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NATIONAL INSTITUTE ON ABUSE Research Report SERIES The so-called “” MDMA continues to be used by millions of Americans across the country, despite evidence of its potential harmful effects. 3,4-methylenedioxymethamphetamine (MDMA, or ) has gained a deceptive reputation as a “safe” drug ( CSTASY) among its users. This illegal drug, which MDMA E has both stimulant and psychedelic properties, is often taken for the Abuse of well-being, , and the distortions in and sensory percep- tions that it produces. MDMA first What is MDMA? became popular in the “” and DMA is an illegal drug It is not uncommon for users to all-night party scene, but its use has now spread to a wide range of settings that acts as both a stim- take a second dose of the drug and demographic subgroups. According ulant and psychedelic, as the effects of the first dose to the 2004 National Survey on Drug M Use and Health, more than 11 million producing an energizing effect, begin to fade. people have tried MDMA at least once. as well as distortions in time and MDMA can the brain by Myths abound about both the acute altering the activity of chemical effects and long-term consequences of and enhanced enjoy- this drug, often called ecstasy or “X.” ment from tactile experiences. messengers, or , Indeed, one reason for the rapid rise in r Typically, MDMA (an acronym which enable nerve cells in the the drug’s popularity is that many young people believe that MDMA is a for its chemical name 3,4-methyl- brain to communicate with one

o new safe drug. But MDMA is not new enedioxymethamphetamine) is another. Research in animals has to the scientific community, as many t laboratories began investigating this taken orally, usually in a tablet shown that MDMA in moderate drug in the 1980s, and the picture or capsule, and its effects last to high doses can be toxic to c emerging from their efforts is of a drug that is far from benign. For example, approximately 3 to 6 hours. The nerve cells that contain MDMA can cause a dangerous increase average reported dose is one and can cause long-lasting e in body temperature that can to two tablets, with each tablet damage to them. Furthermore,

r to kidney failure. MDMA can also increase , pressure, typically containing between MDMA raises body temperature. i and heart wall stress. Animal studies 60 and 120 milligrams of MDMA. show that MDMA can damage specific On rare but largely unpredictable

d neurons in the brain. In humans, the occasions, this has research is not conclusive at this time;

led to severe medical however, a number of studies show that long-term, heavy MDMA users suffer consequences,

e cognitive deficits, including problems including death. with memory. NIDA-supported research is develop- Also, MDMA causes h ing a clearer picture of the potential the release of another dangers of MDMA, and this Research t Report summarizes the latest findings. , We that this compilation of , which scientific will inform readers and help the public recognize is likely the cause of the the risks of MDMA use. increase in heart rate m and Nora D.Volkow,M.D.

o Director that often accompanies National Institute on Drug Abuse MDMA use. r f

U.S. Department of Health and Human Services • National Institutes of Health 2NIDA RESEARCH REPORT SERIES

Although MDMA is known universally among users as Serotonin Present in Cerebral Cortex Neurons ecstasy, researchers have deter- mined that many ecstasy tablets

contain not only MDMA but also CONTROL 2 WEEKS AFTER ECSTASY 7 YEARS AFTER ECSTASY a number of other or drug combinations that can be harm- ful as well. Adulterants found in MDMA tablets purchased on the street include , , the over-the-counter cough suppressant dextromethor- phan, the diet drug , and . Also, as with many other drugs of abuse, MDMA is rarely used alone. It is not uncommon for users to mix Long-term effects in monkeys. The left panel is brain tissue from a normal monkey. The middle MDMA with other substances, and right panels illustrate the loss of serotonin-containing nerve endings following MDMA exposure. such as and marijuana.

