View source for MDMA

{{Drugbox |
| drug_name = MDMA
| IUPAC_name = (''RS'')-1-(benzo[''d''][1,3]dioxol-5-yl)-''N''-methylpropan-2-amine
| imagename = 1 : 1 mixture (racemate)<br />
| CASNo_Ref = {{cascite}}
| ATC_prefix = none
| ATC_suffix =
| image = MDMA (simple).svg
| width = 256
| image2 = MDMA_animation.gif
| CAS_number = 69610-10-2
| ChemSpiderID = 1556
| PubChem = 1615
| C = 11|H = 15|N = 1|O = 2
| molecular_weight = 193.25 g/mol
| Boiling Range (°C): 100-110 (0.4 mm)
| Vapour Pressure (kPa): Negligible
| Solubility in water (g/L): Partly miscible
| smiles = CC(NC)CC1=CC=C(OCO2)C2=C1
| synonyms = (±)-1,3-benzodioxolyl-''N''-methyl-2-propanamine;<br/>(±)-3,4-methylenedioxy-''N''-methyl-α-methyl-2-phenethylamine;<br/><small>DL</small>-3,4-methylenedioxy-''N''-methylamphetamine;<br/>methylenedioxymethamphetamine
| elimination_half-life = 6–10 (though duration of effects is typically actually 3–5 hours)
| metabolism = [[Liver|Hepatic]], [[Cytochrome P450 oxidase|CYP450]] extensively involved, especially [[CYP2D6]]
| excretion = [[Kidney|Renal]]
| legal_AU = S9
| legal_US = Schedule I
| legal_UK = CD Lic
| legal_CA = Schedule III
| routes_of_administration = [[Oral]], [[sublingual]], [[insufflation (medicine)|insufflation]], [[inhalation]] ([[vaporization]]), [[injection (medicine)|injection]],<ref>{{cite web|title= Methylenedioxymethamphetamine (MDMA, ecstasy) |url = http://www.nhtsa.dot.gov/people/injury/research/job185drugs/methylenedioxymethamphetamine.htm|work = Drugs and Human Performance Fact Sheets.|publisher = [[National Highway Traffic Safety Administration]]}}</ref> [[rectal (medicine)|rectal]]
| pregnancy_category = C<ref>[http://findarticles.com/p/articles/mi_m0CYD/is_11_38/ai_102839980 Stimulants, Narcotics, Hallucinogens - Drugs, Pregnancy, and Lactation.], Gerald G. Briggs, ''OB/GYN News'', 1 June 2003.</ref>
}}

'''MDMA''' ('''3,4-Methylenedioxymethamphetamine''', commonly known as '''ecstasy''', often abbreviated '''"E"''' or '''"X"''') is an [[entactogen]]ic drug of the [[phenethylamine]] and [[substituted amphetamine|amphetamine]] families.

MDMA has a tendency to induce [[euphoria]], a sense of [[intimacy]] with others, and diminished [[anxiety]] and depression. Many, particularly in the fields of [[psychology]] and [[cognitive therapy]], have suggested MDMA might have [[therapeutic benefit]]s and facilitate therapy sessions in certain individuals. [[Clinical trial]]s are now testing the therapeutic potential of MDMA for [[post-traumatic stress disorder]] (PTSD) and anxiety associated with terminal cancer.<ref>{{cite news| url=http://www.timesonline.co.uk/tol/life_and_style/health/article3850302.ece|work=The Times|location=London|title=Ecstasy is the key to treating PTSD|first=Amy|last=Turner|date=4 May 2008|accessdate=12 May 2010}}</ref><ref>http://www.msnbc.msn.com/id/6761326/</ref>

MDMA is [[criminalization|criminalized]] in most countries under a [[United Nations]] (U.N.) agreement,<ref>[http://ecstasy.org/qanda/q5.html "Where is Ecstasy Legal?"]</ref> and its [[drug possession|possession]], [[clandestine chemistry|manufacture]], or [[illegal drug trade|sale]] may result in criminal prosecution, although some limited exceptions exist for scientific and medical research. MDMA is one of the most widely used [[recreational drug use|recreational drugs]] in the world{{Citation needed|date=July 2010}} and is taken in a variety of contexts far removed from its roots in psychotherapeutic settings. It is commonly associated with dance parties (or "[[rave party|raves]]") and [[electronic dance music]].<ref name=WHO2004>World Health Organization (2004). [http://books.google.co.uk/books?id=G9OhG-dZdAwC&lpg=PP1&pg=PA97#v=onepage&q=&f=false Neuroscience of psychoactive substance use and dependence].</ref>

There have been debates within scientific, health care, and drug policy circles about the [[adverse drug reaction|risks]] of MDMA, specifically the possibility of [[neurotoxic]] damage to the [[central nervous system]] (CNS). Regulatory authorities in several locations around the world have approved scientific studies administering MDMA to humans to examine its therapeutic potential and its [[drug effect|effect]]s.<ref>[http://www.maps.org/research/ MAPS: Psychedelic Research Worldwide]</ref>

Continuing to study the substance in clinical trials, the [[Multidisciplinary Association for Psychedelic Studies]] released the following statement in October 2008, "We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects. Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD."<ref>[http://www.maps.org/mdma/ MAPS: Psychedelic Research Worldwide]</ref>

The role of the United States government in creating many of the pervasive myths surrounding the drug, including the overstatement of its dangers, was sharply criticized in the television programme ''[[Ecstasy Rising]]'', an ABC journalistic special program hosted by then-anchor [[Peter Jennings]].

==Terminology==
MDMA was first introduced clinically under the names "'''Adam'''" and "'''Empathy'''" when it was used in psychotherapy in the late 1970s and early to mid 1980s.<ref name="urlMDMA / Ecstasy: Not For Chemists - Drug Slang">{{cite web|url = http://mdma.net/ecstasy-mdma.html|title = MDMA / Ecstasy: Not For Chemists - Drug Slang|author = [[David Pearce]]{{Self-published inline|date=December 2009}}}}</ref>{{Self-published inline|date=December 2009}} Later on, upon making it into the recreational drug use scene, it came to be widely known as "'''ecstasy'''", often abbreviated as "'''E'''", "'''X'''", or "'''XTC'''".<ref name="urlMDMA / Ecstasy: Not For Chemists - Drug Slang"/>{{Self-published inline|date=December 2009}}

==History==
{{Globalize|section|UK|USA|date=July 2010}}
MDMA was first synthesized in 1912 by [[Merck KGaA|Merck]] chemist [[Anton Köllisch]]. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to evade an existing patent, held by [[Bayer]], for one such compound: [[hydrastinine]]. At the behest of his superiors Walther Beckh and Otto Wolfes, Köllisch developed a preparation of a hydrastinine [[chemical analogue|analogue]], methylhydrastinine. MDMA was an [[reaction intermediate|intermediate compound]] in the synthesis of methylhydrastinine, and Merck was not interested in its properties at the time.<ref name="pmid17152992">{{cite journal|author = Bernschneider-Reif S, Oxler F, Freudenmann RW|title = The Origin of MDMA ("Ecstasy")--Separating the Facts From the Myths.|journal = Pharmazie|volume = 61|issue = 11|pages = 966–972|year = 2006|month = November|pmid = 17152992|doi = 10.1111/j.1360-0443.2006.01511.x|url = http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=6707}}</ref> On 24 December 1912 Merck filed two patent applications that described the synthesis of MDMA<ref name="DE274350">{{cite web|url = http://v3.espacenet.com/publicationDetails/originalDocument?CC=DE&NR=274350C&FT=D|title = German Patent 274350: Verfahren zur Darstellung von Alkyloxyaryl-, Dialkyloxyaryl- und Alkylendioxyarylaminopropanen bzw. deren am Stickstoff monoalkylierten Derivaten.|author = Firma E. Merck in Darmstadt|date = 16 May 1914|publisher = Kaiserliches Patentamt|accessdate = 12 April 2009}}</ref> and its subsequent conversion to methylhydrastinine.<ref name="DE279194">{{cite web|url = http://v3.espacenet.com/publicationDetails/originalDocument?CC=DE&NR=279194C&FT=D|title = German Patent 279194: Verfahren zur Darstellung von Hydrastinin Derivaten.|author = Firma E. Merck in Darmstadt|date = 15 October 1914|publisher = Kaiserliches Patentamt}}</ref>

Over the following 65 years, MDMA was largely forgotten. Merck records indicate that its [[researcher]]s returned to the compound sporadically. In 1927, Max Oberlin studied the pharmacology of MDMA and observed that its effects on [[blood sugar]] and [[smooth muscle]]s were similar to [[ephedrine]]'s. Researchers at Merck conducted experiments with MDMA in 1952 and 1959.<ref name="pmid17152992"/> In 1953 and 1954, the [[United States Army]] commissioned a study of [[toxicity]] and behavioral effects in animals of injected [[mescaline]] and several analogues, including MDMA. These originally classified investigations were declassified and published in 1973.<ref name="pmid4197635">{{cite journal|author = Hardman HF, Haavik CO, Seevers MH|title = Relationship of the Structure of Mescaline and Seven Analogs to Toxicity and Behavior in Five Species of Laboratory Animals.|journal = Toxicology Applied Pharmacology|volume = 25|issue = 2|pages = 299–309|year = 1973|month = June|pmid = 4197635|doi = 10.1016/S0041-008X(73)80016-X| url = http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=639}}</ref> The first scientific paper on MDMA appeared in 1958 in Yakugaku Zasshi, the ''Journal of the Pharmaceutical Society of Japan''. In this paper, Yutaka Kasuya described the synthesis of MDMA, a part of his research on [[muscle relaxant#Spasmolytics|antispasmodics]].<ref name="kasuya">{{cite journal|author = Kasuya Y|title = Antispasmodics. XI. Synthesis of Aralkylamines and Their Quarternary Ammonium Derivatives.|journal = Yakugaku Zasshi|volume = 78|pages = 509–511|year = 1958}}</ref>

MDMA was being used nonmedically in the United States by 1970.<ref>The first confirmed sample was seized and identified by Chicago Police in 1970, see{{cite journal|author = Sreenivasan VR|title = Problems in Identification of Methylenedioxy and Methoxy Amphetamines.|journal = Journal of Criminal Law, Criminology & Police Science|volume = 63|issue = 2|pages = 304–312|year = 1972|url = http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=1149|doi = 10.2307/1142315|jstor = 1142315|publisher = The Journal of Criminal Law, Criminology, and Police Science, Vol. 63, No. 2}}</ref> In the mid-1970s, [[Alexander Shulgin]], then at [[University of California, Berkeley]], heard from his students about unusual effects of MDMA; among others, the drug had helped one of them to overcome his [[stutter]]. Intrigued, Shulgin synthesized MDMA and tried it himself in 1976.<ref name="isbn0-9630096-0-5">{{cite book|author = Ann Shulgin; Alexander Shulgin|title = PiHKAL: A Chemical Love Story. Part I. Chapter 12.|publisher = Transform Press|year = 1991|isbn=0-9630096-0-5}}</ref> Two years later, he and [[David Nichols]] published the first report on the drug's [[psychotropic]] effect in humans. They described "altered state of consciousness with emotional and sensual overtones" that can be compared "to marijuana,and to [[psilocybin]] devoid of the hallucinatory component".<ref name="isbn0-08-021938-1">{{cite book|author = Shulgin AT; Nichols DE|editor = Willette, Robert E.; Stillman, Richard Joseph|title = The Psychopharmacology of Hallucinogens.|publisher = Pergamon Press|location = New York|year = 1978|pages = 74–83|chapter = Characterization of Three New Psychomimetics. |isbn = 0-08-021938-1|url = http://www.erowid.org/references/refs_view.php?ID=961&C=MDMA}}</ref>

