Shulgin was not the first to synthesise MDMA, but his re‑synthesised and self‑administered use in 1976, his introduction of the drug to psychotherapist Leo Zeff in 1977, and his 1978 human pharmacology paper with David Nichols were pivotal in its modern history. These actions explain why he is often, albeit inaccurately, referred to as MDMA’s “father”.
Aims
Alexander T. Shulgin is widely thought of as the ‘father’ of +/−3,4‐methylenedioxymethamphetamine (MDMA). This paper re‐assesses his role in the modern history of this drug.
Methods
We analysed systematically Shulgin's original publications on MDMA, his publications on the history of MDMA and his laboratory notebook.
Results
According to Shulgin's book PIHKAL (1991), he synthesized MDMA in 1965, but did not try it. In the 1960s Shulgin also synthesized MDMA‐related compounds such as 3,4‐methylenedioxyamphetamine (MDA), 3‐methoxy‐4,5‐methylenedioxyamphetamine (MMDA) and 3,4‐methylenedioxyethylamphetamine (MDE), but this had no impact on his rediscovery of MDMA. In the mid‐1970s Shulgin learned of a ‘special effect’ caused by MDMA, whereupon he re‐synthesized it and tried it himself in September 1976, as confirmed by his laboratory notebook. In 1977 he gave MDMA to Leo Zeff PhD, who used it as an adjunct to psychotherapy and introduced it to other psychotherapists.
Conclusion
Shulgin was not the first to synthesize MDMA, but he played an important role in its history. It seems plausible that he was so impressed by its effects that he introduced it to psychotherapist Zeff in 1977. This, and the fact that in 1978 he published with David Nichols the first paper on the pharmacological action of MDMA in humans, explains why Shulgin is sometimes (erroneously) called the ‘father’ of MDMA.
Papers in Blossom that reference this study
Ramaekers, J. G., Kuypers, K. P. C., Vollenweider, F. X. · Molecular Psychiatry (2026)
Sottile, R. J., Vida, T. · Frontiers in Psychiatry (2022)
Passie, T., Brandt, S. D. · New Psychoactive Substances (2018)
Dunlap, L. E., Andrews, A. M. · ACS Chemical Neuroscience (2018)
MDMA (±3,4-methylenedioxymethamphetamine, commonly 'ecstasy') has a complex pre‑history: first synthesised by Merck in 1912 and intermittently rediscovered during the 20th century, it emerged in the late 1970s and 1980s both as an adjunct to psychotherapy and as a recreational drug before being scheduled in the United States in the mid‑1980s. Alexander T. Shulgin's name became prominent from 1978 onward because he co‑authored the first modern report of MDMA's psychopharmacological effects in humans, but his own accounts of when and how he encountered and disseminated the compound have varied across publications. This paper sets out to clarify Shulgin's actual role in the modern history of MDMA by comparing his published accounts with contemporaneous primary material. Specifically, the investigators examined Shulgin's original publications about MDMA, his historical writings, and entries from his laboratory notebook to establish a more reliable timeline of synthesis, self‑experimentation and dissemination to clinicians and researchers. The study does not attempt to produce a full history of entactogenic drugs more broadly, but focuses on Shulgin's contribution to the 'rediscovery' and early popularisation of MDMA.
Shulgina and colleagues conducted a documentary, archival analysis centred on three source types: Shulgin's published papers on MDMA, his historical and autobiographical writings (including PIKHAL), and his laboratory notebooks. The investigators compared the published narratives with contemporaneous notebook entries in order to corroborate dates, self‑experiments and informal transmissions of the compound. The laboratory notebook examined began in 1960 and was made accessible online in 2007; the extracted text notes that names of many associates were later redacted and replaced with pseudonyms. The authors read entries relating to methylenedioxy compounds and traced references to MDA, MMDA, MDE and MDMA across the notebooks and publications. The paper does not present formal, prespecified inclusion/exclusion criteria for documents nor a detailed search protocol in the extracted text, and it does not report quantitative synthesis methods — the approach is qualitative and historiographic, emphasising comparison of primary records with published accounts. Where available, the authors used dates, dosage records and narrative remarks in the notebook to reconstruct the sequence of events (for example, reports heard by Shulgin in 1975–1976, his own self‑trials in 1976, and subsequent presentations and publications). The extracted text indicates awareness of limitations in the source material (redactions, retrospective notes, and occasional gaps), and these constraints informed interpretation.