A brief history psychotherapy under carefully What is the of MDMA monitored conditions to treat post-traumatic stress disorder. scope of MDMA DMA was developed Nevertheless, the drug gained a abuse in the U.S.? in Germany in the small following among psychia- t is difficult to determine the early 1900s as a parent M trists in the late 1970s and early exact scope of this problem compound to be used to 1980s, with some even calling it because MDMA is often used synthesize other pharmaceuticals. I “penicillin for the soul” because in combination with other During the 1970s, in the United it was perceived to enhance substances, and does not appear States, some psychiatrists began communication in patient in some traditional data sources, using MDMA as a psychothera- sessions and reportedly allowed such as treatment admission rates. More than 11 million persons peutic tool, despite the fact that users to achieve insights about aged 12 or older reported using the drug had never undergone their problems. It was also ecstasy at least once in their formal clinical trials nor received during this time that MDMA first approval from the U.S. and lifetimes, according to the 2004 started becoming available on National Survey on Drug Use Drug Administration (FDA) for the street. In 1985, the U.S. Drug and Health. The number of use in humans. In fact, it was Enforcement Administration (DEA) current (use in past month) only in late 2000 that the FDA banned the drug, placing it on users in 2004 was estimated to approved the first small clinical its list of Schedule I drugs, corre- be 450,000. trial for MDMA that will deter- sponding to those substances The Drug Abuse Warning mine if the drug can be used with no proven therapeutic value. Network, maintained by the safely with 2 sessions of ongoing and Mental NIDA RESEARCH REPORT SERIES 3

Health Services Administration, MDMA use decreased significantly long parties known as reported that mentions of MDMA from 2004 to 2005 among 12th- . However, the profile of in drug abuse-related cases in graders. the typical MDMA user has hospital emergency departments In 2005, 8th-graders reported a been changing. Community-level were 2,221 for the third and significant decrease in perceived data from NIDA’s Community fourth quarters of 2003. The harmfulness in using MDMA Epidemiology Work Group majority of patients who came occasionally. The MTF data also (CEWG), continued to report to emergency departments show that MDMA use extends that use of MDMA has spread mentioning MDMA as a factor across many demographic sub- among populations outside the in their admissions during that groups. Among 12th-graders in scene. time were aged 18–20. 2005, for example, 3.9 percent of Reports also indicate that use is spreading beyond predomi- There is, however, some Whites, 3.0 percent of Hispanic students, and 1.4 percent of nantly White youth to a broader encouraging news from NIDA’s African-Americans reported range of ethnic groups. In Monitoring the Future (MTF) using MDMA in the year prior Chicago, the drug continues to survey, an annual survey used to to the survey. be predominantly used by White track drug abuse trends among youth, but there are increasing adolescents in middle and high Who is reports of its use by African- schools across the country. American adults in their twenties Between 2001 and 2005, annual abusing MDMA? and thirties. Also, indicators in ecstasy use decreased by 52 per- DMA first gained popu- New York suggest that both cent in 8th-graders, 58 percent larity among adolescents the distribution and use of club in 10th-graders, and 67 percent Mand young adults in the drugs are becoming more com- in 12th-graders. Rates of lifetime nightclub scene or weekend- mon in non-White communities.

Monitoring the Future Survey* Trends in Trends in MDMA Prevalence, 2003–2005 Perceived Harmfulness of MDMA Use

10 10 8th-Graders 10th-Graders 10th-Graders 8 8 100 Percentage saying 8th-Graders 12th-Graders 6 6 “great risk” to trying 80 MDMA occasionally 4 4 60 2 2 40 0 0 2003 2004 2005 2003 2004 2005 Percentage saying “great risk” to trying Annual 30-Day 20 MDMA once or twice

*These data are from the 2005 Monitoring the Future survey, funded by the National Institute 0 on Drug Abuse, National Institutes of Health, DHHS, and conducted annually by the University 2003 2004 2005 of Michigan’s Institute for Social Research. “Annual” refers to use at least once during the year preceding an individual‘s response to the survey. “30-day” refers to use at least once during the Perceived risk associated with MDMA use in 30 days preceding an individual‘s response to the survey. selected categories. 4NIDA RESEARCH REPORT SERIES