Shulgin took to occasionally using MDMA for relaxation, referring to it as "my low-calorie martini", and giving the drug to his friends, researchers, and other people whom he thought could benefit from it. One such person was psychotherapist [[Leo Zeff]], who had been known to use [[psychedelic drug|psychedelic]]s in his practice. Zeff was so impressed with the effects of MDMA that he came out of his semi-retirement to [[proselytize]] for it. Over the following years, Zeff traveled around the U.S. and occasionally to Europe, training other psychotherapists in the use of MDMA.<ref name="isbn0-9630096-0-5"/><ref>{{cite news|first = Drake|last = Bennett|url = http://www.nytimes.com/2005/01/30/magazine/30ECSTASY.html|title = Dr. Ecstasy.|work = New York Times Magazine |date = 30 January 2005}}</ref><ref name="isbn0-9660019-6-6">{{cite book|author = Myron J. Stolaroff |title = The Secret Chief Revealed.|publisher = MAPS|year = 2005|pages = 16–18 |isbn=0-9660019-6-6|url = http://www.maps.org/books/scr/}}</ref> Among [[psychedelic therapy|underground psychotherapist]]s, MDMA developed a reputation for enhancing communication during clinical sessions, reducing patients' psychological defenses, and increasing capacity for therapeutic [[introspection]].{{Citation needed|reason=This is a bold claim to make without sources.|date=July 2009}}

In the early 1980s in the U.S., MDMA rose to prominence as "Adam" in trendy nightclubs and gay dance clubs in the [[Dallas]] area.<ref>[http://www.weeklywire.com/ww/06-12-00/austin_music_feature.html ''The Austin Chronicle'' - "Countdown to Ecstasy." by Marc Savlov]</ref> From there, use spread to [[rave]]s in major cities around the country, and then to mainstream society. The drug was first proposed for [[Controlled Substances Act|scheduling]] by the [[Drug Enforcement Administration]] (DEA) in July 1984<ref name="merckehistoryb">{{cite web|year = 2005|url = http://www.mdma.net/merck/history-ecstasy.html|title = Pharmaceutical Company Unravels Drug's Chequered Past.}}</ref> and was classified as a [[Schedule I (US)|Schedule I]] controlled substance in the U.S. on 31 May 1985.<ref>[http://www.erowid.org/chemicals/mdma/mdma_law3.shtml Erowid MDMA Vault: Info #3 on Scheduling.]</ref>

In the late 1980s MDMA, known by that time as "ecstasy", began to be widely used in the UK and other parts of Europe, becoming an integral element of [[rave culture]] and other psychedelic-influenced music scenes. Spreading along with rave culture, illicit MDMA use became increasingly widespread among young adults in universities and later in high schools. MDMA became one of the four most widely used illicit drugs in the U.S., along with [[cocaine]], [[heroin]], and [[Cannabis (drug)|cannabis]].{{Citation needed|date=November 2007}} According to some estimates as of 2004, only marijuana attracts more first time users in the U.S.<ref name=rising>[http://video.google.com/videoplay?docid=-1564288654365150131 ''Primetime'' with Peter Jennings.]</ref>

After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally. Later Charles Grob initiated an ascending-dose safety study in healthy volunteers. Subsequent legally-approved MDMA studies in humans have taken place in the U.S. in Detroit ([[Wayne State University]]), Chicago ([[University of Chicago]]), San Francisco (UCSF and [[California Pacific Medical Center]]), [[Baltimore]] ([[NIDA]]&ndash;[[NIH]] Intramural Program), and [[South Carolina]], as well as in Switzerland (University Hospital of Psychiatry, [[Zürich]]), the Netherlands ([[Maastricht University]]), and Spain ([[Universitat Autònoma de Barcelona]]).<ref>[http://www.maps.org/research/ Bibliography of Psychadelic Research Studies.] collected by the Multidisciplinary Association for Psychedelic Studies</ref>

In 2010 the BBC reported that use of MDMA had decreased in the UK in previous years. This is thought to be due to increased seizures and decreased production of the precursor chemicals used to manufacture MDMA. The availability of legal alternatives to MDMA such as [[mephedrone]] is also thought to have contributed to its decrease in popularity.<ref>{{cite news|url=http://news.bbc.co.uk/1/hi/england/london/8468372.stm|title=Why ecstasy is 'vanishing' from UK nightclubs |date=19 January 2010|publisher=BBC News|accessdate=14 February 2010}}</ref>

==Therapeutic use==
There have long been suggestions that MDMA might be useful in [[psychotherapy]], facilitating [[self-observation|self-examination]] with reduced fear.<ref>[http://www.maps.org/w3pb/new/1990/1990_greer_1120_1.pdf Greer G. Tolbert R. "The Therapeutic Use of MDMA in Ecstasy: The Clinical, Pharmacological, and Neurotoxicological Effects of the Drug MDMA." 1990 (ed Peroutka, SJ) Boston, p. 21-36]</ref><ref name="pmid12691208">{{cite journal|author = Doblin R|title = A Clinical Plan for MDMA (Ecstasy) in the Treatment of Post-Traumatic Stress Disorder (PTSD): Partnering with the FDA.|journal = J Psychoactive Drugs|volume = 34|issue = 2|pages = 185–194|year = 2002|pmid = 12691208|url = http://www.maps.org/w3pb/new/2002/2002_Doblin_20651_2.pdf}}</ref><ref name="pmid17984158">{{cite journal|author = Sessa B, Nutt DJ|title = MDMA, Politics and Medical Research: Have We Thrown the Baby Out With the Bathwater?|journal = J. Psychopharmacol. (Oxford)|volume = 21|issue = 8|pages = 787–791|year = 2007|month = November|pmid = 17984158|doi = 10.1177/0269881107084738|url = http://www.maps.org/w3pb/new/2007/2007_Sessa_22948_1.pdf}}</ref> Indeed, some therapists, including [[Leo Zeff]], [[Claudio Naranjo]], [[George Greer]], Joseph Downing, and Philip Wolfson, used MDMA in their practices until it was made illegal. George Greer synthesized MDMA in the lab of Alexander Shulgin and administered it to about 80 of his clients over the course of the remaining years preceding MDMA's [[List of Schedule I drugs|Schedule I]] placement in 1985. In a published summary of the effects,<ref>{{cite journal|title = Subjective Reports of the Effects of MDMA in a Clinical Setting.|author = Greer, G.; Tolbert, R.|journal = Journal of Psychoactive Drugs|volume = 18|issue = 4|pages = 319–327|year = 1986|url = http://www.heffter.org/pages/subjrep.html|pmid = 2880946|format = {{Dead link|date=June 2010}}}}</ref> the authors reported [[patient]]s felt improved in various, mild [[psychiatric disorder]]s and other personal benefits, especially improved intimate communication with their significant others. In a subsequent publication on the treatment method, the authors reported that one patient with severe pain from [[terminal illness|terminal]] cancer experienced lasting [[analgesic|pain relief]] and improved [[quality of life]].<ref>{{cite journal |title= A Method of Conducting Therapeutic Sessions with MDMA.|author = Greer, G.; Tolbert, R.|journal = Journal of Psychoactive Drugs|volume = 30|issue = 4|pages = 371–379|year = 1998|url = http://www.heffter.org/pages/sessions.html |pmid= 9924843 |format= {{Dead link|date=June 2010}}}}</ref> However, little evidence examining MDMA in psychotherapy practice have used methods that would be considered reliable or convincing in general scientific practice. For example, it is not known to what extent similar patients might improve by chance or from any comparable form of psychotherapy ie. there was no active control condition.

The possible therapeutic potential of MDMA is being tested in several ongoing studies, some sponsored by the [[Multidisciplinary Association for Psychedelic Studies]] (MAPS). Studies in the U.S., Switzerland, and Israel are evaluating the [[efficacy#Healthcare|efficacy]] of MDMA-assisted psychotherapy for treating those diagnosed with [[post-traumatic stress disorder]] (PTSD) or anxiety related to cancer. MAPS reported provisonal results in a conference poster.<ref>[http://www.maps.org/mdma/news_advisory_nov_2008_mithoefer_poster.pdf Promising Results from Pioneering MDMA (Ecstasy)-Assisted Psychotherapy Pilot Study of Subjects with Treatment-Resistant Posttraumatic Stress Disorder (PTSD)]</ref>.

==Non-medical use==
The [[European Monitoring Centre for Drugs and Drug Addiction]] notes that although there are some reports of tablets being sold for as little as €1, most countries in Europe now report typical retail prices in the range of €3 to €9 per tablet.<ref>{{cite book |author=European Monitoring Centre for Drugs and Drug Addiction |title=Annual report: the state of the drugs problem in Europe |year=2008 |publisher=Office for Official Publications of the European Communities |location=Luxembourg |isbn=978-92-9168-324-6 |pages=49 |url=http://www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf |format=PDF}}</ref> The [[United Nations Office on Drugs and Crime]] claimed in its 2008 World Drug Report that typical U.S. retail prices are lower, costing 10 to 15 dollars per tablet, or from 4 to 6 dollars per tablet if bought in batches.<ref>{{cite book |author=United Nations Office on Drugs and Crime |title=World drug report |year=2008 |publisher=United Nations Publications |isbn=978-92-1-148229-4 |page=271 |url=http://www.unodc.org/documents/wdr/WDR_2008/WDR_2008_eng_web.pdf |format=PDF}}</ref> MDMA is expensive in Australia, costing [[Australian dollar|AU$]]20–AU$50 per tablet, but in the Asian community it is AU$20–30 depending on the size. In terms of purity data for Australian MDMA, the average is around 34%, ranging from less than 1% to about 85%. The majority of tablets contain 70–85&nbsp;mg of MDMA. Most ecstasy enters Australia from different markets, the Netherlands, the UK, Asia and the U.S.<ref>[http://www.drugtext.org/library/articles/dillon.htm Drugtext - 10 years of ecstasy and other party drug use in Australia: What have we done and what is there left to do?]</ref>

===Polysubstance use===
{{Main|Poly drug use}}

MDMA is occasionally known for being taken in conjunction with psychedelic drugs, such as [[LSD]] or [[psilocybin mushrooms]], or even common drugs such as [[Cannabis (drug)|cannabis]]. As this practice has become more prevalent, most of the more common combinations have been given nicknames, such as "candy flipping", for MDMA combined with [[LSD]]<ref>{{cite web|url = http://www.cesar.umd.edu/cesar/drugs/ecstasy.asp|title = Ecstasy:CESAR|author = University of Maryland, College Park Center for Substance Abuse Research}}</ref>, "hippie flipping" when combined with [[psilocybin]] mushrooms, and "kitty flipping" when combined with [[ketamine]]. Many users use [[mentholated]] products while taking MDMA for its cooling sensation while experiencing the drug's effects. Examples include menthol [[cigarette]]s, [[Vicks]]<ref>{{cite web|url= http://search2.google.cit.nih.gov/search?q=cache:y3dIYYo3lKwJ:www.drugabuse.gov/DirReports/DirRep500/DirectorReport5.html|title = Director's Report to the National Advisory Council on Drug Abuse.|publisher = National Institute on Drug Abuse |date=May 2000}}</ref> and [[throat lozenge|lozenges]]. This sometimes has [[Wiktionary:deleterious|deleterious]] results on the upper respiratory tract.<ref>[http://www.erowid.org/experiences/exp.php?ID=4287 Erowid Experience Vaults: Vicks Used With Ecstasy - Important Warning About Vicks on Ecstasy.]</ref>

==Chemistry==
[[Image:MDMAjakarta.jpg|right|150px|thumb|An industrial scale [[methamphetamine]] and MDMA [[clandestine chemistry|chemical factory]] in Cikande, [[Indonesia]].]]

