View source for Chemistry:MDMA

{{Short description|Psychoactive drug, often called ecstasy}}
{{hatgrp|
}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 632164040
| drug_name = MDMA
| INN = Midomafetamine<ref name=INN>{{cite news|title=FDA Substance Registration System|url=https://fdasis.nlm.nih.gov/srs/unii/KE1SEN21RM|access-date=31 August 2017|publisher=United States National Library of Medicine|archive-date=31 August 2017|archive-url=https://web.archive.org/web/20170831220013/https://fdasis.nlm.nih.gov/srs/unii/KE1SEN21RM|url-status=dead}}</ref>
| chirality = [[Chemistry:Racemic mixture|Racemic mixture]]
| image = MDMA (simple).svg
| width = 250px
| alt = MDMA structure
| image2 = MDMA molecule from xtal ball.png
| alt2 = Ball-and-stick model of an MDMA molecule
| width2 = 250px

<!--Identifiers-->
| IUPAC_name = (''RS'')-1-(1,3-Benzodioxol-5-yl)-''N''-methylpropan-2-amine<!--From PubChem-->
| pronounce = methylenedioxy{{shy}}methamphetamine:<br />{{IPAc-en|ˌ|m|ɛ|θ|ᵻ|l|iː|n|d|aɪ|ˈ|ɒ|k|s|i}}<br />{{IPAc-en|ˌ|m|ɛ|θ|æ|m|ˈ|f|ɛ|t|əm|iː|n}}
| ATC_prefix = None
| Drugs.com = {{Drugs.com|parent|MDMA}}
| CAS_number_Ref = {{cascite|correct|TOXNET}}
| CAS_number = 42542-10-9
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1556
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = KE1SEN21RM
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01454
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 1391
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 43048
| PubChem = 1615
| IUPHAR_ligand = 4574
| KEGG = D11172
| KEGG_Ref = {{keggcite|correct|kegg}}
| synonyms = {{abbr|3,4-MDMA|3,4-Methylenedioxymethamphetamine}}; Ecstasy (E, X, XTC); Molly; Mandy;<ref name="nature.com">{{cite journal | vauthors = Luciano RL, Perazella MA | title = Nephrotoxic effects of designer drugs: synthetic is not better! | journal = Nature Reviews. Nephrology | volume = 10 | issue = 6 | pages = 314–24 | date = June 2014 | pmid = 24662435 | doi = 10.1038/nrneph.2014.44 | s2cid = 9817771}}</ref><ref name="DrugFacts">{{cite web|title=DrugFacts: MDMA (Ecstasy or Molly)|url=http://www.drugabuse.gov/publications/drugfacts/mdma-ecstasy-or-molly|publisher=National Institute on Drug Abuse|access-date=2 December 2014|url-status=dead|archive-url=https://web.archive.org/web/20141203115531/http://www.drugabuse.gov/publications/drugfacts/mdma-ecstasy-or-molly|archive-date=3 December 2014|df=dmy-all}}</ref> Pingers/Pingas<ref>{{cite web|url=https://theconversation.com/pingers-pingas-pingaz-how-drug-slang-affects-the-way-we-use-and-understand-drugs-129452|title=Pingers, pingas, pingaz: how drug slang affects the way we use and understand drugs|publisher=The Conversation|date=2020-01-08|archive-url=https://web.archive.org/web/20210115205246/https://theconversation.com/pingers-pingas-pingaz-how-drug-slang-affects-the-way-we-use-and-understand-drugs-129452|archive-date=2021-01-15|url-status=live}}</ref>
| PDB_ligand = B41

<!--Chemical data-->
| C=11 | H=15 | N=1 | O=2
| SMILES = CC(NC)CC1=CC=C(OCO2)C2=C1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C11H15NO2/c1-8(12-2)5-9-3-4-10-11(6-9)14-7-13-10/h3-4,6,8,12H,5,7H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = SHXWCVYOXRDMCX-UHFFFAOYSA-N
| density = 1.1
| melting_point =
| melting_notes =
| boiling_point = 105
| boiling_notes = at 0.4&nbsp;mmHg (experimental)<!--Pubchem-->

<!--Clinical/legal data-->
| legal_AU = {{unbulleted list
|S8 (PTSD)
|S9 (all other uses)
}}
| legal_BR = F2
| legal_CA = Schedule I
| legal_DE = Anlage I
| legal_NZ = Class B
| legal_UK = Class A
| legal_US = Schedule I
| legal_UN = Psychotropic Schedule I
| legal_status =
| pregnancy_category =
| pregnancy_US =
| licence_US =
| class = [[Chemistry:Empathogen–entactogen|Empathogen–entactogen]]<br /> [[Chemistry:Stimulant|stimulant]]

<!--Pharmacological data-->
| dependency_liability = [[Medicine:Physical dependence|Physical]]: not typical<ref name=palmer>{{cite book| vauthors = Palmer RB |title=Medical toxicology of drug abuse : synthesized chemicals and psychoactive plants|date=2012|publisher=John Wiley & Sons|location=Hoboken, N.J. |isbn=978-0-471-72760-6|page=139|url=https://books.google.com/books?id=OWFiVaDZnkQC&pg=PA139}}</ref><br />[[Medicine:Psychological dependence|Psychological]]: moderate
| addiction_liability= Low–moderate<ref name="NHM-MDMA">{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | pages = 375 | edition = 2nd | chapter = Chapter 15: Reinforcement and Addictive Disorders}}</ref><ref name=Betzler2017>{{cite journal | vauthors = Betzler F, Viohl L, Romanczuk-Seiferth N | title = Decision-making in chronic ecstasy users: a systematic review | journal = The European Journal of Neuroscience | volume = 45 | issue = 1 | pages = 34–44 | date = January 2017 | pmid = 27859780 | doi = 10.1111/ejn.13480 | s2cid = 31694072 | quote = ...the addictive potential of MDMA itself is relatively small.| doi-access = free }}</ref><ref name="Substance abuse">{{cite journal | vauthors = Jerome L, Schuster S, Yazar-Klosinski BB | title = Can MDMA play a role in the treatment of substance abuse? | journal = Current Drug Abuse Reviews | volume = 6 | issue = 1 | pages = 54–62 | date = March 2013 | pmid = 23627786 | doi = 10.2174/18744737112059990005 | s2cid = 9327169 | quote = Animal and human studies demonstrate moderate abuse liability for MDMA, and this effect may be of most concern to those treating substance abuse disorders. | url = http://pdfs.semanticscholar.org/33fd/4f5decd405dee8d4f280a9158bfb16ae6e27.pdf | archive-url = https://web.archive.org/web/20200803194522/http://pdfs.semanticscholar.org/33fd/4f5decd405dee8d4f280a9158bfb16ae6e27.pdf | url-status = dead | archive-date = 2020-08-03}}</ref>
| elimination_half-life = (''R'')-MDMA: 5.8&nbsp;±&nbsp;2.2&nbsp;hours (variable)<ref name="Toxnet MDMA after-effects">{{cite web|title=3,4-Methylenedioxymethamphetamine|url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+42542-10-9|website=Hazardous Substances Data Bank|publisher=National Library of Medicine|access-date=22 August 2014|date=28 August 2008}}</ref><br />(''S'')-MDMA: 3.6&nbsp;±&nbsp;0.9&nbsp;hours (variable)<ref name="Toxnet MDMA after-effects"/>
| metabolism = [[Biology:Liver|Liver]], CYP450 extensively involved, including [[Biology:CYP2D6|CYP2D6]]
| metabolites = MDA, [[Chemistry:4-Hydroxy-3-methoxymethamphetamine|HMMA]], HMA, [[Chemistry:Alpha-Methyldopamine|DHA]], MDP2P, MDOH<ref name="pmid22392347">{{cite journal | vauthors = Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos M | title = Toxicity of amphetamines: an update | journal = Archives of Toxicology | volume = 86 | issue = 8 | pages = 1167–231 | date = August 2012 | pmid = 22392347 | doi = 10.1007/s00204-012-0815-5 | s2cid = 2873101}}</ref>
| excretion = Kidney
| routes_of_administration = Common: by mouth<ref name=EU2015 /><br /> Uncommon: [[Medicine:Insufflation|snorting]],<ref name=EU2015 /> [[Biology:Inhalation|inhalation]] ([[Physics:Vaporization|vaporization]]),<ref name=EU2015 /> [[Medicine:Injection|injection]],<ref name=EU2015>{{cite web|title=Methylenedioxymethamphetamine (MDMA or 'Ecstasy')|url=http://www.emcdda.europa.eu/publications/drug-profiles/mdma|website=EMCDDA|publisher=European Monitoring Centre for Drugs and Drug Addiction|access-date=17 October 2014|ref=EMCDDA}}</ref><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|url-status=dead|archive-url = https://web.archive.org/web/20120503102427/http://www.nhtsa.gov/people/injury/research/job185drugs/methylenedioxymethamphetamine.htm|archive-date = 3 May 2012|df = dmy-all}}</ref> rectal
| onset = 30–45&nbsp;minutes (by mouth)<ref name=Freye2009/>
| duration_of_action = 4–6&nbsp;hours<ref name=Betzler2017/><ref name=Freye2009/>
| bioavailability = [[Medicine:Oral administration|Oral]]: Unknown<ref name="Freye2009"/>
| protein_bound =
}}

<!-- Definition and uses -->
'''3,4-Methyl{{wbr}}enedioxy{{wbr}}methamphetamine''' ('''MDMA'''), commonly known as '''ecstasy''' ([[Medicine:Tablet (pharmacy)|tablet]] form), and '''molly''' or '''mandy''' (crystal form),<ref>{{Cite journal | vauthors = Palamar JJ |date=2016-12-07 |title=There's Something About Molly: The Under-Researched yet Popular Powder Form of Ecstasy in the United States |journal=The Center for Drug Use and HIV Research |volume=38,1 |issue=Substance abuse |pages=15–17 |doi=10.1080/08897077.2016.1267070 |pmid=27925866 |pmc=5578728 }}</ref><ref>{{Cite web |editor=Håvard Atle Skaug |title=Hva er tryggest av molly og ecstasy? |url=https://www.ung.no/oss/rusmidler/462397.html |access-date=2022-06-20 |publisher=Norwegian Directorate for Children, Youth and Family Affairs |website=Ung.no |language=no |publication-date=2020-12-14 |quote=MDMA er virkestoffet i både Molly-krystaller og Ecstasy-tabletter.}}</ref> is a potent [[Chemistry:Empathogen–entactogen|empathogen–entactogen]] with [[Chemistry:Stimulant|stimulant]] and minor [[Chemistry:Psychedelic drug|psychedelic]] properties, primarily used for recreational purposes.<ref name="Current2013">{{cite journal | vauthors = Meyer JS | title = 3,4-methylenedioxymethamphetamine (MDMA): current perspectives | journal = Substance Abuse and Rehabilitation | volume = 4 | pages = 83–99 | year = 2013 | pmid = 24648791 | pmc = 3931692 | doi = 10.2147/SAR.S37258 | doi-access = free }}</ref> The purported pharmacological effects that may be prosocial include altered sensations, increased energy, empathy, and pleasure.<ref name=Current2013/><!-- quote = desire to experience an altered state of consciousness --><ref name=Drugs2014>{{cite web |title=MDMA|url=https://www.drugs.com/illicit/mdma.html|access-date=30 March 2016| veditors=Anderson L |website=Drugs.com|publisher=Drugsite Trust|date=18 May 2014|url-status=live |archive-url=https://web.archive.org/web/20160323161153/http://www.drugs.com/illicit/mdma.html |archive-date=23 March 2016}}</ref><!-- Quote = producing an energizing effect, as well as distortions in time and perception and enhanced enjoyment from tactile experiences --> When taken by mouth, effects begin in 30 to 45 minutes and last three to six hours.<ref name=Freye2009>{{cite book| vauthors = Freye E |title=Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs|date=28 July 2009|publisher=Springer Netherlands|isbn=978-90-481-2448-0|pages=151–160|chapter=Pharmacological Effects of MDMA in Man|doi=10.1007/978-90-481-2448-0_24}}</ref><ref name=NIH2016/>

<!-- Usage and history -->
MDMA was first synthesized in 1912 by Merck.<ref name="Merck">{{cite journal | vauthors = Freudenmann RW, Öxler F, Bernschneider-Reif S | title = The origin of MDMA (ecstasy) revisited: the true story reconstructed from the original documents | url = http://www.thedea.org/docs/2006_Freudenmann_22846_1.pdf | journal = Addiction | volume = 101 | issue = 9 | pages = 1241–1245 | date = August 2006 | pmid = 16911722 | doi = 10.1111/j.1360-0443.2006.01511.x | quote = Although MDMA was, in fact, first synthesized at Merck in 1912, it was not tested pharmacologically because it was only an unimportant precursor in a new synthesis for haemostatic substances.}}</ref> It was used to enhance [[Medicine:Psychotherapy|psychotherapy]] beginning in the 1970s and became popular as a street drug in the 1980s.<ref name=Drugs2014/><ref name=NIH2016/> MDMA is commonly associated with dance parties, raves, and electronic dance music.<ref name=WHO2004>{{cite book|author=World Health Organization|title=Neuroscience of Psychoactive Substance Use and Dependence|url=https://books.google.com/books?id=G9OhG-dZdAwC&pg=PA97|year=2004|publisher=World Health Organization|isbn=978-92-4-156235-5|pages=97–|url-status=live|archive-url=https://web.archive.org/web/20160428231233/https://books.google.com/books?id=G9OhG-dZdAwC&pg=PA97|archive-date=28 April 2016|df=dmy-all}}</ref> Tablets sold as ecstasy may be [[Chemistry:Cutting agent|mixed]] with other substances such as [[Chemistry:Ephedrine|ephedrine]], [[Chemistry:Amphetamine|amphetamine]], and [[Chemistry:Methamphetamine|methamphetamine]].<ref name=Drugs2014/> In 2016, about 21 million people between the ages of 15 and 64 used ecstasy (0.3% of the world population).<ref name=UN2018>{{cite book |title=World Drug Report 2018 |date=June 2018 |publisher=United Nations |isbn=978-92-1-148304-8 |page=7 |access-date=14 July 2018|url=https://www.unodc.org/wdr2018/prelaunch/WDR18_Booklet_1_EXSUM.pdf}}</ref> This was broadly similar to the percentage of people who use [[Biology:Cocaine|cocaine]] or [[Chemistry:Substituted amphetamine|amphetamine]]s, but lower than for [[Biology:Cannabis (drug)|cannabis]] or [[Chemistry:Opioid|opioid]]s.<ref name=UN2018/> In the United States, as of 2017, about 7% of people have used MDMA at some point in their lives and 0.9% have used it in the last year.<ref>{{cite web |title=MDMA (Ecstasy/Molly) |url=https://www.drugabuse.gov/drugs-abuse/mdma-ecstasymolly |website=National Institute on Drug Abuse |access-date=14 July 2018}}</ref> The lethal risk from one dose of MDMA is estimated to be from 1 death in 20,000 instances to 1 death in 50,000 instances.<ref>{{cite journal | vauthors = White CM | title = How MDMA's pharmacology and pharmacokinetics drive desired effects and harms | journal = Journal of Clinical Pharmacology | volume = 54 | issue = 3 | pages = 245–252 | date = March 2014 | pmid = 24431106 | doi = 10.1002/jcph.266 | s2cid = 6223741 }}</ref>

<!-- Side effects, chemistry and mechanism -->
Short-term adverse effects include [[Medicine:Bruxism|grinding of the teeth]], blurred vision, sweating and a [[Medicine:Tachycardia|rapid heartbeat]],<ref name=Drugs2014/> and extended use can also lead to [[Medicine:Addiction|addiction]], [[Medicine:Amnesia|memory problems]], [[Medicine:Paranoia|paranoia]] and [[Medicine:Insomnia|difficulty sleeping]]. Deaths have been reported due to increased body temperature and dehydration. Following use, people often feel [[Medicine:Depression (mood)|depressed]] and tired, although this effect does not appear in clinical use, suggesting that it is not a direct result of MDMA administration.<ref name=Drugs2014/><ref>{{cite journal | vauthors = Sessa B, Aday JS, O'Brien S, Curran HV, Measham F, Higbed L, Nutt DJ | title = Debunking the myth of 'Blue Mondays': No evidence of affect drop after taking clinical MDMA | journal = Journal of Psychopharmacology | volume = 36 | issue = 3 | pages = 360–367 | date = March 2022 | pmid = 34894842 | doi = 10.1177/02698811211055809 | s2cid = 245184699 }}</ref> MDMA acts primarily by increasing the release of the neurotransmitters [[Chemistry:Serotonin|serotonin]], [[Biology:Dopamine|dopamine]] and noradrenaline in parts of the brain.<ref name=Drugs2014/><ref name=NIH2016>{{cite web|title=DrugFacts: MDMA (Ecstasy/Molly)|url=https://www.drugabuse.gov/publications/drugfacts/mdma-ecstasymolly|website=National Institute on Drug Abuse|access-date=30 March 2016|date=February 2016|url-status=live|archive-url=https://web.archive.org/web/20160323164024/https://www.drugabuse.gov/publications/drugfacts/mdma-ecstasymolly|archive-date=23 March 2016|df=dmy-all}}</ref> It belongs to the [[Chemistry:Substituted amphetamine|substituted amphetamine]] [[Chemistry:Chemical classification|classes of drugs]].<ref name=EU2015/><ref>{{cite book | vauthors = Freye E |title=Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs: A comprehensive review on their mode of action, treatment of abuse and intoxication |date=2009 |publisher=Springer Science & Business Media |isbn=978-90-481-2448-0 |page=147 |url=https://books.google.com/books?id=OTAlolM3XlwC&pg=PA147 |language=en}}</ref> MDMA is structurally similar to [[Biology:Mescaline|mescaline]] (a hallucinogen), methamphetamine (a stimulant), as well as [[Biology:Endogeny|endogenous]] [[Biology:Monoamine neurotransmitter|monoamine neurotransmitter]]s such as [[Chemistry:Serotonin|serotonin]], [[Biology:Norepinephrine|norepinephrine]], and [[Biology:Dopamine|dopamine]].<ref>{{cite journal | vauthors = Lyles J, Cadet JL | title = Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms | journal = Brain Research. Brain Research Reviews | volume = 42 | issue = 2 | pages = 155–168 | date = May 2003 | pmid = 12738056 | doi = 10.1016/S0165-0173(03)00173-5 | s2cid = 45330713 }}</ref>

