The fight for medical approval of MDMA has been going on for 40 years. The FDA has rejected therapies using the substance, further delaying its long road to recognition as a medicine.
The year 2024 was expected to be a watershed moment for MDMA, better known by its street names «ecstasy» or «Molly», to shed its image as a recreational drug. Supporters of the drug have emphasized its potential to treat mental illness, but MDMA research has long been hampered by its status as an illegal drug with no medical use.
The year 2024 was expected to be a watershed moment for MDMA, better known by its street names «ecstasy» or «Molly», to shed its image as a recreational drug. Supporters of the drug have emphasized its potential to treat mental illness, but MDMA research has long been hampered by its status as an illegal drug with no medical use.
This year, the FDA reviewed clinical trials by Lykos Therapeutics that used MDMA in combination with psychotherapy to treat post-traumatic stress disorder (PTSD). However, on Friday, what was supposed to be a significant step in the medical application of psychedelics ended with a denial from the agency.
The decision came as a surprise to many observers when information about MDMA-based therapies began to spread earlier this year. Most clinicians and patients supported research into psychedelics for psychiatric use. In the absence of new treatments for PTSD, MDMA garnered broad bipartisan support in Congress, and the Department of Veterans Affairs was tasked with preparing to launch the treatment.
Nevertheless, even before the FDA's rejection, its advisory board raised concerns about research bias, improper trial conduct, and data reliability. While the rejection did not definitively end the drug's medical prospects, it significantly delayed them. Lykos Therapeutics said the FDA has requested additional Phase 3 studies to thoroughly evaluate the safety and efficacy of the treatment, and according to the company's CEO, this will take several years.
The decision came as a surprise to many observers when information about MDMA-based therapies began to spread earlier this year. Most clinicians and patients supported research into psychedelics for psychiatric use. In the absence of new treatments for PTSD, MDMA garnered broad bipartisan support in Congress, and the Department of Veterans Affairs was tasked with preparing to launch the treatment.
Nevertheless, even before the FDA's rejection, its advisory board raised concerns about research bias, improper trial conduct, and data reliability. While the rejection did not definitively end the drug's medical prospects, it significantly delayed them. Lykos Therapeutics said the FDA has requested additional Phase 3 studies to thoroughly evaluate the safety and efficacy of the treatment, and according to the company's CEO, this will take several years.
The delay was a significant blow to psychedelics advocates who had hoped MDMA would finally find therapeutic use after four decades of struggling for acceptance. Now they are pondering the steps that need to be taken next to advance MDMA in medicine.
How MDMA-therapy came to be
In past BB articles, when we've covered the history of MDMA in therapy, we've talked about the Shulgin Farm, the San Francisco Bay Area home of the late chemist Alexander Shulgin, who synthesized the drug in 1976. Although his lab — a converted tool shed — looked more like a Hollywood version of a methamphetamine lab than the sterile labs of my college chemistry class, it had historical significance because Shulgin is said to have synthesized hundreds of psychoactive substances, some of which he experienced firsthand, including MDMA.
Shulgin admitted that he found MDMA pleasurable, describing it as a «low-calorie martini». However, he did not set out to create recreational drugs.
How MDMA-therapy came to be
In past BB articles, when we've covered the history of MDMA in therapy, we've talked about the Shulgin Farm, the San Francisco Bay Area home of the late chemist Alexander Shulgin, who synthesized the drug in 1976. Although his lab — a converted tool shed — looked more like a Hollywood version of a methamphetamine lab than the sterile labs of my college chemistry class, it had historical significance because Shulgin is said to have synthesized hundreds of psychoactive substances, some of which he experienced firsthand, including MDMA.
Shulgin admitted that he found MDMA pleasurable, describing it as a «low-calorie martini». However, he did not set out to create recreational drugs.
«I'm looking for tools to help in the study of the mind» — he said in a 1996 interview, while believing that his colleagues could use the tools in neuroscience or psychology.
His wife, Ann Shulgin, who died in 2022 and is sometimes referred to as a «lay therapist», viewed psychedelics more strongly as «spiritual tools». In the early 1980s, she and members of the psychotherapy counterculture believed that MDMA could help people by filling them with feelings of love and empathy, relieve shame and deal with trauma or difficult emotions.
«This substance is already quite effective, and many psychiatrists who use it raise the question of whether the traditional concept of the 50-minute psychotherapy session needs to be revisited», Ann wrote in a letter to President Ronald Reagan advocating for the drug's legalization.
This description is remarkably similar to feedback from participants in contemporary trials: An 18-week course of MDMA treatment combined with psychotherapy can significantly alleviate PTSD symptoms that have been untreatable by many years of therapy and prescription of SSRIs. However, the development of MDMA as a therapeutic agent has been hampered by its reputation as a medically useless drug.
