MDMA or Ecstasy (Methylenedioxymethamphetamine)
(Effects) "MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine analog with stimulant and hallucinogenic effects.
"MDMA acts primarily on neurons that produce and release serotonin, but it also affects dopaminergic neurons. MDMA is usually taken as a pill; effects begin 30 to 60 min after ingestion and typically last 4 to 6 h. MDMA is often used at dance clubs, concerts, and rave parties.
"Symptoms and Signs
"MDMA causes a state of excitement and disinhibition and accentuates physical sensation, empathy, and feelings of interpersonal closeness. Toxic effects are similar to those of the other amphetamines but are less common, perhaps because use is more likely to be intermittent. However, even with casual use, significant problems such as hyperthermia and centrally mediated hyponatremia may occur. The effects of intermittent, occasional use are uncertain. Rarely, fulminant hepatic failure occurs.
"Chronic, repeated use may cause problems similar to those of amphetamines, including dependence. Some users develop paranoid psychosis. Cognitive decline may also occur with repeated, frequent use."Source:"Amphetamines," The Merck Manual for Health Care Professionals, Special Subjects: Drug Use and Dependence: Amphetamines, Merck & Co. Inc. (July 2008).
(History) "MDMA is not a new drug. It was first synthesized by the German pharmaceutical firm Merck in 1912. Human experimentation, however, has been traced back to the early 1970s (Eisner, 1989; Shulgin, 1990)."Source:Beck, Jerome and Rosenbaum, Marsha, "Pursuit of Ecstasy: The MDMA Experience." Albany: State University of New York Press, 1994. p. 14.
(Effects) "Ecstasy's effects last 3 to 6 hours. It is a mood elevator that produces feelings of empathy, openness and well-being. People who take it at all night "rave" dances say they enjoy dancing and feeling close to others. It does not produce violence or physical addiction."Source:Beck, J. and Rosenbaum, M. "Pursuit of Ecstasy: The MDMA Experience." Albany: State University of New York Press, 1994.
(Prevalence of Use)
" The number of past year initiates of Ecstasy was 922,000 in 2011, which was similar to the number in 2010 (949,000), but lower than the number in 2009 (1.1 million) (Figure 5.5). The estimate was 1.2 million in 2002, declined to 642,000 in 2003, and increased by about 50 percent between 2005 (615,000) and 2011 (922,000). Most (61.3 percent) of the recent Ecstasy initiates in 2011 were aged 18 or older at the time they first used Ecstasy. Among past year initiates aged 12 to 49, the average age at initiation of Ecstasy in 2011 was 19.6 years, which was similar to the average age in 2010 (19.4 years), but lower than the average age in 2002 (21.2 years).
" In 2011, among persons aged 12 or older, the number of first-time past year Ecstasy users who initiated use prior to the age of 18 was 357,000. This estimate was higher than the estimate in 2005 (209,000)."Source:Substance Abuse and Mental Health Services Administration, Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-44, HHS Publication No. (SMA) 12-4713. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2012, p. 57.
MDMA raises blood pressure and heart rate. Persons with known cardiovascular or heart disease should not take MDMA.
(Cognitive Performance) Studies have indicated that individuals who have used MDMA may have decreased performance in memory tests compared to nonusers. These studies are presently controversial because they involved people who used a variety of other drugs. Furthermore, it is difficult to rule out possible pre-existing differences between research subjects and controls.Source:E. Gouzoulis-Mayfrank; J. Daumann; F. Tuchtenhagen; S. Pelz; S. Becker; H.J. Kunert; B. Fimm; H. Sass; Impaired cognitive performance in drug free users of recreational ecstasy (MDMA), Journal Neurol Neurosurg Psychiatry Vol 68, June 2000, 719-725; K.I. Bolla; U.D.; McCann; G.A. Ricaurte; Memory impairment in abstinent MDMA ('Ecstasy') users, Neurology Vol 51, Dec 1998, 1532-1537.
