New study brings MDMA closer to FDA approval as treatment for PTSD

By Lauren Smith

Updated: 16 November 2023

Trial is the largest and most diverse yet

The phase 3 trial was sponsored by the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS), which says it will use the latest positive findings to push for federal approval of the drug as a pharmaceutical. ^[1]

The latest of several clinical trials of MDMA-assisted therapy conducted by MAPS Public Benefit Corporation (PBC) is the largest and most diverse yet. 

Its 104 participants, from the United States and Israel, had all been diagnosed with moderate or severe PTSD. ^[1] They included victims of childhood trauma, survivors of sexual assault, and combat veterans, who had lived with PTSD for an average of 16 years. Many reported depression and suicidal thoughts and a history of failed treatments, including antidepressants. ^[2][3]

More than a quarter of participants were Hispanic or Latino (27%) and a third (34%) were non-white, meaning the pool is more representative of the 5% of Americans living with PTSD. ^[1][2] 

“We worked long and hard to get a study population that’s more in line with the general population with PTSD,” said Dr. Jennifer Mitchell, a neuroscientist at the University of California San Francisco and lead author of the study. ^[3]

That included offering participants transportation to and from study sites and paying them stipends to compensate for lost wages or cover the cost of childcare. That ensured that the participants aren't “just privileged people with lots of time and resources,” Mitchell said. ^[3]

86% of participants who received MDMA improved

During the study, published last month in Nature Medicine, participants were given three preparatory talk therapy sessions, followed by three treatment sessions, a month apart, in which they were given either MDMA or a placebo pill.

At the end of the study, 86.5% of people who received MDMA reported reduced severity of symptoms. 71% improved enough that they no longer met the diagnostic criteria for PTSD. In comparison, 69% of those who received the placebo improved and 48% no longer met the diagnostic criteria.

The treatment was also well tolerated, with a low dropout rate and participants reporting only minor and transient side effects including muscle tightness, nausea, decreased appetite, and sweating. ^[2] Seven participants also reported cardiovascular side effects, including rapid heart rate, suggesting older patients may need to be evaluated by a cardiologist before undertaking treatment. ^[3]

MAPS said the positive results confirm their findings in earlier trials, including a 2021 study in which 67% of participants given MDMA shed the diagnostic label, compared to 32% in the placebo group.^[1][3]

Criminalization ended exploration of MDMA's therapeutic potential in the 1980s

MDMA, also known as ecstasy or molly, remains a Schedule 1 drug in the United States, among other substances considered by the Drug Enforcement Administration (DEA) to have a high potential for abuse and no accepted medical use. Its criminalization, in 1985, prematurely ended the exploration of the psychedelic stimulant’s potential and its use by therapists in couples counseling and other treatments.

Rick Doblin, founder of MAPS, called the criminalization of MDMA “a tragedy. “It was pretty clear in the late 1970s and early 1980s that MDMA had incredible therapeutic potential,” he told the New York Times. “All the suffering since then, because MDMA was criminalized, is enormous.” ^[3]

Trials make the case for FDA approval, MAPS says

In 2017, the FDA designed MDMA a breakthrough therapy, a drug that early research indicates could treat a serious condition, in a process intended to expedite the drug’s review and authorization. ^[4] That included the FDA working with researchers, including MAPS, to design clinical trials that would deliver the evidence needed for approval. ^[5]

MAPS is now compiling data from 18 trials it’s conducted about MDMA to form the basis of a New Drug Application with the FDA, to be submitted later this year. That could lead to FDA approval of MDMA as early as next year. ^[1]

“Thanks to the combined efforts of dozens of therapists, hundreds of participants who volunteered in MAPS-sponsored trials, and many thousands of generous donors, MDMA-assisted therapy for PTSD is on track to be considered for approval by the FDA in 2024,” Doblin said. ^[1]

For the FDA to approve MDMA-assisted therapy, the DEA would have to reschedule the substance in a lower-risk tier. The administration has become less stringent on psychedelic substances in recent years and is expected to follow a recommendation from the Department of Health and Human Services (HHS) to move cannabis from Schedule I to Schedule III, potentially creating a precedent from MDMA’s rescheduling. ^[6]

Hurdles remain before MDMA-assisted therapy becomes widespread

If the US approves MDMA, it will follow Australia, which since July has permitted the therapeutic use of MDMA for PTSD and psilocybin (magic mushrooms) for treatment-resistant depression. However, access to the drugs is still tightly controlled. Australia only permits psychiatrists who have been pre-approved to prescribe the drugs and requires them to provide a clinical justification and outline a treatment protocol. The drugs can also only be administered in a clinical setting. ^[7]

It remains to be seen what restrictions the FDA will put on therapeutic MDMA use in the United States. and the labeling it will require for the substance.

“Drug-assisted therapy hasn’t been approved before, so there’s not a lot of precedent,” Amy Emerson, chief executive of MAPS Public Benefit Corporation (PBC), told the New York Times.

Therapists will have to be trained to deliver MDMA-assisted therapy, MAPS acknowledges. It’s already running its own therapist education program and partnering with universities to recruit more counselors. ^[3]

It’s also communicating with insurance companies, Medicare, and Medicaid to win coverage for MDMA-assisted therapy when it’s legalized. Patient access groups may provide discounted or free treatment for those who can’t afford treatment or don't have insurance coverage. ^[3]

In the meantime, MAPS is embarking on further research, now to determine how long the effects of MDMA-assisted therapy last. Earlier, Phase 2 studies suggest benefits may persist for up to 12 months. ^[8]

“Previous data has shown that they’re very durable and last for years, but we need to replicate that now in Phase 3 and see if that’s true, and for whom,” Mitchell told The New Scientist. ^[5]