The analysis first situates MDMA in its earlier pharmaceutical history: Merck synthesised MDMA in 1912 and patented it in 1914; preclinical tests occurred in 1927 and toxicology work in the 1950s, with various intermittent appearances in chemical and patent literature through the 1950s and 1960s. Reports of occasional street availability were noted around 1970, and published observations of street presence appeared by 1972. Biographical material shows that Shulgin pursued a career in chemistry and biochemistry through the 1950s, later leaving industrial employment to run a private laboratory where he synthesised and tested many phenethylamines and tryptamines. In the 1960s he synthesised several methylenedioxy compounds related to MDMA: MDA (synthesised by Shulgin in May 1961), MMDA (1962), and mentions of MDE (noted in 1967). Trials with MDA and MMDA included small, apparently inactive doses in the early 1960s, and subsequent therapeutic explorations with psychotherapist Claudio Naranjo yielded favourable reports published in 1967 (MDA) and 1973 (MMDA). Regarding MDMA specifically, Shulgin's book PIKHAL (1991) states that he synthesised MDMA in 1965 but did not try it then; the authors found no corroborating proof of a 1965 synthesis in the laboratory notebook, though they acknowledge the absence of proof is not definitive disproof. Notebook material does, however, document that Shulgin first heard reports of MDMA's distinctive effects in about 1975 and that a notable anecdotal report of 100 mg producing an emotional but positive reaction dates to 30 May 1976. The notebook contains a record of systematic self‑trials by an associate (pseudonym 'Flip') with MDMA doses of 15, 30, 45, 60, 75, 100 and 150 mg: no effect up to 60 mg, 'fuzzy' at 75 mg, 'active' at 100–150 mg. Shulgin's own entries indicate that he performed systematic self‑experiments with MDMA in September/October 1976 and was sufficiently impressed to continue trials. Following those trials, Shulgin presented on MDMA at a December 1976 conference in Bethesda and, together with David Nichols, published in 1978 what the authors identify as the first modern report of MDMA's psychopharmacological effects in humans. The extracted text records that in 1977 Shulgin introduced MDMA to psychotherapist Leo Zeff, who then used it clinically and propagated its use among other therapists in the United States. The authors conclude that Shulgin was not the first person ever to synthesise MDMA, but that he played a key role in rediscovering, testing and disseminating knowledge of its effects from about 1975–1978 onward.
The investigators interpret their findings as distinguishing two things: historical priority of chemical synthesis versus modern rediscovery and dissemination. They argue that although MDMA had prior syntheses and occasional appearances on the illicit market, Shulgin's activities from 1975–1978 were pivotal for contemporary awareness. Evidence from his laboratory notebook corroborates that he heard about MDMA's 'special effects' in 1975, personally experimented with it in September/October 1976, presented those observations at a conference in December 1976, and co‑authored the 1978 human pharmacology report with Nichols. The authors note that Shulgin's own published narratives evolved over time: earlier papers minimised his role, possibly for privacy, while later writings (PIKHAL, 1991, and a German paper in 1997) provide fuller detail. The notebook material helps verify several published claims but also leaves unresolved questions: the extracted text emphasises that the authors found no definitive notebook entry proving Shulgin synthesised MDMA in 1965, even though he later claimed to have done so; redactions and retrospective notations in the notebook limit certainty about some particulars. The authors therefore present a qualified conclusion: Shulgin was instrumental in early human experimentation, clinical introduction (notably via Leo Zeff), and academic dissemination of MDMA, which explains why he is sometimes referred to as the 'father' of MDMA despite not being the original synthesiser. Limitations acknowledged in the extracted text include incomplete documentary proof for certain claims, pseudonymisation of names in the notebook, and the fact that some inferences (for example, whether Shulgin's instructions to a chemist contributed to street availability) remain speculative in the absence of direct evidence. The study does not attempt a comprehensive history of entactogens beyond clarifying Shulgin's role.