<!-- Laws and research -->
MDMA is illegal in most countries<ref name=Drugs2014/><ref>{{cite book| vauthors = Patel V |title=Mental and neurological public health a global perspective|date=2010|publisher=Academic Press/Elsevier|location=San Diego, CA|isbn=978-0-12-381527-9|page=57|edition=1st|url=https://books.google.com/books?id=8fihf3VWbcIC&pg=PA57|url-status=live|archive-url=https://web.archive.org/web/20170910234523/https://books.google.com/books?id=8fihf3VWbcIC&pg=PA57|archive-date=10 September 2017|df=dmy-all}}</ref> and has limited approved 
[[Medicine:Indication|medical uses]] in a small number of countries.<ref name=EU2015/><ref>{{cite news | vauthors = Philipps D |title=Ecstasy as a Remedy for PTSD? You Probably Have Some Questions. |url=https://www.nytimes.com/2018/05/01/us/ecstasy-molly-ptsd-mdma.html |archive-url=https://ghostarchive.org/archive/20220101/https://www.nytimes.com/2018/05/01/us/ecstasy-molly-ptsd-mdma.html |archive-date=2022-01-01 |url-access=limited |access-date=14 July 2018 |newspaper=The New York Times |date=1 May 2018 |language=en}}{{cbignore}}</ref> In the United States, the [[Organization:Food and Drug Administration|Food and Drug Administration]] is evaluating the drug for clinical use {{asof|2021|lc=y}}.<ref>{{cite web | title = A Psychedelic Drug Passes a Big Test for PTSD Treatment | work = The New York Times | vauthors = Nuwer R |  date = 3 May 2021 | url = https://www.nytimes.com/2021/05/03/health/mdma-approval.html}}</ref> Canada has allowed limited distribution of MDMA upon application to and approval by [[Organization:Health Canada|Health Canada]].<ref>{{Cite web| work = Health Canada|date=2022-01-05|title=Subsection 56(1) class exemption for practitioners, agents, pharmacists, persons in charge of a hospital, hospital employees, and licensed dealers to conduct activities with psilocybin and MDMA in relation to a special access program authorization|url=https://www.canada.ca/en/health-canada/services/health-concerns/controlled-substances-precursor-chemicals/policy-regulations/policy-documents/subsection-56-1-class-exemption-conducting-activities-psilocybin-mdma-special-access-program-authorization.html|access-date=2022-02-20 }}</ref><ref>{{Cite web|title=Canada approving psychedelics for therapy is a positive step, experts say - National | work = Globalnews.ca|url=https://globalnews.ca/news/8514429/psychedelic-drugs-therapy-canada/|access-date=2022-02-20 |language=en-US}}</ref>


==Effects==
In general, MDMA users report feeling the onset of subjective effects within 30 to 60 minutes of oral consumption and reaching peak effect at 75 to 120 minutes, which then plateaus for about 3.5 hours.<ref name="mcn">{{cite journal | vauthors = Liechti ME, Gamma A, Vollenweider FX | title = Gender differences in the subjective effects of MDMA | journal = Psychopharmacology | volume = 154 | issue = 2 | pages = 161–8 | date = March 2001 | pmid = 11314678 | doi = 10.1007/s002130000648 | s2cid = 20251888}}</ref> The desired short-term psychoactive effects of MDMA have been reported to include:
* [[Chemistry:Euphoria|Euphoria]] – a sense of general [[Finance:Well-being|well-being]] and happiness<ref name=Current2013/><ref name="Acute amph toxicity" />
* Increased self-confidence, sociability, and perception of facilitated communication<ref name=Betzler2017/><ref name=Current2013 /><ref name="Acute amph toxicity" />
* Entactogenic effects—increased empathy or feelings of closeness with others<ref name=Current2013 /><ref name="Acute amph toxicity" /> and oneself<ref name=Betzler2017/>
* [[Medicine:Mydriasis|Dilated pupils]]<ref name=Betzler2017/>
* Relaxation and reduced anxiety<ref name=Betzler2017/>
* Increased emotionality<ref name=Betzler2017/>
* A sense of inner peace<ref name="Acute amph toxicity" />
* Mild hallucination<ref name="Acute amph toxicity" />
* Enhanced sensation, perception, or sexuality<ref name=Betzler2017/><ref name=Current2013 /><ref name="Acute amph toxicity" />
* Altered sense of time<ref name=NIH2016/>

The experience elicited by MDMA depends on the dose, setting, and user.<ref name=Betzler2017/> The variability of the induced altered state is lower compared to other psychedelics. For example, MDMA used at parties is associated with high motor activity, reduced sense of identity, and poor awareness of surroundings. Use of MDMA individually or in small groups in a quiet environment and when concentrating, is associated with increased lucidity, concentration, sensitivity to aesthetic aspects of the environment, enhanced awareness of emotions, and improved capability of communication.<ref name="pmid22392347" /><ref name="Landriscina">{{cite journal | vauthors = Landriscina F |title=MDMA and the states of Consciousness|journal=Eleusis|date=1995|volume=2|pages=3–9}}</ref> In psychotherapeutic settings, MDMA effects have been characterized by infantile ideas, mood lability, and memories and moods connected with childhood experiences.<ref name="Landriscina" /><ref name="Baggott">{{cite journal | vauthors = Baggott MJ, Kirkpatrick MG, Bedi G, de Wit H | title = Intimate insight: MDMA changes how people talk about significant others | journal = Journal of Psychopharmacology | volume = 29 | issue = 6 | pages = 669–77 | date = June 2015 | pmid = 25922420 | pmc = 4698152 | doi = 10.1177/0269881115581962 }}</ref>

MDMA has been described as an "empathogenic" drug because of its empathy-producing effects.<ref name="Schmid">{{cite journal | vauthors = Schmid Y, Hysek CM, Simmler LD, Crockett MJ, Quednow BB, Liechti ME | title = Differential effects of MDMA and methylphenidate on social cognition | journal = Journal of Psychopharmacology | volume = 28 | issue = 9 | pages = 847–56 | date = September 2014 | pmid = 25052243 | doi = 10.1177/0269881114542454 | s2cid = 25713943 | url = http://edoc.unibas.ch/42235/1/20160316152928_56e96dc8bdaad.pdf }}</ref><ref name="Wardle">{{cite journal | vauthors = Wardle MC, de Wit H | title = MDMA alters emotional processing and facilitates positive social interaction | journal = Psychopharmacology | volume = 231 | issue = 21 | pages = 4219–29 | date = October 2014 | pmid = 24728603 | pmc = 4194242 | doi = 10.1007/s00213-014-3570-x }}</ref> Results of several studies show the effects of increased empathy with others.<ref name="Schmid" /> When testing MDMA for medium and high doses, it showed increased hedonic and arousal continuum.<ref name="Bravo">{{cite book | vauthors = Bravo GL | veditors =Holland J |title=Ecstasy: The complete guide. A comprehensive look at the risks and benefits of MDMA.|date=2001|publisher=Park Street Press|location=Rochester|chapter=What does MDMA feel like?}}</ref><ref name="Metzner">{{cite book | vauthors = Metzner R |chapter=Psychedelic, Psychoactive, and Addictive Drugs and States of Consciousness | veditors = Earleywine M |title=Mind-Altering Drugs: The Science of Subjective Experience |date=2005|publisher=Oxford University|location=New York | chapter-url= http://www.greenearthfound.org/write/psychedelic.html|access-date=8 October 2017|archive-date=9 October 2017 |archive-url= https://web.archive.org/web/20171009092337/http://www.greenearthfound.org/write/psychedelic.html |url-status=dead}}</ref> The effect of MDMA increasing sociability is consistent, while its effects on [[Philosophy:Empathy|empathy]] have been more mixed.<ref>{{cite journal | vauthors = Kamilar-Britt P, Bedi G | title = The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals | journal = Neuroscience and Biobehavioral Reviews | volume = 57 | pages = 433–46 | date = October 2015 | pmid = 26408071 | pmc = 4678620 | doi = 10.1016/j.neubiorev.2015.08.016 }}</ref>

==Use==

===Recreational===

MDMA is often considered the drug of choice within the rave culture and is also used at clubs, festivals, and house parties.<ref name="pmid22392347" /> In the rave environment, the sensory effects of music and lighting are often highly [[Biology:Synergy|synergistic]] with the drug. The psychedelic [[Chemistry:Amphetamine|amphetamine]] quality of MDMA offers multiple appealing aspects to users in the rave setting. Some users enjoy the feeling of mass communion from the inhibition-reducing effects of the drug, while others use it as party fuel because of the drug's stimulatory effects.<ref>{{cite book| vauthors = Reynolds S |title=Generation Ecstasy: Into the World of Techno and Rave Culture|year=1999|publisher=Routledge|isbn=978-0-415-92373-6|page=81|url=https://books.google.com/books?id=tGaRJiXe74UC&q=Generation+Ecstasy+MDMA&pg=PA81}}</ref> MDMA is used less often than other stimulants, typically less than once per week.<ref name=Epstein2013/>

MDMA is sometimes taken in conjunction with other psychoactive drugs such as [[Chemistry:LSD|LSD]], [[Biology:Psilocybin mushroom|psilocybin mushroom]]s, [[Chemistry:2C-B|2C-B]], and [[Chemistry:Ketamine|ketamine]]. The combination with LSD is called "candy-flipping".<ref>{{cite book| veditors = Capuzzi D, Gross DR |title=Youth at Risk: A Prevention Resource for Counselors, Teachers, and Parents|publisher=John Wiley & Sons|isbn=978-1-119-02694-5|page=379 |url= https://books.google.com/books?id=s7iTBQAAQBAJ&q=mdma+flipping&pg=PA367 |date=2014-11-21}}</ref> MDMA is often co-administered with [[Chemistry:Alcohol (drug)|alcohol]], [[Chemistry:Methamphetamine|methamphetamine]], and prescription drugs such as [[Chemistry:Selective serotonin reuptake inhibitor|SSRIs]] with which MDMA has several drug-drug interactions.<ref>{{cite journal | vauthors = Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krähenbühl S, Grouzmann E, Huwyler J, Hoener MC, Liechti ME | display-authors = 6 | title = Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study | journal = PLOS ONE | volume = 7 | issue = 5 | pages = e36476 | date = 2012-05-04 | pmid = 22574166 | doi = 10.1371/journal.pone.0036476 | pmc = 3344887 | bibcode = 2012PLoSO...736476H | veditors = Laks J | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yuki F, Rie I, Miki K, Mitsuhiro W, Naotaka K, Kenichiro N | title = Warning against co-administration of 3,4-methylenedioxymethamphetamine (MDMA) with methamphetamine from the perspective of pharmacokinetic and pharmacodynamic evaluations in rat brain | journal = European Journal of Pharmaceutical Sciences | volume = 49 | issue = 1 | pages = 57–64 | date = April 2013 | pmid = 23395913 | doi = 10.1016/j.ejps.2013.01.014 }}</ref><ref>{{cite journal | vauthors = Hamida SB, Tracqui A, de Vasconcelos AP, Szwarc E, Lazarus C, Kelche C, Jones BC, Cassel JC | display-authors = 6 | title = Ethanol increases the distribution of MDMA to the rat brain: possible implications in the ethanol-induced potentiation of the psychostimulant effects of MDMA | journal = The International Journal of Neuropsychopharmacology | volume = 12 | issue = 6 | pages = 749–759 | date = July 2009 | pmid = 19046482 | doi = 10.1017/s1461145708009693 | s2cid = 24230367 | doi-access = free }}</ref> Three life-threatening reports of MDMA co-administration with [[Chemistry:Ritonavir|ritonavir]] have been reported;<ref>{{cite journal | vauthors = Oesterheld JR, Armstrong SC, Cozza KL | title = Ecstasy: pharmacodynamic and pharmacokinetic interactions | journal = Psychosomatics | volume = 45 | issue = 1 | pages = 84–87 | date = 2004-03-01 | pmid = 14709765 | doi = 10.1176/appi.psy.45.1.84 | doi-access = free }}</ref> with ritonavir having severe and dangerous drug-drug interactions with a wide range of both psychoactive, anti-psychotic, and non-psychoactive drugs.<ref name="pmid31038898">{{cite journal | vauthors = Carpenter M, Berry H, Pelletier AL | title = Clinically Relevant Drug-Drug Interactions in Primary Care | journal = American Family Physician | volume = 99 | issue = 9 | pages = 558–564 | date = May 2019 | pmid = 31038898 | doi =  }}</ref>   <!--Users sometimes use [[Chemistry:Menthol|menthol]]ated products while taking MDMA for its cooling sensation.{{Citation needed|date=October 2017}}-->

===Medical===
{{As of|2017}}, MDMA has no accepted medical indications.{{where|date=October 2023}}<ref name=EU2015 /><ref>{{cite journal | vauthors = Sessa B, Nutt D | title = Making a medicine out of MDMA | journal = The British Journal of Psychiatry | volume = 206 | issue = 1 | pages = 4–6 | date = January 2015 | pmid = 25561485 | doi = 10.1192/bjp.bp.114.152751 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ebrahimian Z, Karimi Z, Khoshnoud MJ, Namavar MR, Daraei B, Haidari MR | title = Behavioral and Stereological Analysis of the Effects of Intermittent Feeding Diet on the Orally Administrated MDMA ("ecstasy") in Mice | journal = Innovations in Clinical Neuroscience | volume = 14 | issue = 1–2 | pages = 40–52 | date = 1 February 2017 | pmid = 28386520 | pmc = 5373794 | quote = MDMA is listed as a Schedule 1 drug by the United States Drug Enforcement Agency, meaning that currently there are no accepted medical uses for MDMA in the United States, there is a lack of accepted safety for use under medical supervision, and there is a high potential for abuse. }}</ref> Before it was widely banned, it saw limited use in psychotherapy.<ref name=Betzler2017/><ref name=EU2015/><ref>{{cite journal | vauthors = Climko RP, Roehrich H, Sweeney DR, Al-Razi J | title = Ecstacy: a review of MDMA and MDA | journal = International Journal of Psychiatry in Medicine | volume = 16 | issue = 4 | pages = 359–72 | year = 1986 | pmid = 2881902 | doi = 10.2190/dcrp-u22m-aumd-d84h | s2cid = 31902958 }}</ref> In 2017 the United States Food and Drug Administration (FDA) approved limited research on MDMA-assisted psychotherapy for [[Medicine:Post-traumatic stress disorder|post-traumatic stress disorder]] (PTSD),<ref>{{Cite news| vauthors = Wan W |date=6 August 2017|title=Ecstasy could be 'breakthrough' therapy for soldiers, others suffering from PTSD|language=en-US|newspaper={{wipe|The Washington Post}}|url=https://www.washingtonpost.com/national/health-science/ecstasy-could-be-breakthrough-therapy-for-soldiers-others-suffering-from-ptsd/2017/08/26/009314ca-842f-11e7-b359-15a3617c767b_story.html|access-date=3 April 2021 }}</ref><ref>{{Cite web| vauthors = Kupferschmidt K |date=26 August 2017|title=All clear for the decisive trial of ecstasy in PTSD patients|url=https://www.science.org/content/article/all-clear-decisive-trial-ecstasy-ptsd-patients|access-date=3 April 2021|website=Science (magazine)|language=en}}</ref> with some preliminary evidence that MDMA may facilitate psychotherapy efficacy for PTSD.<ref>{{cite journal | vauthors = Jerome L, Feduccia AA, Wang JB, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R | display-authors = 6 | title = Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials | journal = Psychopharmacology | volume = 237 | issue = 8 | pages = 2485–2497 | date = August 2020 | pmid = 32500209 | pmc = 7351848 | doi = 10.1007/s00213-020-05548-2 }}</ref><ref name="Zarembo">{{cite news | vauthors = Zarembo A |date=15 March 2014 |title=Exploring therapeutic effects of MDMA on post-traumatic stress |work=Los Angeles Times |url=https://www.latimes.com/local/la-me-mdma-20140316-story.html |access-date=2023-04-07}}</ref><ref>{{Cite journal | vauthors = Singleton SP, Wang J, Mithoefer M, Hanlon CA, George MS, Mithoefer A, Mithoefer O, Coker AR, Klosinski B, Emerson AL, Doblin R | display-authors = 6 |date=2023 |title=Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder |journal=Frontiers in Psychiatry |volume=13 | page = 947622 |doi=10.3389/fpsyt.2022.947622 | pmid = 36713926 | pmc = 9879604 |issn=1664-0640| doi-access = free }}</ref>

===Other===
Small doses of MDMA are used by some religious practitioners as an [[Chemistry:Entheogen|entheogen]] to enhance prayer or meditation.<ref name="MDMA and Religion">{{cite web | url = http://csp.org/practices/entheogens/docs/saunders-ecstasy_rel.html | vauthors = Saunders N | date = 29 July 1995 | title = The Agony and Ecstasy of God's path | archive-url = https://web.archive.org/web/20130424024232/http://csp.org/practices/entheogens/docs/saunders-ecstasy_rel.html | archive-date=24 April 2013 | work = Council on Spiritual Practices (CSP) | access-date = 11 June 2011 }}</ref> MDMA has been used as an adjunct to [[Philosophy:New Age|New Age]] spiritual practices.<ref name="Watson & Beck">{{cite journal | vauthors = Watson L, Beck J | title = New age seekers: MDMA use as an adjunct to spiritual pursuit | journal = Journal of Psychoactive Drugs | volume = 23 | issue = 3 | pages = 261–70 | year = 1991 | pmid = 1685513 | doi = 10.1080/02791072.1991.10471587 }}</ref>

===Forms===
MDMA has become widely known as ecstasy (shortened "E", "X", or "XTC"), usually referring to its tablet form, although this term may also include the presence of possible [[Chemistry:Adulterant|adulterant]]s or diluents. The UK term "mandy" and the US term "molly" colloquially refer to MDMA in a crystalline powder form that is thought to be free of adulterants.<ref name="nature.com"/><ref name=DrugFacts/><ref name="DEA 2015 assessment" /> MDMA is also sold in the form of the hydrochloride salt, either as loose crystals or in [[Medicine:Capsule (pharmacy)|gelcaps]].<ref name="Molly S05E07" /><ref name="Molly S06E05" /> MDMA tablets can sometimes be found in a shaped form that may depict characters from [[Social:Popular culture|popular culture]], likely for deceptive reasons.{{clarify|date=October 2023}} These are sometimes collectively referred to as "fun tablets".<ref>{{cite web | vauthors = Kelly M | date = 20 June 2019 | work = Nintendo Enthusiast | title = Man arrested for possession of ecstasy tablets shaped like Wario | url = https://www.nintendoenthusiast.com/man-arrested-for-possession-of-ecstasy-tablets-shaped-like-wario/}}</ref><ref>{{cite web | author=<!--Not stated--> | title = Groesbeck: Students caught with deceptively shaped Ecstasy pills | date = 31 October 2019 | work = KWTX | url = https://www.kwtx.com/content/news/Students-caught-with-deceptively-shaped-Ecstasy-pills-at-local-school-564188221.html}}</ref>

Partly due to the global supply shortage of sassafras oil—a problem largely assuaged by use of improved or alternative modern methods of synthesis—the purity of substances sold as molly have been found to vary widely. Some of these substances contain [[Chemistry:Methylone|methylone]], [[Chemistry:Ethylone|ethylone]], MDPV, [[Chemistry:Mephedrone|mephedrone]], or any other of the group of compounds commonly known as bath salts, in addition to, or in place of, MDMA.<ref name=DrugFacts /><ref name="DEA 2015 assessment" /><ref name="Molly S05E07">{{cite AV media |date=13 August 2014 |title=Molly Madness |medium=TV documentary |url= <!--Link for WP:V - https://www.youtube.com/watch?v=F-0Zw05A1Y0 -->|publisher=National Geographic Channel | work = Drugs, Inc. |asin=B00LIC368M }}</ref><ref name="Molly S06E05">{{cite AV media |date=10 December 2014 |title=Manic Molly |medium=TV documentary |url= <!--Link for WP:V - https://www.youtube.com/watch?v=pd1-triBJFw -->|publisher=National Geographic Channel | work = Drugs, Inc. |asin=B00LIC368M }}</ref> Powdered MDMA ranges from pure MDMA to crushed tablets with 30–40% purity.<ref name=EU2015 /> MDMA tablets typically have low purity due to bulking agents that are added to dilute the drug and increase profits (notably lactose) and binding agents.<ref name=EU2015 /> Tablets sold as ecstasy sometimes contain 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDEA), other amphetamine derivatives, caffeine, opiates, or painkillers.<ref name=Betzler2017/> Some tablets contain little or no MDMA.<ref name=Betzler2017/><ref name=EU2015 /><ref name="Toxnet MDMA after-effects"/> The proportion of seized ecstasy tablets with MDMA-like impurities has varied annually and by country.<ref name=EU2015 /> The average content of MDMA in a preparation is 70 to 120&nbsp;mg with the purity having increased since the 1990s.<ref name=Betzler2017/>