MDMA goes underground
Although underground therapists began to believe in the therapeutic potential of MDMA in the early 1980s, the euphoric effects of the substance soon ceased to be within the realm of medical use. MDMA went beyond therapeutic purposes, began to be produced in illegal laboratories and became popular in nightclubs under the names «ecstasy» or «X».
This was against the backdrop of the War on Drugs, when psychedelics such as LSD had already been banned. By 1985, MDMA quickly came under strict restrictions after the Drug Enforcement Administration said it posed a public health risk.
MDMA goes underground
Although underground therapists began to believe in the therapeutic potential of MDMA in the early 1980s, the euphoric effects of the substance soon ceased to be within the realm of medical use. MDMA went beyond therapeutic purposes, began to be produced in illegal laboratories and became popular in nightclubs under the names «ecstasy» or «X».
This was against the backdrop of the War on Drugs, when psychedelics such as LSD had already been banned. By 1985, MDMA quickly came under strict restrictions after the Drug Enforcement Administration said it posed a public health risk.
«There were many sensationalized articles in the press about MDMA. 'Brain scans were showing: that people who used MDMA had holes in their brains’ All of this was completely wrong!», according to Paul Daly, a close friend of the Shulgins and chief scientist at the Alexander Shulgin Research Institute.
One of the most serious studies on the harms of MDMA, conducted in the early 2000s, suggested that it could cause brain damage similar to Parkinson's disease, but that study was retracted after significant methodological errors were discovered. Nevertheless, there is evidence that MDMA can lead to increased heart rate, cardiovascular disease, and negative mental health experiences.
Despite warnings from DARE programs and news reports about the risks associated with ecstasy, proponents of legalization continued to insist on the need to recognize MDMA as a safe and relatively respectable substance.
One of the most serious studies on the harms of MDMA, conducted in the early 2000s, suggested that it could cause brain damage similar to Parkinson's disease, but that study was retracted after significant methodological errors were discovered. Nevertheless, there is evidence that MDMA can lead to increased heart rate, cardiovascular disease, and negative mental health experiences.
Despite warnings from DARE programs and news reports about the risks associated with ecstasy, proponents of legalization continued to insist on the need to recognize MDMA as a safe and relatively respectable substance.
How MDMA got into medicine
Immediately after the ban on MDMA, Rick Doblin, a friend of the Shulgins, took up activism. With the goals of «mass mental health» and the «spiritual rebirth of humanity», he founded the Multidisciplinary Association for Psychedelic Studies (MAPS), an organization he still heads today and considered one of the leading advocates for psychedelics.
«In order to bring psychedelics back from the underground, we needed a patient group that would generate public sympathy and on which drugs from big pharmaceutical companies would have little effect» — Doblin recounted in a 2021 interview with Marianne Williamson, self-help guru and former presidential candidate.
The group Doblin mentions includes military veterans who suffer from high levels of post-traumatic stress disorder. They are treated with SSRIs as their primary treatment, which are partially effective and have been used for many years.
Immediately after the ban on MDMA, Rick Doblin, a friend of the Shulgins, took up activism. With the goals of «mass mental health» and the «spiritual rebirth of humanity», he founded the Multidisciplinary Association for Psychedelic Studies (MAPS), an organization he still heads today and considered one of the leading advocates for psychedelics.
«In order to bring psychedelics back from the underground, we needed a patient group that would generate public sympathy and on which drugs from big pharmaceutical companies would have little effect» — Doblin recounted in a 2021 interview with Marianne Williamson, self-help guru and former presidential candidate.
The group Doblin mentions includes military veterans who suffer from high levels of post-traumatic stress disorder. They are treated with SSRIs as their primary treatment, which are partially effective and have been used for many years.
Doblin's organization and its pharmaceutical division Lykos Therapeutics are responsible for the clinical trial that the FDA reviewed this month. Several months before the agency's decision was published, however, the trial design was criticized for failing to meet the gold standard for clinical trials, which involves double-blind studies. Participants could often tell whether they had received the drug or a placebo because of MDMA's apparent psychedelic effects. Moreover, some participants felt pressured to report positive results because their participation was positioned as «history-making» and «part of a movement» to legalize psychedelics.
The recent FDA decision was a major blow to years of efforts to medically utilize MDMA. Still, interest in psychedelics has never been higher: they are heavily discussed at the Department of Veterans Affairs, appearing on health podcasts and being researched at educational institutions around the world.
In his statement, Doblin showed no hint of abandoning his 40-year mission to integrate psychedelics into medical practice: «Our collective commitment to MDMA-assisted therapy remains unwavering».
The recent FDA decision was a major blow to years of efforts to medically utilize MDMA. Still, interest in psychedelics has never been higher: they are heavily discussed at the Department of Veterans Affairs, appearing on health podcasts and being researched at educational institutions around the world.
In his statement, Doblin showed no hint of abandoning his 40-year mission to integrate psychedelics into medical practice: «Our collective commitment to MDMA-assisted therapy remains unwavering».