[[Safrole]], a colorless or slightly black oil, extracted from the root-bark or the fruit of [[sassafras]] plants is the primary precursor for all manufacture of MDMA. There are numerous synthetic methods available in the literature to convert safrole into MDMA via different intermediates.<ref>{{cite journal |author=Milhazes N, Martins P, Uriarte E, ''et al.'' |title=Electrochemical and spectroscopic characterisation of amphetamine-like drugs: application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors |journal=Anal. Chim. Acta |volume=596 |issue=2 |pages=231–41 |year=2007 |pmid=17631101 |doi=10.1016/j.aca.2007.06.027}}</ref><ref>{{cite journal |author=Milhazes N, Cunha-Oliveira T, Martins P, ''et al.'' |title=Synthesis and cytotoxic profile of 3,4-methylenedioxymethamphetamine ("ecstasy") and its metabolites on undifferentiated PC12 cells: A putative structure-toxicity relationship |journal=Chem. Res. Toxicol. |volume=19 |issue=10 |pages=1294–304 |year=2006 |pmid=17040098 |doi=10.1021/tx060123i}}</ref><ref>Reductive aminations of carbonyl compounds with borohydride and borane reducing agents. Baxter, Ellen W.; Reitz, Allen B. ''Organic Reactions'' (Hoboken, New Jersey, United States) (2002), 59</ref><ref>{{cite journal |author=Gimeno P, Besacier F, Bottex M, Dujourdy L, Chaudron-Thozet H |title=A study of impurities in intermediates and 3,4-methylenedioxymethamphetamine (MDMA) samples produced via reductive amination routes |journal=Forensic Sci. Int. |volume=155 |issue=2-3 |pages=141–57 |year=2005|pmid=16226151 |doi=10.1016/j.forsciint.2004.11.013}}</ref> One common route is via the [[MDP2P]] (3,4-[[methylenedioxy]]<nowiki>phenyl</nowiki>-2-propanone, also known as piperonyl acetone) intermediate. This intermediate can be produced in at least two different ways. One method is to [[Isomerization|isomerize]] safrole to [[isosafrole]] in the presence of a strong base and then oxidize [[isosafrole]] to MDP2P. Another, reportedly better{{Citation needed|reason=How is it better and where is this reported?|date=July 2009}}, method is to make use of the [[Wacker process]] to oxidize safrole directly to the MDP2P (3,4-methylenedioxy phenyl-2-propanone) intermediate. This can be done with a [[palladium]] catalyst. Once the MDP2P intermediate has been prepared, a [[reductive amination]] leads to MDMA, a [[racemate]] {1:1 mixture of  (''R'')-1-(benzo[''d''][1,3]dioxol-5-yl)-''N''-methylpropan-2-amine and (''S'')-1-(benzo[''d''][1,3]dioxol-5-yl)-''N''-methylpropan-2-amine}.
Another method for the synthesis of [[racemic]] MDMA is addition of hydrogen bromide to safrole and reaction of the adduct with methylamine.

:[[Image:MDMA Synthesis 1.svg|800px]]
:[[Image:MDMA Synthese 2.svg|500px]]

Relatively small quantities of essential oil are required to make large numbers of MDMA pills. The essential oil of ''[[Ocotea cymbarum]]'' typically contains between 80 and 94% safrole. This would allow 500&nbsp;ml of the oil, which retails at between $20 and $100, to be used to produce an estimated 1,300 to 2,800 tablets containing approximately 120&nbsp;mg of MDMA each.<ref>[http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg1105/mg1105.html Nov 2005 DEA Microgram newsletter]</ref>

==Pharmacology==

{{details|Effects of MDMA on the human body}}

MDMA acts as a [[releasing agent]] of [[serotonin]], [[norepinephrine]], and [[dopamine]].<ref name="pmid1982265">{{cite journal|author = Fitzgerald JL, Reid JJ|title = Effects of methylenedioxymethamphetamine on the release of monoamines from rat brain slices|journal = European Journal of Pharmacology|volume = 191|issue = 2|pages = 217–20|year = 1990|month = November|pmid = 1982265|doi =10.1016/0014-2999(90)94150-V}}</ref> It enters neurons via carriage by the [[monoamine transporter]]s.<ref name="pmid1982265"/> Once inside, MDMA inhibits the [[vesicular monoamine transporter]], which results in increased concentrations of serotonin, norepinephrine, and dopamine into the [[cytoplasm]],<ref name="pmid12742084">{{cite journal|author = Bogen IL, Haug KH, Myhre O, Fonnum F|title = Short- and long-term effects of MDMA ("ecstasy") on synaptosomal and vesicular uptake of neurotransmitters in vitro and ex vivo|journal = Neurochemistry International|volume = 43|issue = 4-5|pages = 393–400|year = 2003|pmid = 12742084|doi =10.1016/S0197-0186(03)00027-5}}</ref> and induces their release by [[transporter reversal|reversing]] their respective transporters through a process known as [[phosphorylation]].<ref name="pmid17209801">{{cite journal|author = Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR|title = New insights into the mechanism of action of amphetamines|journal = Annual Review of Pharmacology and Toxicology|volume = 47|pages = 681–98|year = 2007|pmid = 17209801|doi = 10.1146/annurev.pharmtox.47.120505.105140|url = http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.pharmtox.47.120505.105140?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov}}</ref> It also acts as a weak [[5-HT1 receptor|5-HT<sub>1</sub>]] and [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] [[agonist]], and its more efficacious metabolite [[3,4-methylenedioxyamphetamine|MDA]] likely augments this action.<ref name="pmid2899513">{{cite journal|author = Battaglia G, Brooks BP, Kulsakdinun C, De Souza EB|title = Pharmacologic profile of MDMA (3,4-methylenedioxymethamphetamine) at various brain recognition sites|journal = European Journal of Pharmacology|volume = 149|issue = 1-2|pages = 159–63|year = 1988|month = April|pmid = 2899513|doi =10.1016/0014-2999(88)90056-8}}</ref><ref name="pmid2871581">{{cite journal|author = Lyon RA, Glennon RA, Titeler M|title = 3,4-Methylenedioxymethamphetamine (MDMA): stereoselective interactions at brain 5-HT1 and 5-HT2 receptors|journal = Psychopharmacology|volume = 88|issue = 4|pages = 525–6|year = 1986|pmid = 2871581}}</ref><ref name="pmid7824160">{{cite journal|author = Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA|title = Effect of the R(-) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors|journal = Neuroscience Letters|volume = 177|issue = 1-2|pages = 111–5|year = 1994|pmid = 7824160|doi = 10.1016/0304-3940(94)90057-4}}</ref><ref name="pmid12761331">{{cite journal|author = Setola V, Hufeisen SJ, Grande-Allen KJ, ''et al.''|title = 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro|journal = Molecular Pharmacology|volume = 63|issue = 6|pages = 1223–9|year = 2003|month = June|pmid = 12761331|doi = 10.1124/mol.63.6.1223}}</ref>

MDMA's unusual [[entactogen]]ic effects have been hypothesized to be, at least partly, the result of indirect [[oxytocin]] secretion via activation of the serotonin system.<ref>{{cite web|title = Ecstasy Really Does Unleash the Love Hormone.|date = 4 April 2007|publisher = [[New Scientist]]|url = http://www.newscientist.com/article/dn11530-ecstasy-really-does-unleash-the-love-hormone.html}}</ref> Oxytocin is a [[hormone]] released following events like [[hugging]], [[orgasm]], and [[childbirth]], and is thought to facilitate [[pair bond|bonding]] and the establishment of [[trust (social sciences)|trust]].<ref>{{cite journal |author=Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ |title=Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness |journal=Horm Behav |volume=56 |issue=1 |pages=128–32 |year=2009 |pmid=19344725 |doi=10.1016/j.yhbeh.2009.03.019 }}</ref> Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]]. A [[placebo-controlled]] study in 15 human volunteers found that 100&nbsp;mg MDMA increased blood levels of oxytocin and the amount of oxytocin increase was [[correlated]] with the subjective prosocial effects of MDMA.<ref name="pmid19562632">{{cite journal|author = Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ, van Gerven JM, Buitelaar JK, Verkes RJ.|title = Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration|journal = Soc Neurosci|volume = 4|issue = 4|pages = 359–366|year = 2009|pmid = 19562632|doi = 10.1080/17470910802649470| url = http://www.maps.org/w3pb/new/2009/2009_Dumont_23083_1.pdf}}</ref>

==Pharmacokinetics==
[[Image:1g MDMA-HCl.jpg|thumb|right|MDMA crystals]]

MDMA reaches maximal [[concentration]]s in the [[blood stream]] between 1.5 and 3 hours after [[ingestion]]. It is then slowly [[metabolism|metabolized]] and [[excretion|excreted]], with levels decreasing to half their peak concentration over approximately 8 hours. Thus, there are still high MDMA levels in the body when the experiential effects have mostly ended, indicating that acute [[drug tolerance|tolerance]] has developed to the actions of MDMA. Taking additional supplements of MDMA at this point therefore produces higher concentrations of MDMA in the blood and brain than might be expected based on the perceived effects.

[[Metabolite]]s of MDMA that have been identified in humans include [[MDA (drug)|3,4-methylenedioxyamphetamine]] (MDA), [[:Image:HMMA.PNG|4-hydroxy-3-methoxy-methamphetamine]] (HMMA), [[:Image:HMA2.png|4-hydroxy-3-methoxyamphetamine]] (HMA), [[:Image:DHA.png|3,4-dihydroxyamphetamine]] (DHA) (also called alpha-methyldopamine (α-Me-DA)), [[MDP2P|3,4-methylenedioxyphenylacetone]] (MDP2P), and [[:Image:MDOH.png|N-hydroxy-3,4-methylenedioxyamphetamine]] (MDOH). The contributions of these metabolites to the psychoactive and [[toxic]] effects of MDMA are an area of active research. 65% of MDMA is excreted unchanged in the [[urine]] (additionally 7% is metabolized into MDA) during the 24 hours after ingestion.<ref name="pmid2893845">{{cite journal|title = The complications of 'ecstasy' (MDMA)|author = Verebey K, Alrazi J, Jaffe JH|journal = JAMA|year = 1988|volume = 259|issue = 11|pages = 1649–1650|url = http://www.erowid.org/references/refs_view.php?ID=1015|pmid = 2893845|doi = 10.1001/jama.259.11.1649}}</ref>

MDMA is known to be metabolized by two main [[metabolic pathway]]s: (1) ''O''-demethylenation followed by [[Catechol-O-methyl transferase|catechol-''O''-methyltransferase]] (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) ''N''-dealkylation, deamination, and oxidation to the corresponding [[benzoic acid]] derivatives conjugated with [[glycine]]. The metabolism may be primarily by [[cytochrome P450 oxidase|cytochrome P450]] (CYP450) [[enzyme]]s ([[CYP2D6]] (in humans, but CYP2D1 in [[mice]]), and [[CYP3A4]]) and COMT. Complex, nonlinear [[pharmacokinetics]] arise via autoinhibition of [[CYP2D6]] and CYP2D8, resulting in [[rate equation|zeroth order kinetics]] at higher doses. It is thought that this can result in sustained and higher [[concentration]]s of MDMA if the user takes consecutive doses of the drug.