MDMA is usually consumed by mouth. It is also sometimes [[Medicine:Insufflation|snorted]].<ref name=Drugs2014/>

{{multiple image
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<!-- Image 1 -->
| image1      = Ecstasy monogram.jpg
| width1      = 434
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| alt1        = Image of Ecstasy tablets
| caption1    = Ecstasy tablets which may contain MDMA

<!-- Image 2 -->
| image2      = Tan MDMA Crystals.jpg
| width2      = 4032
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| alt2        = Image of a chunk of impure MDMA
| caption2    = A salt of MDMA (typically white) with impurities, resulting in a tan discoloration

<!-- Image 3 -->
| image3      = Crushed MDMA crystals.jpg
| width3      = 4032
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| alt3        = 1 gram crushed MDMA crystals
| caption3    = Crushed MDMA (1 gram) crystals

<!-- Image 4 -->
| image4      =
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| alt4        = Image of highly pure MDMA in capsules
| caption4    = High purity MDMA in capsules
}}

==Adverse effects==

===Short-term===
Acute adverse effects are usually the result of high or multiple doses, although single dose toxicity can occur in susceptible individuals.<ref name="Current2013" /> The most serious short-term physical health risks of MDMA are [[Medicine:Hyperthermia|hyperthermia]] and [[Medicine:Dehydration|dehydration]].<ref name="Acute amph toxicity" /><ref name="Hyponatremia" /> Cases of life-threatening or fatal [[Medicine:Hyponatremia|hyponatremia]] (excessively low sodium concentration in the blood) have developed in MDMA users attempting to prevent dehydration by [[Medicine:Water intoxication|consuming excessive amounts of water]] without replenishing electrolytes.<ref name="Acute amph toxicity" /><ref name="Hyponatremia" /><ref name="hyperpyrexia">{{cite journal | vauthors = White CM | title = How MDMA's pharmacology and pharmacokinetics drive desired effects and harms | journal = Journal of Clinical Pharmacology | volume = 54 | issue = 3 | pages = 245–52 | date = March 2014 | pmid = 24431106 | doi = 10.1002/jcph.266 | s2cid = 6223741 }}</ref>

The immediate adverse effects of MDMA use can include:
{{div col|colwidth=27em}}
* [[Medicine:Bruxism|Bruxism]] (grinding and clenching of the teeth)<ref name=Betzler2017/><ref name="pmid22392347" /><ref name=Current2013 />
* [[Medicine:Dehydration|Dehydration]]<ref name="pmid22392347"/><ref name="Acute amph toxicity" /><ref name="Hyponatremia" />
* [[Medicine:Diarrhea|Diarrhea]]<ref name="Acute amph toxicity" />
* [[Medicine:Erectile dysfunction|Erectile dysfunction]]<ref name=Betzler2017/><ref>{{cite journal | vauthors = Spauwen LW, Niekamp AM, Hoebe CJ, Dukers-Muijrers NH | title = Drug use, sexual risk behaviour and sexually transmitted infections among swingers: a cross-sectional study in The Netherlands | journal = Sexually Transmitted Infections | volume = 91 | issue = 1 | pages = 31–6 | date = February 2015 | pmid = 25342812 | doi = 10.1136/sextrans-2014-051626 | quote = It is known that some recreational drugs (eg, MDMA or GHB) may hamper the potential to ejaculate or maintain an erection. | doi-access = free }}</ref>
* [[Medicine:Hyperthermia|Hyperthermia]]<ref name=Betzler2017/><ref name="pmid22392347" /><ref name="Hyponatremia" />
* Increased wakefulness or [[Medicine:Insomnia|insomnia]]<ref name=Betzler2017/><ref name="Acute amph toxicity" />
* Increased perspiration and sweating<ref name="Acute amph toxicity" /><ref name="Hyponatremia" />
* Increased [[Heart rate|heart rate]] and [[Physics:Blood pressure|blood pressure]]<ref name=Betzler2017/><ref name="pmid22392347" /><ref name="Hyponatremia" />
* Increased [[Medicine:Psychomotor agitation|psychomotor]] activity<ref name=Betzler2017/>
* Loss of [[Medicine:Appetite|appetite]]<ref name=Betzler2017/><ref name="Toxnet MDMA after-effects"/>
* Nausea and vomiting<ref name=Current2013 />
* Visual and auditory hallucinations (rarely)<ref name=Betzler2017/>
{{div col end}}

Other adverse effects that may occur or persist for up to a week following cessation of moderate MDMA use include:<ref name="Toxnet MDMA after-effects" /><ref name=Current2013 />

;Physiological
{{div col|colwidth=18em}}
* Insomnia<ref name="Toxnet MDMA after-effects" />
* Loss of appetite<ref name="Toxnet MDMA after-effects" />
* Tiredness or lethargy<ref>{{Cite web|url=http://emedicine.medscape.com/article/821572-overview#showall|title=MDMA Toxicity: Background, Pathophysiology, Epidemiology| vauthors = Hahn IH |date=25 March 2015|website=Medscape|access-date=14 May 2016}}</ref><ref>{{Cite book|chapter-url=https://books.google.com/books?id=yGeBj9U6Za8C|title=Drug Abuse and Addiction in Medical Illness: Causes, Consequences and Treatment| vauthors = Parrott AC |date=2012|publisher=Springer Science & Business Media|isbn=978-1-4614-3375-0| veditors = Verster J, Brady K, Galanter M, Conrod P |page=179|chapter=13. MDMA and LSD }}</ref>
* Trismus (lockjaw)<ref name="Current2013" />
{{div col end}}
;Psychological
{{div col|colwidth=18em}}
* [[Medicine:Anhedonia|Anhedonia]]<ref name="Toxnet MDMA after-effects" />
* Anxiety or paranoia<ref name="Toxnet MDMA after-effects"/>
* Depression<ref name="Toxnet MDMA after-effects" /><ref name="Current2013" />
* Impulsiveness<ref name="Toxnet MDMA after-effects" />
* Irritability<ref name="Toxnet MDMA after-effects" />
* Memory impairment<ref name="Current2013" />
* Restlessness<ref name="Toxnet MDMA after-effects" />
{{div col end}}

Administration of MDMA to mice causes [[Biology:DNA damage (naturally occurring)|DNA damage]] in their brain,<ref>{{cite journal | vauthors = Alvarenga TA, Andersen ML, Ribeiro DA, Araujo P, Hirotsu C, Costa JL, Battisti MC, Tufik S | display-authors = 6 | title = Single exposure to cocaine or ecstasy induces DNA damage in brain and other organs of mice | journal = Addiction Biology | volume = 15 | issue = 1 | pages = 96–99 | date = January 2010 | pmid = 19878142 | doi = 10.1111/j.1369-1600.2009.00179.x | s2cid = 21347765 }}</ref> especially when the mice are sleep deprived.<ref>{{cite journal | vauthors = Alvarenga TA, Ribeiro DA, Araujo P, Hirotsu C, Mazaro-Costa R, Costa JL, Battisti MC, Tufik S, Andersen ML | display-authors = 6 | title = Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice | journal = Human & Experimental Toxicology | volume = 30 | issue = 9 | pages = 1275–1281 | date = September 2011 | pmid = 21071548 | doi = 10.1177/0960327110388535 | bibcode = 2011HETox..30.1275A | s2cid = 25477893 }}</ref> Even at the very low doses that are comparable to those self-administered by humans, MDMA causes [[Biology:Oxidative stress|oxidative stress]] and both [[Biology:DNA damage (naturally occurring)|single and double-strand breaks in the DNA]] of the [[Biology:Hippocampus|hippocampus]] region of the mouse brain.<ref>{{cite journal | vauthors = Frenzilli G, Ferrucci M, Giorgi FS, Blandini F, Nigro M, Ruggieri S, Murri L, Paparelli A, Fornai F | display-authors = 6 | title = DNA fragmentation and oxidative stress in the hippocampal formation: a bridge between 3,4-methylenedioxymethamphetamine (ecstasy) intake and long-lasting behavioral alterations | journal = Behavioural Pharmacology | volume = 18 | issue = 5–6 | pages = 471–481 | date = September 2007 | pmid = 17762515 | doi = 10.1097/FBP.0b013e3282d518aa | s2cid = 38285923 }}</ref>

===Long-term===
{{As of|2015}}, the long-term effects of MDMA on human brain structure and function have not been fully determined.<ref name="Abstinent MDMA fMRI review">{{cite journal | vauthors = Garg A, Kapoor S, Goel M, Chopra S, Chopra M, Kapoor A, McCann UD, Behera C | title = Functional Magnetic Resonance Imaging in Abstinent MDMA Users: A Review | journal = Current Drug Abuse Reviews | volume = 8 | issue = 1 | pages = 15–25 | date = 2015 | pmid = 25731754 | doi = 10.2174/1874473708666150303115833 }}</ref> However, there is consistent evidence of structural and functional deficits in MDMA users with high lifetime exposure.<ref name="Abstinent MDMA fMRI review" /> These structural or functional changes appear to be dose dependent and may be less prominent in MDMA users with only a moderate (typically <50 doses used and <100 tablets consumed) lifetime exposure. Nonetheless, moderate MDMA use may still be [[Chemistry:Neurotoxicity|neurotoxic]] and what constitutes moderate use is not clearly established.<ref name="mueller2015">{{cite journal | vauthors = Mueller F, Lenz C, Steiner M, Dolder PC, Walter M, Lang UE, Liechti ME, Borgwardt S | title = Neuroimaging in moderate MDMA use: A systematic review | journal = Neuroscience and Biobehavioral Reviews | volume = 62 | pages = 21–34 | date = March 2016 | pmid = 26746590 | doi = 10.1016/j.neubiorev.2015.12.010 | doi-access = free }}</ref>

Furthermore, it is not clear yet whether "typical" recreational users of MDMA (1 to 2 pills of 75 to 125&nbsp;mg MDMA or analogue every 1 to 4 weeks) will develop neurotoxic brain lesions.<ref>{{cite journal | vauthors = Gouzoulis-Mayfrank E, Daumann J | title = Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines | journal = Dialogues in Clinical Neuroscience | volume = 11 | issue = 3 | pages = 305–17 | date = 2009 | doi = 10.31887/DCNS.2009.11.3/egmayfrank | pmid = 19877498 | pmc = 3181923 }}</ref> Long-term exposure to MDMA in humans has been shown to produce marked [[Medicine:Neurodegeneration|neurodegeneration]] in striatal, hippocampal, [[Biology:Prefrontal cortex|prefrontal]], and occipital serotonergic [[Biology:Axon terminal|axon terminal]]s.<ref name="Abstinent MDMA fMRI review" /><ref name="Meth MDMA NTox">{{cite journal | vauthors = Halpin LE, Collins SA, Yamamoto BK | title = Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine | journal = Life Sciences | volume = 97 | issue = 1 | pages = 37–44 | date = February 2014 | pmid = 23892199 | pmc = 3870191 | doi = 10.1016/j.lfs.2013.07.014 | quote = In contrast, MDMA produces damage to serotonergic, but not dopaminergic axon terminals in the striatum, hippocampus, and prefrontal cortex (Battaglia et al., 1987, O'Hearn et al., 1988). The damage associated with Meth and MDMA has been shown to persist for at least 2 years in rodents, non-human primates and humans (Seiden et al., 1988, Woolverton et al., 1989, McCann et al., 1998, Volkow et al., 2001a, McCann et al., 2005) }}</ref> Neurotoxic damage to serotonergic axon terminals has been shown to persist for more than two years.<ref name="Meth MDMA NTox" /> Elevations in brain temperature from MDMA use are positively correlated with MDMA-induced neurotoxicity.<ref name="pmid22392347" /><ref name="Abstinent MDMA fMRI review" /> However, most studies on MDMA and serotonergic neurotoxicity in humans focus more on heavy users who consume as much as seven times or more the amount that most users report taking. The evidence for the presence of serotonergic neurotoxicity in casual users who take lower doses less frequently is not conclusive.<ref>{{cite journal | vauthors = Szigeti B, Winstock AR, Erritzoe D, Maier LJ | title = Are ecstasy induced serotonergic alterations overestimated for the majority of users? | journal = Journal of Psychopharmacology | volume = 32 | issue = 7 | pages = 741–748 | date = July 2018 | pmid = 29733742 | doi = 10.1177/0269881118767646 | s2cid = 13660975 | quote = Given the dose-response relationship between MDMA exposure and SERT reductions and the statistically non-significant SERT binding differences for users with use levels similar to the majority of real-life users, it can be speculated that SERT levels may not be significantly affected for most recreational ecstasy users. }}</ref> 

However, adverse neuroplastic changes to brain microvasculature and [[Biology:White matter|white matter]] have been observed to occur in humans using low doses of MDMA.<ref name="pmid22392347" /><ref name="Abstinent MDMA fMRI review" /> Reduced gray matter density in certain brain structures has also been noted in human MDMA users.<ref name="pmid22392347" /><ref name="Abstinent MDMA fMRI review" /> Global reductions in gray matter volume, thinning of the parietal and orbitofrontal cortices, and decreased hippocampal activity have been observed in long term users.<ref name="Betzler2017" /> The effects established so far for recreational use of ecstasy lie in the range of moderate to severe effects for [[Biology:Serotonin transporter|serotonin transporter]] reduction.<ref>{{cite journal | vauthors = Roberts CA, Jones A, Montgomery C | title = Meta-analysis of molecular imaging of serotonin transporters in ecstasy/polydrug users | journal = Neuroscience and Biobehavioral Reviews | volume = 63 | pages = 158–67 | date = April 2016 | pmid = 26855234 | doi = 10.1016/j.neubiorev.2016.02.003 | doi-access = free }}</ref>

Impairments in multiple aspects of cognition, including attention, learning, memory, visual processing, and sleep, have been found in regular MDMA users.<ref name=Betzler2017/><ref name=Current2013 /><ref name=Pharm2014>{{cite journal | vauthors = Parrott AC | title = The potential dangers of using MDMA for psychotherapy | journal = Journal of Psychoactive Drugs | volume = 46 | issue = 1 | pages = 37–43 | year = 2014 | pmid = 24830184 | doi = 10.1080/02791072.2014.873690 | s2cid = 23485480 | url = https://www.researchgate.net/publication/262381558 }}</ref><ref name="Abstinent MDMA fMRI review" /> The magnitude of these impairments is correlated with lifetime MDMA usage<ref name=Current2013 /><ref name=Pharm2014 /><ref name="Abstinent MDMA fMRI review" /> and are partially reversible with abstinence.<ref name=Betzler2017/> Several forms of memory are impaired by chronic ecstasy use;<ref name=Current2013 /><ref name=Pharm2014 /> however, the effects for memory impairments in ecstasy users are generally small overall.<ref>{{cite journal|vauthors=Rogers G, Elston J, Garside R, Roome C, Taylor R, Younger P, Zawada A, Somerville M|date=January 2009|title=The harmful health effects of recreational ecstasy: a systematic review of observational evidence|journal=Health Technology Assessment|volume=13|issue=6|pages=iii–iv, ix–xii, 1–315|doi=10.3310/hta13050|pmid=19195429|doi-access=free|hdl=10871/11534|hdl-access=free}}</ref><ref name="Meta analysis - MDMA memory impairment">{{cite journal | vauthors = Kuypers KP, Theunissen EL, van Wel JH, de Sousa Fernandes Perna EB, Linssen A, Sambeth A, Schultz BG, Ramaekers JG | title = Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective | journal = PLOS ONE | volume = 11 | issue = 2 | pages = e0149438 | year = 2016 | pmid = 26907605 | pmc = 4764468 | doi = 10.1371/journal.pone.0149438 | bibcode = 2016PLoSO..1149438K | doi-access = free }}</ref> MDMA use is also associated with increased impulsivity and depression.<ref name=Betzler2017/>

Serotonin depletion following MDMA use can cause depression in subsequent days. In some cases, depressive symptoms persist for longer periods.<ref name=Betzler2017/> Some studies indicate repeated recreational use of ecstasy is associated with depression and anxiety, even after quitting the drug.<ref>{{cite journal | vauthors = Laws KR, Kokkalis J | title = Ecstasy (MDMA) and memory function: a meta-analytic update | journal = Human Psychopharmacology | volume = 22 | issue = 6 | pages = 381–8 | date = August 2007 | pmid = 17621368 | doi = 10.1002/hup.857 | s2cid = 25353240 }}</ref> Depression is one of the main reasons for cessation of use.<ref name=Betzler2017/>

At high doses, MDMA induces a [[Biology:Neuroimmune system|neuroimmune response]] that, through several mechanisms, increases the permeability of the [[Biology:Blood–brain barrier|blood–brain barrier]], thereby making the brain more susceptible to environmental toxins and [[Biology:Pathogen|pathogen]]s.<ref name="MDMA BBB">{{cite journal | vauthors = Kousik SM, Napier TC, Carvey PM | title = The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation | journal = Frontiers in Pharmacology | volume = 3 | pages = 121 | year = 2012 | pmid = 22754527 | pmc = 3386512 | doi = 10.3389/fphar.2012.00121 | doi-access = free }}</ref><ref>{{cite book| vauthors = McMillan B, Starr C |title=Human biology |date=2014 |publisher=Brooks/Cole Cengage Learning |location=Belmont, CA |isbn=978-1-133-59916-6 |edition=10th }}</ref>{{Page needed|date=September 2015}} In addition, MDMA has immunosuppressive effects in the [[Biology:Peripheral nervous system|peripheral nervous system]] and pro-inflammatory effects in the [[Biology:Central nervous system|central nervous system]].<ref>{{cite journal | vauthors = Boyle NT, Connor TJ | title = Methylenedioxymethamphetamine ('Ecstasy')-induced immunosuppression: a cause for concern? | journal = British Journal of Pharmacology | volume = 161 | issue = 1 | pages = 17–32 | date = September 2010 | pmid = 20718737 | pmc = 2962814 | doi = 10.1111/J.1476-5381.2010.00899.X }}</ref>