Other NIDA research shows As noted, MDMA is not a body temperature (). that MDMA has also become a benign drug. MDMA can produce Treatment of hyperthermia popular drug among urban gay a variety of adverse health requires prompt medical attention, males. Reports have shown that effects, including nausea, chills, as it can rapidly lead to muscle some gay and bisexual men take sweating, involuntary teeth breakdown, which can in turn MDMA and other club drugs in clenching, muscle cramping, and result in kidney failure. In addi- myriad venues. This is concerning blurred vision. MDMA overdose tion, dehydration, , given that the use of club drugs can also occur—the symptoms and may occur in has been linked to high-risk sex- can include high blood pressure, susceptible individuals. MDMA ual behaviors that may lead to faintness, attacks, and can also reduce the pumping HIV or other sexually transmitted in severe cases, a loss of efficiency of the heart, of parti- diseases. Many gay males in big and . cular concern during periods of cities report using MDMA as part Because of its stimulant increased physical activity, further of a multiple-drug experience properties and the environments complicating these problems. that includes marijuana, cocaine, in which it is often taken, MDMA MDMA is rapidly absorbed methamphetamine, , is associated with vigorous physi- into the human bloodstream, but and other legal and illegal cal activity for extended periods. once in the body, MDMA meta- substances. This can lead to one of the most bolites interfere with the body’s significant, although rare, acute ability to metabolize, or break What are the adverse effects—a marked rise in down, the drug. As a result, effects of MDMA? DMA has become a Effects of MDMA popular drug, in part because of the positive M Reported Undesirable Effects Potential Adverse Health Effects: effects that a person may experience within an hour or (up to 1 week post-MDMA, or longer): ■ Nausea ■ Chills so after taking a single dose. ■ ■ Sweating Those effects include feelings of ■ Restlessness ■ Involuntary jaw clenching mental stimulation, emotional ■ and teeth grinding ■ warmth, toward others, ■ Muscle cramping a general of well being, ■ Impulsiveness ■ Blurred vision and decreased anxiety. In ■ Aggression ■ Marked rise in body addition, users report enhanced ■ disturbances temperature (hyperthermia) sensory perception as a hallmark ■ Lack of appetite ■ Dehydration of the MDMA experience. ■ Thirst ■ High blood pressure ■ Because of the drug’s stimulant ■ Reduced in and Heart failure ■ properties, when used in club from sex Kidney failure ■ or dance settings, MDMA can ■ Significant reductions in also enable users to dance for mental abilities Symptoms of MDMA Overdose: extended periods. However, ■ High blood pressure there are some users who report ■ Faintness undesirable effects immediately, ■ Panic attacks including anxiety, agitation, and ■ Loss of consciousness ■ recklessness. Seizures NIDA RESEARCH REPORT SERIES 5 additional doses of MDMA can produce unexpectedly high blood The Neurobiology of Ecstasy (MDMA) levels, which could worsen the cardiovascular and other toxic effects of this drug. MDMA also interferes with the of other drugs, including some of the adulterants that may be found in MDMA tablets. In the hours after taking the drug, MDMA produces significant reductions in mental abilities. These changes, particularly those affecting memory, can last for up to a week, and possibly longer in regular users. The fact that MDMA markedly impairs MDMA alters brain chemistry by binding to serotonin transporters. information processing empha- sizes the potential dangers of performing complex or skilled What does MDMA effects experienced by MDMA activities, such as driving a car, users. However, by releasing while under the influence of do to the brain? large amounts of serotonin, this drug. DMA affects the brain MDMA causes the brain to Over the course of a week by increasing the become significantly depleted of following moderate use of the activity of at least three this important neurotransmitter, M contributing to the negative drug, many MDMA users report neurotransmitters (the chemical a range of , messengers of brain cells): behavioral aftereffects that users including anxiety, restlessness, serotonin, , and often experience for several days irritability, and sadness that in norepinephrine. Like other after taking MDMA. some individuals can be as , MDMA causes Numerous studies in animals severe as true clinical . these neurotransmitters to be have demonstrated that MDMA Similarly, elevated anxiety, released from their storage can damage serotonin-containing impulsiveness, and aggression, sites in neurons, resulting in in- neurons; some of these studies as well as sleep disturbances, creased neurotransmitter activity. have shown these effects to be lack of appetite, and reduced Compared to the very potent long lasting. This suggests that interest in and pleasure from sex stimulant, methamphetamine, such damage may occur in have been observed in regular MDMA causes greater serotonin humans as well; however, MDMA users. Some of these release and somewhat lesser measuring serotonin damage in disturbances may not be directly dopamine release. Serotonin is a humans is more difficult. Studies attributable to MDMA, but may neurotransmitter that plays an have shown that some heavy be related to some of the other important role in the regulation MDMA users experience long- drugs often used in combination of mood, sleep, , appetite, lasting , depression, and with MDMA, such as cocaine or and other behaviors. The excess selective impairment of working marijuana, or to adulterants com- release of serotonin by MDMA memory and attention processes. monly found in MDMA tablets. likely causes the mood elevating Such memory impairments have 6NIDA RESEARCH REPORT SERIES