Because the [[enzyme]] [[CYP2D6]] is deficient or totally absent in some people<ref>[http://www.emedicine.com/emerg/topic927.htm eMedicine - Toxicity, MDMA: Article by David Yew]</ref>, it was once hypothesized that these people might have elevated risk when taking MDMA. However, there is still no evidence for this theory and available evidence argues against it.<ref>{{cite journal |author=de la Torre R, Farré M, Roset PN, ''et al.'' |title=Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition |journal=Ther Drug Monit |volume=26 |issue=2 |pages=137–44 |year=2004 |pmid=15228154 |doi= 10.1097/00007691-200404000-00009|url= http://www.maps.org/w3pb/new/2004/2004_de_20593_2.pdf}}</ref> It is now thought that the contribution of CYP2D6 to MDMA metabolism in humans is less than 30% of the metabolism. Indeed, an individual lacking CYP2D6 was given MDMA in a controlled clinical setting and a larger study gave MDMA to healthy volunteers after inhibiting CYP2D6 with [[paroxetine]]. Lack of the enzyme caused a modest increase in drug exposure and decreases in some [[metabolite]]s, but physical effects did not appear appreciably elevated. While there is little or no evidence that low CYP2D6 activity increases risks from MDMA, it is likely that MDMA-induced CYP2D inhibition will increase risk of those prescription drugs that are metabolized by this enzyme. MDMA-induced CYP2D inhibition appears to last for up to a week after MDMA exposure.

MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides.<ref name="pmid17643356">{{cite journal|author = Shima N, Kamata H, Katagi M, Tsuchihashi H, Sakuma T, Nemoto N|title = Direct Determination of Glucuronide and Sulfate of 4-Hydroxy-3-methoxymethamphetamine, the Main Metabolite of MDMA, in Human Urine.|journal = J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.|volume = 857|issue = 1|pages = 123–129|year = 2007|month = September|pmid = 17643356|doi = 10.1016/j.jchromb.2007.07.003}}</ref>

[[File:NDMA-Formel.png|thumb|right|The (''R'')-[[enantiomer]] (top) and the (''S'')-enantiomer of MDMA]]
MDMA is a [[chirality (chemistry)|chiral]] compound and has been almost exclusively administered as a [[racemic|racemate]]. However, an early uncontrolled report suggests that the (''S'')-[[enantiomer]] is significantly more [[potency (pharmacology)|potent]] in humans than the (''R'')-enantiomer<ref name="fallon">{{cite journal|title = Stereospecific Analysis and Enantiomeric Disposition of 3,4-Methylenedioxymethamphetamine (Ecstasy) in Humans.|author = J. K. Fallon, A. T. Kicman, J. A. Henry, P. J. Milligan, D. A. Cowan, A. J. Hutt|journal = Clinical Chemistry|date=1 July 1999| volume = 45|issue = 7|pages = 1058–1069|url = http://www.clinchem.org/cgi/reprint/45/7/1058|pmid = 10388483}}</ref><ref>{{cite journal
| title = Simultaneous Determination of Amphetamine, Methamphetamine, Methylenedioxyamphetamine (MDA), Methylenedioxymethamphetamine (MDMA), and Methylenedioxyethylamphetamine (MDEA) Enantiomers by GC–MS.|author = D. Hensley, J. T. Cody|journal = Journal of Analytical Toxicology|year = 1999|volume = 23|issue = 6|pages = 518–523|url = http://www.maps.org/w3pb/new/1999/1999_hensley_175_1.pdf
| pmid = 10517560}}</ref> indicate that the disposition of MDMA is stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. For example, Fallon ''et al.''<ref name="fallon"/> reported that the area under the [[blood plasma]] concentration versus time curve (AUC) was two to four times higher for the (''R'')-enantiomer than the (''S'')-enantiomer after a 40&nbsp;mg oral dose in human volunteers. Similarly, the plasma half-life of (''R'')-MDMA was significantly longer than that of the (''S'')-enantiomer (5.8&nbsp;±&nbsp;2.2&nbsp;hours vs 3.6&nbsp;±&nbsp;0.9&nbsp;hours). However, because MDMA has dose dependent kinetics, it is likely that these half-lives would be higher at more typical doses (100&nbsp;mg is sometimes considered a typical dose). Given as the racemate, MDMA has a [[half-life]] of around 8 hours.

===Detection of use===
MDMA and MDA may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDMA or its major metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are generally less than 10% those of the parent drug.<ref>Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA. Plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine after controlled oral administration to young adults. Ther. Drug Monit. 30: 320-332, 2008.</ref><ref>Barnes AJ, De Martinis BS, Gorelick DA et al. Disposition of MDMA and metabolites in human sweat following controlled MDMA administration. Clin. Chem. 55: 454-462, 2009.</ref><ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, California, 2008, pp. 997-999.</ref>

===Drug interactions===
There are a number of reported potentially dangerous possible interactions between MDMA and other drugs. Several cases have been reported of death in individuals who ingested MDMA while taking [[ritonavir]] (Norvir), which inhibits multiple [[CYP450]] enzymes. Toxicity or death has also been reported in people who took MDMA in combination with certain [[monoamine oxidase inhibitor]]s (MAOIs) such as [[phenelzine]] (Nardil), [[tranylcypromine]] (Parnate), or [[moclobemide]] (Aurorix, Manerix).<ref>{{cite journal |author=Vuori E, Henry JA, Ojanperä I, ''et al.'' |title=Death following ingestion of MDMA (ecstasy) and moclobemide |journal=Addiction |volume=98 |issue=3 |pages=365–8 |year=2003 |pmid=12603236 |doi=10.1046/j.1360-0443.2003.00292.x |url=http://www.mdma.net/toxicity/moclobemide.html}}</ref> On the other hand, [[Monoamine oxidase B|MAO<sub>B</sub>]] inhibitors like [[selegiline]] (Deprenyl; Eldepryl, Zelapar, Emsam) do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats.<ref>[http://thedea.org/neurotoxicity.html#prozac The Prozac Misunderstanding], at TheDEA.org</ref>

People taking any type of [[serotonin reuptake inhibitor]] (SRI) on a chronic basis commonly find that the psychedelic and [[entactogen]]ic effects of MDMA are near fully abolished, leaving merely stimulation instead. Many people attempt taking a dose around 3x as high and this appears to work as a remedy for the problem to some degree. Additionally, upon discontinuation of the prolonged administration of the SRI in question, such individuals may still not be able to properly experience the full desired effects of MDMA at normal doses for anywhere from a few weeks to as long as several months.

There is a possible risk of experiencing [[serotonin syndrome]] if MDMA is combined with another [[serotonergic]] drug.<ref>http://www.informaworld.com/smpp/content~content=a780538207~db=all Qualitative review of serotonin syndrome, ecstasy (MDMA) and the use of other serotonergic substances: hierarchy of risk (by Silins E, Copeland J, Dillon P.)</ref>

Commercial sassafras oil generally is a by-product of [[camphor]] production in [[Asia]] or comes from related trees in [[Brazil]]. Safrole is a precursor for the [[Clandestine chemistry|clandestine manufacture]] of [[Methylenedioxymethamphetamine|MDMA]] (ecstasy), and as such, its transport is monitored internationally.
Roots of Sassafras can also be steeped to make tea and were used in the flavoring of traditional [[root beer]] until being banned for mass production by the [[U.S. Food and Drug Administration|FDA]]. Laboratory animals that were given oral doses of sassafras tea or sassafras oil that contained large doses of safrole developed permanent [[liver]] damage or various types of [[cancer]]. In humans liver damage can take years to develop and it may not have obvious signs.

==Effects==
{{details|Effects of MDMA on the human body}}
[[File:Ecstacy monogram.jpg|thumb|Illicit tablets containing MDMA]]
[[Image:Ecstasy.jpg|thumb|right|MDMA capsules and pressed tablets]]

The primary effects attributable to MDMA consumption are predictable and fairly consistent amongst users. Generally, users report feeling effects within 30–60 minutes of consumption, hitting a peak at approximately 1–1.5 hours, reaching a plateau that lasts about 2–3 hours, followed by a [[comedown (drugs)|comedown]] of a few hours which may be accompanied by [[fatigue (medical)|fatigue]] and minor effects.<ref>{{cite web|title= Erowid MDMA Vault: Effects.|url = http://www.erowid.org/chemicals/mdma/mdma_effects.shtml|publisher = [[Erowid]]}}</ref><ref>{{cite web|title = What Is Ecstasy?|url = http://www.dancesafe.org/documents/druginfo/ecstasy.php|publisher = DanceSafe}}</ref><ref>{{cite web|title = MDMA Technical FAQ.|url = http://www.thedea.org/technicalFAQ.html|publisher = TheDEA.org |date=May 2003}}</ref>

===Subjective effects===
The most common [[therapeutic effect|effect]]s reported by users include:<ref name="urlAn Analysis of MDMA-Induced Neurotoxicity">{{cite web|url = http://mdma.net/kobie/index.html|title = An Analysis of MDMA-Induced Neurotoxicity.|author = Whetstone, Kobie J.|date = 16 April 2009- 11 June 2009}}</ref>

*A general and [[subjective]] [[altered state of consciousness|alteration in consciousness]]
*A strong sense of [[inner peace]] and [[self-acceptance]]
*Diminished [[aggression]], [[hostility]], and [[jealousy]]
*Diminished [[fear]], [[anxiety]], and [[insecurity]]
*Extreme [[mood (psychology)|mood]] lift with accompanying [[euphoria]]
*Feelings of [[empathy]], [[compassion]], and [[forgiveness]] towards others
*Feelings of [[intimacy]] and even [[love]] for others
*Improved [[self-confidence]]
*The ability to discuss normally [[anxiety]]-provoking topics with marked ease
*An intensification of [[perception]], particularly [[tactile]] [[Wikt:sensation|sensation]] or [[somatosensory system|touch]], as well as [[hearing (sense)|hearing]] and [[visual perception|vision]]
*Substantial enhancement of the appreciation for quality of music
*Mild [[psychedelia]], consisting of [[mental imagery]] and [[auditory]] and [[visual]] [[distortion]]s
*[[Stimulation]], [[arousal]], and [[hyperactivity]] (e.g., many users get an "uncontrollable urge to dance" while under the influence)
*Increased [[energy (psychological)|energy]] and [[endurance]]
*Increased [[alertness]], [[awareness]], and [[wakefulness]]
*Increased [[desire (emotion)|desire]], [[motivation|drive]], and [[motivation]]
*[[Analgesia]] or decreased [[pain]] [[stimulus (physiology)|sensitivity]]

===Side effects===
In January 2001, an overview of the subjective side effects of MDMA was published by Liechti, Gamma, and Vollenweider in the journal ''Psychopharmacology''. Their paper was based on clinical research conducted over several years involving 74 healthy volunteers.

The researchers found that there were a number of common side effects and that many of the effects seemed to occur in different amounts based on gender. The top side effects reported were difficulty concentrating, jaw clenching, [[bruxism|grinding of the teeth]] during sleep, lack of appetite, and [[dry mouth]]/thirst (all occurring in more than 50% of the 74 volunteers).