MDMA may increase the risk of cardiac valvulopathy in heavy or long-term users due to activation of serotonin [[Biology:5-HT2B receptor|5-HT<sub>2B</sub> receptor]]s.<ref name="pmid24361689">{{cite journal | vauthors = Cavero I, Guillon JM | title = Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy | journal = Journal of Pharmacological and Toxicological Methods | volume = 69 | issue = 2 | pages = 150–161 | date = 2014 | pmid = 24361689 | doi = 10.1016/j.vascn.2013.12.004 }}</ref><ref name="pmid28676029">{{cite journal | vauthors = Padhariya K, Bhandare R, Canney D, Velingkar V | title = Cardiovascular Concern of 5-HT2B Receptor and Recent Vistas in the Development of Its Antagonists | journal = Cardiovascular & Hematological Disorders Drug Targets | volume = 17 | issue = 2 | pages = 86–104 | date = 2017 | pmid = 28676029 | doi = 10.2174/1871529X17666170703115111 }}</ref>  MDMA induces cardiac [[Biology:Epigenetics|epigenetic changes]] in [[Biology:DNA methylation|DNA methylation]], particularly hypermethylation changes.<ref>{{cite journal | vauthors = Koczor CA, Ludlow I, Hight RS, Jiao Z, Fields E, Ludaway T, Russ R, Torres RA, Lewis W | display-authors = 6 | title = Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart | journal = Toxicological Sciences | volume = 148 | issue = 1 | pages = 183–191 | date = November 2015 | pmid = 26251327 | pmc = 4731408 | doi = 10.1093/toxsci/kfv170 }}</ref>

===Reinforcement disorders===
<!--Dependence-->
Approximately 60% of MDMA users experience [[Medicine:Drug withdrawal|withdrawal]] symptoms when they stop taking MDMA.<ref name="Toxnet MDMA after-effects"/> Some of these symptoms include fatigue, loss of appetite, depression, and trouble concentrating.<ref name="Toxnet MDMA after-effects"/> [[Chemistry:Drug tolerance|Tolerance]] to some of the desired<!-- (e.g., euphoria) - need ref--> and adverse<!-- (e.g., loss of appetite) - need ref--> effects of MDMA is expected to occur with consistent MDMA use.<ref name="Toxnet MDMA after-effects"/> A 2007 [[Delphi method|delphic analysis]] of a panel of experts in pharmacology, psychiatry, law, policing and others estimated MDMA to have a psychological dependence and physical dependence potential roughly three-fourths to four-fifths that of cannabis.<ref name="pmid17382831">{{cite journal |vauthors=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=1047–1053 |date=March 2007 |pmid=17382831 |doi=10.1016/S0140-6736(07)60464-4 |s2cid=5903121 |author-link4=Colin Blakemore}}<br/>Lay summary: {{cite web |date=23 March 2007 |title=Scientists want new drug rankings |website=BBC News |url=http://news.bbc.co.uk/2/hi/health/6474053.stm}}</ref>

<!--Addiction-->
MDMA has been shown to induce [[Biology:ΔFosB|ΔFosB]] in the [[Biology:Nucleus accumbens|nucleus accumbens]].<ref name="MDMA ΔFosB">{{cite journal | vauthors = Olausson P, Jentsch JD, Tronson N, Neve RL, Nestler EJ, Taylor JR | title = DeltaFosB in the nucleus accumbens regulates food-reinforced instrumental behavior and motivation | journal = The Journal of Neuroscience | volume = 26 | issue = 36 | pages = 9196–204 | date = September 2006 | pmid = 16957076 | pmc = 6674495 | doi = 10.1523/JNEUROSCI.1124-06.2006 }}</ref> Because MDMA releases dopamine in the [[Biology:Striatum|striatum]], the mechanisms by which it induces ΔFosB in the nucleus accumbens are analogous to other dopaminergic psychostimulants.<ref name="MDMA ΔFosB" /><ref name="Nestler">{{cite journal | vauthors = Robison AJ, Nestler EJ | title = Transcriptional and epigenetic mechanisms of addiction | journal = Nature Reviews. Neuroscience | volume = 12 | issue = 11 | pages = 623–37 | date = October 2011 | pmid = 21989194 | pmc = 3272277 | doi = 10.1038/nrn3111 }}</ref>  Therefore, chronic use of MDMA at high doses can result in [[Biology:Neuroplasticity|altered brain structure]] and drug addiction that occur as a consequence of ΔFosB overexpression in the nucleus accumbens.<ref name="Nestler" /> MDMA is less addictive than other stimulants such as methamphetamine and cocaine.<ref>{{cite book| vauthors = Mack AH, Brady KT, Miller SI, Frances RJ |title=Clinical Textbook of Addictive Disorders|publisher=Guilford Publications |isbn=978-1-4625-2169-2 |page=169 |url=https://books.google.com/books?id=88W_CwAAQBAJ&pg=PA171 |quote=MDMA's addictive liability appears to be lower than that of other drugs of abuse....|date=2016-05-12}}</ref><ref>{{cite journal | vauthors = Favrod-Coune T, Broers B | title = The Health Effect of Psychostimulants: A Literature Review | journal = Pharmaceuticals | volume = 3 | issue = 7 | pages = 2333–2361 | date = July 2010 | pmid = 27713356 | pmc = 4036656 | doi = 10.3390/ph3072333 | quote = It seems to present a smaller addiction potential than cocaine or methamphetamine. | doi-access = free }}</ref> Compared with amphetamine, MDMA and its metabolite MDA are less reinforcing.<ref>{{cite book | vauthors = Ries R, Miller SC, Fiellin DA |title=Principles of addiction medicine. |date=2009 |publisher=Wolters Kluwer/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-7477-2 |page=226 |edition=4th |url=https://books.google.com/books?id=j6GGBud8DXcC&pg=PA226 |quote=MDA and MDMA are less reinforcing than amphetamine...}}</ref>

<!--Diagnostic criteria-->
One study found approximately 15% of chronic MDMA users met the DSM-IV diagnostic criteria for [[Medicine:Substance dependence|substance dependence]].<ref name=Steinkellner2011>{{cite journal | vauthors = Steinkellner T, Freissmuth M, Sitte HH, Montgomery T | title = The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine | journal = Biological Chemistry | volume = 392 | issue = 1–2 | pages = 103–15 | date = January 2011 | pmid = 21194370 | pmc = 4497800 | doi = 10.1515/BC.2011.016 | quote = ...approximately 15% of routine MDMA users recently fit the diagnostic criteria for MDMA dependence according to the Diagnostic and Statistical Manual, fourth edition/DSMIV. }}</ref> However, there is little evidence for a specific diagnosable MDMA dependence syndrome because MDMA is typically used relatively infrequently.<ref name=Epstein2013>{{cite book | veditors = McCrady BS, Epstein EE | title = Addictions: a comprehensive guidebook|date=2013|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-975366-6 |page=299|edition=Second|url=https://books.google.com/books?id=MUYfAQAAQBAJ&pg=PA299}}</ref>

<!--Treatment-->
There are currently no medications to treat MDMA addiction.<ref>{{cite book| vauthors = Mack AH, Brady KT, Miller SI, Frances RJ |title=Clinical Textbook of Addictive Disorders|publisher=Guilford Publications|isbn=978-1-4625-2169-2 |page=171 |url= https://books.google.com/books?id=88W_CwAAQBAJ&q=mdma+addiction&pg=PA171 |quote=There are no known pharmacological treatments for MDMA addiction.|date=2016-05-12}}</ref>

===During pregnancy===
MDMA is a moderately teratogenic drug (i.e., it is toxic to the fetus).<ref name=vorhees>{{cite journal | vauthors = Vorhees CV | title = Methods for detecting long-term CNS dysfunction after prenatal exposure to neurotoxins | journal = Drug and Chemical Toxicology | volume = 20 | issue = 4 | pages = 387–99 | date = November 1997 | pmid = 9433666 | doi = 10.3109/01480549709003895 }}</ref><ref name=meamar>{{cite journal | vauthors = Meamar R, Karamali F, Sadeghi HM, Etebari M, Nasr-Esfahani MH, Baharvand H | title = Toxicity of ecstasy (MDMA) towards embryonic stem cell-derived cardiac and neural cells | journal = Toxicology in Vitro | volume = 24 | issue = 4 | pages = 1133–8 | date = June 2010 | pmid = 20230888 | doi = 10.1016/j.tiv.2010.03.005 | quote = In summary, MDMA is a moderate teratogen that could influence cardiac and neuronal differentiation in the ESC model and these results are in concordance with previous in vivo and in vitro models. }}</ref> [[Biology:Uterus|In utero]] exposure to MDMA is associated with a [[Chemistry:Neurotoxicity|neuro]]- and [[Medicine:Cardiotoxicity|cardiotoxicity]]<ref name=meamar/> and impaired motor functioning. Motor delays may be temporary during infancy or long-term. The severity of these developmental delays increases with heavier MDMA use.<ref name=Pharm2014 /><ref name=singer>{{cite journal | vauthors = Singer LT, Moore DG, Fulton S, Goodwin J, Turner JJ, Min MO, Parrott AC | title = Neurobehavioral outcomes of infants exposed to MDMA (Ecstasy) and other recreational drugs during pregnancy | journal = Neurotoxicology and Teratology | volume = 34 | issue = 3 | pages = 303–10 | year = 2012 | pmid = 22387807 | pmc = 3367027 | doi = 10.1016/j.ntt.2012.02.001 }}</ref>

==Overdose==
MDMA overdose symptoms vary widely due to the involvement of multiple organ systems. Some of the more overt overdose symptoms are listed in the table below. The number of instances of fatal MDMA intoxication is low relative to its usage rates. In most fatalities, MDMA was not the only drug involved. Acute toxicity is mainly caused by [[Medicine:Serotonin syndrome|serotonin syndrome]] and sympathomimetic effects.<ref name=Steinkellner2011/> Sympathomimetic side effects can be managed with [[Chemistry:Carvedilol|carvedilol]].<ref>{{cite journal | vauthors = Hysek C, Schmid Y, Rickli A, Simmler LD, Donzelli M, Grouzmann E, Liechti ME | title = Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans | journal = British Journal of Pharmacology | volume = 166 | issue = 8 | pages = 2277–88 | date = August 2012 | pmid = 22404145 | pmc = 3448893 | doi = 10.1111/j.1476-5381.2012.01936.x }}</ref> MDMA's toxicity in overdose may be exacerbated by caffeine, with which it is frequently cut in order to increase volume.<ref>{{cite journal | vauthors = Vanattou-Saïfoudine N, McNamara R, Harkin A | title = Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and related psychostimulants: mechanisms and mediators | journal = British Journal of Pharmacology | volume = 167 | issue = 5 | pages = 946–59 | date = November 2012 | pmid = 22671762 | pmc = 3492978 | doi = 10.1111/j.1476-5381.2012.02065.x }}</ref> A scheme for management of acute MDMA toxicity has been published focusing on treatment of hyperthermia, hyponatraemia, serotonin syndrome, and multiple organ failure.<ref>{{cite journal | vauthors = Hall AP, Henry JA | title = Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management | journal = British Journal of Anaesthesia | volume = 96 | issue = 6 | pages = 678–85 | date = June 2006 | pmid = 16595612 | doi = 10.1093/bja/ael078 | doi-access = free }}</ref>

{| class="wikitable unsortable" style="margin: 1em auto;"
|+ Symptoms of overdose
! scope="col" style="text-align:center"| System
! scope="col" | Minor or moderate overdose<ref name=pmid15228154/> || Severe overdose<ref name=pmid15228154/>
|-
! scope="row"| Cardiovascular
|
||
* [[Medicine:Disseminated intravascular coagulation|Disseminated intravascular coagulation]]<ref name="Acute amph toxicity" />
* [[Medicine:Intracranial hemorrhage|Intracranial hemorrhage]]<ref name="Acute amph toxicity" />
* Severe [[Medicine:Hypertension|hypertension]]<ref name="Acute amph toxicity" /><ref name=oxford/> or [[Medicine:Hypotension|hypotension]]<ref name="Acute amph toxicity" />
* Hypotensive bleeding<ref name=Betzler2017/>
|-
! scope="row"| [[Biology:Central nervous system|Central nervous<br />system]]
|
* Hyperreflexia<ref>{{cite journal | vauthors = de la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Camí J | title = Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition | journal = Therapeutic Drug Monitoring | volume = 26 | issue = 2 | pages = 137–44 | date = April 2004 | pmid = 15228154 | doi = 10.1097/00007691-200404000-00009 }}</ref>
* [[Medicine:Psychomotor agitation|Agitation]]<ref name="Acute amph toxicity" /><ref name=oxford/>
* Mental confusion<ref name="Acute amph toxicity" />
* [[Medicine:Paranoia|Paranoia]]<ref name="Acute amph toxicity" /><ref name=oxford/>
* [[Medicine:Stimulant psychosis|Stimulant psychosis]]<ref name=Betzler2017/><ref name="pmid22392347" />
|
* [[Medicine:Cognitive deficit|Cognitive and memory impairment]]<ref name="Acute amph toxicity" /> potentially to the point of retrograde or anterograde amnesia<ref>{{cite journal | vauthors = Chummun H, Tilley V, Ibe J | title = 3,4-methylenedioxyamfetamine (ecstasy) use reduces cognition | journal = British Journal of Nursing | volume = 19 | issue = 2 | pages = 94–100 | year = 2010 | pmid = 20235382 }}</ref>
* Coma<ref name="pmid22392347" /><ref name=oxford>{{cite book | vauthors = Kellum JA, Gunn SR, Singer M |title=Oxford American Handbook of Critical Care | date = 2008  |publisher=Oxford University Press |isbn=978-0-19-530528-9 | oclc = 1003197730  | page = 464 }}</ref>
* [[Medicine:Convulsion|Convulsion]]s<ref name="Acute amph toxicity" /><ref name=oxford/>
* [[Unsolved:Hallucination|Hallucination]]s<ref name="Acute amph toxicity" /><ref name=oxford/>
* Loss of consciousness<ref name="pmid22392347" />
* [[Medicine:Serotonin syndrome|Serotonin syndrome]]<ref name="pmid22392347" /><ref name="Acute amph toxicity" /><ref name="hyperpyrexia" />
|-
! scope="row"|Musculoskeletal
|
|
* [[Medicine:Hypertonia|Muscle rigidity]]<ref name="Acute amph toxicity" />
* [[Medicine:Rhabdomyolysis|Rhabdomyolysis]] (i.e., rapid muscle breakdown)<ref name="Acute amph toxicity" /><ref name="hyperpyrexia" />
|-
! scope="row"| Respiratory
|
|
* [[Medicine:Acute respiratory distress syndrome|Acute respiratory distress syndrome]]<ref name="Acute amph toxicity" />
|-
! scope="row"| Urinary
|
|
* [[Medicine:Acute kidney injury|Acute kidney injury]]<ref name="Acute amph toxicity" /><ref>{{cite journal | vauthors = Pendergraft WF, Herlitz LC, Thornley-Brown D, Rosner M, Niles JL | title = Nephrotoxic effects of common and emerging drugs of abuse | journal = Clinical Journal of the American Society of Nephrology | volume = 9 | issue = 11 | pages = 1996–2005 | date = November 2014 | pmid = 25035273 | pmc = 4220747 | doi = 10.2215/CJN.00360114 }}</ref>
|-
! scope="row"| Other
|
|
* [[Medicine:Cerebral edema|Cerebral edema]]<ref name="pmid22392347" />
* [[Medicine:Hepatitis|Hepatitis]]<ref name="Acute amph toxicity" /><ref name="hyperpyrexia" />
* Hyperpyrexia (a life-threatening elevation of body temperature greater than or equal to {{convert|40.0|or|41.5|C|F|1}})<ref name="Acute amph toxicity" /><ref name="hyperpyrexia" />
* [[Medicine:Hyponatremia|Hyponatremia]] (Syndrome of inappropriate antidiuretic hormone)<ref name="Acute amph toxicity">{{cite journal | vauthors = Greene SL, Kerr F, Braitberg G | title = Review article: amphetamines and related drugs of abuse | journal = Emergency Medicine Australasia | volume = 20 | issue = 5 | pages = 391–402 | date = October 2008 | pmid = 18973636 | doi = 10.1111/j.1742-6723.2008.01114.x | s2cid = 20755466 }}</ref><ref name="Hyponatremia">{{cite journal | vauthors = Keane M | title = Recognising and managing acute hyponatraemia | journal = Emergency Nurse | volume = 21 | issue = 9 | pages = 32–6; quiz 37 | date = February 2014 | pmid = 24494770 | doi = 10.7748/en2014.02.21.9.32.e1128 }}</ref><ref name="hyperpyrexia" />
|}

== Interactions ==

A number of drug interactions can occur between MDMA and other drugs, including [[Chemistry:Serotonin|serotonergic]] drugs.<ref name="Toxnet MDMA after-effects"/><ref>{{cite journal | vauthors = Silins E, Copeland J, Dillon P | title = Qualitative review of serotonin syndrome, ecstasy (MDMA) and the use of other serotonergic substances: hierarchy of risk | journal = The Australian and New Zealand Journal of Psychiatry | volume = 41 | issue = 8 | pages = 649–55 | date = August 2007 | pmid = 17620161 | doi = 10.1080/00048670701449237 | s2cid = 25832516 }}</ref> MDMA also interacts with drugs which inhibit CYP450 enzymes, like [[Chemistry:Ritonavir|ritonavir]] (Norvir), particularly [[Biology:CYP2D6|CYP2D6]] inhibitors.<ref name="Toxnet MDMA after-effects"/> Life-threatening reactions and death have occurred in people who took MDMA while on ritonavir.<ref name="pmid32228243">{{cite journal | vauthors = Papaseit E, Pérez-Mañá C, Torrens M, Farré A, Poyatos L, Hladun O, Sanvisens A, Muga R, Farré M | title = MDMA interactions with pharmaceuticals and drugs of abuse | journal = Expert Opin Drug Metab Toxicol | volume = 16 | issue = 5 | pages = 357–369 | date = May 2020 | pmid = 32228243 | doi = 10.1080/17425255.2020.1749262 | s2cid = 214750903 | url = }}</ref> Concurrent use of MDMA high dosages with another serotonergic drug can result in a life-threatening condition called [[Medicine:Serotonin syndrome|serotonin syndrome]].<ref name=Betzler2017/><ref name="Toxnet MDMA after-effects"/> Severe overdose resulting in death has also been reported in people who took MDMA in combination with certain [[Biology:Monoamine oxidase inhibitor|monoamine oxidase inhibitor]]s,<ref name=Betzler2017/><ref name="Toxnet MDMA after-effects"/> such as [[Biology:Phenelzine|phenelzine]] (Nardil), [[Biology:Tranylcypromine|tranylcypromine]] (Parnate), or [[Biology:Moclobemide|moclobemide]] (Aurorix, Manerix).<ref>{{cite journal | vauthors = Vuori E, Henry JA, Ojanperä I, Nieminen R, Savolainen T, Wahlsten P, Jäntti M | title = Death following ingestion of MDMA (ecstasy) and moclobemide | journal = Addiction | volume = 98 | issue = 3 | pages = 365–8 | date = March 2003 | pmid = 12603236 | doi = 10.1046/j.1360-0443.2003.00292.x }}</ref> [[Chemistry:Serotonin reuptake inhibitor|Serotonin reuptake inhibitor]]s such as [[Chemistry:Citalopram|citalopram]] (Celexa), [[Chemistry:Duloxetine|duloxetine]] (Cymbalta), [[Chemistry:Fluoxetine|fluoxetine]] (Prozac), and [[Chemistry:Paroxetine|paroxetine]] (Paxil) have been shown to block most of the subjective effects of MDMA.<ref name="HalberstadtNichols2020">{{cite book| vauthors = Halberstadt AL, Nichols DE |title=Handbook of the Behavioral Neurobiology of Serotonin|chapter=Serotonin and serotonin receptors in hallucinogen action|series=Handbook of Behavioral Neuroscience|volume=31|year=2020|pages=843–863|issn=1569-7339|doi=10.1016/B978-0-444-64125-0.00043-8|isbn=9780444641250|s2cid=241134396}}</ref> [[Chemistry:Norepinephrine reuptake inhibitor|Norepinephrine reuptake inhibitor]]s such as [[Chemistry:Reboxetine|reboxetine]] (Edronax) have been found to reduce emotional excitation and feelings of stimulation with MDMA but do not appear to influence its entactogenic or mood-elevating effects.<ref name="HalberstadtNichols2020" />

