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A Look at the History of MDMA Research

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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 thus illegal, seriously halting most research. However, In the mid-1980, several papers were published before the ban took place.



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 the 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)


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


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Results from part 1 of MAPS’ phase 3 trial


In January 2023, MAPS announced that the second part of its Phase 3 trial of MDMA-assisted therapy for PTSD had 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.

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