been associated with a decrease because of the misperception that 43 percent of those who reported in serotonin metabolites or other it is a safe drug. The potential ecstasy use met the accepted markers of serotonin function. adverse effects of MDMA on the diagnostic criteria for depend- Imaging studies in MDMA users developing fetus are of great ence, as evidenced by continued have shown changes in brain concern. Behavioral studies in use despite knowledge of activity in regions involved in animals have found significant physical or psychological harm, cognition, , and motor adverse effects on tests of learn- withdrawal effects, and tolerance function. However, improved ing and memory from exposure (or diminished response), and imaging technologies and more to MDMA during a developmen- 34 percent met the criteria for research are needed to confirm tal period equivalent to the third drug abuse. Almost 60 percent these findings and to elucidate trimester in humans. However, of people who use MDMA the exact nature of the effects of the effects of MDMA on animals report withdrawal symptoms, MDMA on the . earlier in development are including fatigue, loss of It is also important to keep unclear; therefore, more research appetite, depressed feelings, in mind that many users of is needed to determine what and trouble concentrating. ecstasy may unknowingly be the effects of MDMA are on MDMA affects many of the taking other drugs that are sold the developing human nervous same neurotransmitter systems as ecstasy, and/or they may system. in the brain that are targeted intentionally use other drugs, by other addictive drugs. such as marijuana, which could Is MDMA addictive? Experiments have shown that contribute to these behavioral or some people, MDMA animals prefer MDMA, much effects. Additionally, most studies can be addictive. A survey like they do cocaine, over other in people do not have behavioral of young adult and adoles- pleasurable stimuli, another measures from before the users F cent MDMA users found that hallmark of most addictive drugs. began taking drugs, making it difficult to rule out pre-existing conditions. Factors such as gender, dosage, frequency and Life-Threatening Effects intensity of use, age at which use began, the use of other drugs, as well as genetic and environmental factors all may play a role in some of the cog- nitive deficits that result from MDMA use and should be taken into consideration when studying the effects of MDMA in humans. Given that most MDMA users are young and in their reproduc- tive years, it is possible that some female users may be pregnant when they take MDMA, either inadvertently or intentionally NIDA RESEARCH REPORT SERIES 7

expectancies, and behaviors, and to increase skills in coping with life’s stressors. Drug abuse recovery support groups may be effective in combination with behavioral interventions to support long-term, drug-free recovery. There are currently no pharmacological treatments for dependence on MDMA. Where can I get more scientific information on MDMA? o learn more about MDMA and other drugs of abuse, Tcontact the National Clearinghouse for Alcohol and Drug Information (NCADI) at 800–729–6686. Information specialists are available to help What do we know Are there effective you locate information and about preventing treatments for resources. Fact sheets, including MDMA abuse? MDMA abuse? InfoFacts, on the health effects ecause social context and here are no specific treat- of MDMA, other drugs of abuse, networks seem to be an ments for MDMA abuse. and other drug abuse topics are important component of T The most effective treatments available on the NIDA Web site B (www.drugabuse.gov), and can MDMA use, the use of peer-led for drug abuse and advocacy and drug prevention are cognitive behavioral interven- be ordered free of charge in programs may be a promising tions that are designed to help English and Spanish from NCADI approach to reduce MDMA use modify the patient’s thinking, at www.health.org. among adolescents and young adults. High schools and colleges Access information NIDA Web Sites can serve as important venues on the Internet drugabuse.gov for delivering messages about • What’s new on the NIDA Web site marijuana-info.org the effects of MDMA use. • Information on drugs of abuse steroidabuse.org Providing accurate scientific • Publications and communications clubdrugs.org information regarding the effects (including NIDA NOTES) .drugabuse.gov • Calendar of events of MDMA is important if we hiv.drugabuse.gov hope to reduce the damaging • Links to NIDA organizational units • Funding information (including program .drugabuse.gov effects of this drug. Education announcements and deadlines) is one of the most important • International activities NCADI tools for use in preventing • Links to related Web sites (access to Web Web site: health.org MDMA abuse. sites of many other organizations in the field) Phone no.: 800–729–6686 8NIDA RESEARCH REPORT SERIES

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