On balance, the authors conclude that Alexander T. Shulgin conducted extensive 1960s research on methylenedioxy compounds that brought him close to MDMA, but they found no incontrovertible notebook evidence that he synthesised MDMA in the 1960s as part of that line of work. From about 1975–1976 Shulgin became centrally involved in the modern rediscovery: he heard reports of MDMA's distinctive effects, performed the first systematic self‑trials in September/October 1976, presented those observations at a scientific conference in December 1976 and co‑authored the first modern human pharmacology paper in 1978. By introducing MDMA to Leo Zeff, who promoted its psychotherapeutic use, Shulgin significantly contributed to the dissemination and popularisation of the drug, accounting for why later narratives sometimes ascribe to him an outsized, if not strictly original, role in MDMA's history.
Today +/-3,4-methylenedioxymethamphetamine (also known as MDMA or 'ecstasy') is a popular, illicit recreational drug. In spite of public opinion, MDMA is not a new substance. It was first synthesized in 1912 by the chemist Arthur Koellisch and was rediscovered more than once between the 1920s and 1960s. In the late 1970s and 1980s, it was used occasionally as an adjunct to psychotherapy and increasingly as a recreational drug. MDMA was placed into Schedule I by the US Drug Enforcement Administration (DEA) in July 1985 by the invocation of the Emergency Scheduling Act and was permanently scheduled on 13 November 1986. Alexander T. Shulgin's role in the history of MDMA became prominent in 1978 after publishing with medicinal chemist, David Nichols (Purdue University, Indiana), the first report of the psychopharmacological effects of MDMA in humans. Well into the 1990s, Shulgin published not only influential papers on the chemistry and psychopharmacology of MDMA but also on its history; yet Shulgin has offered slightly different versions of his role in the history of MDMA in hispublications. To come to a clearer understanding of the significance of Shulgin in the public awareness of what is MDMA, it is necessary to take a closer look at these publications and then compare the facts offered with Shulgin's laboratory notebooks. Nota bene: it is not the aim of this paper to write an overall history of the 'entactogenic' drugs.
MDMA was first synthesized in the context of the search for haemostatics at the pharmaceutical company Merck KGaA (of Darmstadt, Germany) in 1912 and patented in 1914. The first pre-clinical pharmacological tests with MDMA were performed at Merck in 1927 during searches for adrenaline-or ephedrine-like substances. In 1952, a Merck chemist conducted toxicological tests with MDMA. From 1953 to 1954, the toxic effects of MDMA were studied in five species of laboratory animals at the University of Michigan. In 1959, a Merck chemist interested in the production of new stimulants worked with MDMA, but it remains unclear as to whether he evaluated effects in humans. In 1960, two Polish chemists published a paper describing the synthesis of MDMA as an intermediary product. The next phase of MDMA research commenced when Alexander T. Shulgin (Fig.) appeared on the stage.
According to papers based on Shulgin's autobiography and on interviews, Shulgin's curriculum vitae can be summarized as follows: born in 1925 in Berkeley, CA, USA, Shulgin pursued studies in chemistry and biochemistry after serving in the US Navy during World War II. He earned a PhD from the University of California at Berkeley in 1955. In 1955, while working at Dow Chemical Company in Walnut Creek, CA, he had his first experience with the hallucinogen mescaline, which was not illegal at that time. Two years later he created one of the world's first biodegradable insecticides for Dow Chemical. In return, Dow Chemical gave him the freedom to study whatever interested him. Shulgin turned towards discovering psychoactive drugs. He synthesized and tested the effects of more than 200 potentially psychoactive substances, often by taking them himself or with a close circle of collaborators. Eventually Dow Chemical was disappointed at having its address noted on these Shulgin publications. In 1966, Shulgin left Dow Chemical to work as a research chemist and consultant. In his private laboratory at Lafayette, CA, he continued to develop psychoactive drugs, among them many new psychedelic phenethylamines, amphetamines and tryptamines. During this time Shulgin received a Schedule I registration for research and cooperated with the DEA. In 1991, together with his second wife Ann, he published PIKHAL (Phenethylamines I Have Known And Loved), a fictionalized autobiographical work with an appendix describing the synthesis and effects of 179 phenethylamines. In the early 1990s, Shulgin relinquished his Schedule I license. In 1993, the DEA raided his laboratory. There were no Scheduled substances found during the incident, and no charges were filed. In his continuing work, Dr Shulgin has scrupulously avoided synthesis of controlled substances, and continues legitimate research in collaboration with scientists at many institutions worldwide.