Liechti, et al. also measured some of the test subjects for blood pressure, heart rate, and body temperature against a placebo control. No statistically significant changes were seen.<ref>Liechti ME, Gamma A, Vollenweider FX (2001). "[http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=1098&DocPartID=936 Gender Differences in the Subjective Effects of MDMA]". ''Psychopharmacology'' '''154''':161-168.</ref><ref>Erowid (September 2001). [http://www.erowid.org/chemicals/mdma/mdma_effects3.shtml Short-Term Side Effects of MDMA].</ref>

===After effects===
Effects reported by some users once the [[acute (medicine)|acute]] effects of MDMA have worn off include:

*Psychological
**Anxiety and paranoia<ref name=rutgers/>
**Depression<ref name="rutgers">{{cite web |url=http://health.rutgers.edu/brochures/ecstacy.htm |title=Ecstasy |work=health.rutgers.edu |accessdate=May 25, 2010}}</ref><ref name="btw">{{cite web |url=http://www.betweenthelines.net.au/drug-facts/ecstasy-basics |title=Ecstasy basics |work=betweenthelines.net.au |accessdate=May 25, 2010}}</ref><ref name="nsw">{{cite web |url=http://www.communitybuilders.nsw.gov.au/download/ecstasy.pdf |title=Ecstacy |work=communitybuilders.nsw.gov.au |publisher=NSW Department of Health |accessdate=May 25, 2010}}</ref><ref name=mydr/><ref name=vic/><ref name=erowid/>
**Irritability<ref name="mydr">{{cite web |url=http://www.mydr.com.au/addictions/ecstasy-effects-on-the-body |title=Ecstasy: effects on the body |work=ydr.com.au |accessdate=May 25, 2010}}</ref>
**Fatigue<ref name="vic">{{cite web |url=http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Ecstasy |title=Ecstacy |work=betterhealth.vic.gov.au |accessdate=May 25, 2010}}</ref><ref name=erowid/>
**Impaired attention, focus, and concentration,<ref name =nsw/> as well as drive and motivation (due to depleted serotonin levels)<ref name=btw/>
**Residual feelings of empathy, emotional sensitivity, and a sense of closeness to others ([[afterglow (drug culture)|afterglow]])

*Physiological
**Dizziness, lightheadedness, or vertigo<ref name="erowid">{{cite web |url=http://www.erowid.org/chemicals/mdma/mdma_basics.shtml |title=MDMA Basics |work=erowid.org |accessdate=May 25, 2010}}</ref>
**Loss of appetite<ref name=btw/><ref name =nsw/>
**Gastrointestinal disturbances, such as diarrhea or constipation<ref name=rutgers/>
**Insomnia<ref name=rutgers/><ref name=btw/><ref name =nsw/>
**Aches and pains, usually from excessive physical activity (e.g., dancing)<ref name=btw/><ref name =nsw/><ref name=vic/>
**Exhaustion<ref name=mydr/><ref name=erowid/>
**Jaw soreness, from [[trismus]] or [[bruxism]]<ref name=erowid/><ref>{{cite web |url=http://www.mdma.net/bruxism/index.html |title=Effects of 3,4-methylenedioxymethamphetamine ('Ecstasy') on the jaw-opening reflex |author=Arrue A, Gomez FM, Giralt MT |date=April 2004 |work=mdma.net |accessdate=May 25, 2010}}</ref><ref>{{cite web |url=http://www.bruxism.org.uk/what-is-bruxism.php |title=What Is Bruxism? |work=bruxism.org.uk |accessdate=May 25, 2010}}</ref>

When they occur, these after [[subacute]] effects are typically reported to last up to 3 to 7 days, with the exception of depression, which in some cases has become chronic.

===Overdose===
{{Ref improve section|date=November 2009}}

Upon [[overdose]], the potentially serious [[serotonin syndrome]], [[stimulant psychosis]], and/or [[hypertensive crisis]], among other dangerous [[adverse drug reaction|adverse reaction]]s, may come to prominence, the symptoms of which can include the following:

*Psychological
**[[Disorientation]] and/or [[mental confusion|confusion]]
**[[Anxiety]], [[paranoia]], and/or [[panic attack]]s
**[[Hypervigilance]] or increased sensitivity to [[perceptual]] [[stimulus (physiology)|stimuli]], accompanied by significantly increased [[coercion|threat]] detection
**[[Hypomania]] or full-blown [[mania]]
**[[Derealization]] and/or [[depersonalization]]
**[[Hallucination]]s and/or [[delusion]]s
**[[Thought disorder]] or [[thought disorder|disorganized thinking]]
**[[Cognitive deficit|Cognitive and memory impairment]] potentially to the point of [[retrograde amnesia|retrograde]] or [[anterograde amnesia]]
**Acute [[delirium]] and/or [[insanity]]

*Physiological
**[[Myoclonus]] or involuntary and intense [[muscle twitching]]
**[[Hyperreflexia]] or overresponsive or overreactive [[reflex]]es
**[[Tachypnoea]] or rapid [[breathing]] and/or [[dyspnea]] or shortness of breath
**[[Palpitation]]s or abnormal awareness of the [[cardiac cycle|beating of the heart]]
**[[Angina pectoris]] or severe [[chest pain]], as well as [[pulmonary hypertension]] (PH)
**[[Cardiac arrhythmia]] or abnormal [[electrical conduction system of the heart|electrical activity]] of the heart
**[[Shock (circulatory)|Circulatory shock]] or [[cardiogenic shock]]
**[[Vasculitis]] or [[toxicity|destruction]] of [[blood vessel]]s
**[[Cardiotoxicity]] or damage to the heart
**Cardiac arrest, [[myocardial infarction]], and/or [[heart failure]]
**[[Hemorrhage]] and/or stroke
**Severe [[hyperthermia]], potentially resulting in [[organ failure]]

*Miscellaneous
**[[Syncope (medicine)|Syncope]] or fainting or [[loss of consciousness]]
**[[Organ failure]] (as mentioned above)
**Possible brain damage
**Coma and/or death

===Chronic use===
Some studies indicate that repeated recreational users of MDMA have increased rates of depression and anxiety, even after quitting the drug.<ref name="MDMAchronic2">{{cite journal |author=Verheyden SL, Henry JA, Curran HV |title=Acute, sub-acute and long-term subjective consequences of 'ecstasy' (MDMA) consumption in 430 regular users |journal=Hum Psychopharmacol |volume=18 |issue=7 |pages=507–17 |year=2003|pmid=14533132 |doi=10.1002/hup.529}}</ref><ref name="MDMAchronic3">{{cite journal |author=Verheyden SL, Maidment R, Curran HV |title=Quitting ecstasy: an investigation of why people stop taking the drug and their subsequent mental health |journal=J. Psychopharmacol. (Oxford) |volume=17 |issue=4 |pages=371–8 |year=2003 |pmid=14870948 |doi= 10.1177/0269881103174014}}</ref> Meta-analytic reviews of the published literature on memory show that ecstasy users suffer significant short-term and long-term verbal memory impairment—with 70-80% of ecstasy users displaying significantly impaired memory. Moreover, this research shows that the memory impairment is not proportional to the lifetime number of tablets consumed and so, may occur with relatively low usage.<ref>{{cite journal |author=Laws KR, Kokkalis J |title=Ecstasy (MDMA) and memory function: a meta-analytic update |journal=Human Psychopharmacology: Clinical and Experimental |volume=22 |issue=6 |pages=381–88 |year=2007 |doi=10.1002/hup.857}}</ref>. Other meta analyses have also reported significant impairment of wider aspects of cognitive function, such as executive function.<ref name="MDMAchronic4">{{cite journal |author=Rodgers J, Buchanan T, Scholey AB, Heffernan TM, Ling J, Parrott AC |title=Patterns of drug use and the influence of gender on self-reports of memory ability in ecstasy users: a web-based study |journal=J. Psychopharmacol. (Oxford) |volume=17 |issue=4 |pages=389–96 |year=2003 |pmid=14870950 |doi= 10.1177/0269881103174016}}</ref> Many factors, including total lifetime MDMA consumption, the duration of abstinence between uses, the environment of use, poly-drug use/abuse, quality of [[mental health]], various lifestyle choices, and predispositions to develop clinical depression and other disorders may contribute to various possible health consequences. MDMA use has been occasionally associated with [[liver]] damage,<ref>{{cite journal |author=Jones AL, Simpson KJ |title=Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications |journal=Aliment. Pharmacol. Ther. |volume=13 |issue=2 |pages=129–33 |year=1999 |pmid=10102941 |doi=10.1046/j.1365-2036.1999.00454.x |url=http://www.maps.org/w3pb/new/1999/1999_jones_16_1.pdf|format=PDF}}</ref> excessive wear of teeth,<ref>{{cite journal |author=Milosevic A, Agrawal N, Redfearn P, Mair L |title=The occurrence of toothwear in users of Ecstasy (3,4-methylenedioxymethamphetamine) |journal=Community Dent Oral Epidemiol |volume=27 |issue=4 |pages=283–7 |year=1999 |pmid=10403088 |doi= 10.1111/j.1600-0528.1998.tb02022.x|url=http://www.maps.org/w3pb/new/1999/1999_milosevic_84_1.pdf|format=PDF}}</ref> and (very rarely) [[hallucinogen persisting perception disorder]].<ref>{{cite journal |author=Creighton FJ, Black DL, Hyde CE |title='Ecstasy' psychosis and flashbacks |journal=Br J Psychiatry |volume=159 |pages=713–5 |year=1991|pmid=1684523 |doi= 10.1192/bjp.159.5.713|url=http://www.maps.org/w3pb/new/1991/1991_creighton_526_1.pdf|format=PDF}}</ref>

==Legal issues==
{{Globalize|section|UK|USA|date=July 2010}}
MDMA is legally controlled in most of the world under the UN [[Convention on Psychotropic Substances]] and other international agreements, although exceptions exist for research. Generally, the unlicensed use, sale or manufacture of MDMA are all criminal offenses.

