Given this capacity, a number of practitioners and researchers interested in insight-oriented psychotherapy believed it would be an ideal agent to enhance therapy. It was used extensively for this purpose, until it became illegal in 1985.
In the early 1980's, MDMA had an explosion in popularity. The drug's capacity to induce feelings of connection, as well as a psychomotor agitation, that can be pleasurably relieved by dancing, made it the ideal "party drug." In spite of widespread usage during the early 1980s, the drug did not attract much attention from law enforcement officials. This is not particularly surprising in that individuals on the drug tend to be complacent and docile.
Events in Texas, especially in the Dallas/Fort Worth area, changed this lack of notoriety. Until 1985, the drug was not scheduled or regulated and its use was legal. A distribution network in Texas began an aggressive marketing campaign and, for a time, the drug was available over the counter at bars, at convenience stores, and even through a toll-free number. This attracted the attention of then Texas Senator Lloyd Bentsen (the future vice presidential candidate, and Secretary of the Treasury). He petitioned the FDA, and the compound was placed on Schedule I on an emergency basis as of July 1, 1985. Originally, three hearings were scheduled to determine MDMA's permanent scheduling status. At that time, the compound's neurotoxicity was already an issue; as a result, MDMA was placed on Schedule I on a permanent basis. Schedule I refers to substances that have no therapeutic value, and which are considered to have high abuse potential. Clinical use is therefore prohibited, and because of the intense regulation of Schedule I compounds, research with MDMA is technically possible, but very difficult to execute.
Physiological Effects
The chemical synthesis of MDMA is relatively simple, and it is often made in illicit laboratories. In addition, it is often "cut" with other substances so the purity and dosage varies substantially. It currently sells in urban areas for about $25 to $30 per 125 mg tablet, which produces the sought after effect in most intermittent users.
Tablets of MDMA are usually taken by mouth. Other methods of administration are much less popular, and virtually unheard of. The usual single dosage is between 100-150 mg. The effect of MDMA occurs in several stages. The initial stage begins with the onset of effect 20-40 minutes after ingestion and is experienced as a sudden, amphetamine-like "rush." Other effects, that simultaneously accompany the "rush," can be nausea, usually mild, but sometimes severe enough to cause vomiting, as well as the intense desire to defecate, known as a "disco dump."
The second, or "plateau stage," of drug effect lasts between three and six hours. Most users experience this feeling as a powerful connection to those around them; this may include the larger world. According to most users, this profound feeling of relatedness to the rest of the world is the reason to take the drug. In general, people on the drug appear to be less aggressive, and less impulsive than their non-drug using counterparts. Users also experience an altered perception of time and a decreased inclination to perform mental and physical tasks. Although the desire for sex can increase, the ability to achieve arousal and orgasm for both sexes is greatly diminished. It has thus been termed a sensual, not a sexual, drug. People on the drug also have mild feelings of restlessness, teeth grinding, jaw clenching, loss of appetite, sweating, hot flashes, tremor and "goose bumps." This array of physical effects and behaviors produced by MDMA is remarkably similar across mammalian species.
The common after-effects can be pronounced, and may last 24 hours, or even longer. The most dramatic "hangover" effect is a sometimes-severe feeling of depression and listlessness. Users of MDMA can experience lethargy, anorexia, decreased motivation, sleepiness, depressed mood and fatigue. There are sometimes more severe after-effects. These include changes in thinking, convulsions, deregulated temperature control, changes in blood pressure, a racing heart rate, kidney failure, and even death.
There are numerous case reports of a single dose of MDMA precipitating severe psychiatric illness. MDMA does induce a range of depressive symptoms and anxiety in some individuals, and for that reason, people with depression and anxiety should be specifically cautioned about the dangers of using MDMA. Many of these reports represent single cases and there are often other potential explanations for these occurrences. Still, the growing number of such adverse events is cause for concern.
Mechanism of Action
MDMA is a "dirty drug," because it affects a number of neurotransmitter systems, in particular, serotonin and dopamine-containing neurons. MDMA's primary mechanism of action is as an indirect serotonergic agonist. After being ingested, MDMA is taken up by the serotonin cell through an active channel where it causes the release of stored serotonin. The drug also blocks re-uptake of this neurotransmitter, contributing to its length of action. (It also inhibits further synthesis, but this effect probably does not contribute to the intoxicating effects. It may however, contribute to sustained feelings of depression reported by some users, and the diminished magnitude of subjective effects if the next dose is taken within a few days of the first.) The drug's effects and side effects including anorexia, psychomotor agitation, difficulty in achieving orgasm, and profound feelings of empathy, can all be explained as results of the flooding of the serotonin system.
Unlike other substances of abuse, where to escalating dosage and frequency are common, people who use MDMA on a regular basis tend not increase dosage as time goes on. Because the drug depletes serotonin stores and inhibits synthesis of new serotonin, subsequent doses produce a diminished "high,"and a worsening of the drug's undesirable effects. Many users, who are at first enamored with the drug, eventually lose interest, usually citing the substantial side effects. It is rare, although certainly possible, to find someone who uses the drug very often (more than once per week) over the course of years. There is an adage on college campuses about Ecstasy that captures this phenomenon: "freshmen love it, sophomores like it, juniors are ambivalent, and seniors are afraid of it." Those who do continue to use the drug over longer periods of time usually tend to use the drug only periodically. It is therefore reserved for "special occasions." Many young people report "saving" their ecstasy use for special occasions, especially for important raves, or parties.