3,4-Methylenedioxyamphetamine (MDA), 3-methoxy-4,5-methylenedioxyamphetamine (MMDA) and especially 3,4-methylenedioxyethylamphetamine (MDE) are substances which have a great similarity to MDMA. Their possible role in Shulgin's discovery of the psychotomimetic effects of MDMA will be discussed here. MDA was first synthesized in 1910. Pre-clinical tests by the US military were completed in the mid-1950s. Early trials as an antidepressant and anorexic agent produced inconclusive results. The psychopharmacological effects of MDA in humans were described by Alles in 1959. Shulgin, most probably following Alles' research, synthesized MDA in May 1961. He tried it in May 1961 at a small (inactive) dose [4.5 mg per os (p.o.)]and again in August 1965 at small (inactive) doses (15.2-35 mg p.o.) with 'no effect'. According to Shulgin, he synthesized and tested MMDA in 1962and published about its psychoactive effects in 1964. His laboratory book corroborates that Shulgin performed trials with MMDA in 1962and in 1965 while researching MDA-like compounds. During the mid-1960s, Shulgin initiated tests on the psychotherapeutic potential of MDA and MMDA with psychotherapist Claudio Naranjo MD at the Department of Anthropological Medicine, University of Chile (Santiago de Chile). The results were favourable and were published in 1967 on MDAand in 1973 on MMDA. Shulgin, according to PHIKAL, synthesized MDMA in 1965. We have found no evidence for that in his laboratory notebooks (see below) but, of course, nor can we disprove this statement. Regardless, Shulgin did not perform self-trials with MDMA in the 1960s. One could have expected that if he had come to synthesize it as a result of a planned research line regarding the intoxicating effects of the methylenedioxy compounds, then he would have performed his usual self-trials. In 1967, Shulgin mentioned in his laboratory notebook 3,4-methylenedioxyethylamphetamine (MDE), a new compound almost identical chemically with MDMA. There is only a very short notice about MDE contained in his laboratory book in which he described how he was informed in June 1967 by a certain 'KOZ' (pseudonym for Claudio Naranjo MD) that 100 mg MDE produced 'N.R.' (= no reaction)(MDE is psychoactive above 130 mg). It may be speculated that because of Naranjo's report, Shulgin did not test MDE (and related compounds such as MDMA) himself during the next few years. It is evident, then, that Shulgin's interest in methylenedioxy compounds brought him very close to MDMA during the 1960s (we have to leave open if he actually synthesized it in 1965), but he did not realize its special effects during that time.
In 1978, Shulgin, together with medicinal chemist David Nichols, published a paper dealing with the effects of MDMA in humans. This paper goes back to a presentation Shulgin gave in late December 1976 at a conference entitled 'The psychopharmacology of hallucinogens' in Bethesda, MD. The authors erroneously attribute the first synthesis of MDMA in 1960 to the Polish chemists Biniecki & Krajewski. Shulgin & Nichols wrote that, according to a paper by Gaston & Rasmussenand a personal communication by C. Helisten from the PharmChem Foundation at Palo Alto, MDMA had made an occasional appearance on the illicit street-drug market in 1970. The description of the 'psychotomimetic' effects of MDMA in this paper is very brief: 'Qualitatively, the drug appears to evoke an easily controlled altered state of consciousness with emotional and sensual overtones. It can be compared in its effect to marijuana, to psilocybin devoid of the hallucinatory component, or to low levels of MDA'. In 1986, Shulgin described the background and chemistry of MDMA in a special paper.. Shulgin also mentioned recent studies on MDMA as an adjunct to psychotherapy, but did not give any hint regarding his own role in 'initiating' the psychotherapist, who was then responsible for introducing MDMA to many other psychotherapists in the United States (this was revealed in Shulgin & Shulgin, see below, and by Stolaroff). In 1990, Shulgin wrote a comprehensive 'history of MDMA'. He mentioned the Merck initial synthesis (1912), the Merck patent (1914), another Merck patent from 1920 describing a chemical modification of MDMA, and the work of the Polish chemists Biniecki & Krajewski. According to this study, the first