===United Kingdom===

MDMA was made illegal in 1977 by a modification order to the existing [[Misuse of Drugs Act 1971]]. Although MDMA was not named explicitly in this legislation, the order extended the definition of Class A drugs to include various ring-substituted phenethylamines,<ref>http://www.statutelaw.gov.uk/content.aspx?LegType=All+Primary&PageNumber=57&NavFrom=2&parentActiveTextDocId=1367412&ActiveTextDocId=1367472&filesize=411</ref> thereby making it illegal to sell, buy, or possess the drug without a license. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking. See [[list of drugs illegal in the United Kingdom|list of drugs illegal in the UK]] for more information. In February 2009 an official independent scientific advisory board to the UK government recommended that MDMA be re-classified to Class B, but this recommendation was immediately rejected by the government (see [[MDMA#Recommendation_to_downgrade_MDMA_to_Class_B_in_the_UK_.28Feb_2009.29|Recommendation to downgrade MDMA]]). This 2009 report on MDMA stated:<ref name="drugs.homeoffice.gov.uk">[http://drugs.homeoffice.gov.uk/publication-search/acmd/mdma-report A review of MDMA ('ecstasy'), its harms and classification under the Misuse of Drugs Act 1971], Advisory Council on the Misuse of Drugs (ACMD), 11 February 2009</ref>

{{quote|The original classification of MDMA in 1977 under the Misuse of Drugs Act 1971 as a Class A drug was carried out before it had become widely used and with limited knowledge of its pharmacology and toxicology. Since then use has increased enormously, despite it being a Class A drug. As a consequence, there is now much more evidence on which to base future policy decisions.... Recommendation 1: A harm minimisation approach to the widespread use of MDMA should be continued.... Recommendation 6: MDMA should be re-classified as a Class B drug.}}

===United States===
In the U.S., MDMA was legal and unregulated until 31 May 1985, at which time it was emergency scheduled to [[Controlled Substances Act|DEA Schedule I]], for drugs deemed to have no medical uses and a high potential for abuse. During [[Drug Enforcement Administration|DEA]] hearings to schedule MDMA, most experts recommended [[Controlled Substances Act|DEA Schedule III]] prescription status for the drug, due to beneficial usage of MDMA in psychotherapy. The Administrative Law Judge (ALJ) overseeing the hearings, Francis Young, also recommended that MDMA be placed in Schedule III. The DEA then classified MDMA as Schedule I.<ref>{{cite web|title=Documents from the DEA Scheduling Hearing of MDMA, |author=MAPS| url=http://www.maps.org/dea-mdma/}}</ref><ref>[http://www.cognitiveliberty.org/dll/mdmaindex.htm MDMA (Ecstasy) Law & Policy] Center for Cognitive Liberty & Ethics</ref> However, in ''Grinspoon v. Drug Enforcement Administration'', 828 F.2d 881 (1st Cir. 1987), the First Circuit Court of Appeals remanded the scheduling determination for reconsideration by the DEA.<ref>''Grinspoon v. Drug Enforcement Administration'', 828 F.2d 881 (1st Cir. 1987)</ref> MDMA was temporarily removed from Schedule I.<ref>''Schedules of Controlled Substances; Deletion of 3,4-Methylenedioxymethamphetamine (MDMA) From Schedule I of the Controlled Substances Act'', 53 Fed. Reg. 2,225 (DEA 1988)</ref> Ultimately, in 1988, the DEA re-evaluated its position on remand and subsequently placed MDMA into Schedule I of the Controlled Substances Act.<ref>''Schedules of Controlled Substances; Scheduling of 3,4-Methylenedioxymethamphetamine (MDMA) Into Schedule I of the Controlled Substances Act; Remand'', 53 Fed. Reg. 5,156 (DEA 22 Feb. 1988)</ref> In 2001, responding to a mandate from the [[U.S. Congress]], the [[U.S. Sentencing Commission]], resulted in an increase in the penalties for MDMA by nearly 3,000%,<ref>[http://www.erowid.org/chemicals/mdma/references/media/2001_ap_sentencing_1.shtml SF Gate News 21 March 2001]</ref> despite scientific protest calling for a decrease in the penalties for MDMA possession and distribution.<ref>[http://www.erowid.org/chemicals/mdma/mdma_sentencing_fas1.pdf Federation of American Scientists MDMA Testimony (PDF)]</ref> The increase makes 1&nbsp;gram of MDMA (four pills at 250&nbsp;mg per pill's total weight regardless of purity, standard for Federal charges) equivalent to 1&nbsp;gram of [[heroin]] (approximately fifty doses) or 2.2 pounds (1&nbsp;kg) of [[Cannabis (drug)|cannabis]] for sentencing purposes at the federal level.<ref>[http://www.ussc.gov/2007guid/2d1_1.html U.S. Federal Sentencing Guidelines (2007)]</ref> See also the [[RAVE act|RAVE Act of 2003]].

===World Health Organization===
In 1985 the [[World Health Organization]]'s Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the [[Convention on Psychotropic Substances|1971 Convention on Psychotropic Substances]], despite noting:<ref name="whqlibdoc.who.int">[http://whqlibdoc.who.int/trs/WHO_TRS_729.pdf 22nd report of the Expert Committee on Drug Dependence] World Health Organization, 1985]</ref>

{{quote|No data are available concerning its clinical abuse liability, nature and magnitude of associated public health or social problems.}}

The decision to recommend scheduling of MDMA was not unanimous:<ref name="whqlibdoc.who.int"/>

{{quote|One member, Professor Paul Grof (Chairman), felt that the decision on the recommendation should be deferred awaiting, in particular, the data on the substance's potential therapeutic usefulness and that at this time international control is not warranted.}}

The [[Convention on Psychotropic Substances|1971 Convention]] has a provision in Article 7(a) that allows use of Schedule I drugs for "scientific and very limited medical purposes." The committee's report stated:<ref name="whqlibdoc.who.int"/><ref>[http://www.ecstasy.org/books/e4x/e4x.ap.01/e4x.ap.01.015.html E for Ecstasy by Nicholas Saunders, Appendix 1: Reference Section]</ref>

{{quote|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.}}

==Health concerns==
{{Main|Effects of MDMA on the human body}}
[[Image:Rational scale to assess the harm of drugs (mean physical harm and mean dependence).svg|thumb|right|250px|Relative physical harm and dependence of ecstasy (the British medical journal [[The Lancet]])<ref>{{cite journal |author=Nutt D, King LA, Saulsbury W, Blakemore C |title=Development of a rational scale to assess the harm of drugs of potential misuse |journal=Lancet |volume=369 |issue=9566 |pages=1047–53 |year=2007 |pmid=17382831 |doi=10.1016/S0140-6736(07)60464-4}}</ref>]]

While the short-term adverse effects and contraindications of MDMA are fairly well known, there is significant debate within the scientific and medical communities regarding possible long-term physical and psychological effects of MDMA.

===Short-term health concerns===
Short-term physical health risks of MDMA consumption include [[hyperthermia]],<ref>{{cite journal |author=Nimmo SM, Kennedy BW, Tullett WM, Blyth AS, Dougall JR |title=Drug-induced hyperthermia |journal=Anaesthesia |volume=48 |issue=10 |pages=892–5 |year=1993 |pmid=7902026 |doi= 10.1111/j.1365-2044.1993.tb07423.x}}</ref><ref>{{cite journal |author=Malberg JE, Seiden LS |title=Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat |journal=J. Neurosci. |volume=18 |issue=13 |pages=5086–94 |year=1998 |pmid=9634574}}</ref> and [[hyponatremia]].<ref>{{cite journal |author=Wolff K, Tsapakis EM, Winstock AR, ''et al.'' |title=Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population |journal=J. Psychopharmacol. (Oxford) |volume=20 |issue=3 |pages=400–10 |year=2006|pmid=16574714 |doi=10.1177/0269881106061514}}</ref> Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive [[perspiration]] puts the body at further risk as the stimulatory and euphoric qualities of the drug may render the user oblivious to their energy expenditure for quite some time. [[Diuretics]] such as alcohol may exacerbate these risks further. Although one study<ref>{{cite journal |author=Dumont GJ, Kramers C, Sweep FC, Willemsen JJ,Touw DJ, Schoemaker RC, van Gerven JM, Buitelaar JK, Verkes RJ|pmid=19074534 |title=Ethanol co-administration moderates 3,4-methylenedioxymethamphetamine effects on human physiology|journal=J Psychopharmacol|year=2010|volume=24(2)|pages=165–74 |issue=2 |doi=10.1177/0269881108100020}}</ref> argues that MDMA itself causes fluid retention and increased body temperature, while alcohol is a [[diuretics|diuretic]] and lowers the body temperature. Therefore, it is possible that a small amount of alcohol may help counteract a few of the adverse effects of MDMA.

===Long-term effects on serotonin and dopamine===
MDMA causes a reduction in the concentration of [[serotonin transporter]]s (SERTs) in the brain. The rate at which the brain recovers from serotonergic changes is unclear. One study demonstrated lasting serotonergic changes in animals occurring due to MDMA exposure<ref name="Fischer">{{cite journal |author=Fischer C, Hatzidimitriou G, Wlos J, Katz J, Ricaurte G |title=Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") |journal=J. Neurosci. |volume=15 |issue=8 |pages=5476–85 |year=1995 |pmid=7643196}}</ref>. Other studies have suggested that the brain may recover from serotonergic damage.<ref>{{cite journal |author=Scheffel U, Szabo Z, Mathews WB, ''et al.'' |title=In vivo detection of short- and long-term MDMA neurotoxicity--a positron emission tomography study in the living baboon brain |journal=Synapse |volume=29 |issue=2 |pages=183–92 |year=1998 |pmid=9593108 |doi= 10.1002/(SICI)1098-2396(199806)29:2<183::AID-SYN9>3.0.CO;2-3|url=http://www.erowid.org/references/refs_view.php?ID=367}}</ref><ref name="pmid11576026">{{cite journal |author=Reneman L, Lavalaye J, Schmand B, ''et al.'' |title=Cortical serotonin transporter density and [[verbal memory]] in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"): preliminary findings |journal=Arch. Gen. Psychiatry |volume=58 |issue=10 |pages=901–6 |year=2001 |pmid=11576026 |doi= 10.1001/archpsyc.58.10.901}}</ref>

Some studies show that MDMA may be [[neurotoxicity|neurotoxic]] in humans.<ref>[http://www.dancesafe.org/slideshow/slide19.html Neurotoxicity] at Dancesafe.org</ref><ref>[http://www.erowid.org/chemicals/mdma/mdma_neurotoxicity1.shtml#introduction Does MDMA Cause Brain Damage?], Matthew Baggott, and John Mendelson</ref> Other studies, however, suggest that any potential brain damage may be at least partially reversible following prolonged abstinence from MDMA.<ref name="pmid11576026"/><ref>[http://www.maps.org/mdma/nyt120203.html Research on Ecstasy Is Clouded by Errors], Donald G. McNeil Jr., ''New York Times'', 2 December 2003.</ref> However, other studies suggest that SERT-depletion arises from long-term MDMA use due to receptor [[Downregulation|down-regulation]], rather than true neurotoxicity.<ref>"p-Chlorophenylalanine Changes Serotonin Transporter mRNA Levels and Expression of the Gene Product", [[Journal of Neurochemistry]], 1996. [http://thedea.org/docs/1996_rattray_1.pdf Online copy] (pdf)</ref>
Depression and deficits in memory have been shown to occur more frequently in long-term MDMA users.<ref>[http://www.dancesafe.org/documents/druginfo/depression.php Depression] at DanceSafe.org</ref><ref name="Wareing">{{cite journal|url=http://www.erowid.org/chemicals/mdma/references/journal/2000_wareing_brit-psychology_1/2000_wareing_brit-psychology_1_text.pdf|format=PDF| title=Working memory deficits in current and previous users of MDMA (‘ecstasy’)| author=Wareing, M. and Fisk, J.E. and Murphy, P.N.|journal=Br J Psychol|volume=91|pages=181–8|year=2000|doi=10.1348/000712600161772|pmid=10832513|issue=Pt 2}}</ref> However, some recent studies have suggested that MDMA use may not be associated with chronic depression.<ref>[[n:Study claims recreational ecstasy use and depression unrelated|Study claims recreational ecstasy use and depression unrelated]], Wikinews,
26 April 2006]</ref><ref name="Guillot 2006">{{cite journal |author=Guillot C, Greenway D |title=Recreational ecstasy use and depression |journal=J. Psychopharmacol. (Oxford) |volume=20 |issue=3 |pages=411–6 |year=2006 |pmid=16574715 |doi=10.1177/0269881106063265 |url=http://www.maps.org/w3pb/new/2007/2007_Guillot_22900_1.pdf}}</ref>

