Pharmacy Practice in Focus: Health Systems March 2025
Volume14 Issue 2
MDMA Rejected: The Story of a Study Participant Entrenched in Ethical Violations and a Data Breach
The health care community was left largely unaware of the controversy that occurred at one of the clinical trial sites.
On August 9, 2024, the FDA issued a complete response letter (CRL) for Lykos Therapeutics’ midomafetamine (MDMA) capsules for the treatment of posttraumatic stress disorder (PTSD), dealing a major setback to MDMA’s pathway to regulatory approval and to the general movement toward a broader acknowledgment among the health care community of the clinical benefits of psychedelic medicines.1,2
eleased to the public), the FDA noted that it could not approve MDMA for PTSD based on the data submitted to date, requesting that Lykos conduct another phase 3 trial to “further study the safety and efficacy” of the drug. The CRL followed the recommended rejection of MDMA on June 4, 2024, by an independent FDA advisory panel that cited questions about the reliability of the submitted clinical trial data.2,3
Yet, the primary and secondary outcomes from 2 pivotal clinical trials backing MDMA’s approval were successfully met. In the randomized, double-blind, placebo-controlled phase 3 MAPP1 trial (NCT03537014) and the confirmatory phase 3 MAPP2 trial (NCT04077437), treatment with MDMA led to a significant reduction in the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) score, which measures PTSD symptom severity, in addition to a large increase in total Sheehan Disability Scale score compared with placebo.4 There were no serious adverse events in the MDMA arms of either trial.1
Based on these data, many psychedelic proponents decried the rejection by the FDA, citing the significant unmet need for an effective therapy in this patient population.
“The delay in FDA approval of MDMA-assisted therapy has been heartbreaking, not just for MAPS [Multidisciplinary Association for Psychedelic Studies] but for the thousands of people still suffering from PTSD who have reached out to us, desperate for effective treatment,” Betty Aldworth, director of communications and education for MAPS, an organization that has historical associations with Lykos, said in a prepared statement over email to Pharmacy Practice in Focus: Health Systems. “Despite support from 80 members of Congress, veterans groups, and trauma experts, the FDA continues to delay. Many people are using psychedelics in unregulated settings because they see them as their last chance to heal.”
This rejection leaves the health care community with a critical question: How could the FDA reject a drug with such strong efficacy and safety data from clinical trials and with such significant therapeutic potential? According to Michael Mithoefer, MD, former senior medical director at MAPS and clinical investigator for MDMA/PTSD studies, the phase 3 trial data show that approximately two-thirds of study participants lost the diagnosis of PTSD because of treatment with MDMA.
“If these treatments can get approved, it would be a huge leap forward,” Mithoefer said in the email statement.5
Notably, clinical research in medicine often is not designed to investigate the social benefits of a drug, yet MDMA is particularly beneficial in supporting interpersonal and internal well-being and health. For example, clinical investigations by MAPS Israel have investigated the benefits of MDMA in healing collective trauma among 400 Israeli survivors after the terrorist attack on October 7, 2023.5 According to Keren Tzarfaty, cofounder and executive director of MAPS Israel, trauma can take over on a personal and social level if left unaddressed.5
Kevin Lanzo, PharmD, a clinical psychopharmacologist, cofounder of the Psychedelic Pharmacists Association, and psychedelic researcher familiar with the Lykos story, explained, “From a pharmacological standpoint, MDMA facilitates the development of relationships, either with others or with yourself. If you have a damaged relationship with yourself, which can be the case in mental health disorders, MDMA can help repair that, such as in the case of PTSD.”
This article will dive deeper into the FDA’s rejection of MDMA to understand what went wrong in this landmark effort toward an FDA approval of a psychedelic medicine, which is the first to have reached this critical juncture. At the center of the controversy that ensued following the FDA CRL, we find a clinical trial participant with significant need for treatment, as well as a complex and potentially destructive relationship between her and 2 health care professionals at one of the clinical trial sites, leading to unauthorized access to trial data and accusations of sexual misconduct.
The Trial Participant
The podcast Cover Story: Power Trip, hosted by Lily Kay Ross and David Nickels, conducted a thorough investigation into the potential MDMA approval several years before the rejection occurred, with a noted interest in the experiences of participants in the trial. The podcast, a collaboration between New York magazine and Psymposia, an independent nonprofit media group, focused on the experiences of one participant in particular: Meaghan Buisson. In the podcast series, Buisson shared details of her negative experiences in the trial and her challenging relationship with the 2 health care professionals leading the trial site where she was a participant.6,7
According to Lanzo, Psymposia as an organization may have played a role in the FDA advisory committee meeting’s decision to recommend rejecting MDMA. At an open public hearing session during the meeting, 5 individuals from Psymposia—without identifying themselves as being associated with the organization—spoke out against MDMA’s approval, Lanzo explained. During the open session, Psymposia made claims similar to those made in the podcast series, with one individual reading a statement on behalf of Buisson. However, Lanzo noted that it is very unlikely that any of the FDA advisory committee reviewers had, in fact, listened to the Power Trip podcast series that discussed Buisson’s case in further detail, as well as other aspects of the MDMA clinical trials. Notably, Lanzo explained that a majority of Psymposia and New York’s gathered reporting regarding Buisson appears to be supported by evidence.
In the podcast, Buisson said she was 19 years old when she started speed racing, which she explained can be a brutal, competitive sport. Buisson, who had a difficult childhood and experienced multiple sexual assaults during that time, pushed her body to the limit in this sport, which resulted in multiple serious injuries, including frequent traumatic brain injuries and broken bones. As her mental health deteriorated following these injuries, she began to seek out psychological treatment through various avenues, including trying several psychiatric drugs and seeking counseling from a therapist. However, this did not alleviate her symptoms.7
