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Pharmacy Practice in Focus: Health Systems
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
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In the full CRL to Lykos (which has still not been released 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
In 2014, she connected with an MDMA phase 2 clinical trial site in Vancouver, British Columbia, Canada, becoming 1 of 6 enrollees at the trial site. Her therapists were Richard Yensen, PhD, and Donna Dryer, a married couple who were medically licensed—Dryer was a psychiatrist and went to medical school and Yensen was a psychotherapist—and part of the MAPS community. Given the nature of the psychedelics clinical trial space at this time, MAPS did not have many options available for trial investigators, according to Lanzo. However, Dryer and Yensen were qualified and, to Buisson, seemed responsible; she described Yensen as a “larger, softer, fuzzier character,” according to the podcast.7
Tapes Reveal Misconduct
According to podcast hosts Ross and Nickels, MDMA trial sessions typically last for 8 hours. In Buisson’s case, those long sessions occurred in a cramped basement, with a twin bed in the middle of the room. Cameras used for clinical trial oversight purposes were placed in the room to document the sessions. Buisson’s memory of her experience while on MDMA in that room was hazy, so she requested MAPS release her tapes to her. Once reviewed, she came to understand what had happened to her while she was under the influence in that basement.6,7
While undergoing her MDMA session, Buisson recounts reliving a vivid sexual assault from her youth. While this was occurring, Yensen bear-hugged her and put his weight on her body to help her “break through,” despite Buisson’s ongoing and audible protestations for him to stop. Throughout the session, both Yensen and Dryer remained closely physical with her. According to Ross and Nickels, who watched and recounted more than 75 hours of video recordings from her sessions, throughout these sessions, Yensen “is in almost constant physical contact with Meaghan,” ranging from light hand touches or brushes of the hair to lying in the bed with Buisson and Dryer. The most extreme version of this contact was when Yensen pinned Buisson’s body down as she relived her past sexual assault.8
Ross and Nickels noted that at multiple points, Buisson cried out for Yensen to “get off me.” At one point during the recording, following a period of Yensen cuddling and nuzzling Buisson’s body, Yensen can be heard kissing Buisson on the forehead after Dryer had left the room.8
Investigators Turned Manipulators
The videotapes that MAPS released document only part of the unfurling complex relationship between Buisson and her therapists, particularly with Yensen. The Power Trip hosts explain that, following the end of the phase 2 trial sessions, Buisson—who was not financially stable at the time and wanted to continue receiving MDMA treatment—decided, in collaboration with Yensen and Dryer, to move to the small remote island where they operated their clinic in order to continue the therapeutic relationship. Over a period following the trial sessions, the lines continued to blur.7
Lanzo explained that Buisson’s relationship with Dryer and Yensen developed to a point where she became an administrative assistant for them at their home on Cortes Island in Vancouver, helping answer emails from MAPS for her therapists and, at one point, even providing her own medical information when she was requested to do so by clinical trial investigators external to the site. Buisson was also provided access to the trial data by Yensen and Dryer as a part of her administrative assistant role, which allowed her to view clinical trial information about the other trial participants at the site.3,8 Notably, this breach of clinical trial site data goes against established research standards for responsibly conducted clinical trials, according to Lanzo.
Ultimately, after months of subtle manipulation, Buisson’s “dependency” on Yensen built to a point where “it became extremely normalized to curl up for hours on the sofa and cuddle together,” according to Buisson on the podcast. She explained that, over the course of a winter, Yensen progressed from touching to kissing to intercourse. Then in May 2016, when Buisson rejected further attempts, citing her discomfort with the relationship, Yensen told her over email that her experiences were not “related to reality.”7
In 2018, MAPS received an ethics complaint from Buisson regarding the sexual relationship that had occurred after the treatment sessions had concluded. After an investigation, both Yensen and Dryer confirmed to MAPS that Yensen was engaged in a sexual relationship with Buisson—a violation of Section 6 of the MAPS Code of Ethics for Psychedelic Psychotherapy. The investigators were barred from all MAPS-related activities and from becoming providers of MAPS-affiliated MDMA therapy in the future.9
In 2021, when the Power Trip hosts showed MAPS staff the videotapes of Buisson’s trial sessions, a compliance review of the available documentation of the trial—including all available videos—was initiated. After review, MAPS determined that Yensen and Dryer “substantially deviated from the MDMA-assisted therapy treatment manual on several occasions during the treatment period” and notified the FDA.10
An insider involved with MAPS and the clinical trial, who wished to remain anonymous for this story, provided additional context surrounding the videotapes in the trial. The insider noted that protocols for phase 2 trials considered session videos available for “process improvement” of the psychotherapy, not proper trial data. Therefore, when Buisson filed her complaint to MAPS, the tapes weren’t looked at because MAPS did not consider them to be study data, as the allegations were not made about the sessions themselves.