[[Retracted article on toxicity of MDMA on dopamine cells|One study]] on MDMA toxicity, by [[George A. Ricaurte]] of Johns Hopkins School of Medicine, which claimed that a single recreational dose of MDMA could cause [[Parkinson's Disease]] in later life due to severe dopaminergic stress, was actually [[neurotoxicity of MDMA controversy|retracted]] by Ricaurte himself after he discovered his lab had administered not MDMA but [[methamphetamine]], which is known to cause dopaminergic changes similar to the serotonergic changes caused by MDMA.<ref>[http://www.wired.com/techbiz/media/news/2003/09/60328 Ecstasy Study Botched, Retracted], Kristen Philipkoski, Wired.com, 09.05.03</ref> Ricaurte blamed this mistake on a labeling error by the chemical supply company that sold the material to his lab, but the supply company responded that there was no evidence of a labeling error on their end. Most studies have found that levels of the [[dopamine transporter]] (or other markers of dopamine function) in MDMA users deserve further study or are normal.<ref>{{cite journal |author=McCann UD, Ricaurte GA |title=Caveat emptor: editors beware |journal=Neuropsychopharmacology |volume=24 |issue=3 |pages=333–6 |year=2001 |pmid=11256359 |doi=10.1016/S0893-133X(00)00171-8 |url=http://www.maps.org/w3pb/new/2001/2001_mccann_1129_1.pdf|format=PDF}}</ref><ref>{{cite journal |author=Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI |title=The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") |journal=Pharmacol. Rev. |volume=55 |issue=3 |pages=463–508 |year=2003 |pmid=12869661 |doi=10.1124/pr.55.3.3}}</ref><ref>{{cite journal |author=Zakzanis KK, Campbell Z, Jovanovski D |title=The neuropsychology of ecstasy (MDMA) use: a quantitative review |journal=Hum Psychopharmacol |volume=22 |issue=7 |pages=427–35 |year=2007 |pmid=17896346 |doi=10.1002/hup.873 }}</ref><ref>{{cite journal |author=Gijsman HJ, Verkes RJ, van Gerven JM, Cohen AF |title=MDMA study |journal=Neuropsychopharmacology |volume=21 |issue=4 |pages=597 |year=1999 |pmid=10481843 |doi=10.1016/S0893-133X(99)00021-4 |url=http://www.maps.org/w3pb/new/1999/1999_gijsman_295_1.pdf|format=PDF}}</ref><ref>{{cite journal |author=Kish SJ |title=How strong is the evidence that brain serotonin neurons are damaged in human users of ecstasy? |journal=Pharmacol. Biochem. Behav. |volume=71 |issue=4 |pages=845–55 |year=2002|pmid=11888575 |doi=10.1016/S0091-3057(01)00708-0 }}</ref><ref>{{cite journal |author=Kish SJ |title=What is the evidence that Ecstasy (MDMA) can cause Parkinson's disease? |journal=Mov. Disord. |volume=18 |issue=11 |pages=1219–23 |year=2003 |pmid=14639660 |doi=10.1002/mds.10643 |url=http://www.maps.org/w3pb/new/2003/2003_kish_6239_1.pdf|format=PDF}}</ref><ref>Aghajanian & Liebermann (2001) '[http://www.maps.org/w3pb/new/2001/2001_aghajanian_1130_1.pdf Caveat Emptor: Reseearchers Beware]' Neuropsychopharmacology 24,3:335-6</ref>

===Purity and dosage of "ecstasy"===
[[Image:Ecstasy MDMA Molly.jpg|thumb|MDMA powder]]
Another concern associated with MDMA use is toxicity from chemicals other than MDMA in ecstasy tablets. Due to its near-universal illegality, the purity of a substance sold as ecstasy is unknown to the typical user. The MDMA content of tablets varies widely between regions and different brands of pills and fluctuates somewhat each year. Pills may contain other active substances meant to stimulate in a way similar to MDMA, such as [[amphetamine]], [[methamphetamine]], [[ephedrine]], or [[caffeine]], all of which may be comparatively cheap to produce and can help to boost overall profits. In some cases, tablets sold as ecstasy do not even contain any MDMA. Instead they may contain an assortment of presumably undesirable drugs and substances, such as [[paracetamol]], [[ibuprofen]], [[talcum powder]], etc.<ref>[http://ecstasydata.org/datastats.php?row=Summary&percent=1 Summary Statistics for EcstasyData.org Lab Testing Results]</ref>

There have been a number of deaths attributed to [[para-Methoxyamphetamine|PMA]], a potent and highly neurotoxic hallucinogenic amphetamine, being sold as ecstasy.<ref>{{cite journal |author=Refstad S |title=Paramethoxyamphetamine (PMA) poisoning; a 'party drug' with lethal effects |journal=Acta Anaesthesiol Scand |volume=47 |issue=10 |pages=1298–9 |year=2003 |pmid=14616331 |doi= 10.1046/j.1399-6576.2003.00245.x}}</ref><ref>{{cite journal |author=Lamberth PG, Ding GK, Nurmi LA |title=Fatal paramethoxy-amphetamine (PMA) poisoning in the Australian Capital Territory |journal=Med. J. Aust. |volume=188 |issue=7 |pages=426 |year=2008 |pmid=18393753}}</ref> PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA. Hence, a user who believes he is consuming two 120&nbsp;mg pills of MDMA could actually be consuming a dose of PMA that is potentially lethal, depending on the purity of the pill. Not only does PMA cause the release of serotonin, but also acts as a [[monoamine oxidase inhibitor| monoamine oxidase inhibitor, MAOI]]. When combined with an MDMA or an MDMA-like substance, [[serotonin syndrome]] can result.<ref>J Pharm Pharmacol. 1980 Apr;32(4):262-6.</ref> Combining MAO inhibitors with certain legal prescription and over the counter medications can also lead to (potentially fatal) serotonin syndrome.

===Harm assessment===
The chief executive of the UK Medical Research Council stated that MDMA is "on the bottom of the scale of harm", and was rated to be of lesser concern than alcohol, [[tobacco]], as well as several classes of prescription medications, when examining the harmfulness of twenty popular recreational drugs. The UK study placed great weight on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. - They did not evaluate or rate the negative impact of ecstasy on the cognitive health of ecstasy users e.g. poorer memory. Based on these factors, the study placed MDMA at number 18 in the list of 20 popular drugs.<ref>[http://news.bbc.co.uk/2/hi/health/6474053.stm Scientists want new drug rankings], BBC News, 23 March 2007</ref>

[[David Nutt]], a former chairman of the UK [[Advisory Council on the Misuse of Drugs]], stated in the ''Journal of Psychopharmacology'' in January 2009 that ecstasy use compared favorably with horse riding in terms of risk, with ecstasy leading to around 30 deaths a year in the UK compared to about 10 from horse riding, and "acute harm to person" occurring in approximately 1 in 10,000 episodes of ecstasy use compared to about 1 in 350 episodes of horse riding.<ref name="equasy">{{cite journal |author=Nutt DJ |title=Equasy-- an overlooked addiction with implications for the current debate on drug harms |journal=J Psychopharmacol |volume=23 |issue=1 |pages=3–5 |year=2009 |pmid=19158127 |doi=10.1177/0269881108099672|url=http://www.encod.org/info/EQUASY-A-HARMFUL-ADDICTION.html}}</ref> Dr. Nutt notes the lack of a balanced risk assessment in public discussions of MDMA:<ref name="equasy"/>
<blockquote>
The general public, especially the younger generation, are disillusioned with the lack of balanced political debate about drugs. This lack of rational debate can undermine the trust in government in relation to drug misuse and thereby undermining the government's message in public information campaigns. The media in general seem to have an interest in scare stories about illicit drugs, though there are some exceptions (Horizon, 2008).<ref name="Horizon 2008">Horizon (2008) Britain's most dangerous drugs. Tuesday 5 February 2008, 9pm, BBC Two.</ref> A telling review of 10-year media reporting of drug deaths in Scotland illustrates the distorted media perspective very well (Forsyth, 2001).<ref name="Forsyth 2001">Forsyth, AJM (2001) Distorted? A quantitative exploration of drug fatality reports in the popular press. Int J Drug Policy 12: 435–453.</ref> During this decade, the likelihood of a newspaper reporting a death from paracetamol was in {{sic}} per 250 deaths, for diazepam it was 1 in 50, whereas for amphetamine it was 1 in 3 and for ecstasy '''every''' associated death was reported.
</blockquote>
A spokesperson for the ACMD clarified that "The recent article by Professor David Nutt published in the Journal of Psychopharmacology was done in respect of his academic work and not as chair of the ACMD."<ref>[http://news.bbc.co.uk/1/hi/uk/7876425.stm Ecstasy 'not worse than riding'], BBC News, 7 February 2009</ref>

====Recommendation to downgrade MDMA to Class B in the UK (Feb 2009)====
In 2000, the UK Police Foundation issued the [[Runciman Report]] which reviewed the medical and social harms of MDMA and recommended: "Ecstasy and related compounds should be transferred from Class A to Class B."<ref>[http://www.druglibrary.org/schaffer/Library/studies/runciman/default.htm Drugs and the law: Report of the inquiry into the Misuse of Drugs Act 1971] London: Police Foundation, 2000, [[Runciman Report]]</ref> In 2002, the Home Affairs Committee of the UK House of Commons, issued a report, ''The Government's Drugs Policy: Is it working?'', which also recommended that MDMA should be reclassified to a Class B drug.<ref>[http://www.publications.parliament.uk/pa/cm200102/cmselect/cmhaff/318/31802.htm "The Government's Drugs Policy: Is it working?"] House of Commons, Home Affairs Committee, May 2002</ref> The UK government rejected both recommendations, saying that re-classification of MDMA would not be considered without a recommendation from the Advisory Council on the Misuse of Drugs, the official UK scientific advisory board on drug abuse issues.<ref>
[Fifth Report], UK House of Commons, Science and Technology Committee, (July 2006)
[[Drug classification: making a hash of it?|Drug classification: Making a hash of it?]]
</ref>

In February 2009, the UK Advisory Council on the Misuse of Drugs issued ''A review of MDMA ('ecstasy'), its harms and classification under the Misuse of Drugs Act 1971'', which recommended that MDMA be re-classified in the UK from a class A drug to a class B drug.<ref name="drugs.homeoffice.gov.uk"/>

From the Discussion section of the ACMD report on MDMA:
<blockquote>
'''Physical harms:''' ''(10.2)'' Use of MDMA is undoubtedly harmful. High doses may lead to death: by direct toxicity, in situations of hyperthermia/dehydration, excessive water intake, or for other reasons. However, fatalities are relatively low given its widespread use, and are substantially lower than those due to some other Class A drugs, particularly heroin and cocaine. Although it is no substitute for abstinence, the risks can be minimised by following advice such as drinking appropriate amounts of water (see Annex E). ''(10.3)'' Some people experience acute medical consequences as a result of MDMA use which can lead to hospital admission, sometimes with the requirement for intensive care. MDMA poisonings are not currently increasing in number and are less frequent than episodes due to cocaine. ''(10.4)'' MDMA appears not to have a high propensity for dependence or withdrawal reactions although a number of users seek help through treatment services. ''(10.5)'' MDMA appears to have little acute or enduring effect on the mental health of the average user, and unlike amphetamines and cocaine, it is seldom implicated in significant episodes of paranoia. ''(10.6)'' There is presently little evidence of longer-term harms to the brain in terms of either its structure or function. However, there is evidence for some small decline in a variety of domains, including verbal memory, even at low cumulative dose. The magnitude of such deficits appears to be small and their clinical relevance is unclear. The evidence shows that MDMA has been misused in the UK for 20 years but it should be noted that long-term effects of use cannot be ruled out. ''(10.7)'' Overall, the ACMD judges that the physical harms of MDMA more closely equate with those of amphetamine than of heroin or cocaine.
</blockquote>