In the early and mid 1990s, there was a rash of deaths associated with the use of MDMA. These deaths mostly occurred at raves and appear to be similar to certain features of both the "Serotonin Syndrome" and the Neuroleptic Malignant Syndrome. The Serotonin Syndrome is a clinical phenomenon that occurs with an excess of the neurotransmitter serotonin and is characterized by confusion, restlessness, increased temperature, sweating, increased reflexes, diarrhea, and muscle twitches. The Neuroleptic Malignant Syndrome (NMS) is more often associated with the use of anti-psychotic medicine (dopamine blockers) and dehydration, and its symptoms consist of confusion, increased temperature, elevated levels of muscle enzymes, and autonomic dysfunction. Both syndromes exist on a spectrum of severity, but in their most severe form they are life threatening, and may lead to death.
Raves are often held in hot, crowded conditions. Some clubs turned off their water supplies in an effort to maximize profits by selling bottled water. The hot, crowded conditions, physical exertion, and subsequent dehydration, combined with the drug effects, contributed to the deaths. After these incidents, the English government mandated an open water supply at all clubs; deaths of this kind appear to have since diminished, though they do still occur. In recent years, one of the principal aims of harm reduction efforts, in Europe and the United States, aimed at young people who take the drug, is to remind them that if they are going to take the drug, they must keep well hydrated.
Although rare, there have been anecdotal reports of MDMA causing Post Hallucinogenic Perception Disorder. This disorder is a prolonged re-experience of the perceptual distortion produced during the MDMA "high." Post Hallucinogenic Perceptual Disorder is more commonly associated with LSD ingestion, and can last for months, even years. Although symptoms tend to diminish over time, there are no effective treatments for this disorder.
MDMA and Neurotoxicity
In laboratory animals, the ingestion of MDMA causes a decrease in the serum and spinal fluid levels of serotonin metabolites in a dose-dependent fashion and damages brain serotonin neurons. In non-human primates, the neurotoxic dose approximates the recreational dose taken by humans. Like its close structural relative MDA, MDMA has been found to damage serotonin neurons in all animal species tested to date.
Unequivocal data demonstrating that similar changes occur in the human brain do not yet exist, but the indirect clinical evidence is disconcerting. MDMA users have significantly less serotonin metabolites in their spinal fluid than matched controls. Clear deficits and major neurotoxicity appear to be related to total cumulative dose in animals. In addition, MDMA produces a 30-35% drop in serotonin metabolism in humans. It is possible that even one dose of MDMA may cause lasting damage to the serotonin system. Furthermore, such damage might only become apparent with time, or under conditions of stress. Users with no initial complications may manifest problems over time.
There have been reports of individuals with lasting neuro-psychiatric disturbances after MDMA use and it warrants particular caution, because the axonal destruction, though apparent on sophisticated cognitive testing, may not be readily apparent for many years after use. However, there is a growing number of recent studies demonstrating that individuals who currently use ecstasy do have cognitive changes compared to those who have never taken the drug. The use of ecstasy may affect the reserves of the serotonin system by severely diminishing them. As individuals age, they may not have the same level of stores of functional serotonin cells once available. This results in low serotonin levels, which are associated with such serious consequences as depression, violence, and suicide.
The clinical impact of serotonergic damage is not clear, since some animal data suggest that even significant destruction of serotonin neurons leads to little functional impairment. Recent studies in humans, using matched controls of people who have not ever taken MDMA, have demonstrated that the use of the drug does have an impact on memory, and a number of other cognitive functions. The drug's probable neurotoxicity is the most significant concern about its use.
Ketamine, GHB, rohypnol, and others.
Club drugs also consist of a number of other substances of abuse. Among these are Ketamine ("special K"), rohypnol ("roofies") and GHB - gamma-hydroxybutyrate ("liquid Ecstasy"); in Britain, as GBH ("grievous bodily harm"). Ketamine is a disassociative anesthetic, and causes people to appear disconnected from the world. GHB is prized for its ability to relax and cause stimulation at the same time. It is exceedingly easy to overdose from GHB; the intoxicating dose and the lethal dose are quite similar. Rohypnol is a short acting benzodiazepine that is better known as "the date rape drug," as it causes short-term memory loss in people who use it, and can be surreptitiously dropped into an unsuspecting victim's drink.
Conclusion
The substances discussed above are used at raves, and at clubs, often in combination, and often by very young people. This is serious cause for concern for several reasons. Among these reasons are that the younger a person begins using drugs, and the more often, the more likely he or she will progress to having a serious drug problem. It is understandable why so many adolescents may find raves, and the club drugs used there, so appealing. Ecstasy, in particular, is alluring and seductive. But as stated above, there is a darker side to this story. It is likely that permanent damage to the serotonin system is occurring in individuals who use Ecstasy and other club drugs. The extent and consequences of this damage may not become apparent for decades.
Source: http://www.house.gov/judiciary/mcdo0615.htm
