Editor’s note: This story has been updated since its original publication date on Aug. 8 to reflect the FDA’s decision on MDMA.
The FDA’s decision to decline approval on MDMA-assisted therapy for post-traumatic stress disorder (PTSD), represented a significant setback for proponents of psychedelic therapies and delayed the potential introduction of the first new FDA-approved PTSD treatment in over two decades.
This FDA’s decision on Aug. 9 followed a June 2024 advisory committee vote that recommended against approval, citing concerns about study design and potential safety risks. The agency has requested additional clinical trial data from Lykos Therapeutics, the company seeking approval.
Lykos Therapeutics has stated its intention to meet with the FDA to discuss a path forward, which may include conducting another Phase 3 trial.
While PTSD is often linked to experiences in the veteran population — and while veterans are slightly more likely to have PTSD than civilians — the National Center for PTSD estimates that as many as 13 million Americans have the disorder, with women more likely to develop the disorder than men.
The FDA’s action underscores the ongoing challenges in bringing psychedelic therapies into mainstream clinical practice, despite promising early research results.
MDMA-assisted therapy for PTSD has been a topic of intense research and debate in recent years. This is certainly not the first or last time journalists will report on psychedelics as a potential therapy for multiple conditions.
This latest decision has set precedent for the level of scrutiny and the quantity and quality of research required as the FDA puts to task companies that are bringing psychedelic treatment protocols forward for clinical use. It’s crucial for journalists to understand the windy road it took for the medication to get to this point, and offer that context in our continued reporting.
Research milestones
MDMA-assisted therapy for PTSD has been a topic of intense research and debate in recent years. Initial research on MDMA for PTSD began in the early 2000s, with promising results from small-scale trials. Between 2004 and 2017, six Phase 2 trials were conducted, showing significant reductions in PTSD symptoms among participants receiving MDMA-assisted therapy. Two Phase 3 trials, completed in 2021 and 2022, demonstrated that 67-71% of participants experienced post-traumatic growth, no longer met PTSD diagnostic criteria after three MDMA-assisted therapy sessions, compared to 32-48% in the placebo groups. Then, an observational follow-up study suggested that the treatment’s effects may last for at least six months.
Here’s a list of major studies on MDMA for PTSD and their key findings:
- MAPS Phase 2 Trials (2004-2017):
Six Phase 2 trials were conducted, showing significant reductions in PTSD symptoms among participants receiving MDMA-assisted therapy. - MAPS Phase 3 MAPP1 Trial (2021):
This randomized, double-blind, placebo-controlled study found that 67% of participants who received MDMA-assisted therapy no longer met PTSD diagnostic criteria after three sessions, compared to 32% in the placebo group. - MAPS Phase 3 MAPP2 Trial (2023):
This confirmatory study replicated the MAPP1 results, with 71.2% of participants no longer meeting PTSD criteria after MDMA-assisted therapy. The study also demonstrated efficacy across a diverse population, including those with comorbidities. - Long-term follow-up study (2023):
An observational study suggested that the treatment effects of MDMA-assisted therapy for PTSD may last for at least six months. - MPLONG safety studies:
Multiple ongoing studies have shown that MDMA has been administered to approximately 1,700 human subjects with only one serious adverse reaction reported.
What to consider
As a Schedule I controlled substance, MDMA faces unique regulatory hurdles. The U.S. Drug Enforcement Administration defines Schedule I substances as “drugs with no currently accepted medical use and a high potential for abuse.” Reporting should address how this status might affect potential approval and implementation, such as how reluctant clinicians may be to prescribe the medication. If approved, MDMA would likely be rescheduled from Schedule I to a less restrictive category, easing research and clinical use.
It’s important to note that the studies specifically examined MDMA-assisted therapy, not MDMA use alone — the therapy protocol is an integral part of the treatment approach, and that’s what the FDA would emphasize in their approval. Journalists should reiterate that the drug is not intended for use without professional guidance.
While the Phase 3 trial results appear promising, it’s important to note that the FDA Psychopharmacologic Drugs Advisory Committee voted 10-1 against recommending approval of MDMA for PTSD treatment in June 2024, citing concerns about study design and potential bias. The committee also raised issues about cardiovascular risks and the potential for abuse, given MDMA’s euphoric effects. The FDA typically follows its advisory committee’s recommendations. Then again, the FDA has previously approved drugs against both advisory committee recommendations, as seen with aducanumab for Alzheimer’s disease in 2021.
While anecdotal evidence can be compelling, it should be balanced with scientific data and expert analysis. Include diverse viewpoints from researchers, clinicians, and regulatory experts to provide a balanced perspective. Acknowledge the gaps in current research, such as the need for larger, more diverse study populations and longer-term follow-up data.
The FDA’s decision could set precedents for evaluating other psychedelic therapies in development. A negative decision could discourage future regulatory submissions for drug-therapy combinations and impact other ongoing psychedelic research, Mason Marks, M.D., J.D., a visiting professor at Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School wrote in a recent JAMA editorial. There’s also ongoing debate about the future role of advisory committees in FDA decision-making.
Regardless of the outcome, enthusiasm for psychedelic research is likely to continue due to the pressing need for novel PTSD treatments.
