After Latest Clinical Trial, MDMA Therapy For PTSD Is ‘On Track’ For FDA Consideration Next Year

A new peer-reviewed study in the journal Nature says treatment with MDMA reduced symptoms in patients with moderate to severe PTSD.

The Phase 3 trial findings mean federal regulators could consider approving the drug for wider use as soon as next year, says the Multidisciplinary Association for Psychedelic Studies (MAPS), which sponsored the research.

“Thanks to the combined efforts of dozens of therapists, hundreds of participants who volunteered in MAPS-sponsored trials, and many thousands of generous donors,” said Rick Doblin, the group’s founder and president, “MDMA-assisted therapy is on track to be considered for approval by the FDA in 2024.”

The randomized, double-blinded, placebo-controlled trial involved 104 people with PTSD who received either MDMA or a placebo, then paired the experience with talk therapy. Participants were scored on both PTSD symptoms as well as functional impairment.

“In this confirmatory phase 3 study of participants with moderate to severe PTSD, MDMA-AT significantly improved PTSD symptoms and functional impairment.”

The findings—that MDMA “significantly attenuated PTSD symptomology versus placebo with therapy”—add to a body of literature already indicating the substance could be a game-changer. Conventional therapies and medications work for only about half of patients.

Researchers said the substance enhances therapy by helping break down boundaries that might otherwise prevent patients from processing past trauma.

“MDMA simultaneously induces prosocial feelings and softens responses to emotionally challenging and fearful stimuli,” the study says, “potentially enhancing the ability of individuals with PTSD to benefit from psychotherapy by reducing sensations of fear, threat and negative emotionality.”

On the road to federal approval, MAPS Public Benefit Corp. (MAPS PBC), which is a subsidiary of the nonprofit MAPS, will now file a new drug application with the Food and Drug Administration (FDA) later this year, the organization said Thursday. That could mean FDA approval as soon as next year, which would eventually make MDMA therapy more widely available.

FDA in 2017 designated MDMA as a “breakthrough therapy” based on previous MAPS-sponsored trials. In total, the organization says findings from 18 of its Phase 2 and Phase 3 trials will form the basis of the new drug application at FDA.

Not only was treatment “generally well tolerated” among patients with PTSD, the new study says, but also showed robust results across participants.

“A substantial proportion of participants displayed comorbid features associated with high treatment resistance, such as major depression, multiple sources of trauma (including childhood and combat trauma) and dissociative subtype PTSD,” authors wrote. “Given the diverse population and degree of participant complexity, the replication of efficacy is particularly notable.”

“This confirmatory phase 3 trial showed consistent benefits of MDMA-AT in an ethnoracially diverse group of individuals with longstanding moderate to severe PTSD and numerous comorbidities.”

They added that “treatment was not significantly affected by disease severity, risk of hazardous alcohol or substance use disorder, severe adverse childhood experiences or dissociative subtype.”

As for safety issues, nothing new came to light, the report says. Common issues “were similar to to previous studies and consistent with the expected effects of MDMA,” including “mild, transient” increases in blood pressure and heart rate.

Suicidal ideation “was observed in both groups,” the study notes, but “MDMA did not appear to increase this risk, and no suicidal behavior was observed.”

While MDMA appears to offer a novel treatment option, authors also caution that the study isn’t an apples-to-apples comparison between treatment methods. Although MDMA effect sizes were “higher than those observed in SSRI studies,” they said, “the superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison.”

“The complex relationship between SSRI use/history and MDMA-AT treatment efficacy was beyond the scope of the current statistical analysis plan and sample size,” the study says, “but will be important to consider in future studies. In addition, further study of MDMA with other forms of psychotherapy for PTSD should be explored.”

Authors said it’s also possible that the “manualized inner-directed therapy that was developed for use with MDMA” has value on its own given the “notable effect seen in placebo with therapy.”

While practitioners in the psychedelic therapy space have long recognized the therapeutic potential of MDMA, some observers nevertheless described the new study as historic.

“Today’s publication in Nature Medicine marks a watershed moment in the evolution of mental health care, underscoring the urgency of equipping our therapists with the skills and knowledge necessary to provide psychedelic therapy,” said Ingmar Gorman, co-founder of Fluence, which offers educational courses on psychedelic therapy for mental health practitioners.

A separate study, by researchers at New York University’s Langone Center for Psychedelic Medicine and the Centre for Psychedelic Research at Imperial College London, recently found that pairing MDMA with either psilocybin or LSD helped people overcome the “challenging experiences” associated with use of psilocybin or LSD alone.

All three substances—LSD, psilocybin and MDMA—are currently classified as Schedule I controlled substances under federal law, which for decades has hampered research efforts. But amid more indications that the drugs could be potent treatment tools for a variety of mental health disorders, lawmakers and regulators are warming to reform.

A year ago, the Biden administration said it was “actively exploring” the possibility of creating a federal task force to investigate the therapeutic potential of psilocybin, MDMA and others ahead of the anticipated approval of the substances for prescription use. Bipartisan congressional lawmakers, state legislators and military veterans had previously sent letters to the head of the U.S. Department of Health and Human Services (HHS) urging regulators to consider establishing an “interagency taskforce on the proper use and deployment of psychedelic medicine and therapy.”

Lawmakers at the time noted that even National Institute on Drug Abuse (NIDA) Director Nora Volkow had said that the “train has left the station” on psychedelics and had written that “people are going to use them regardless of whether regulators act.”

Sens. Cory Booker (D-NJ) and Brian Schatz (D-HI) separately pushed top federal officials to provide an update on research into the therapeutic potential of psychedelics, arguing that ongoing federal prohibition has stymied studies.

The Drug Enforcement Administration (DEA) late last year proposed higher manufacturing quotas for MDMA, LSD, psilocyn, mescaline and other substances to be used for research. “DEA is committed to ensuring an adequate and uninterrupted supply of controlled substances in order to meet the estimated legitimate medical, scientific, research, and industrial needs of the U.S., for lawful export requirements, and for the establishment and maintenance of reserve stocks,” the agency said at the time.

In February of this year, Australia legalized MDMA and psilocybin for use by prescription.

Psilocybin Associated With ‘Significantly’ Reduced Symptoms Of Major Depression After One Dose, American Medical Association Study Finds

Photo courtesy of Pretty Drugthings on Unsplash.