Editing MDMA (section)

===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 [[chemical synthesis|synthesized]] and [[patent]]ed in 1912 by [[Merck KGaA|Merck]] chemist [[Anton Köllisch]].<ref name="Passie2023">{{cite book | last=Passie | first=Torsten | title=The History of MDMA | publisher=Oxford University Press | date=29 June 2023 | isbn=978-0-19-886736-4 | doi=10.1093/oso/9780198867364.001.0001 | url=https://books.google.com/books?id=KSvCEAAAQBAJ&pg=PA6 | pages=6–16, 18, 27, 29, 32, 40}}</ref><ref name="Bernschneider-ReifOxlerFreudenmann2006">{{cite journal | vauthors = Bernschneider-Reif S, Oxler F, Freudenmann RW | title = The origin of MDMA ("ecstasy")--separating the facts from the myth | journal = Pharmazie | volume = 61 | issue = 11 | pages = 966–972 | date = November 2006 | pmid = 17152992 | doi = | url = }}</ref> At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to avoid an existing patent held by [[Bayer]] for one such compound: [[hydrastinine]]. Köllisch developed a preparation of a hydrastinine [[chemical analogue|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 [[reaction intermediate|intermediate compound]] in the synthesis of methylhydrastinine. Merck was not interested in MDMA itself at the time.<ref name="Bernschneider-ReifOxlerFreudenmann2006" /> 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|archive-date = 28 August 2021|archive-url = https://web.archive.org/web/20210828153545/https://worldwide.espacenet.com/publicationDetails/originalDocument?locale=en_EP&FT=D&CC=DE&NR=274350C|url-status = live}}</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|access-date = 20 July 2009|archive-date = 28 August 2021|archive-url = https://web.archive.org/web/20210828153659/https://worldwide.espacenet.com/publicationDetails/originalDocument?locale=en_EP&FT=D&CC=DE&NR=279194C|url-status = live}}</ref> Merck records indicate its researchers returned to the compound sporadically. A 1920 Merck patent describes a chemical modification to MDMA.<ref name="Passie2023" /><ref name="Shulgin1990">{{cite book | last=Shulgin | first=Alexander T. | veditors = Peroutka SJ | title=Ecstasy: The Clinical, Pharmacological and Neurotoxicological Effects of the Drug MDMA | chapter=History of MDMA | publisher=Springer US | publication-place=Boston, MA | volume=9 | date=1990 | isbn=978-1-4612-8799-5 | doi=10.1007/978-1-4613-1485-1_1 | url=http://link.springer.com/10.1007/978-1-4613-1485-1_1 | access-date=15 May 2025 | pages=1–20 (2, 14)}}</ref>

MDMA's [[structural analog|analogue]] [[3,4-methylenedioxyamphetamine]] (MDA) was first synthesized in 1910 as a [[chemical derivative|derivative]] of [[adrenaline]].<ref name="Passie2023" /> [[Gordon A. Alles]], the discoverer of the [[psychoactive drug|psychoactive]] effects of [[amphetamine]], also discovered the psychoactive effects of MDA in 1930 in a [[self-experiment]] in which he administered a high dose (126{{nbsp}}mg) to himself.<ref name="Passie2023" /><ref name="Alles1959a">{{cite book | author=[[Gordon A. Alles]] | chapter = Some Relations Between Chemical Structure and Physiological Action of Mescaline and Related Compounds / Structure and Action of Phenethylamines | veditors = Abramson HA | title = Neuropharmacology: Transactions of the Fourth Conference, September 25, 26, and 27, 1957, Princeton, N. J. | location = New York | publisher = Josiah Macy Foundation | date = 1959 | pages = 181–268 | oclc = 9802642 | url = https://books.google.com/books?id=sDQLAQAAMAAJ&q=%22Some+relations+between+chemical+structure+and+physiological+action+of+mescaline+and+related+compounds%22 | chapter-url = https://web.archive.org/web/20250321230359/https://bitnest.netfirms.com/external/Books/NeuropharmacologyTrans.4.181#page=5 }}</ref><ref name="Alles1959b">{{cite book | author = [[Gordon A. Alles]] | chapter = Subjective Reactions to Phenethylamine Hallucinogens | title = A Pharmacologic Approach to the Study of the Mind | date = 1959 | publisher = CC Thomas | location = Springfield | pages = 238–250 (241–246) | isbn = 978-0-398-04254-7 | url = https://books.google.com/books?id=x45rAAAAMAAJ | chapter-url = https://archive.org/details/pharmacologicapp0000univ/page/238/mode/1up}}</ref> However, he did not subsequently describe these effects until 1959.<ref name="BenzenhöferPassie2010">{{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 | url = }}</ref><ref name="Alles1959a" /><ref name="Alles1959b" /> MDA was later tested as an [[appetite suppressant]] by [[Smith, Kline & French]] and for other uses by other groups in the 1950s.<ref name="Passie2023" /> In relation to the preceding, the psychoactive effects of MDA were discovered well before those of MDMA.<ref name="Passie2023" /><ref name="BenzenhöferPassie2010" />

In 1927, Max Oberlin studied the pharmacology of MDMA while searching for substances with effects similar to [[adrenaline]] or [[ephedrine]], the latter being structurally similar to MDMA. Compared to ephedrine, Oberlin observed that it had similar effects on [[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="Bernschneider-ReifOxlerFreudenmann2006" />

Outside of Merck, other researchers began to investigate MDMA. In 1953 and 1954, the [[United States Army]] commissioned a study of [[toxicity]] and behavioral effects in animals injected with [[mescaline]] and several analogues, including MDMA. Conducted at the [[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 | bibcode = 1973ToxAP..25..299H | url = http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=639 | hdl = 2027.42/33868 | hdl-access = free | access-date = 19 April 2009 | archive-date = 21 October 2008 | archive-url = https://web.archive.org/web/20081021151006/http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=639 | url-status = live }}</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="Bernschneider-ReifOxlerFreudenmann2006" /><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>

MDA appeared as a [[recreational drug]] in the mid-1960s.<ref name="Passie2023" /> MDMA may have been in non-medical use in the western United States in 1968.<ref name="Passie2023" /><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 | access-date = 11 August 2015 | archive-date = 4 March 2016 | archive-url = https://web.archive.org/web/20160304090940/http://www.maps.org/images/pdf/1986_siegel_1.pdf | url-status = live }}</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|access-date = 19 April 2009|archive-date = 21 October 2008|archive-url = https://web.archive.org/web/20081021200016/http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=1149|url-status = live}}</ref> MDMA likely emerged as a substitute for 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|archive-date=17 November 2015|archive-url=https://web.archive.org/web/20151117042408/http://www.nytimes.com/1988/12/11/nyregion/psychedelic-drug-called-ecstasy-gains-popularity-in-manhattan-nightclubs.html?pagewanted=2|url-status=live}}</ref> a drug at the time popular among users of psychedelics<ref name="Professor X"/> which was made a [[List of Schedule I controlled substances (U.S.)|Schedule 1 controlled 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|archive-date=4 August 2015|archive-url=https://web.archive.org/web/20150804125927/https://www.erowid.org/chemicals/mdma/mdma_info6.shtml|url-status=live}}</ref><ref name=exploration/>