reports that MDMA was becoming available on the street were published in 1972, with observations from 1970 in Illinois and Indiana. According to Shulgin's 1990 paper, MDMA was first introduced into clinical practice (no names were given) on the West Coast in the latter part of 1976 and was used by therapists on the East Coast a few months later. In this paper, Shulgin's role was reduced to the fact that, together with David Nichols, he had published the first paper on the pharmacological action of MDMA in humans in 1978. The first part of Shulgin's book PIKHALis autobiographical. Shulgin's 'alter ego' in PIKHAL is called 'Shura'. In his book Shulgin gave the first detailed account of how he rediscovered MDMA. He wrote on p. 69 of the book: 'In fact I had synthesized it [= MDMA] back at Dole [= Dow Chemical] in 1965'. However, according to Shura/Shulgin, he had not tried it then and had forgotten about it until the 1970s. We should insert here that we have no reason to doubt Shulgin's statement about his synthesis of MDMA in 1965, but we should mention that we could not find proof for it in his laboratory notebook (see below). According to PIKHAL, the story continues as follows: Shura/Shulgin met a young professor of chemistry called 'Noel Chestnut' in 1967. It must have been some years later, although no date is given, that while 'Chestnut' held lecture tours in other parts of the world Shura/Shulgin was made 'daddy-inresidence' for 'Chestnut's' graduate students in San Francisco. Shulgin wrote (still on p. 69): 'One of these was a dear, dear sprite appropriately named Merrie Kleinman, who told me that she had done an experiment with two close friends of hers, and that they had used 100 milligrams of N-methylated MDA (MDMA). She shared very little about the experience, but implied that it was quite emotional, and that there had been a basically good reaction from all three of them'. Shulgin then reported the experiences of other people with MDMA he had heard of at that time and mentioned that he himself had taken MDMA a little later, together with other people (without revealing the exact time). He finally revealed that in 1977 he had introduced MDMA to a retired psychologist in Oakland, CA. According to Shura/Shulgin, this psychologist (pseudonym: Adam Fisher; later identified as Leo Zeff) was so impressed by the effects of MDMA that he abandoned retirement and introduced MDMA to many psychotherapists across the United States. Even more details (and slightly different ones) are offered in Shulgin's German-only paper of 1997. Shulgin wrote that in about 1970 he had sent a letter to a chemist, who was the founder of a chemical company in Los Angeles. The chemist had asked for instructions on how to prepare N-methylated MDA (MDMA). Shulgin sent him the instructions on how to make MDMA via the conversion of MDA to the formamide that is reduced with lithium aluminium hydride. According to a letter Shulgin received from the chemist a little later, the chemist had provided access to this information to one of his 'clients' who studied psychology in the Midwest. Perhaps Shulgin mentions this because (although this is only speculation) he had the notion that his 'instruction' had led to the appearance of MDMA on the streets in some cities in the Midwest in the early 1970s. Another new detail is revealed in this paper: Shulgin wrote that he had first heard of the special effects of MDMA from a young student 'in around 1975'. According to Shulgin, the student (no name is given) was the brother of a dentist who had paid a visit to San Francisco. He had told Shulgin that he had read a publication by Shulgin on '2C-D' (2,5-dimethoxy-4methyl-phenethylamine) and '2C-B' (4-bromo-2,5dimethoxyphenethylamine) and that he had taken some 'N-methyls', especially N-methylated MDA (= MDMA), which had an 'amphetamine-like content'. According to the paper from 1997 the next mention of MDMA (in the middle of the year 1976) came from a female student who had taken 100 mg of MDMA together with two friends. This student had been named as 'Merrie Kleinman' in PIKHAL. Shulgin then mentions a colleague from the University of San Francisco who had synthesized and taken MDMA. Shulgin finally reveals that he took MDMA for the first time in September 1976 (which is confirmed by his laboratory notebook; see below).