==Pharmacology==
=== Pharmacodynamics ===
MDMA is a [[Chemistry:Substituted amphetamine|substituted amphetamine]] structurally, and a [[Chemistry:Monoamine releasing agent|monoamine-releasing agent]] mechanistically. Like other monoamine-releasing agents, MDMA enters monoaminergic neurons through [[Biology:Monoamine transporter|monoamine transporter]]s. MDMA has high affinity for dopamine, norepinephrine and serotonin transporters, with some preference for the latter. The ''methylenedioxy-'' substitution provides the serotonergic activity, as most other substituted amphetamines show negligible affinity for the serotonin transporter.{{Citation needed|date=July 2023}}

Neurotransmitter release induced by monoamine-releasing agents differs significantly from the regular, [[Biology:Action potential|action potential]]-evoked neurotransmitter release. Inside the neuron, MDMA inhibits [[Biology:Vesicular monoamine transporter 2|VMAT2]] and activates [[Biology:TAAR1|TAAR1]]. TAAR1 agonism results in the phosphorylation of monoamine transporters by [[Biology:Protein kinase A|PKA]] and [[Biology:Protein kinase C|PKC]], which either internalizes the transporter, or reverses its flux direction.<ref>{{cite journal | vauthors = Underhill S, Amara S |title=MDMA and TAAR1-mediated RhoA Activation in Serotonin Neurons |journal=The FASEB Journal |date=18 April 2020 |volume=34 |issue=1 |page=1 |doi=10.1096/fasebj.2020.34.s1.05856 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Underhill SM, Hullihen PD, Chen J, Fenollar-Ferrer C, Rizzo MA, Ingram SL, Amara SG | title = Amphetamines signal through intracellular TAAR1 receptors coupled to Gα<sub>13</sub> and Gα<sub>S</sub> in discrete subcellular domains | journal = Molecular Psychiatry | volume = 26 | issue = 4 | pages = 1208–1223 | date = April 2021 | pmid = 31399635 | pmc = 7038576 | doi = 10.1038/s41380-019-0469-2 }}</ref> VMAT2 inhibition prevents the packaging of the cytosolic monoamines into the [[Biology:Synaptic vesicle|synaptic vesicle]]s, which allows them to instead be pumped out of the neuron by the phosphorylated transporters. The end result is that the neuron constantly "leaks" neurotransmitters into the synapse, regardless of any signal received.<ref>{{cite journal | vauthors = Lizarraga LE, Cholanians AB, Phan AV, Herndon JM, Lau SS, Monks TJ | title = Vesicular monoamine transporter 2 and the acute and long-term response to 3,4-(±)-methylenedioxymethamphetamine | journal = Toxicological Sciences | volume = 143 | issue = 1 | pages = 209–219 | date = January 2015 | pmid = 25370842 | pmc = 4274386 | doi = 10.1093/toxsci/kfu222 }}</ref>

MDMA has two enantiomers, ''(S)''-MDMA and ''(R)''-MDMA. Recreationally used MDMA is the [[Chemistry:Racemic mixture|equimolar mixture of both]]. ''(S)''-MDMA causes the entactogenic effects of the racemate, because it releases serotonin, norepinephrine and dopamine much more efficiently via monoamine transporters. It also has higher affinity towards 5-HT<sub>2C</sub>R. ''(R)''-MDMA has notable agonism towards 5-HT<sub>2A</sub>R,<ref>{{cite journal | vauthors = Pitts EG, Curry DW, Hampshire KN, Young MB, Howell LL | title = (±)-MDMA and its enantiomers: potential therapeutic advantages of R(-)-MDMA | journal = Psychopharmacology | volume = 235 | issue = 2 | pages = 377–392 | date = February 2018 | pmid = 29248945 | doi = 10.1007/s00213-017-4812-5 | s2cid = 3343930 }}</ref> which supposedly contributes to the mild [[Chemistry:Psychedelic|psychedelic]] hallucinations induced by high doses of MDMA in humans.<ref>{{cite journal | vauthors = Liechti ME, Vollenweider FX | title = Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies | journal = Human Psychopharmacology | volume = 16 | issue = 8 | pages = 589–598 | date = December 2001 | pmid = 12404538 | doi = 10.1002/hup.348 | s2cid = 45640843 }}</ref>

===Pharmacokinetics===
[[File:Main metabolic pathways of MDMA in humans.svg|thumb|Main metabolic pathways of MDMA in humans.]]
The MDMA [[Chemistry:Concentration|concentration]] in the blood stream starts to rise after about 30 minutes,<ref>{{cite journal | vauthors = Mas M, Farré M, de la Torre R, Roset PN, Ortuño J, Segura J, Camí J | title = Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 290 | issue = 1 | pages = 136–45 | date = July 1999 | pmid = 10381769 }}</ref> and reaches its maximal [[Chemistry:Concentration|concentration]] in the blood stream between 1.5 and 3 hours after [[Biology:Ingestion|ingestion]].<ref name="TORRE1">{{cite journal | vauthors = de la Torre R, Farré M, Ortuño J, Mas M, Brenneisen R, Roset PN, Segura J, Camí J | display-authors = 6 | title = Non-linear pharmacokinetics of MDMA ('ecstasy') in humans | journal = British Journal of Clinical Pharmacology | volume = 49 | issue = 2 | pages = 104–9 | date = February 2000 | pmid = 10671903 | pmc = 2014905 | doi = 10.1046/j.1365-2125.2000.00121.x }}</ref> It is then slowly [[Biology:Metabolism|metabolized]] and [[Biology:Excretion|excreted]], with levels of MDMA and its metabolites decreasing to half their peak concentration over the next several hours.<ref name="TORRE2">{{cite journal | vauthors = Farré M, Roset PN, Lopez CH, Mas M, Ortuño J, Menoyo E, Pizarro N, Segura J, Cami J | display-authors = 6 | title = Pharmacology of MDMA in humans | journal = Annals of the New York Academy of Sciences | volume = 914 | issue = 1 | pages = 225–37 | date = September 2000 | pmid = 11085324 | doi = 10.1111/j.1749-6632.2000.tb05199.x | bibcode = 2000NYASA.914..225D | s2cid = 29247621 | doi-access = free }}</ref> The duration of action of MDMA is usually four to six hours, after which serotonin levels in the brain are depleted.<ref name=Betzler2017/> Serotonin levels typically return to normal within 24–48 hours.<ref name=Betzler2017/>

[[Biology:Metabolite|Metabolite]]s of MDMA that have been identified in humans include [[Chemistry:3,4-Methylenedioxyamphetamine|3,4-methylenedioxyamphetamine]] (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine<!--File:HMA2.png--> (HMA), [[Chemistry:Alpha-Methyldopamine|3,4-dihydroxyamphetamine]] (DHA) (also called alpha-methyldopamine (α-Me-DA)), 3,4-methylenedioxyphenylacetone (MDP2P), and 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH). The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research. 80% of MDMA is metabolised in the liver, and about 20% is excreted unchanged in the [[Biology:Urine|urine]].<ref name="pmid22392347"/>

MDMA is known to be metabolized by two main [[Biology:Metabolic pathway|metabolic pathway]]s: (1) ''O''-demethylenation followed by catechol-''O''-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) ''N''-dealkylation, deamination, and oxidation to the corresponding [[Chemistry:Benzoic acid|benzoic acid]] derivatives conjugated with [[Chemistry:Glycine|glycine]].<ref name=pmid15228154>{{cite journal | vauthors = de la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Camí J | title = Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition | journal = Therapeutic Drug Monitoring | volume = 26 | issue = 2 | pages = 137–44 | date = April 2004 | pmid = 15228154 | doi = 10.1097/00007691-200404000-00009 | quote = It is known that some recreational drugs (e.g., MDMA or GHB) may hamper the potential to ejaculate or maintain an erection. }}</ref> The metabolism may be primarily by cytochrome P450 (CYP450) [[Biology:Enzyme|enzyme]]s [[Biology:CYP2D6|CYP2D6]] and [[Biology:CYP3A4|CYP3A4]] and COMT. Complex, nonlinear [[Medicine:Pharmacokinetics|pharmacokinetics]] arise via autoinhibition of [[Biology:CYP2D6|CYP2D6]] and CYP2D8, resulting in [[Chemistry:Rate equation|zeroth order kinetics]] at higher doses. It is thought that this can result in sustained and higher [[Chemistry:Concentration|concentration]]s of MDMA if the user takes consecutive doses of the drug.<ref name = "Kolbrich_2008">{{cite journal | vauthors = Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA | title = Plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine after controlled oral administration to young adults | journal = Therapeutic Drug Monitoring | volume = 30 | issue = 3 | pages = 320–32 | date = June 2008 | pmid = 18520604 | pmc = 2663855 | doi = 10.1097/FTD.0b013e3181684fa0 }}</ref>{{primary source inline|date=October 2014}}

MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides.<ref name="pmid17643356">{{cite journal | vauthors = 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 = Journal of Chromatography B | volume = 857 | issue = 1 | pages = 123–9 | date = September 2007 | pmid = 17643356 | doi = 10.1016/j.jchromb.2007.07.003 }}</ref> MDMA is a [[Biology:Chirality|chiral]] compound and has been almost exclusively administered as a racemate. However, the two enantiomers have been shown to exhibit different kinetics. The disposition of MDMA may also be stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. Evidence suggests<ref name="fallon">{{cite journal | vauthors = Fallon JK, Kicman AT, Henry JA, Milligan PJ, Cowan DA, Hutt AJ | title = Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans | journal = Clinical Chemistry | volume = 45 | issue = 7 | pages = 1058–69 | date = July 1999 | pmid = 10388483 | doi = 10.1093/clinchem/45.7.1058 | doi-access = free }}</ref> that the area under the [[Biology:Blood plasma|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. Likewise, the plasma half-life of (''R'')-MDMA was significantly longer than that of the (''S'')-enantiomer (5.8&nbsp;±&nbsp;2.2 hours vs 3.6&nbsp;±&nbsp;0.9 hours).<ref name="Toxnet MDMA after-effects"/> However, because MDMA excretion and metabolism have nonlinear kinetics,<ref name="mueller">{{cite journal | vauthors = Mueller M, Peters FT, Maurer HH, McCann UD, Ricaurte GA | title = Nonlinear pharmacokinetics of (+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") and its major metabolites in squirrel monkeys at plasma concentrations of MDMA that develop after typical psychoactive doses | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 327 | issue = 1 | pages = 38–44 | date = October 2008 | pmid = 18591215 | doi = 10.1124/jpet.108.141366 | s2cid = 38043715 }}</ref> the half-lives would be higher at more typical doses (100&nbsp;mg is sometimes considered a typical dose).<ref name="TORRE1" />

==Chemistry==
{| style="float:right"
|{{Annotated image 4
| caption = MDMA is a [[Chemistry:Racemic mixture|racemic mixture]] and exists as two enantiomers: (''R'')- and (''S'')-MDMA.
| header =
| header_align =
| header_background =
| alt = Racemic MDMA structure diagram
| image = (±)-MDMA-Formel Structural Formulae.svg
| align = right
| width = 200
| height = 195
| image-width = 200
| image-left = 0
| image-top = 0
| annot-font-size = 16
| icon = none
| annotations =
{{Annotation|60|70|(''R'')-MDMA}}
{{Annotation|60|175|(''S'')-MDMA}}
}}
|-
|{{multiple image
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<!-- Image 1 -->
| image1    = White MDMA salt in a bag.jpg
| width1    = 200
| alt1      = A powdered salt of MDMA
| caption1  = A powdered salt of MDMA

<!-- Image 2 -->
| image2    = MDMAjakarta.jpg
| width2    = 200
| alt2      = Reactors used in synthesis
| caption2  = Reactors used to synthesize MDMA on an industrial scale in a [[Chemistry:Clandestine chemistry|clandestine chemical factory]] in Cikande, Indonesia
}}
|}
MDMA is in the substituted methylenedioxyphenethylamine and [[Chemistry:Substituted amphetamine|substituted amphetamine]] [[Chemistry:Chemical classification|classes of chemicals]]. As a [[Chemistry:Free base|free base]], MDMA is a colorless oil insoluble in water.<ref name=EU2015 /> The most common salt of MDMA is the hydrochloride salt;<ref name=EU2015 />  pure MDMA hydrochloride is water-soluble and appears as a white or off-white powder or crystal.<ref name=EU2015 />

===Synthesis===
There are numerous methods available to synthesize MDMA via different intermediates.<ref>{{cite journal | vauthors = Milhazes N, Martins P, Uriarte E, Garrido J, Calheiros R, Marques MP, Borges F | title = Electrochemical and spectroscopic characterisation of amphetamine-like drugs: application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors | journal = Analytica Chimica Acta | volume = 596 | issue = 2 | pages = 231–41 | date = July 2007 | pmid = 17631101 | doi = 10.1016/j.aca.2007.06.027 | bibcode = 2007AcAC..596..231M | hdl = 10316/45124 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Milhazes N, Cunha-Oliveira T, Martins P, Garrido J, Oliveira C, Rego AC, Borges F | title = Synthesis and cytotoxic profile of 3,4-methylenedioxymethamphetamine ("ecstasy") and its metabolites on undifferentiated PC12 cells: A putative structure-toxicity relationship | journal = Chemical Research in Toxicology | volume = 19 | issue = 10 | pages = 1294–304 | date = October 2006 | pmid = 17040098 | doi = 10.1021/tx060123i | hdl = 10316/12872 | url = https://estudogeral.sib.uc.pt/bitstream/10316/12872/1/Synthesis%20and%20Cytotoxic%20Profile.pdf | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Baxter EW, Reitz AB |title = Reductive aminations of carbonyl compounds with borohydride and borane reducing agents. | journal = Organic Reactions | date = April 2004 | volume = 59 | page = 59 | location = Hoboken, New Jersey, United States | doi = 10.1002/0471264180.or059.01 |isbn = 0471264180 }}</ref><ref>{{cite journal | vauthors = 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 Science International | volume = 155 | issue = 2–3 | pages = 141–57 | date = December 2005 | pmid = 16226151 | doi = 10.1016/j.forsciint.2004.11.013 }}</ref> The original MDMA synthesis described in Merck's patent involves brominating [[Chemistry:Safrole|safrole]] to 1-(3,4-methylenedioxyphenyl)-2-bromopropane and then reacting this adduct with methylamine.<ref>{{cite journal | vauthors = Palhol F, Boyer S, Naulet N, Chabrillat M | title = Impurity profiling of seized MDMA tablets by capillary gas chromatography | journal = Analytical and Bioanalytical Chemistry | volume = 374 | issue = 2 | pages = 274–81 | date = September 2002 | pmid = 12324849 | doi = 10.1007/s00216-002-1477-6 | s2cid = 42666306 }}</ref><ref>{{cite journal | vauthors = Renton RJ, Cowie JS, Oon MC | title = A study of the precursors, intermediates and reaction by-products in the synthesis of 3,4-methylenedioxymethylamphetamine and its application to forensic drug analysis | journal = Forensic Science International | volume = 60 | issue = 3 | pages = 189–202 | date = August 1993 | pmid = 7901132 | doi = 10.1016/0379-0738(93)90238-6 }}</ref> Most illicit MDMA is synthesized using MDP2P (3,4-methylenedioxyphenyl-2-propanone) as a precursor. MDP2P in turn is generally synthesized from [[Chemistry:Piperonal|piperonal]], [[Chemistry:Safrole|safrole]] or [[Chemistry:Isosafrole|isosafrole]].<ref name="World Drug Report 2014">{{cite book|title=World Drug Report 2014|date=June 2014|publisher=[[Organization:United Nations Office on Drugs and Crime|United Nations Office on Drugs and Crime]]|location=Vienna, Austria|isbn=978-92-1-056752-7|url=http://www.unodc.org/documents/wdr2014/World_Drug_Report_2014_web.pdf|access-date=1 December 2014|pages = 2, 3, 123–152 | veditors = Mohan J }}</ref>  One method is to [[Chemistry:Isomerization|isomerize]] safrole to isosafrole in the presence of a strong base, and then oxidize [[Chemistry:Isosafrole|isosafrole]] to MDP2P. Another method uses the [[Chemistry:Wacker process|Wacker process]] to oxidize safrole directly to the MDP2P intermediate with a [[Chemistry:Palladium|palladium]] catalyst. Once the MDP2P intermediate has been prepared, a [[Chemistry:Reductive amination|reductive amination]] leads to racemic MDMA (an equal parts mixture of (''R'')-MDMA and (''S'')-MDMA).{{citation needed|date=January 2015}} Relatively small quantities of essential oil are required to make large amounts of MDMA. The essential oil of ''[[Biology:Ocotea cymbarum|Ocotea cymbarum]]'', for example, typically contains between 80 and 94% safrole. This allows 500&nbsp;mL of the oil to produce between 150 and 340 grams of MDMA.<ref>{{cite journal | url = https://www.justice.gov/dea/pr/micrograms/2005/mg1105.pdf | date = 11 November 2005 | title = Early Warning - MDMA and MDA Producers Using Ocotea Cymbarum as a Precursor | journal = DEA Microgram Newsletter | volume = 38 | issue = 11 | page = 166 | archive-url = https://web.archive.org/web/20121018052300/http://www.justice.gov/dea/pr/micrograms/2005/mg1105.pdf | archive-date=18 October 2012 | publisher = Drug Enforcement Agency, U.S. Department of Justice }}</ref>
{{multiple image
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<!-- Image 1 -->
| image1    = MDMA Synthesis 1.svg
| width1    = 600
| alt1      = Synthesis of MDMA from piperonal
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<!-- Image 2 -->
| image2    = MDMA Synthese 2.svg
| width2    = 400
| alt2      = Synthesis of MDMA from piperonal
| caption2  = Synthesis of MDMA from piperonal

<!-- Image 3 -->
| image3 = MDA from safrole en.png
| width3 = 400
| alt3 = Synthesis of MDMA and related analogs from safrole
| caption3 = Synthesis of MDMA and related analogs from safrole
}}
{{clear left}}

===Detection in body fluids===
MDMA and MDA may be quantitated in blood, plasma or urine to monitor for use, 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, in general, less than 10% those of the parent drug.<ref name = "Kolbrich_2008" /><ref>{{cite journal | vauthors = Barnes AJ, De Martinis BS, Gorelick DA, Goodwin RS, Kolbrich EA, Huestis MA | title = Disposition of MDMA and metabolites in human sweat following controlled MDMA administration | journal = Clinical Chemistry | volume = 55 | issue = 3 | pages = 454–62 | date = March 2009 | pmid = 19168553 | pmc = 2669283 | doi = 10.1373/clinchem.2008.117093 }}</ref><ref>{{cite book | vauthors = Baselt RC |title=Disposition of toxic drugs and chemicals in man |date=2011 |publisher=Biomedical Publications |location=Seal Beach, Ca. |isbn=978-0-9626523-8-7 |edition=9th | pages = 1078–1080 }}</ref>
{{clear}}