<blockquote>
'''Societal harms:''' ''(10.8)'' MDMA use seems to have few societal effects in terms of intoxication-related harms or social disorder. However, the ACMD notes the very small proportion of cases where ‘ecstasy’ use has been implicated in sexual assault. ''(10.9)'' Disinhibition and impulsive, violent or risky behaviours are not commonly seen under the influence of MDMA, unlike with cocaine, amphetamines, heroin and alcohol. ''(10.10)'' The major issue for law enforcement is ‘ecstasy's’ position, alongside other Class A drugs, as a commodity favoured by organised criminal groups. It is therefore generally associated with a range of secondary harms connected with the trafficking of illegal drugs.
</blockquote>

The UK Home Office rejected the recommendation of its independent scientific advisory board to downgrade MDMA to Class B, "saying it is not prepared to send a message to young people that it takes ecstasy less seriously".<ref>{{cite journal |author=Kmietowicz Z |title=UK government rejects advice from drugs adviser to downgrade ecstasy |journal=BMJ |volume=338|pages=b592 |year=2009 |pmid=19218326 |doi=10.1136/bmj.b592}}</ref><ref>[http://press.homeoffice.gov.uk/documents/2009-02-10-Campbell-Nutt-Ec1.pdf Campbell A (Home Office minister). Letter to professor David Nutt (chair of the ACMD). (2009)]</ref>

The government's veto was criticized in scientific publications. [[Colin Blakemore]], Professor of Neuroscience, Oxford, stated in the British Medical Journal, "The government's decisions compromise its commitment to evidence based policy".<ref>{{cite journal |author=Blakemore C |title=Classification of cannabis and ecstasy in the UK |journal=BMJ |volume=338 |pages=b731 |year=2009 |pmid=19158127 |doi=10.1136/bmj.b731 |issue=1}}</ref> Also in response, an editorial in the New Scientist noted "A much larger percentage of people suffer a fatal acute reaction to peanuts than to MDMA.... Sadly, perspective is something that is generally lacking in the long and tortuous debate over illegal drugs."<ref>[http://www.newscientist.com/article/mg20126953.300-editorial-drugs-drive-politicians-out-of-their-minds.html Editorial: Drugs drive politicians out of their minds] [[New Scientist]]] (11 February 2009)</ref>

==Environmental concerns==
Demand for [[safrole]], a substance used in the manufacture of MDMA, is causing rapid and illicit harvesting of the ''[[Cinnamomum parthenoxylon]]'' tree in [[Southeast Asia]], in particular the [[Cardamom Mountains]] in [[Cambodia]]<ref>{{cite web
 |last = Campbell
 |first = Sam
 |title = Harvested to make Ecstasy, Cambodia's trees are felled one by one.
 |publisher = GlobalPost
 |date = 30 August 2009
 |url = http://www.globalpost.com/dispatch/asia/090812/drugs-ecstasy-cambodia?page=0,0
 |accessdate = 2 September 2009
}}</ref>. However, it is not clear what proportion of illicitly harvested safrole is going toward MDMA production, as over 90% of the global safrole supply (approx 2000 metric tons per year) is used to manufacture pesticides, fragrances, and other chemicals<ref name=Blickman2009>[http://www.irrawaddy.org/article.php?art_id=15050 Harvesting Trees to Make Ecstasy Drug] Tom Blickman (3 February 2009)</ref><ref name="Rocha1999">[http://www.hort.purdue.edu/newcrop/proceedings1999/v4-479.html Piper hispidinervum: A Sustainable Source of Safrole] Rocha S.F.R. and Lin Chau Ming. 1999. In: J. Janick (ed.), Perspectives on new crops and new uses. ASHS Press, Alexandria, Virginia.</ref>. Sustainable harvesting of safrole is possible from leaves and sticks of certain plants.<ref name="Blickman2009" /><ref name="Rocha1999"/>

==See also==
<div style="-moz-column-count:2; column-count:2; -webkit-column-count:2;">

===Effects classification===
*[[Anorectic]]
*[[Antidepressant]]
*[[Anxiolytic]]
*[[Entactogen]]
*[[Entheogen]]
*[[Euphoriant]]
*[[Hallucinogen]]
*[[Psychedelic drug|Psychedelic]]
*[[Stimulant]]
*[[Sympathomimetic]]

===Pharmacological classification===
*[[Adrenergic]]
*[[Dopaminergic]]
*[[Oxytocic]]
*[[Serotonergic]]
*[[Releasing agent]]
*[[Reuptake inhibitor]]

===Chemical classification===
*[[Substituted phenethylamine]]
*[[Substituted amphetamine]]
*[[Substituted methylenedioxyphenethylamine]]

===Similar or related compounds===
*[[Amphetamine]]
*[[Methamphetamine]]
*[[Methylenedioxyamphetamine]] (MDA)
*[[Methylenedioxyethylamphetamine]] (MDEA)
*[[Methylbenzodioxolylbutanamine]] (MBDB)
*[[Methylone]] (MDMC; bk-MDMA)
*[[Paramethoxyamphetamine|''para''-Methoxyamphetamine]] (PMA)

===Miscellaneous===
*[[Electronica]]
*[[Psychotherapy]]
*[[Rave]] (or [[dance party]])
*[[DanceSafe]]
</div>

==References==
{{Reflist|2}}

==Further reading==
*Julie Holland - "[http://books.google.com/books?id=CUCcyklcO00C Ecstasy: The Complete Guide: A Comprehensive Look at the Risks and Benefits of MDMA]" Park Street Press (2001).
*Jerome Beck, Marsha Rosenbaum - "[http://books.google.com/books?id=SwdedK36bVMC Pursuit of Ecstasy: The MDMA Experience]" SUNY Press (1994).
*Leslie Iversen - "[http://books.google.com/books?id=CkAaAZRLfOcC Speed, Ecstasy, Ritalin: The Science of Amphetamines]" Oxford University Press (2008).
*[[David Pearce (philosopher)|David Pearce]] - "[http://mdma.net Utopian Pharmacology: Mental Health in the Third Millenium: MDMA and Beyond]" (2008).
*Kobie Whetstone - "[http://www.mdma.net/kobie/simple.html The Brain Damage of MDMA ("Ecstasy"): Causes and Prevention for the Recreational User]" (2009).
*Kobie Whetstone - "[http://mdma.net/kobie An Analysis of MDMA-induced Neurotoxicity]" (2009).
*Earth Erowid - "[http://www.erowid.org/chemicals/mdma/mdma_article3.shtml Do Antioxidants Protect Against MDMA Hangover, Tolerance, and Neurotoxicity?]" Erowid Extracts (2001).
*Marsha Rosenbaum, [[Rick Doblin]] - "[http://www.psychedelic-library.org/rosenbaum.htm Why MDMA Should Not Have Been Made Illegal]" SAGE Publications (1991).
*[[Nature (journal)|Nature News]] - "[http://www.nature.com/news/2008/081119/full/456293d.html Ecstasy Could Augment the Benefits of Psychotherapy]" (2008).
*[[Nature (journal)|Nature News]] - "[http://www.nature.com/news/2010/100416/full/news.2010.188.html Party drug could ease trauma long term]" (2010).
*Reuters Health - "[http://www.reuters.com/article/scienceNews/idUSTRE52I6V720090320 Ecstasy May Help PTSD Victims Get Better]" (2009).
*[[The Economist]] - "[http://www.economist.com/science/displaystory.cfm?STORY_ID=12792611 Agony and Ecstasy: Ecstasy May Be Good For Those Who Can’t Get Over Something Truly Horrible]" (2008).
*[[New Scientist]] - "[http://www.newscientist.com/article/mg20126954.500-ecstasys-longterm-effects-revealed.html Ecstasy's Long-Term Effects Revealed]" (2009).
*Matt Palmquist Miller-McCune - "[http://www.miller-mccune.com/health/the-ecstasy-and-the-agony-1391 The Ecstasy and the Agony]" (August 2009).
*[[Advisory Council on the Misuse of Drugs|ACMD]] - "[http://drugs.homeoffice.gov.uk/publication-search/acmd/mdma-report MDMA (Ecstasy): A Review of its Harms and Classification Under the Misuse of Drugs Act 1971]" UK Home Office (2009).
*[[National Institute on Drug Abuse|NIDA]] InfoFacts - "[http://www.nida.nih.gov/InfoFacts/ecstasy.html MDMA (Ecstasy)]" (August 2008).

==External links==
*[[Alexander Shulgin]] & [[Ann Shulgin]] - [[PiHKAL]]: "[http://pihkal.info/read.php?domain=pk&id=109 #109 MDMA: MDM; ADAM; Ecstasy; 3,4-Methylenedioxy-''N''-methylamphetamine]" (1991).
*[[ABC News]] - "[http://thedea.org/media.html Primetime Special: Peter Jennings - Ecstasy Rising]" (2004).
*[[Erowid|The Vaults of Erowid]]: "[http://www.erowid.org/chemicals/mdma/mdma.shtml MDMA ("Ecstasy")]".
*[[Erowid|Erowid Experience Vaults]]: "[http://www.erowid.org/experiences/subs/exp_MDMA.shtml MDMA ("Ecstasy", "E", "X") Reports]".
*[[DanceSafe]]: "[http://www.dancesafe.org/documents/druginfo/ecstasy.php What is Ecstasy?]".
*[[Multidisciplinary Association for Psychedelic Studies|MAPS]]: "[http://www.maps.org/research/mdma/ R&D Medicines > MDMA]".
*[http://www.ecstasydata.org/ EcstasyData.org: Providing Access to Lab Testing Results for Street Ecstasy Tablets].
*[http://www.pillreports.com/ PillReports.com: Ecstasy Test Results Database by Enlighten].
*[http://www.thecrimson.com/article/2000/4/20/fifteen-minutes-e-is-for-ecstasy Fifteen Minutes: E is for Ecstasy]
{{Drug use}}
{{Entactogens}}
{{Hallucinogens}}
{{Stimulants}}
{{Adrenergics}}
{{Dopaminergics}}
{{Serotonergics}}
{{Phenethylamines}}

{{Use dmy dates|date=August 2010}}

{{DEFAULTSORT:Mdma}}
[[Category:Entactogens and Empathogens]]
[[Category:Amphetamines]]
[[Category:Class A drugs]]
[[Category:Euphoriants]]
[[Category:Benzodioxoles]]

[[ca:MDMA]]
[[de:MDMA]]
[[es:MDMA]]
[[eu:MDMA]]
[[fr:MDMA]]
[[he:אקסטזי]]
[[hr:MDMA]]
[[id:Metilendioksimetamfetamin]]
[[it:MDMA]]
[[nl:3,4-methyleendioxymethamfetamine]]
[[ja:メチレンジオキシメタンフェタミン]]
[[no:MDMA]]
[[pl:3,4-metylenodioksymetamfetamina]]
[[ro:MDMA]]
[[ru:3,4-метилендиоксиметамфетамин]]
[[sr:Екстази]]
[[fi:MDMA]]
[[sv:Ecstasy]]
[[ur:مدما]]
[[vi:Thuốc lắc]]
[[zh:MDMA]]
[[Category:2Fix]]