The most reliable sources for Shulgin's history with MDMA are his laboratory notebooks. The first of these books (started in 1960) was made accessible in 2007 via the internet. It is important to realize that two of Shulgin's assistants have erased the names of most people mentioned in the notebook and have inserted pseudonyms such as Marty, Fredo, etc. To read Shulgin's entries regarding MDMA correctly, it is important to note that the notebook had not been kept on a day-to-day basis. Often Shulgin began a new page with the description of a new substance and later completed notes regarding the time before and-more often-the time after the synthesis or the first trial. The context of p. 186 (cf. Fig.), where he recorded his first trials with MDMA, makes clear that the page was begun in 1976, although the first two entries refer to 1975. These two entries beginning with '~' were obviously recording what he remembered. The first '~'-entry is: '~1975: Marty-reports considerable amphetamine-like content'. It is evident that 'Marty' is identical with 'the brother of a dentist' mentioned in Shulgins paper from 1997. The second '~'-entry concerns the graduate student mentioned in PIKHAL('Merrie Kleinman') and in Shulgin's publication of 1997 (anonymous): '~5/30/ 1976: 100 mg Fredo (+ 2) Rapid onset in ~1 h-lasts to 3 then drops off quickly-mydriasis persists to 4 h. Emotional experience and basically good reaction by all three-little detail' (p. 186). Directly above the '(+ 2)' Shulgin had drawn a downward-pointing arrow. The text that follows explains: '2 other people, not ++ in scale of + 4-one is Amos I think' (p. 186). In a box on the right-hand side of p. 186 (it is unclear when Shulgin added it), the trials of a certain 'Flip' with 'N-methyls', especially with 'N-methylated MDA' (= MDMA) are listed. 'Flip' had taken 15, 30, 45, 60, 75, 100 and 150 mg of MDMA. Up to 60 mg the result was 'no effect'; 75 mg made him 'fuzzy', 100 mg and 150 mg made him 'active'. It is obvious that 'Flip', who is with certainty identical with the unnamed colleague mentioned in Shulgin's paper from 1997 who had then tried some trimethoxymethamphetamines, had performed a relatively systematic self-trial with MDMA before Shulgin. In the same box there is a short entry about a certain 'C. B.', who took either 75 or 175 (not completely legible) mg of something (most probably MDMA). The result was 'fine control'. The entries that record the first series of trials of Shulgin himself are listed on the left-hand side of p. 186. Because of their importance, these entries will be cited in full (ATS stands for Alexander T.The entries make clear that Shulgin performed his first self-experiments with MDMA in September/October 1976 in a systematic manner. They tell us that he was quite impressed by the effect so he continued his trials, as shown by a remark at the bottom of p. 186 of the notebook.
In the 1960s Alexander T. Shulgin conducted extensive research on methylenedioxy compounds (i.e. MDA, MDE, MMDA). This brought him very close to the synthesis of MDMA, but we have found no proof that he synthesized MDMA while following this research line at that time. Shulgin played an important role in the history of MDMA, especially so during the 1980s and into the 1990s, when the psychoactive effects of this drug were popularized. A closer look at his early descriptionsreveals how he initially minimized his role in the history of MDMA, most probably because he wanted to protect his privacy. The first time he published an almost complete account was in his book PIKHAL (1991). Shulgin's best account appears in his Germanlanguage paper of 1997. On the basis of his laboratory notebook, now available via the internet, we could verify some of his published details. Shulgin's laboratory notebook, for example, confirms the important fact that in 1975 Shulgin had first heard about a special effect caused by MDMA. Of greatest significance is the laboratory notebook entries of Shulgin performing his first selftrials with MDMA in September/October 1976. The first report on MDMA was given at a conference in December 1976 and then published in 1978. In 1978 two other publicationsand a conference presentationby Shulgin and his coworkers described the effects of MDMA in more detail, and contributed significantly to the distribution of knowledge about it (see also). There is no evidence so far that Shulgin was led by his own lines of research to the synthesis of MDMA, even in spite of the fact that he synthesized some closely related substances during the 1960s. In summary, Shulgin played a major role in the history of MDMA since 1975/76. He was, as far as we know, the first to perform systematic self-trials with it (1975/76), he was the first to speak at a scientific conference (1976) and to publish (1978) on its 'psychotomimetic effects', as he called it, in humans. He also played a major role in its history by introducing MDMA to Leo Zeff PhD, who propagated it as an adjunct for psychotherapy.
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Passie, T., Benzenhöfer, U. · Journal of Psychoactive Drugs (2016)
Jerome, L., Schuster, S., Yazar-Klosinski, B. · Current Drug Abuse Reviews (2013)