3 Reasons Why FDA Rejected MDMA for PTSD Treatment in 2024

According to the official press release from the drug sponsor Lykos Therapeutics, the US Food and Drug Administration (FDA) has decided not to approve the use of MDMA (commonly known as ecstasy) as a means of treating post-traumatic stress disorder (PTSD). The FDA has asked the company to conduct further Phase 3 clinical trials to fully assess the safety and efficacy of this therapy.

Lykos Therapeutics' original application was based on the positive results of two advanced clinical trials that combined MDMA with talk therapy to treat PTSD. Approximately 200 participants were involved in Lykos' trials, with a treatment regimen involving three 8-hour sessions under the supervision of two therapists, along with MDMA. The sessions were spaced about a month apart and supplemented with additional talk therapy.

MDMA, as a hallucinogen, is classified as a psychoactive drug with the potential to promote emotional communication, enhance intimacy, and increase emotional openness. This was the FDA's first consideration of using hallucinogens for medical purposes, and this novel therapy could have far-reaching implications for a highly demanding field, but the review process also raised questions about how to use it safely in a clinical setting. Under the Controlled Substances Act, MDMA is currently listed as "having no currently accepted medical use and a high potential for abuse." Reclassifying MDMA would require collaboration between multiple federal agencies and significant policy changes.

In June of this year, an independent FDA advisory committee voted overwhelmingly against the therapy, primarily due to concerns about the integrity of the specific trials that were about to be reviewed. Although the committee members recognized the exploratory nature and potential of the Lykos Therapeutics trials, they raised key issues about the lack of safety information and the bias in the efficacy data. They also noted that it is difficult to assess the contribution of the accompanying talk therapy to the efficacy, as this area is not under the FDA's regulatory purview.

In a research briefing prior to the committee meeting, the FDA stated, "Participants appear to have experienced rapid, clinically meaningful, and durable improvements in PTSD symptoms." However, the FDA at the time expressed concerns about safety data, in addition to the ambiguity in the efficacy data. Although MDMA has a risk of abuse, the FDA warned that the study did not adequately assess its adverse events in the context of the treatment regimen.

Reports of illegal MDMA use indicate that it may pose a threat to heart and liver health. The FDA noted that the Phase III clinical trials showed significant increases in participants' blood pressure and pulse, but certain related assessments were not yet complete. Liver health status was only evaluated in a small subset of trial participants in the early stages of the clinical trials.

In its statement on Friday, Lykos Therapeutics said that additional trials could take years, but the company believes the concerns raised by the FDA and its advisors can be addressed. Lykos plans to meet with the agency to discuss its recommendations and request reconsideration.

Lykos emphasized in its Friday press release, "Lykos will work over the coming months to address the FDA's concerns and utilize agency procedures to resolve scientific disagreements." "Following the FDA meeting, Lykos expects to provide updates on next steps for resubmission."

According to estimates from the National Center for PTSD, approximately 5% of American adults (about 13 million people) suffer from PTSD each year. However, current treatment options, including antidepressants and certain forms of cognitive behavioral therapy, have limitations in scope and effectiveness, and there are almost no other options to help those who do not respond well to traditional therapies.

The non-profit consumer advocacy organization Public Citizen testified before the FDA advisory committee in June, opposing the approval of this therapy, and expressed its appreciation for Friday's decision. In a statement, Dr. Robert Steinbrook, director of the Public Citizen Health Research Group, said, "Although psychedelics have potential in mental health care, FDA approval of new drugs should always be based on rigorous evidence of safety and efficacy." "By rejecting the approval of MDMA, the FDA will encourage this company and other researchers of psychedelic drugs to conduct more rigorous clinical trials."

However, the chairman of the Veterans Mental Health Leadership Alliance, Martin Steele, and Reason for Hope, questioned the FDA's decision, believing that the FDA has sufficient tools to ensure that this new therapy can be introduced slowly and cautiously, at least with a conditional approval, while collecting safety data, conducting post-marketing studies, and implementing stricter risk mitigation strategies.