A Look at the History of MDMA Research

Microdose is devoting the month of May to an exploration of MDMA (MDMay, get it?). Today, we take a look at MDMA research. Stay tuned for more on molly throughout the coming weeks


The landscape of mental health treatment is evolving, thanks to the current psychedelic renaissance. Leading the way is MDMA, with this compound and its clinical trials on the cusp of FDA approval. To help give context to the road to FDA approval, this article dives into some of the history of MDMA research


MDMA Research and MDMA for PTSD

MDMA research, although still in its relative infancy, is revealing promising potential for this substance in the field of mental health. The Multidisciplinary Association for Psychedelic Studies (MAPS) is a key player in this research, conducting numerous clinical trials to explore MDMA’s safety and therapeutic efficacy.

One of the most exciting avenues of MDMA research is its potential use for treating post-traumatic stress disorder (PTSD). MAPS has spearheaded successful Phase 2 and Phase 3 clinical trials, focusing on the use of MDMA-assisted psychotherapy for individuals with chronic, treatment-resistant PTSD. These studies have demonstrated significant reductions in PTSD symptoms.


An Overview of MDMA Research

  • Alexander “Sasha” Shulgin, a pioneering researcher, had been studying psychedelics since the early 1960s and spearheaded research into MDMA. His published work on these substances goes all the way back to 1964, with a landmark paper in Nature
  • Shulgin continued his research into the 1970s and 80s, and with chemist David E. Nichols, published the first paper on the pharmacology of MDMA and MDMA effects on humans in 1978:  Characterization of Three New Psychotomimetcs. Shulgin AT, Nichols DE. The Psychopharmacology of Hallucinogen (1978)


Early MDMA paper by Shulgin


In May 1985, MDMA was made a Schedule One drug and made illegal, seriously halting most research. However In the mid-1980, several papers were published before the ban took place.


  • This paper described the positive effects of MDMA with individuals, couples and groups. This article is a summary report of data gathered from the first 29 people administered MDMA in a clinical setting:  Subjective Reports of the Effects of MDMA in a Clinical Setting, George Greer & Requa Tolbert (1986)
  • According to this research summary, in 1988 the Swiss Medical Society for Psycholytic Therapy conducted individual and group psychotherapy with MDMA and LSD, following over 100 patients who received an average of eight therapeutic sessions with positive long term results.


Following this dark period of little or no MDMA research, contemporary studies began to re-enter the mainstream, focused mainly on PTSD.


  • In 2010, the first controlled clinical study on MDMA-assisted psychotherapy was published. The results were impressive. At 12-month follow-up, 83% of the experimental group no longer met the criteria for PTSD (compared with 25% of the placebo group). See the full paper here:  The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol. Mithoefer MC, Wagner TM, Mithoefer AT, Jerome L, Doblin R. (2010)
  • Then in 2013, there was a pilot study sponsored by MAPS, designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD:  A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)
  • With more clinical studies in 2018, coming together to form a Phase 2 trial that further backed-up previous positive results: 3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial


And then to today and the modern MAPS-led era of research, with MDMA therapy on the cusp of FDA approval.


Results from part 1 of MAPS’ phase 3 trial


  • In 2021, MAPS published the first of its Phase 3 results and the outcomes were extremely positive. 88% of participants with severe PTSD experienced a clinically significant reduction in PTSD diagnostic scores two months after their third session of MDMA-assisted therapy, compared to 60% of placebo participants. Additionally, 67% of participants in the MDMA group compared to 32% of participants in the placebo group no longer met the criteria for PTSD two months after the sessions (source: MAPS)  MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder, Nature.com
  • In January 2023, MAPS announced that the second part of its Phase 3 trial of MDMA-assisted therapy for PTSD has confirmed prior positive trial results. MAPP2, the second Phase 3 trial of MDMA-assisted therapy, treated 104 participants living with PTSD with either MDMA-assisted therapy or placebo with therapy. The results confirmed findings from MAPP1; no serious adverse events were observed among the participants. The full data from MAPP2 is expected to be published in a peer-reviewed journal later this year and will support MAPS PBC’s new drug application to be filed with the U.S. Food and Drug Administration (FDA).

A successful outcome in this confirmatory Phase 3 trial would set the stage for a likely FDA approval of MDMA for PTSD.


For a more detailed summary of early studies and MDMA research from 1977 to 1985, check out this paper: The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985)

And for more on MAPS research and to learn more about their clinical trials, check out their resource page here.

The post A Look at the History of MDMA Research appeared first on Microdose.

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