==History==

===Early research and use===
{{multiple image
| total_width = 300

| image1 = Merck MDMA Synthesis Patent.pdf
| alt1 = Merck MDMA synthesis patent
| caption1 =

| image2 = Merck patent for synthesizing methylhydrastinine from MDMA.pdf
| alt2 = Merck patent for synthesizing methylhydrastinine from MDMA
| caption2 =

| footer = German patents for MDMA synthesis and the subsequent methylhydrastinine synthesis filed by Merck on 24 December 1912 and issued in 1914
}}
MDMA was first synthesized in 1912 by Merck chemist Anton Köllisch. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to avoid an existing patent held by [[Company:Bayer|Bayer]] for one such compound: [[Chemistry:Hydrastinine|hydrastinine]]. Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine, at the request of fellow lab members, Walther Beckh and Otto Wolfes. MDMA (called methylsafrylamin, safrylmethylamin or N-Methyl-a-Methylhomopiperonylamin in Merck laboratory reports) was an [[Chemistry:Reaction intermediate|intermediate compound]] in the synthesis of methylhydrastinine. Merck was not interested in MDMA itself at the time.<ref name="pmid17152992">{{cite journal | vauthors = Bernschneider-Reif S, Oxler F, Freudenmann RW | title = The origin of MDMA ("ecstasy")--separating the facts from the myth | journal = Die Pharmazie | volume = 61 | issue = 11 | pages = 966–72 | date = November 2006 | pmid = 17152992 | url = http://www.ingentaconnect.com/content/govi/pharmaz/2006/00000061/00000011/art00015 }}</ref> On 24 December 1912, Merck filed two patent applications that described the synthesis and some chemical properties 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|access-date =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>

Merck records indicate its researchers returned to the compound sporadically. A 1920 Merck patent describes a chemical modification to MDMA.<ref>{{cite book | vauthors = Shulgin AT | veditors = Peroutka SJ |title=Ecstasy : the clinical, pharmacological, and neurotoxicological effects of the drug MDMA|date=1990|publisher=Kluwer Academic Publishers|location=Boston|isbn=978-0-7923-0305-3|pages=2, 14|chapter=1. History of MDMA}}</ref> In 1927, Max Oberlin studied the pharmacology of MDMA while searching for substances with effects similar to [[Biology:Adrenaline|adrenaline]] or [[Chemistry:Ephedrine|ephedrine]], the latter being structurally similar to MDMA. Compared to ephedrine, Oberlin observed that it had similar effects on [[Biology:Vascular smooth muscle|vascular smooth muscle]] tissue, stronger effects at the uterus, and no "local effect at the eye". MDMA was also found to have effects on blood sugar levels comparable to high doses of ephedrine. Oberlin concluded that the effects of MDMA were not limited to the sympathetic nervous system. Research was stopped "particularly due to a strong price increase of safrylmethylamine", which was still used as an intermediate in methylhydrastinine synthesis. Albert van Schoor performed simple toxicological tests with the drug in 1952, most likely while researching new stimulants or circulatory medications. After pharmacological studies, research on MDMA was not continued. In 1959, Wolfgang Fruhstorfer synthesized MDMA for pharmacological testing while researching stimulants. It is unclear if Fruhstorfer investigated the effects of MDMA in humans.<ref name="pmid17152992"/>

Outside of Merck, other researchers began to investigate MDMA. In 1953 and 1954, the United States Army commissioned a study of [[Medicine:Toxicity|toxicity]] and behavioral effects in animals injected with [[Biology:Mescaline|mescaline]] and several analogues, including MDMA. Conducted at the [[Organization:University of Michigan|University of Michigan]] in Ann Arbor, these investigations were declassified in October 1969 and published in 1973.<ref name="pmid4197635">{{cite journal | vauthors = 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 and Applied Pharmacology | volume = 25 | issue = 2 | pages = 299–309 | date = June 1973 | pmid = 4197635 | doi = 10.1016/S0041-008X(73)80016-X | url = http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=639 | hdl = 2027.42/33868 | hdl-access = free }}</ref><ref name=Shulgin/> A 1960 Polish paper by Biniecki and Krajewski describing the synthesis of MDMA as an intermediate was the first published scientific paper on the substance.<ref name="pmid17152992"/><ref name="Shulgin"/><ref>{{cite journal | vauthors = Biniecki S, Krajewski E |title=Production of d,1-N-methyl-beta-(3,4-methylenedioxyphenyl)-isopropylamine and d,1-N-methyl-beta-(3,4-dimthoxyphenyl)-isopropylamine.|journal=Acta Polon Pharm|date=1960|volume=17|pages=421–5|language=pl}}</ref>

MDMA may have been in non-medical use in the western United States in 1968.<ref name="Siegel 1986">{{cite journal | vauthors = Siegel RK | title = MDMA. Nonmedical use and intoxication | journal = Journal of Psychoactive Drugs | volume = 18 | issue = 4 | pages = 349–54 | date = October 1986 | pmid = 2880950 | doi = 10.1080/02791072.1986.10472368 | url = http://www.maps.org/images/pdf/1986_siegel_1.pdf }}</ref> An August 1970 report at a meeting of crime laboratory chemists indicates MDMA was being used recreationally in the Chicago area by 1970.<ref name="Shulgin"/><ref>The first confirmed sample was seized and identified by Chicago Police in 1970, see {{cite journal| vauthors = Sreenivasan VR|title = Problems in Identification of Methylenedioxy and Methoxy Amphetamines|journal = Journal of Criminal Law, Criminology, and 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}}</ref> MDMA likely emerged as a substitute for its analog methylenedioxyamphetamine (MDA),<ref name="Foderaro 1988">{{cite news| vauthors = Foderaro LW |title=Psychedelic Drug Called Ecstasy Gains Popularity in Manhattan Nightclubs|url=https://www.nytimes.com/1988/12/11/nyregion/psychedelic-drug-called-ecstasy-gains-popularity-in-manhattan-nightclubs.html?pagewanted=2|access-date=27 August 2015|work=The New York Times|date=11 December 1988}}</ref> a drug at the time popular among users of psychedelics<ref name="Professor X"/> which was made a Schedule 1 substance in the United States in 1970.<ref name="Beck 1987">{{cite web| vauthors = Beck JE |title=Drug Abuse Series: MDMA|url=https://erowid.org/chemicals/mdma/mdma_info6.shtml|website=Erowid|publisher=Drug Abuse Information and Monitoring Project|access-date=6 August 2015|date=April 1987}}</ref><ref name=exploration/>

=== Shulgin's research ===
[[File:Shulgin sasha 2011 hanna jon.jpg|thumb|Alexander and Ann Shulgin in December 2011]]

American chemist and psychopharmacologist Alexander Shulgin reported he synthesized MDMA in 1965 while researching methylenedioxy compounds at [[Company:Dow Chemical Company|Dow Chemical Company]], but did not test the psychoactivity of the compound at this time. Around 1970, Shulgin sent instructions for N-methylated MDA (MDMA) synthesis to the founder of a Los Angeles chemical company who had requested them. This individual later provided these instructions to a client in the Midwest. Shulgin may have suspected he played a role in the emergence of MDMA in Chicago.<ref name="Shulgin">{{cite journal | vauthors = Benzenhöfer U, Passie T | title = Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin | journal = Addiction | volume = 105 | issue = 8 | pages = 1355–61 | date = August 2010 | pmid = 20653618 | doi = 10.1111/j.1360-0443.2010.02948.x }}</ref>

Shulgin first heard of the psychoactive effects of N-methylated MDA around 1975 from a young student who reported "amphetamine-like content".<ref name="Shulgin"/> Around 30 May 1976, Shulgin again heard about the effects of N-methylated MDA,<ref name="Shulgin"/> this time from a graduate student in a medicinal chemistry group he advised at [[Organization:San Francisco State University|San Francisco State University]]<ref name="Professor X"/><ref>{{cite web |title=Alexander 'Sasha' Shulgin |url=http://www.shulginresearch.org/home/about/alexander-sasha-shulgin/ |publisher=Alexander Shulgin Research Institute|access-date=8 January 2015|archive-date=20 December 2014 |archive-url=https://web.archive.org/web/20141220131529/http://www.shulginresearch.org/home/about/alexander-sasha-shulgin/|url-status=dead}}</ref> who directed him to the University of Michigan study.<ref name=PiHKAL/> She and two close friends had consumed 100&nbsp;mg of MDMA and reported positive emotional experiences.<ref name=Shulgin/> Following the self-trials of a colleague at the [[Organization:University of San Francisco|University of San Francisco]], Shulgin synthesized MDMA and tried it himself in September and October 1976.<ref name="Shulgin"/><ref name="Professor X"/> Shulgin first reported on MDMA in a presentation at a conference in Bethesda, Maryland in December 1976.<ref name="Shulgin"/> In 1978, he and David E. Nichols published a report on the drug's psychoactive effect in humans. They described MDMA as inducing "an easily controlled altered state of consciousness with emotional and sensual overtones" comparable "to marijuana, to [[Chemistry:Psilocybin|psilocybin]] devoid of the hallucinatory component, or to low levels of MDA".<ref name="isbn0-08-021938-1">{{cite book|vauthors=Shulgin AT, Nichols DE |editor1=Willette, Robert E. |editor2=Stillman, Richard Joseph |title=The Psychopharmacology of Hallucinogens |publisher=Pergamon Press |location=New York |year=1978 |pages=74–83 |chapter=Characterization of Three New Psychotomimetics |isbn=978-0-08-021938-7 |chapter-url=http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&ID=961&DocPartID=832}}</ref>

While not finding his own experiences with MDMA particularly powerful,<ref name=PiHKAL/><ref name="Dr. Ecstasy"/> Shulgin was impressed with the drug's disinhibiting effects and thought it could be useful in therapy.<ref name="Dr. Ecstasy"/> Believing MDMA allowed users to strip away habits and perceive the world clearly, Shulgin called the drug ''window''.<ref name=PiHKAL/><ref name="rising"/> Shulgin occasionally used MDMA for relaxation, referring to it as "my low-calorie martini", and gave the drug to friends, researchers, and others who he thought could benefit from it.<ref name=PiHKAL>{{cite book| vauthors=Shulgin AT, Shulgin A |author-link2=Ann Shulgin|title=PiHKAL: A Chemical Love Story |date=1991|publisher=Transform Press|location=Berkeley, CA|isbn=978-0-9630096-0-9|edition=7th printing, 1st|chapter= Chapters 12, 22|title-link=PiHKAL}}</ref> One such person was Leo Zeff, a psychotherapist who had been known to use psychedelic substances in his practice. When he tried the drug in 1977, Zeff was impressed with the effects of MDMA and came out of his semi-retirement to promote its use in therapy. Over the following years, Zeff traveled around the United States and occasionally to Europe, eventually training an estimated four thousand psychotherapists in the therapeutic use of MDMA.<ref name="Dr. Ecstasy">{{cite news| vauthors=Bennett D |url=https://www.nytimes.com/2005/01/30/magazine/30ECSTASY.html|title=Dr. Ecstasy |work=The New York Times Magazine |date=30 January 2005}}</ref><ref>{{cite book| vauthors=Shulgin A |veditors=Doblin R |editor1-link=Rick Doblin |title=The Secret Chief Revealed |date=2004|publisher=Multidisciplinary Association for Psychedelic Studies|location=Sarasota, Fl|isbn=978-0-9660019-6-9|pages=17–18 |edition=2nd|chapter-url=http://maps.org/images/pdf/books/scr/scr.pdf|access-date=7 January 2015|chapter=Tribute to Jacob|url-status=dead|archive-date=16 September 2018|archive-url=https://web.archive.org/web/20180916024833/http://www.maps.org/images/pdf/books/scr/scr.pdf}}</ref> Zeff named the drug ''Adam'', believing it put users in a state of primordial innocence.<ref name="Professor X">{{cite magazine| vauthors=Brown E |title=Professor X|magazine=Wired|date=September 2002 |url=http://archive.wired.com/wired/archive/10.09/professorx.html?pg=3&topic=&topic_set= |access-date=4 January 2015}}</ref>

Psychotherapists who used MDMA believed the drug eliminated the typical fear response and increased communication. Sessions were usually held in the home of the patient or the therapist. The role of the therapist was minimized in favor of patient self-discovery accompanied by MDMA induced feelings of empathy. Depression, substance use disorders, relationship problems, premenstrual syndrome, and autism were among several psychiatric disorders MDMA assisted therapy was reported to treat.<ref name=exploration/> According to psychiatrist George Greer, therapists who used MDMA in their practice were impressed by the results. Anecdotally, MDMA was said to greatly accelerate therapy.<ref name="Dr. Ecstasy"/> According to David Nutt, MDMA was widely used in the western US in couples counseling, and was called ''empathy''. Only later was the term ''ecstasy'' used for it, coinciding with rising opposition to its use.<ref name=Nutt/>

===Rising recreational use===

In the late 1970s and early 1980s, "Adam" spread through personal networks of psychotherapists, psychiatrists, users of psychedelics, and yuppies. Hoping MDMA could avoid criminalization like LSD and mescaline, psychotherapists and experimenters attempted to limit the spread of MDMA and information about it while conducting informal research.<ref name="exploration">{{cite journal | vauthors = Pentney AR | title = An exploration of the history and controversies surrounding MDMA and MDA | journal = Journal of Psychoactive Drugs | volume = 33 | issue = 3 | pages = 213–21 | date = 2001 | pmid = 11718314 | doi = 10.1080/02791072.2001.10400568 | s2cid = 31142434 }}</ref><ref name=Eisner/> Early MDMA distributors were deterred from large scale operations by the threat of possible legislation.<ref name="Beck & Rosenbaum">{{cite book| vauthors = Beck J, Rosenbaum M |title=Pursuit of Ecstasy : The MDMA Experience|date=1994|publisher=State Univ. of New York Press|location=Albany|isbn=978-0-7914-1817-8|chapter-url=https://books.google.com/books?id=SwdedK36bVMC|chapter=The Distribution of Ecstasy|url-access=registration|url=https://archive.org/details/pursuitofecstasy0000beck}}</ref> Between the 1970s and the mid-1980s, this network of MDMA users consumed an estimated 500,000 doses.<ref name=Current2013/><ref name="isbn0803936788">{{cite book| vauthors = Doblin R, Rosenbaum M | veditors = Inciardi JA |title=The Drug Legalization Debate|date=1991|publisher=SAGE Publications, Inc.|location=London|isbn=978-0-8039-3678-2|edition=2nd|chapter-url=http://www.drugtext.org/pdf/Dance/party-drugs-clubbing/why-mdma-should-not-have-been-made-illegal.pdf|access-date=10 August 2015|chapter=Chapter 6: Why MDMA Should Not Have Been Made Illegal|url=https://archive.org/details/druglegalization00inci}}</ref>

A small recreational market for MDMA developed by the late 1970s,<ref name="isbn9781847656414">{{cite book| vauthors = Collin M, Godfrey J |title=Altered State: The Story of Ecstasy Culture and Acid House.|date=2010|publisher=Profile Books|location=London|isbn=978-1-84765-641-4|edition=Updated new|chapter-url=https://books.google.com/books?id=fc8x9qeCekQC|chapter=The Technologies of Pleasure}}</ref> consuming perhaps 10,000 doses in 1976.<ref name="Beck 1987"/> By the early 1980s MDMA was being used in Boston and New York City nightclubs such as Studio 54 and Paradise Garage.<ref>{{cite news|vauthors=Savlov M|title=Countdown to Ecstasy: A New Drug for a New Millennium|url=http://www.weeklywire.com/ww/06-12-00/austin_music_feature.html|access-date=6 August 2015|work=The Austin Chronicle|publisher=Weekly Wire|date=12 June 2000|archive-date=21 January 2016|archive-url=https://web.archive.org/web/20160121022839/http://weeklywire.com/ww/06-12-00/austin_music_feature.html|url-status=dead}}</ref><ref>{{cite magazine| vauthors = Owen F, Gavin L |title=Molly Isn't Who You Think She Is: A Deeper Look at MDMA|url=http://www.playboy.com/articles/molly-party-drug-ecstasy|access-date=6 August 2015|magazine=Playboy|date=20 October 2013|archive-date=27 July 2015|archive-url= https://web.archive.org/web/20150727080003/http://www.playboy.com/articles/molly-party-drug-ecstasy |url-status=dead}}</ref> Into the early 1980s, as the recreational market slowly expanded, production of MDMA was dominated by a small group of therapeutically minded Boston chemists. Having commenced production in 1976, this "Boston Group" did not keep up with growing demand and shortages frequently occurred.<ref name="Beck & Rosenbaum"/>

Perceiving a business opportunity, Michael Clegg, the Southwest distributor for the Boston Group, started his own "Texas Group" backed financially by Texas friends.<ref name="Beck & Rosenbaum"/><ref>{{cite book| vauthors = Sylvan R |title=Trance Formation: The Spiritual and Religious Dimensions of Global Rave Culture|date=2005|publisher=Routledge|location=New York, NY|isbn=978-0-415-97090-7|pages=21–22|chapter=A Brief History of the Rave Scene}}</ref> In 1981,<ref name="Beck & Rosenbaum"/> Clegg had coined "Ecstasy" as a slang term for MDMA to increase its marketability.<ref name=rising/><ref name=Eisner>{{cite book| vauthors = Eisner B |title=Ecstasy : The MDMA Story|date=1994|publisher=Ronin Publishing|location=Berkeley, CA|isbn=978-0-914171-68-3|edition=Expanded 2nd|url=https://books.google.com/books?id=8aqUu5M6UpwC}}</ref> Starting in 1983,<ref name="Beck & Rosenbaum"/> the Texas Group mass-produced MDMA in a Texas lab<ref name=Eisner/> or imported it from California<ref name="rising"/> and marketed tablets using pyramid sales structures and toll-free numbers.<ref name="isbn0803936788"/> MDMA could be purchased via credit card and taxes were paid on sales.<ref name="Beck & Rosenbaum"/> Under the brand name "Sassyfras", MDMA tablets were sold in brown bottles.<ref name=Eisner/> The Texas Group advertised "Ecstasy parties" at bars and discos, describing MDMA as a "fun drug" and "good to dance to".<ref name="Beck & Rosenbaum"/> MDMA was openly distributed in {{wipe|Austin, Texas}} and Dallas–Fort Worth area bars and nightclubs, becoming popular with yuppies, college students, and gays.<ref name="Foderaro 1988" /><ref name="Beck & Rosenbaum"/><ref name="isbn0803936788"/>