(Mortality) The Drug Abuse Warning Network estimates that ecstasy was involved in -- though not necessarily the cause of -- nine deaths in 1998. According to DAWN's 2002 mortality report: "The DAWN metropolitan area profiles include information on 'club drugs' as a group, combining all mentions of methylenedioxymethamphetamine (MDMA or Ecstasy), Ketamine, gamma hydroxy butyrate (GHB) and its precursor gamma butyrolactone (GBL), and flunitrazepam (Rohypnol). As in prior years, these substances accounted for very few deaths in any of the DAWN metropolitan areas. Seven metropolitan areas reported no deaths involving these drugs, and only 7 metropolitan areas reported more than 5 mentions of club drugs. The areas with the highest numbers in 2002 were New York (19 mentions), Miami (9), Chicago (7), New Orleans (7), Philadelphia (9), Boston (6), and San Diego (6). Club drugs were rarely reported alone."Source:Substance Abuse and Mental Health Services Administration, Office of Applied Studies, "Mortality Data From the Drug Abuse Warning Network, 2002," DAWN Series D25, DHHS Publication No. (SMA) 043875 (Rockville, MD), 2004, pp. 9-10.
(Mortality) "Deaths associated with club drugs other than methamphetamine are quite rare in DAWN data.
"• Cumulatively, 2,601 deaths associated with methamphetamine abuse, 46 deaths associated with Ketamine, and 27 with MDMA were reported by participating medical examiners over the 5-year period from 1994 to 1998.
"• There were no notable increases in deaths involving club drugs from 1994 to 1998."Source:Substance Abuse and Mental Health Services Administration, Office of Applied Studies, "The DAWN Report: Club Drugs," (Rockville, MD: December 2000), p. 1.
Some of these deaths are related to overheating. MDMA slightly raises body temperature. This is potentially lethal in hot environments where there is vigorous dancing and the lack of adequate fluid replacement. Many of these tragic deaths are preventable with simple harm reduction techniques such as having free water available and rooms where people can rest and relax.Source:C.M. Milroy; J.C. Clark; A.R.W. Forrest, Pathology of deaths associated with "ecstasy" and "eve" misuse, Journal of Clinical Pathology Vol 49 (1996) 149-153.
One of the risks associated with Ecstasy is the possibility of obtaining adulterated drugs that may be more toxic than MDMA. Some of the reported deaths attributed to Ecstasy may likely caused by other, more dangerous drugs.Source:Laboratory Pill Analysis Program, DanceSafe. For results visit www.DanceSafe.org. See also: Byard RW et al., Amphetamine derivative fatalities in South Australia -- is "Ecstasy" the culprit?, American Journal of Forensic Medical Pathology, 1998 (Sep) 19(3): 261-5. Also see: C.M. Milroy; J.C. Clark; A.R.W. Forrest, Pathology of deaths associated with "ecstasy" and "eve" misuse, Journal of Clinical Pathology Vol 49 (1996) 149-153.
Deaths from adulterated drugs are another consequence of a zero tolerance approach. The drug should be tested for purity to minimize the risk from adulterated drugs by those who consume it.
(Harm Reduction) "In the context of new synthetic drugs there are some well-established approaches to reduce harm such as handing out condoms for free or giving out drinking water to reduce or stabilise body temperature and to avoid heatstroke. In addition, there are possible harms in the party scene that can be countered by pill-testing projects only. All pill-testing projects inform consumers about very dangerous and unexpected pills on site, through magazines and posters or through the Internet."Source:Kriener, Harald, Renate Billeth, Christoph Gollner, Sophie Lachout, Paul Neubauer, Rainer Schmid, "An Inventory of On-Site Pill-Testing Interventions in the EU" (Lisbon, Portugal: European Monitoring Centre for Drugs and Drug Addiction, 2001), p. 12.
(Harm Reduction and Dosage Information) "Apart from warnings issued against dangerous and unexpected pills, dosage makes a difference. In terms of neurotoxicity, several scientific studies pointed out that, among other factors, the probability for possible neurotoxic damage in the serotonergic system grows with the amount of MDMA being consumed. Therefore, most pill-testing projects inform potential consumers that they should not, if at all, consume more than 1,5–1,8 mg MDMA/kg bodyweight because of possible long-term damages to an important region of the brain. These messages, that are often followed by consumers of ecstasy, are only meaningful if consumers are in a position to have their pills chemically analysed. Otherwise they are unable to follow this or similar advice."Source:Kriener, Harald, Renate Billeth, Christoph Gollner, Sophie Lachout, Paul Neubauer, Rainer Schmid, "An Inventory of On-Site Pill-Testing Interventions in the EU" (Lisbon, Portugal: European Monitoring Centre for Drugs and Drug Addiction, 2001), p. 12.
