In a decisive vote on Tuesday, a federal advisory committee rejected the use of MDMA, widely known as ecstasy, as a treatment for post-traumatic stress disorder (PTSD). Despite the innovative potential of MDMA-assisted therapy, concerns regarding the integrity of the reviewed trials influenced the committee’s decision.
The independent committee, after reviewing presentations from the US Food and Drug Administration (FDA), Lykos Therapeutics, and public members, voted on recommendations to be made to the FDA. Only two of the 11 committee members deemed the treatment effective, while nine did not. Additionally, just one member believed the treatment’s benefits outweighed its risks, with the remaining ten dissenting.
This was a historic moment as it marked the first time FDA advisers considered a psychedelic drug for medical use. MDMA, an entactogen known for inducing emotional openness and connectedness, is currently classified as a Schedule I drug under the Controlled Substances Act. A change in this status would represent a significant policy shift.
Although the FDA will make the final decision regarding the treatment’s approval, the agency typically follows the recommendations of its advisory committees.
Approximately 5% of US adults, or about 13 million people, suffer from PTSD annually, according to the National Center for PTSD. Current treatments, including antidepressants and cognitive behavioral therapy, have limited effectiveness, highlighting the need for new alternatives.
Lykos Therapeutics presented positive data from two late-stage clinical trials using MDMA in conjunction with therapy to treat PTSD. While many committee members acknowledged the potential of this treatment, they raised critical concerns about the trials’ bias and incomplete safety data.
Around 200 participants took part in the Lykos trials, which included three eight-hour MDMA sessions, each a month apart, under the supervision of two therapists, along with additional therapy sessions. The FDA noted participants showed “rapid, clinically meaningful, durable improvement” in their PTSD symptoms. However, several factors complicated the data interpretation, challenging the benefit-risk assessment.
The double-blind design of the studies was compromised as most participants could identify their treatment group due to MDMA’s profound effects, undermining the results’ validity. Additionally, the Institute for Clinical and Economic Review highlighted significant concerns about the trials’ bias in a report published in March.
Safety concerns also emerged, with MDMA’s potential for abuse and associated health risks, such as increased blood pressure and pulse, not adequately assessed in the trials. The FDA emphasized incomplete assessments related to heart and liver health, further questioning the treatment’s safety.
Dr. Paul Holtzheimer, deputy director for research at the National Center for PTSD, echoed these concerns, voting against the treatment. “Premature introduction of a treatment can stifle development and lead to the adoption of treatments that are not fully known to be safe or effective,” he said.
Dr. Walter Dunn, the sole committee member to vote in favor of the treatment, acknowledged the treatment’s potential but expressed low confidence in the risk-benefit analysis. He emphasized the importance of psychotherapy in the treatment program, which is beyond the FDA’s regulatory scope, and highlighted the need for specific safety guardrails.
Lykos CEO Amy Emerson expressed the company’s commitment to safety and acknowledged the urgent need for new treatment options. She emphasized the importance of the advisory committee meeting as a significant milestone in the approval process.
Interest in psychedelics as therapeutics is growing, with drugs like ketamine and psilocybin mushrooms also being studied for various mental health disorders. However, experts caution against viewing psychedelics as universal solutions, stressing the need for careful study of each drug’s safety and efficacy profiles.
Dr. Joshua Gordon, director of the National Institute of Mental Health, noted the promise and potential of such treatments but emphasized the need for rigorous study to determine their impact.
Dr. Rachel Yehuda, director of the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai’s Icahn School of Medicine, highlighted the importance of ongoing research and responsible implementation to avoid premature adoption of unproven treatments.
Dr. Jon Alpert, chair of the American Psychiatric Association’s research council, warned of the risks of unmonitored use of psychedelics and emphasized the importance of strict regulations and comprehensive monitoring for any approved treatment.
The Lykos treatment program’s intensive nature poses additional challenges, given the shortage of mental health professionals in the US. As discussions continue, the future of MDMA-assisted therapy remains uncertain, but the need for innovative treatments for PTSD is clear.