Recreational use also increased after several cocaine dealers switched to distributing MDMA following experiences with the drug.<ref name="isbn0803936788"/>  A California laboratory that analyzed confidentially submitted drug samples first detected MDMA in 1975. Over the following years the number of MDMA samples increased, eventually exceeding the number of MDA samples in the early 1980s.<ref>{{cite journal | vauthors = Parrott AC | title = Is ecstasy MDMA? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity | journal = Psychopharmacology | volume = 173 | issue = 3–4 | pages = 234–41 | date = May 2004 | pmid = 15007594 | doi = 10.1007/s00213-003-1712-7 | s2cid = 3347303 | url = http://psy.swansea.ac.uk/staff/parrott/p-IsEcstasyMDMA-Psychopharm-2004.pdf }}</ref><ref>{{cite journal | vauthors = Renfroe CL | title = MDMA on the street: Analysis Anonymous | journal = Journal of Psychoactive Drugs | volume = 18 | issue = 4 | pages = 363–9 | date = October 1986 | pmid = 2880953 | doi = 10.1080/02791072.1986.10472371 }}</ref> By the mid-1980s, MDMA use had spread to colleges around the United States.<ref name="Beck & Rosenbaum"/>{{rp|33}}

===Media attention and scheduling===

====United States====
[[File:Federal Register notice of planned MDMA scheduling.pdf|thumb|27 July 1984 Federal Register notice of the proposed MDMA scheduling]]

In an early media report on MDMA published in 1982, a [[Organization:Drug Enforcement Administration|Drug Enforcement Administration]] (DEA) spokesman stated the agency would ban the drug if enough evidence for abuse could be found.<ref name="Beck & Rosenbaum"/> By mid-1984, MDMA use was becoming more noticed. Bill Mandel reported on "Adam" in a 10 June San Francisco Chronicle article, but misidentified the drug as [[Chemistry:MMDA (drug)|methyloxymethylenedioxyamphetamine]] (MMDA). In the next month, the World Health Organization identified MDMA as the only substance out of twenty phenethylamines to be seized a significant number of times.<ref name="Eisner" />

After a year of planning and data collection, MDMA was proposed for scheduling by the DEA on 27 July 1984 with a request for comments and objections.<ref name=Eisner/><ref>{{cite journal|title=Schedules of Controlled Substances Proposed Placement of 3,4-Methylenedioxymethamphetamine in Schedule I|journal=Federal Register|date=27 July 1984|volume=49|issue=146|page=30210|url=http://maps.org/research-archive/dea-mdma/pdf/0194.PDF|access-date=15 January 2015}}</ref> The DEA was surprised when a number of psychiatrists, psychotherapists, and researchers objected to the proposed scheduling and requested a hearing.<ref name="exploration"/> In a Newsweek article published the next year, a DEA pharmacologist stated that the agency had been unaware of its use among psychiatrists.<ref>{{cite news | vauthors = Adler J, Abramson P, Katz S, Hager M |title=Getting High on 'Ecstasy' |url=http://www.maps.org/research-archive/hmma/Newsweek4.85.pdf |access-date=1 February 2015 |work=Newsweek Magazine |date=15 April 1985|location=Life/Style|page=96}}</ref> An initial hearing was held on 1 February 1985 at the DEA offices in Washington, D.C., with administrative law judge Francis L. Young presiding.<ref name=Eisner/> It was decided there to hold three more hearings that year: Los Angeles on 10 June, Kansas City, Missouri on 10–11 July, and Washington, D.C., on 8–11 October.<ref name=exploration/><ref name=Eisner/>

Sensational media attention was given to the proposed criminalization and the reaction of MDMA proponents, effectively advertising the drug.<ref name=exploration/> In response to the proposed scheduling, the Texas Group increased production from 1985 estimates of 30,000 tablets a month to as many as 8,000 per day, potentially making two million ecstasy tablets in the months before MDMA was made illegal.<ref name=comprehensive>{{cite book| vauthors = Holland J | veditors = Holland J |title=Ecstasy: the complete guide; a comprehensive look at the risks and benefits of MDMA|date=2001|publisher=Park Street Press|location=Rochester, VT|isbn=978-0-89281-857-0 |chapter=The History of MDMA}}</ref> By some estimates the Texas Group distributed 500,000 tablets per month in Dallas alone.<ref name=rising/> According to one participant in an ethnographic study, the Texas Group produced more MDMA in eighteen months than all other distribution networks combined across their entire histories.<ref name="Beck & Rosenbaum"/> By May 1985, MDMA use was widespread in California, Texas, southern Florida, and the northeastern United States.<ref name="Siegel 1986"/><ref name="New York Times"/> According to the DEA there was evidence of use in twenty-eight states<ref>{{cite web|title=MDMA – FDA REPORT, 1985|url=https://www.erowid.org/chemicals/mdma/mdma_law3.shtml|website=Erowid|publisher=Food and Drug Administration|access-date=11 August 2015|date=1985}}</ref> and Canada.<ref name="Siegel 1986"/> Urged by Senator Lloyd Bentsen, the DEA announced an emergency Schedule I classification of MDMA on 31 May 1985. The agency cited increased distribution in Texas, escalating street use, and new evidence of MDA (an analog of MDMA) neurotoxicity as reasons for the emergency measure.<ref name="New York Times">{{cite news|title=U.S. will ban 'ecstasy,' a hallucinogenic drug|url=https://www.nytimes.com/1985/06/01/us/us-will-ban-ecstasy-a-hallucinogenic-drug.html|newspaper=The New York Times|access-date=29 April 2015|date=1 June 1985|agency=The Associated Press}}</ref><ref>{{cite news| vauthors = Baker K |title=DEA To Ban "Ecstasy" – The Drug MDMA|url=https://apnews.com/26214cd32a8b4c05e361158df14715b0|access-date=7 August 2015|agency=The Associated Press|date=30 May 1985}}</ref><ref>{{cite news| vauthors = Corwin M |title=U.S. to Ban Use of Drug MDMA : Street Abuse Cited; Used by Psychiatrists|url=https://articles.latimes.com/1985-05-31/news/mn-14566_1_street-drugs|access-date=11 August 2015|newspaper=Los Angeles Times|date=31 May 1985}}</ref> The ban took effect one month later on 1 July 1985<ref name=comprehensive/> in the midst of Nancy Reagan's "Just Say No" campaign.<ref>{{cite news| vauthors = Weber B |title=Alexander Shulgin, Psychedelia Researcher, Dies at 88|url=https://www.nytimes.com/2014/06/08/us/alexander-shulgin-psychedelia-researcher-dies-at-88.html?_r=0|access-date=28 August 2015|work=The New York Times|date=7 June 2014}}</ref><ref>{{cite news| vauthors = Vastag B |title=Chemist Alexander Shulgin, popularizer of the drug Ecstasy, dies at 88|url=https://www.washingtonpost.com/national/health-science/chemist-alexander-shulgin-popularizer-of-the-drug-ecstasy-dies-at-88/2014/06/03/19fd9580-eb34-11e3-b98c-72cef4a00499_story.html|access-date=28 August 2015|newspaper=The Washington Post|publisher=WP Company LLC|date=3 June 2014}}</ref>

As a result of several expert witnesses testifying that MDMA had an accepted medical usage, the administrative law judge presiding over the hearings recommended that MDMA be classified as a Schedule III substance. Despite this, DEA administrator John C. Lawn overruled and classified the drug as Schedule I.<ref name=exploration/><ref name=Harpers>{{cite news|title= Ecstasy has its pros and cons|newspaper= Kokomo Tribune| location = Kokomo, Indiana| date = 23 November 1985 | page=6| url=https://newspaperarchive.com/profile/Robert_Thomas/clipnumber/34618/ |agency=Harper's Bazaar |via=newspaperarchive.com}} {{free access}}</ref> Harvard psychiatrist Lester Grinspoon then sued the DEA, claiming that the DEA had ignored the medical uses of MDMA, and the federal court sided with Grinspoon, calling Lawn's argument "strained" and "unpersuasive", and vacated MDMA's Schedule I status.<ref>{{cite web |title=Lester Grinspoon, M.d., Petitioner, v. Drug Enforcement Administration, Respondent, 828 F.2d 881 (1st Cir. 1987) |url=https://law.justia.com/cases/federal/appellate-courts/F2/828/881/368975/ |website=Justia Law |publisher=US Court of Appeals for the First Circuit}}</ref> Despite this, less than a month later Lawn reviewed the evidence and reclassified MDMA as Schedule I again, claiming that the expert testimony of several psychiatrists claiming over 200 cases where MDMA had been used in a therapeutic context with positive results could be dismissed because they were not published in medical journals.<ref name=exploration/> In 2017, the FDA granted [[Medicine:Breakthrough therapy|breakthrough therapy]] designation for its use with psychotherapy for PTSD. However, this designation has been questioned and problematized.<ref name="Halvorsen 1689–1690">{{cite journal | vauthors = Halvorsen JØ, Naudet F, Cristea IA | title = Challenges with benchmarking of MDMA-assisted psychotherapy | journal = Nature Medicine | volume = 27 | issue = 10 | pages = 1689–1690 | date = October 2021 | pmid = 34635857 | doi = 10.1038/s41591-021-01525-0 | s2cid = 238636360 | url = https://hal.archives-ouvertes.fr/hal-03414583/file/Halvorsen%20et%20al%20-%202021%20-%20Challenges%20with%20benchmarking%20of%20MDMA-assisted%20psychotherapy.pdf }}</ref>

====United Nations====
While engaged in scheduling debates in the United States, the DEA also pushed for international scheduling.<ref name=comprehensive/> In 1985 the [[Organization:World Health Organization|World Health Organization]]'s Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the 1971 United Nations [[Medicine:Convention on Psychotropic Substances|Convention on Psychotropic Substances]]. The committee made this recommendation on the basis of the pharmacological similarity of MDMA to previously scheduled drugs, reports of illicit trafficking in Canada, drug seizures in the United States, and lack of well-defined therapeutic use. While intrigued by reports of psychotherapeutic uses for the drug, the committee viewed the studies as lacking appropriate methodological design and encouraged further research. Committee chairman Paul Grof dissented, believing international control was not warranted at the time and a recommendation should await further therapeutic data.<ref>{{cite book|title=WHO Expert Committee on Drug Dependence: Twenty-second Report.|date=1985|publisher=World Health Organization|location=Geneva|isbn=978-9241207294|url=http://whqlibdoc.who.int/trs/WHO_TRS_729.pdf|access-date=29 August 2012|archive-url=https://web.archive.org/web/20141019192225/http://whqlibdoc.who.int/trs/WHO_TRS_729.pdf|archive-date= 19 October 2014|pages=24–25}}</ref> The Commission on Narcotic Drugs added MDMA to Schedule I of the convention on 11 February 1986.<ref>{{cite web |url=http://www.unodc.org/documents/commissions/CND/Drug_Resolutions/1980-1989/1986/CND_Decision-1986-07_S-IX.pdf |title=Decision to place MDMA into Schedule I |publisher=Commission on Narcotic Drugs |date=11 February 1986 |website=UNODC |access-date=9 May 2015}}</ref>

===Post-scheduling===
[[File:1995-04-08 Vibe Tribe 09 (10937582).jpg|thumb|A 1995 Vibe Tribe rave in Erskineville, New South Wales, Australia being broken up by police. MDMA use spread globally along with rave culture.]]
[[File:Ecstasy - Is it Really the Dream Drug.ogv|thumb|A 2000 United States Air Force video dramatizing the dangers of MDMA misuse]]
The use of MDMA in Texas clubs declined rapidly after criminalization, although by 1991 the drug remained popular among young middle-class whites and in nightclubs.<ref name="Beck & Rosenbaum"/>{{rp|46}} In 1985, MDMA use became associated with acid house on the Spanish island of Ibiza.<ref name="Beck & Rosenbaum"/>{{rp|50}}<ref>{{cite news| vauthors = McKinley JC |title=Overdoses of 'Molly' Led to Electric Zoo Deaths|url=http://artsbeat.blogs.nytimes.com/2013/09/12/overdoses-of-molly-led-to-electric-zoo-deaths/?_r=0|access-date=9 December 2013|newspaper=The New York Times|date=12 September 2013}}</ref> Thereafter in the late 1980s, the drug spread alongside rave culture to the UK and then to other European and American cities.<ref name="Beck & Rosenbaum"/>{{rp|50}} Illicit MDMA use became increasingly widespread among young adults in universities and later, in high schools. Since the mid-1990s, MDMA has become the most widely used amphetamine-type drug by college students and teenagers.<ref name="Goldfrank 2011">{{cite book| vauthors = Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE |title=Goldfrank's toxicologic emergencies|date=2011|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-160593-9|edition=9th}}</ref>{{rp|1080}} MDMA became one of the four most widely used illicit drugs in the US, along with [[Biology:Cocaine|cocaine]], [[Chemistry:Heroin|heroin]], and [[Biology:Cannabis (drug)|cannabis]].<ref name=rising>{{cite news| vauthors = Jennings P |title=Ecstasy Rising|work=Primetime Thursday|issue=Special edition|publisher=ABC News|date=1 April 2004 |url=http://www.thedocumentarygroup.com/PJP/Transcripts%20Files/Script_Ecstasy.doc |url-status=dead|archive-url=https://web.archive.org/web/20150527163756/http://www.thedocumentarygroup.com/PJP/Transcripts%20Files/Script_Ecstasy.doc|archive-date=27 May 2015|df=dmy-all}}</ref>
According to some estimates as of 2004, only marijuana attracts more first time users in the US.<ref name="rising"/>

After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally. Later,{{when|date=January 2015}} Charles Grob initiated an ascending-dose safety study in healthy volunteers. Subsequent FDA-approved MDMA studies in humans have taken place in the United States in Detroit ([[Organization:Wayne State University|Wayne State University]]), Chicago ([[Organization:University of Chicago|University of Chicago]]), San Francisco (UCSF and California Pacific Medical Center), Baltimore ([[Organization:National Institute on Drug Abuse|NIDA]]–NIH Intramural Program), and South Carolina. Studies have also been conducted in Switzerland (University Hospital of Psychiatry, [[Place:Zürich|Zürich]]), the Netherlands ([[Organization:Maastricht University|Maastricht University]]), and Spain (Universitat Autònoma de Barcelona).<ref>{{cite web | url = http://www.maps.org/research/ | title = Bibliography of Psychedelic Research Studies. | work = Multidisciplinary Association for Psychedelic Studies (MAPS) | location = Santa Cruz, CA | archive-url = https://web.archive.org/web/20131203011733/http://www.maps.org/research/ | archive-date=3 December 2013 }}</ref>

"Molly", short for 'molecule', was recognized as a slang term for crystalline or powder MDMA in the 2000s.<ref>{{cite web|title= What Is Molly and Why Is It Dangerous? |url = https://www.nbcnews.com/health/health-news/what-molly-why-it-dangerous-n311291 | vauthors = James SD |publisher = NBCNews.com|date = 23 February 2015|access-date = 23 February 2015|quote=Why is it called Molly?  That's short for "molecule."  "You can put a ribbon and bow on it and call it a cute name like 'Molly' and people are all in," said Paul Doering, professor emeritus of pharmacology at the University of Florida.}}</ref><ref>{{cite news| vauthors = Aleksander I |title=Molly: Pure, but Not So Simple|url=https://www.nytimes.com/2013/06/23/fashion/molly-pure-but-not-so-simple.html |archive-url=https://ghostarchive.org/archive/20220101/https://www.nytimes.com/2013/06/23/fashion/molly-pure-but-not-so-simple.html |archive-date=2022-01-01 |url-access=limited|access-date=24 February 2015|work=The New York Times|date=21 June 2013}}{{cbignore}}</ref>

In 2010, the BBC reported that use of MDMA had decreased in the UK in previous years. This may be due to increased seizures during use and decreased production of the precursor chemicals used to manufacture MDMA. Unwitting substitution with other drugs, such as [[Chemistry:Mephedrone|mephedrone]] and [[Chemistry:Methamphetamine|methamphetamine]],<ref>{{cite news|url=http://scientopia.org/blogs/drugmonkey/2010/09/19/mephedrone-4-methylmethcathinone-appearing-in-ecstasy-in-the-netherlands/|title=Mephedrone (4-Methylmethcathinone) appearing in "Ecstasy" in the Netherlands|date=19 September 2010|access-date=31 December 2012|archive-date=5 November 2012|archive-url=https://web.archive.org/web/20121105125943/http://scientopia.org/blogs/drugmonkey/2010/09/19/mephedrone-4-methylmethcathinone-appearing-in-ecstasy-in-the-netherlands/|url-status=dead}}</ref> as well as legal alternatives to MDMA, such as [[Chemistry:Benzylpiperazine|BZP]], [[Chemistry:Methylenedioxypyrovalerone|MDPV]], and [[Chemistry:Methylone|methylone]], are 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|work=BBC News|access-date=14 February 2010}}</ref>

In 2017 it was found that some pills being sold as MDMA contained [[Chemistry:Pentylone|pentylone]], which can cause very unpleasant agitation and paranoia.<ref>{{cite journal | vauthors = Bish J |title=Watch Out for Pentylone, the Horrible New MDMA Additive |journal=Vice |date=Aug 4, 2017 |url=https://www.vice.com/en_uk/article/pagjxg/watch-out-for-pentylone-the-horrible-new-mdma-additive}}</ref>

According to David Nutt, when [[Chemistry:Safrole|safrole]] was restricted by the United Nations in order to reduce the supply of MDMA, producers in China began using [[Chemistry:Anethole|anethole]] instead, but this gives para-methoxyamphetamine (PMA, also known as "Dr Death"), which is much more toxic than MDMA and can cause overheating, muscle spasms, seizures, unconsciousness, and death. People wanting MDMA are sometimes sold PMA instead.<ref name=Nutt>{{cite web | url = https://www.bbc.co.uk/programmes/w3cswgvh | title = Ecstasy on Prescription | work = BBC Business Daily | date = 29 May 2018 }}</ref>

==Society and culture==
{{Global estimates of illicit drug users}}

===Legal status===
MDMA is legally controlled in most of the world under the UN [[Medicine:Convention on Psychotropic Substances|Convention on Psychotropic Substances]] and other international agreements, although exceptions exist for research and limited medical use. In general, the unlicensed use, sale or manufacture of MDMA are all criminal offences.

====Australia====
In Australia, MDMA was rescheduled on 1 July 2023 as a schedule 8 substance (available on prescription) when used in the treatment of PTSD, while remaining a schedule 9 substance (prohibited) for all other uses. For the treatment of PTSD, MDMA can only be prescribed by psychiatrists with specific training and authorisation.<ref>{{cite web |title=MDMA and psilocybin: What GPs need to know |url=https://www1.racgp.org.au/newsgp/gp-opinion/mdma-and-psilocybin-what-gps-need-to-know#:~:text=It%20means%20psilocybin%20and%20MDMA,restricts%20supply%20to%20clinical%20trials. |website=RACGP |access-date=2023-06-13}}</ref>
In 1986, MDMA was declared an illegal substance because of its allegedly harmful effects and potential for misuse.{{citation needed|date=July 2018}}. Any non-authorised sale, use or manufacture is strictly prohibited by law. Permits for research uses on humans must be approved by a recognized [[Organization:National Health and Medical Research Council|ethics committee]] on human research.