(Global Manufacture) "The number of 'ecstasy' laboratories seized worldwide declined from 52 in 2009 to 44 laboratories in 2010. Countries reporting 'ecstasy' manufacture in 2010 (by number of laboratories seized) were Australia (17), Canada (13), Indonesia (12), Malaysia (1) and Argentina (1). Despite a decline in reported 'ecstasy' manufacture, it is worth noting that some countries, such as Australia and Indonesia, reported an increase in the manufacturing capability or size of laboratories. Also of note is the fact that some countries, such as Canada, New Zealand and Turkey, reported incidences of possible polydrug manufacture, in which 'ecstasy' was also being manufactured in illicit methamphetamine laboratories. In Europe, despite increased seizures of the drug, no 'ecstasy' laboratories were reported to UNODC as having been seized in 2010 (see figure 46). However, several 'ecstasy' laboratories were discovered in 2011."
(Retracted Claims About Negative Effects) Some assertions about the negative health affects of MDMA use are exaggerated, and researchers have been forced to retract their more extreme claims. Dr. George Ricuarte wrote the journal Science on Sept. 12, 2003:
"We write to retract our report 'Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ('ecstasy')' (1), following our recent discovery that the drug used to treat all but one animal in that report came from a bottle that contained methamphetamine instead of the intended drug, MDMA. Notably, methamphetamine would be expected to produce the same pattern of combined dopaminergic/serotonergic neurotoxicity (2) as that seen in the animals reported in our paper (1)."Source:Ricuarte, George A., Jie Yuan, George Hatzidimitriou, Branden J. Cord, Una D. McCann, "Retraction," Letter to Science Magazine, Sept. 12, 2003, Vol. 31, p. 1479.
On-Site Pill Testing
"Pill testing interventions are important measures to enter into contact with hard-to-reach populations and to raise their interest in preventive and harm reduction messages."Source:Kriener, Harald, Renate Billeth, Christoph Gollner, Sophie Lachout, Paul Neubauer, Rainer Schmid, "An Inventory of On-Site Pill-Testing Interventions in the EU" (Lisbon, Portugal: European Monitoring Centre for Drugs and Drug Addiction, 2001), p. 60.
(On-Site Pill Testing Evaluation)
" Despite the lack of empirical data - for health systems in general and information and prevention projects in particular - it is crucial to know about new substances and consumption trends, otherwise there is a high risk of loosing credibility with well-informed users of psychoactive substances. Pill-testing projects can be an important source of information on new substances and consumption trends as they are in closest possible contact with the relevant scenes, more so than other organisations within the prevention system. They have, furthermore, an insight into most substances that are actually being consumed, and know who and where, in which manner, and why these substances are being consumed.
" Pill-testing interventions have to be part of a global strategy for prevention and harm reduction in recreational settings.
" By using the information from on-site pill-testing interventions, a national warning system could deepen its data pool in terms of social contexts: who are the people consuming these substances, how, where and why are they consuming these substances in this and that particular way and which information can be passed on to potential consumers in a meaningful and successful manner?
" Due to the lack and difficulties of evaluation, on one hand there is still no strict scientific proof for the protective impact of on-site pill testing interventions, but on the other hand there is also no scientific evidence to conclude that such interventions would rather promote drug use or might be used by dealers for marketing purposes. Bringing together pieces of evidence is however often a first step for deciding on new intervention models."Source:Kriener, Harald, Renate Billeth, Christoph Gollner, Sophie Lachout, Paul Neubauer, Rainer Schmid, "An Inventory of On-Site Pill-Testing Interventions in the EU" (Lisbon, Portugal: European Monitoring Centre for Drugs and Drug Addiction, 2001), pp. 60-61.
(Psilocybin and Addiction) "The results of the present study have implications for understanding the abuse of hallucinogens. Although psilocybin is regulated by the federal government under the most restrictive category (Schedule I) of the Controlled Substances Act, the National Institute on Drug Abuse (2001, 2005) does not consider psilocybin and the other classical hallucinogens to be drugs of 'addiction' because they do not produce compulsive drug-seeking behavior as do classic addicting drugs such as cocaine, amphetamine, heroin, and alcohol. This conclusion is consistent with observations that psilocybin and other classic hallucinogens do not maintain reliable drug self-administration in animal laboratory models of drug abuse (Griffiths et al. 1980; Fantegrossi et al. 2004) and that most recreational users of classical hallucinogens decrease or stop their use over time (National Institute on Drug Abuse 2001). In the present study, psilocybin did not produce a classic euphorigenic profile of effects: measures of anxiety and dysphoria (monitor ratings of anxiety: AIA scale on the APZ Questionnaire, LSD scale on the ARCI) were significantly greater after psilocybin than after methylphenidate"Source:Griffiths, R. R.; Richards, W. A.; McCann, U.; Jesse, R., " Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance,"Psychopharmacology (Heidelberg, Germany: August 2006), Volume 187, Number 3, p. 281.
Clinical and Empirical Research
(Cognitive Impairment) "In summary, our data suggest that ecstasy use over a period of months or a few years may cause long term impairment of cognitive performance even when ecstasy is taken in typical recreational and not necessarily very high doses."Source:E. Gouzoulis-Mayfrank; J. Daumann; F. Tuchtenhagen; S. Pelz; S. Becker;H.J. Kunert; B. Fimm; H. Sass; "Impaired cognitive performance in drug free users of recreational ecstasy (MDMA)," Journal of Neurology, Neurosurgery, & Psychiatry, (June 2000) Vol. 68, p. 724.
(Sociability and Empathy) "We found that MDMA (1.5 mg/kg only) altered a behavioral indicator of social cognition. Specifically, it robustly reduced recognition of fearful faces, without changing recognition of other emotions from facial or vocal cues. Although previous studies have confirmed that the drug induces subjective feelings related to sociability and empathy, this is the first published demonstration of an overt behavioral effect of MDMA in humans."Source:Bedi, Gillinder; Hyman, David; and de Wit, Harriet, "Is Ecstasy an “Empathogen”? Effects of 3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others," Biological Psychiatry (Dallax, TX: Society of Biological Psychiatry, December 15, 2010) Vol. 68, Issue 12, p. 1137.
(Effect on Memory) "The main finding of the current longitudinal study is that continued use of MDMA is associated with different aspects of memory decline. For example, the ability to recall a short passage of prose being read aloud immediately and after a delay was found to decline significantly. This decline suggests impairment in retrospective memory, given that performance on the three RBMT prospective tests—1) remembering to ask the experimenter to telephone for a taxi; 2) remembering to deliver a message; and 3) remembering to ask for the return of a personal belonging—did not decline with continued MDMA use. Moreover, no changes in test scores were observed in terms of orientation for time and place and knowing the date.
"This investigation also indicates that vocabulary and the ability to recall first and second names may be adversely affected by the frequency of MDMA use, and that the ability to immediately recall a route may be related to the duration of MDMA use."Source:Konstantine K. Zakzanis and Donald A. Young, "Memory impairment in abstinent MDMA (“Ecstasy”) users: A longitudinal investigation," Neurology (56). April 2001, p. 967.
(Neurocognitive Effects from Long-Term MDMA Use) "Using this rigorous approach, we found few consistent differences between ecstasy users and non-users on wide-ranging measures of verbal and visuospatial memory, verbal fluency, attention, processing speed, manipulative dexterity and executive cortical functions. Ecstasy users exhibited lower vocabulary scores than non-users, but this finding probably indicates differences in pre-morbid ability rather than neurotoxicity of ecstasy, as vocabulary is generally preserved even after neurological insults [26,45,46]. Indeed, assuming that these differences in pre-morbid verbal ability are valid, the absence of significant differences on most other tests, including tests of verbal memory, becomes even more striking. Although we found a few other significant differences between the overall groups of users and non-users, these differences proved to be concentrated primarily in moderate users, rather than heavy users—suggesting that they were unlikely due to neurotoxicity of ecstasy. More likely, such differences represent chance associations—a phenomenon to be fully expected, given that we performed multiple comparisons without formal statistical correction."Source:Halpern, John H.; Sherwood, Andrea R.; Hudson, James I.; Gruber, Staci; Kozin, David; Pope Jr, Harrison G., "Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs," Addiction Research Report (London, United Kingdom: Society for the Study of Addiction, April 2011), Volume 166, Issue 4, p. 783.