In Western Australia under the Misuse of Drugs Act 1981 4.0g of MDMA is the amount required determining a court of trial, 2.0g is considered a presumption with intent to sell or supply and 28.0g is considered trafficking under Australian law.<ref>{{cite web|title=Misuse of Drugs Act 1981|url=https://www.slp.wa.gov.au/legislation/statutes.nsf/main_mrtitle_4607_homepage.html|publisher=The Government of Western Australia|agency=Department of the Premier and Cabinet|date=23 October 1981}}</ref>

The Australian Capital Territory has passed legislation to decriminalise the possession of small amounts of MDMA, due to take effect in October 2023.<ref>{{cite news |title=ACT government decriminalises small amounts of illicit drugs including speed, heroin and cocaine |url=https://www.abc.net.au/news/2022-10-20/act-decriminalises-small-amounts-of-illicit-drugs-heroin-cocaine/101552008 |website=ABC News |date=20 October 2022 |publisher=Australian Broadcasting Corporation |access-date=2023-06-13}}</ref>

====United Kingdom====
In the United Kingdom, MDMA was made illegal in 1977 by a modification order to the existing [[Medicine:Misuse of Drugs Act 1971|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 name="Drugs 2.0">{{cite book| vauthors = Power M |title=Drugs 2.0 : the web revolution that's changing how the world gets high|date=2013|publisher=Portobello|location=London|isbn=978-1-84627-459-6 |url=https://books.google.com/books?id=gj6zMQEACAAJ&q=Drugs+2.0|format=epub file}}</ref><ref name="UK legality">{{cite web | url = http://www.statutelaw.gov.uk/content.aspx?LegType=All+Primary&PageNumber=57&NavFrom=2&parentActiveTextDocId=1367412&ActiveTextDocId=1367472&filesize=411 | title = Misuse of Drugs Act 1971 | work = Statutelaw.gov.uk | date = 5 January 1998 | access-date = 11 June 2011 }}</ref> The drug is therefore illegal to sell, buy, or possess without a licence in the UK. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking.

Some researchers such as David Nutt have criticized the scheduling of MDMA, which he determined to be a relatively harmless drug.<ref>{{Cite news | vauthors = Hope C |date = 7 February 2009 |title = Ecstasy 'no more dangerous than horse riding'|url = https://www.telegraph.co.uk/news/uknews/law-and-order/4537874/Ecstasy-no-more-dangerous-than-horse-riding.html|website = Telegraph.co.uk |access-date = 4 December 2015}}</ref><ref>{{cite journal | vauthors = Nutt DJ | title = Equasy-- an overlooked addiction with implications for the current debate on drug harms | journal = Journal of Psychopharmacology | volume = 23 | issue = 1 | pages = 3–5 | date = January 2009 | pmid = 19158127 | doi = 10.1177/0269881108099672 | s2cid = 32034780 }}</ref>  An editorial he wrote in the ''Journal of Psychopharmacology'', where he compared the risk of harm for horse riding (1 adverse event in 350) to that of ecstasy (1 in 10,000) resulted in his dismissal as well as the resignation of his colleagues from the ACMD.<ref name="johnson">{{cite news|url=https://www.theguardian.com/politics/2009/nov/02/drug-policy-alan-johnson-nutt|title=Why Professor David Nutt was shown the door| vauthors = Johnson A |date=2 November 2009|newspaper=The Guardian|access-date=3 November 2009 | location=London}}</ref>

====United States====
In the United States, MDMA is listed in 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 February 1988).</ref> In a 2011 federal court hearing, the American Civil Liberties Union successfully argued that the sentencing guideline for MDMA/ecstasy is based on outdated science, leading to excessive prison sentences.<ref>{{cite web | url = https://www.aclu.org/criminal-law-reform/court-rejects-harsh-federal-drug-sentencing-guideline-scientifically-unjustified | title = Court Rejects Harsh Federal Drug Sentencing Guideline as Scientifically Unjustified | work = American Civil Liberties Union | date = 15 July 2011 | access-date = 29 August 2012 }}</ref>  Other courts have upheld the sentencing guidelines.  The United States District Court for the Eastern District of Tennessee explained its ruling by noting that "an individual federal district court judge simply cannot marshal resources akin to those available to the Commission for tackling the manifold issues involved with determining a proper drug equivalency."<ref name="papers.ssrn.com">{{Cite journal|ssrn=2481227 | vauthors = Hennig AC |title=An Examination of Federal Sentencing Guidelines' Treatment of MDMA ('Ecstasy') |journal=Belmont Law Review |volume=1 |page=267 |year=2014}}</ref>

====Netherlands====
In the Netherlands, the Expert Committee on the List (Expertcommissie Lijstensystematiek Opiumwet) issued a report in June 2011 which discussed the evidence for harm and the legal status of MDMA, arguing in favor of maintaining it on List I.<ref name="papers.ssrn.com"/><ref>{{cite web | url = http://www.rijksoverheid.nl/documenten-en-publicaties/rapporten/2011/06/27/rapport-drugs-in-lijsten.html | title = Rapport Drugs in Lijsten | archive-url = https://web.archive.org/web/20120306112130/http://www.rijksoverheid.nl/documenten-en-publicaties/rapporten/2011/06/27/rapport-drugs-in-lijsten.html | archive-date = 6 March 2012 | work = Rijksoverheid.nl | date = 27 June 2011 | access-date = 29 August 2012 }}</ref><ref>{{cite web|title=Committee: the current system of the Opium Act does not have to be changed|url=http://www.government.nl/documents-and-publications/press-releases/2011/06/24/committee-the-current-system-of-the-opium-act-does-not-have-to-be-changed.html|website=government.nl|date=24 June 2011|access-date=29 August 2012|archive-date=29 April 2012|archive-url=https://web.archive.org/web/20120429071421/http://www.government.nl/documents-and-publications/press-releases/2011/06/24/committee-the-current-system-of-the-opium-act-does-not-have-to-be-changed.html|url-status=dead}}</ref>

====Canada====
In Canada, MDMA is listed as a Schedule 1<ref name="CDSA Schedule I: Amphetamines">{{cite web|title=Schedule I|url=http://isomerdesign.com/Cdsa/schedule.php?schedule=1&section=18.5&structure=C|work=Controlled Drugs and Substances Act|publisher=Isomer Design|access-date=9 December 2013|archive-date=10 November 2013|archive-url=https://web.archive.org/web/20131110200556/http://isomerdesign.com/Cdsa/schedule.php?schedule=1&section=18.5&structure=C|url-status=dead}}</ref> as it is an analogue of amphetamine.<ref name="Definitions and Interpretations">{{cite web|title=Definitions and interpretations|url=http://isomerdesign.com/Cdsa/definitions.php?structure=C|work=Controlled Drugs and Substances Act|publisher=Isomer Design|access-date=9 December 2013}}</ref> The Controlled Drugs and Substances Act was updated as a result of the Safe Streets and Communities Act changing amphetamines from Schedule III to Schedule I in March 2012. In 2022 the federal government granted British Columbia a 3-year exemption, legalizing the possession of up to {{Convert|2.5|g|oz}} of MDMA in the province from February 2023 until February 2026.<ref>{{Cite web |title=Decriminalizing people who use drugs in B.C. |url=https://www2.gov.bc.ca/gov/content/overdose/decriminalization |access-date=2023-03-08 |website=Government of BC |publisher=Government Communications and Public Engagement}}</ref><ref>{{Cite news |date=March 7, 2023 |title=B.C. recorded 211 toxic drug deaths — almost 7 a day — in January, coroner reports |work=CBC.ca |url=https://www.cbc.ca/news/canada/british-columbia/bc-toxic-drugs-deaths-january-2023-1.6770643 |access-date=March 8, 2023}}</ref>

===Demographics===
[[File:UNODC 2016 World Drug Report use of ecstasy in 2014 (page 1 crop).jpg|upright=1.5|thumb|UNODC map showing the use of ecstasy by country in 2014 for the global population aged 15–64]]
In 2014, 3.5% of 18 to 25 year-olds had used MDMA in the United States.<ref name=Betzler2017/> In the European Union as of 2018, 4.1% of adults (15–64 years old) have used MDMA at least once in their life, and 0.8% had used it in the last year.<ref name="European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)">{{Cite web|url=http://www.emcdda.europa.eu/data/stats2018/gps_en|title=Statistical Bulletin 2018 —&nbsp;prevalence of drug use | publisher = European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) |access-date=2019-02-05}}</ref> Among young adults, 1.8% had used MDMA in the last year.<ref name="European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)" />

In Europe, an estimated 37% of regular club-goers aged 14 to 35 used MDMA in the past year according to the 2015 European Drug report.<ref name="Betzler2017" /> The highest one-year prevalence of MDMA use in Germany in 2012 was 1.7% among people aged 25 to 29 compared with a population average of 0.4%.<ref name="Betzler2017" /> Among adolescent users in the United States between 1999 and 2008, girls were more likely to use MDMA than boys.<ref>{{cite journal | vauthors = Wu P, Liu X, Pham TH, Jin J, Fan B, Jin Z | title = Ecstasy use among US adolescents from 1999 to 2008 | journal = Drug and Alcohol Dependence | volume = 112 | issue = 1–2 | pages = 33–8 | date = November 2010 | pmid = 20570447 | pmc = 2967577 | doi = 10.1016/j.drugalcdep.2010.05.006 }}</ref>

===Economics===

====Europe====
In 2008 the European Monitoring Centre for Drugs and Drug Addiction noted that although there were some reports of tablets being sold for as little as €1, most countries in Europe then reported typical retail prices in the range of €3 to €9 per tablet, typically containing 25–65&nbsp;mg of MDMA.<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 |page=49 |url=http://www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf |access-date=1 December 2008 |archive-date=25 April 2013 |archive-url=https://web.archive.org/web/20130425191815/http://www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf |url-status=dead }}</ref> By 2014 the EMCDDA reported that the range was more usually between €5 and €10 per tablet, typically containing 57–102&nbsp;mg of MDMA, although MDMA in powder form was becoming more common.<ref>{{cite book | chapter = Ecstasy: high purity powder available | title = European Drug Report | date = 2014 | page = 26 | publisher = European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) | url = http://www.emcdda.europa.eu/attachements.cfm/att_228272_EN_TDAT14001ENN.pdf | isbn = 978-92-9168-694-0 | doi = 10.2810/32306 | author1 = European Monitoring Centre for Drugs Drug Addiction | access-date = 4 June 2014 | archive-date = 7 September 2014 | archive-url = https://web.archive.org/web/20140907142119/http://www.emcdda.europa.eu/attachements.cfm/att_228272_EN_TDAT14001ENN.pdf | url-status = dead }}</ref>

====North America====
The [[Organization:United Nations Office on Drugs and Crime|United Nations Office on Drugs and Crime]] stated in its 2014 World Drug Report that US ecstasy retail prices range from US$1 to $70 per pill, or from $15,000 to $32,000 per kilogram.<ref>{{cite web|title=Ecstasy-type substances Retail and wholesale prices* and purity levels, by drug, region and country or territory|url=http://www.unodc.org/documents/wdr2014/Statistics/Prices_ATS.xls|publisher=United Nations Office on Drugs and Crime|access-date=2 January 2015|archive-date=8 December 2015|archive-url=https://web.archive.org/web/20151208142205/http://www.unodc.org/documents/wdr2014/Statistics/Prices_ATS.xls}}</ref> A new research area named Drug Intelligence aims to automatically monitor distribution networks based on image processing and machine learning techniques, in which an Ecstasy pill picture is analyzed to detect correlations among different production batches.<ref>{{cite journal | vauthors = Camargo J, Esseiva P, González F, Wist J, Patiny L | title = Monitoring of illicit pill distribution networks using an image collection exploration framework | journal = Forensic Science International | volume = 223 | issue = 1–3 | pages = 298–305 | date = November 2012 | pmid = 23107059 | doi = 10.1016/j.forsciint.2012.10.004 | url = http://www.fsijournal.org/article/S0379-0738(12)00458-6/abstract }}</ref> These novel techniques allow police scientists to facilitate the monitoring of illicit distribution networks.

{{As of|October 2015}}, most of the MDMA in the United States is produced in British Columbia, Canada and imported by Canada-based Asian transnational criminal organizations.<ref name="DEA 2015 assessment">{{cite book | title=2015 National Drug Threat Assessment Summary | chapter-url=http://www.dea.gov/docs/2015%20NDTA%20Report.pdf | website=Drug Enforcement Administration | publisher=United States Department of Justice: Drug Enforcement Administration | access-date=10 April 2016 | chapter=MDMA (3,4-Methylenedioxymethamphetamine) | pages=85–88 | date=October 2015 | archive-date=10 April 2016 | archive-url=https://web.archive.org/web/20160410100038/http://www.dea.gov/docs/2015%20NDTA%20Report.pdf | url-status=dead }}</ref> The market for MDMA in the United States is relatively small compared to [[Chemistry:Methamphetamine|methamphetamine]], [[Biology:Cocaine|cocaine]], and [[Chemistry:Heroin|heroin]].<ref name="DEA 2015 assessment" /> In the United States, about 0.9 million people used ecstasy in 2010.<ref name=Drugs2014/>

====Australia====
MDMA is particularly expensive in Australia, costing [[Finance:Australian dollar|A$]]15–A$30 per tablet. 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 MDMA enters Australia from the Netherlands, the UK, Asia, and the US.<ref>{{cite web | vauthors = Dillon P | url = http://www.drugtext.org/library/articles/dillon.htm | title = 10 years of ecstasy and other party drug use in Australia: What have we done and what is there left to do? | work = Drugtext.org | archive-url = https://web.archive.org/web/20120209142314/http://www.drugtext.org/library/articles/dillon.htm | archive-date = 9 February 2012 }}</ref>

====Corporate logos on pills====

A number of ecstasy manufacturers brand their pills with a logo, often being the logo of an unrelated corporation.<ref>{{cite web|url=https://www.erowid.org/chemicals/mdma/mdma_images.shtml|title=Erowid MDMA Vault : Images|access-date=3 March 2016}}</ref> Some pills depict logos of products or media popular with children, such as Shaun the Sheep.<ref>{{cite web | vauthors = Cork T | date = 31 July 2015 |url=http://www.westerndailypress.co.uk/sick-dealers-peddle-Shaun-Sheep-Ecstasy-tablets/story-27521142-detail/story.html |title=Now sick dealers peddle Shaun the Sheep Ecstasy tablets |work=Western Daily Press|access-date=3 March 2016 |url-status=dead |archive-url=https://web.archive.org/web/20150812022920/http://www.westerndailypress.co.uk/sick-dealers-peddle-Shaun-Sheep-Ecstasy-tablets/story-27521142-detail/story.html |archive-date=12 August 2015|df=dmy-all}}</ref>

==Research==

In 2017, doctors in the UK began the first clinical study of MDMA in alcohol use disorder.<ref>{{cite news | vauthors = Devlin H |url= https://www.theguardian.com/science/2017/jun/30/world-first-trials-mdma-treat-alcohol-addiction-set-begin?CMP=fb_gu |title= World's first trials of MDMA to treat alcohol addiction set to begin|work=The Guardian|date=30 June 2017}}</ref>

The potential for MDMA to be used as a rapid-acting antidepressant has been studied in clinical trials, but as of 2017 the evidence on efficacy and safety were insufficient to reach a conclusion.<ref>{{cite journal | vauthors = Patel R, Titheradge D | title = MDMA for the treatment of mood disorder: all talk no substance? | journal = Therapeutic Advances in Psychopharmacology | volume = 5 | issue = 3 | pages = 179–88 | date = June 2015 | pmid = 26199721 | pmc = 4502590 | doi = 10.1177/2045125315583786 }}</ref> A 2014 review of the safety and efficacy of MDMA as a treatment for various disorders, particularly PTSD, indicated that MDMA has therapeutic efficacy in some patients;<ref name=Pharm2014 /> however, it emphasized that issues regarding the controlability of MDMA-induced experiences and neurochemical recovery must be addressed.<ref name=Pharm2014/> The author noted that [[Chemistry:Oxytocin|oxytocin]] and {{smallcaps all|D}}-cycloserine are potentially safer co-drugs in PTSD treatment, albeit with limited evidence of efficacy.<ref name=Pharm2014 /> This review and a second corroborating review by a different author both concluded that, because of MDMA's demonstrated potential to cause lasting harm in humans (e.g., serotonergic neurotoxicity and persistent memory impairment), "considerably more research must be performed" on its efficacy in PTSD treatment to determine if the potential treatment benefits outweigh its potential to harm to a patient.<ref name=Current2013 /><ref name=Pharm2014 />{{clear}}

MDMA in combination with psychotherapy has been studied as a treatment for [[Medicine:Post-traumatic stress disorder|post-traumatic stress disorder]], and four clinical trials provide moderate evidence in support of this treatment.<ref>{{cite journal | vauthors = Breeksema JJ, Niemeijer AR, Krediet E, Vermetten E, Schoevers RA | title = Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies | journal = CNS Drugs | volume = 34 | issue = 9 | pages = 925–946 | date = September 2020 | pmid = 32803732 | pmc = 7447679 | doi = 10.1007/s40263-020-00748-y | type = Systematic review }}</ref> However, the lack of appropriate blinding of participants likely leads to overestimation of treatments effects due to high levels of response expectancy.<ref>{{cite journal | vauthors = Muthukumaraswamy SD, Forsyth A, Lumley T | title = Blinding and expectancy confounds in psychedelic randomized controlled trials | journal = Expert Review of Clinical Pharmacology | volume = 14 | issue = 9 | pages = 1133–1152 | date = September 2021 | pmid = 34038314 | doi = 10.1080/17512433.2021.1933434 | s2cid = 235215630 }}</ref><ref>{{cite journal | vauthors = Burke MJ, Blumberger DM | title = Caution at psychiatry's psychedelic frontier | journal = Nature Medicine | volume = 27 | issue = 10 | pages = 1687–1688 | date = October 2021 | pmid = 34635858 | doi = 10.1038/s41591-021-01524-1 | s2cid = 238635462 }}</ref> In addition, there are no trials comparing MDMA-assisted psychotherapy for PTSD with existent evidence-based psychological treatments for PTSD, which seems to attain similar or better treatment effects compared with that achieved by MDMA-assisted psychotherapy.<ref name="Halvorsen 1689–1690"/>

In 2018 researchers identified MDMA as a psychoplastogen which refers to a compound capable of promoting [[Biology:Neuroplasticity|neuroplasticity]] and received the “breakthrough therapy” designation by the [[Organization:Food and Drug Administration|Food and Drug Administration]] for treating [[Medicine:Post-traumatic stress disorder|PTSD]].<ref>{{cite journal | vauthors = Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE | display-authors = 6 | title = Psychedelics Promote Structural and Functional Neural Plasticity | language = English | journal = Cell Reports | volume = 23 | issue = 11 | pages = 3170–3182 | date = June 2018 | pmid = 29898390 | doi = 10.1016/j.celrep.2018.05.022 | pmc = 6082376 }}</ref>

== References ==
{{Reflist}}

== External links ==
* [https://maps.org/mdma/ptsd/mapp2/ A Multi-Site Phase 3 Study of MDMA-Assisted Therapy for PTSD (MAPP2)]

* {{cite web | url = https://www.drugabuse.gov/publications/drugfacts/mdma-ecstasymolly | title = MDMA Facts and Statistics | work = National Institute on Drug Abuse | date = 15 June 2020 }}
* {{cite web | url = http://www.emcdda.europa.eu/publications/drug-profiles/mdma | title = Methylenedioxymethamphetamine (MDMA or 'Ecstasy') drug profile | work = European Monitoring Centre for Drugs and Drug Addiction }}
* {{cite web | url = http://www.maps.org/research/mdma | title = MDMA-Assisted Psychotherapy | work = Multidisciplinary Association for Psychedelic Studies }}

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