Treatment of Post Traumatic Stress Disorder
(Treatment of Trauma in US) In 2004, the Drug Enforcement Administration gave permission for the first US trial of MDMA for use in treating trauma:
"Capping a 17-year effort by a small but committed group of activists, the federal Drug Enforcement Administration has agreed to let a South Carolina physician treat 12 trauma victims with the illegal street drug ecstasy in what will be the first U.S.-approved study of the recreational drug's therapeutic potential.
"The DEA's move marks a historic turn for a drug that has long been both venerated and vilified."
(Effectiveness) "This pilot study demonstrates that MDMA-assisted psychotherapy with close follow-up monitoring and support can be used with acceptable and short-lived side effects in a carefully screened group of subjects with chronic, treatment-resistant PTSD. In this group, MDMA-assisted psychotherapy compared with the same psychotherapy with inactive placebo produced clinically and statistically significant improvements in PTSD symptoms as measured by standard symptom scales. This difference was immediate and was maintained throughout the time period. There were no drug-related serious adverse events and no evidence of impaired cognitive function as measured by neuropsychological testing."Source:Mithoefer, Michael C; Wagner, Mark T; Mithoefer, Ann; Jerome, Lisa; and Doblin, Rick, "The safety and efficacy of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study," Journal of Psychopharmacology (Cambridge, United Kingdom: British Association for Psychopharmacology, July 19, 2010) Vol. 24, No. 7, p. 11.
(MDMA Therapy Benefits) "It is notable that no subjects reported any harm from study participation and all of them reported some degree of benefit. Consistent with the investigators‘ clinical observations in the original study, the responses we obtained on the questionnaire indicated that participants often experienced benefits beyond decreased PTSD symptoms. This is not a radical idea; many forms of psychotherapy produce benefits in terms of psychological growth and development that are not limited to improvements in a specific disorder that may have been the original target of therapy (Tedeschi and Calhoun, 2006; Zoellner and Maercker, 2006). Such benefits may prove to be a particularly prominent and valuable feature of MDMA-assisted psychotherapy. Some of the areas of benefit that were endorsed on the LTFU [Long Term Follow Up] Questionnaire, such as an increased self-awareness, improved relationships, an enhanced spiritual life, and more involvement in the community or world, represent effects that are not fully measured by the PTSD symptom scales."Source:Mithoefer, Michael C., et al., "Durability of improvement in posttraumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study," Journal of Psychopharmacology, published online Nov. 20, 2012, DOI: 10.1177/0269881112456611.
(MDMA Therapy and Neurocognitive Function) "Favorable reports about cognitive function, memory, and concentration on the LTFU Questionnaire were consistent with findings from formal measures of cognitive function that were taken before and after psychotherapy with MDMA versus placebo, in the original study. Though reports from actual testing are more reliable than reports of perceived cognitive function, this long-term self-reported evidence is still important, because of the controversy surrounding theories that there are potential risks of neurocognitive decline resulting from MDMA administration, as has been suggested by animal studies and some retrospective studies in recreational drug users (Thomasius et al., 2006; Kalechstein et al., 2007; Laws and Kokkalis, 2007; Zakzanis et al., 2007; De Sola Llopis et al., 2008; Jager et al., 2008; Schilt et al., 2008; Brown et al., 2010; Kish et al., 2010; Verbaten, 2010) and one prospective study (Schilt et al., 2007)."Source:Mithoefer, Michael C., et al., "Durability of improvement in posttraumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study," Journal of Psychopharmacology, published online Nov. 20, 2012, DOI: 10.1177/0269881112456611.
(MDMA Therapy and Substance Abuse) "The data we obtained about illicit drug use from the LTFU [Long Term Follow Up] Questionnaire supports the hypothesis that MDMA can be administered in a clinical setting with minimal risk that the subjects will subsequently seek out and self-administer 'street ecstasy,' or become dependent on the drug. This is consistent with the comments from many study subjects, who expressed the strong opinion that the therapeutic setting and close follow-up were essential elements of the treatment, and they did not think MDMA should be used without this level of clinical monitoring and therapeutic support."Source:Mithoefer, Michael C., et al., "Durability of improvement in posttraumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study," Journal of Psychopharmacology, published online Nov. 20, 2012, DOI: 10.1177/0269881112456611.