“The big mistake MAPS made was, in making their public statement, they incorrectly claimed the tapes were a safety measure,” the insider said. “When Psymposia got the tapes, they were able to revive a phase 2 story, making it seem relevant to the present while flaying MAPS for ignoring the tapes.”
Journal Retraction Seals Lykos’ Fate
On August 10, 2024, a day after the FDA’s CRL being issued to Lykos, medical journal Psychopharmacology retracted 3 papers that studied MDMA-assisted therapy, including a meta-analysis of the pooled phase 2 trials that featured Buisson’s data. Combined with the FDA’s rejection, these journal retractions represent a major setback for Lykos, MAPS, and the overall path to MDMA’s approval.10
According to Lanzo, Buisson’s anonymous data—which she had access to once she became an administrative assistant, in addition to other participants’ data—were originally included in the submitted phase 2 paper. Notably, Lykos was not informed that Buisson was working as an administrative assistant at the trial site when they originally submitted their phase 2 paper to the journal, as Buisson was employed by Yensen and Dryer directly without any association with MAPS in her employment. However, although Lykos submitted a correction to the journal to remove her data from the original phase 2 data once they had uncovered the situation with Buisson, her data were still included in the pooled analysis, with the anonymous insider offering that Lykos was either too late or had apparently forgotten to redact those data as well.
Before the open public hearing session during the FDA advisory committee meeting, the journal allegedly asked Lykos to change the pooled analysis data. However, following the overwhelmingly negative response from the meeting, Psychopharmacology didn’t give Lykos the opportunity to make changes; instead, the journal quickly redacted the paper.
“The editors have retracted this article after they were informed of protocol violations amounting to unethical conduct at the MP4 study site by researchers associated with this project,” the study authors wrote in their retraction note, referring to the conduct at Yensen and Dryer’s site on Cortes Island. “The authors have subsequently confirmed that they were aware of these violations at the time of submission of this article but did not disclose this information to the journal or remove data generated by this site from their analysis.”11
The MAPS insider interviewed for this story explained how the main problem lies with MAPS’ lack of immediate response to the abuse allegations. “When they reacted, they didn’t react strong enough,” they said. “The fear is that the leadership of MAPS may not have taken the story seriously.”
This controversy has laid bare one of the many challenges of conducting clinical trials investigating psychedelic medicines: Patients in such trials are under the influence of psychoactive substances, making them vulnerable in ways that are somewhat unique to the modern clinical trial landscape. For such trials, patients require ethical and sound oversight by trial investigators, who must ensure they are safe from potential harm, not only from the patients’ own actions but also potentially from the actions of other trial investigators.
“This case [involving Buisson] emphasizes the unique challenge of researching drugs that facilitate the development of relationships,” Lanzo said. “If proper safeguards are not put in place, then cases of adverse events may be more social than physical.”
Additionally, Buisson’s case isn’t the first instance where a patient undergoing psychedelic-assisted therapy experienced sexual abuse from their therapist, either during or after treatment.12 Clearly, the health care landscape may need to review its approach to licensure for those who provide this type of therapy to patients.
Following this landmark effort to approve MDMA, the future of Lykos, MAPS, and psychoactive medicine in clinical research remains murky. In the next article in the series, we dive further into the aftermath of the trial for MAPS and Lykos, as well as the planned future for MDMA.
REFERENCES
1. Gallagher A. FDA declines to approve MDMA for PTSD. Pharmacy Times. August 9, 2024. Accessed January 7, 2025. https://www.pharmacytimes.com/view/fda-declines-to-approve-mdma-for-ptsd
2. Lykos Therapeutics announces complete response letter for midomafetamine capsules for PTSD. News release. Lykos Therapeutics; August 9, 2024. Accessed January 7, 2025. https://news.lykospbc.com/2024-08-09-Lykos- Therapeutics-Announces-Complete-Response-Letter-for-Midomafetamine-Capsules-for-PTSD
3. Antrim A. FDA advisory panel rejects MDMA-assisted therapy for PTSD. Pharmacy Times. June 4, 2024. Updated June 5, 2024. Accessed January 14, 2025. https://www.pharmacytimes.com/view/fda-advisory-panel-rejects-mdma-assisted-therapy-for-ptsd
4. Singewald N, Sartori SB, Reif A, Holmes A. Alleviating anxiety and taming trauma: novel pharmacotherapeutics for anxiety disorders and post-traumatic stress disorder. Neuropharmacology. 2023;226:109418. doi:10.1016/j.neuropharm.2023.109418
5. Busby M. Israeli group to study MDMA therapy for October 7 survivors with PTSD. The Intercept. February 14, 2024. Accessed January 14, 2025. https://theintercept.com/2024/02/14/gaza-israel-mdma-ptsd-study/
6. Cover Story: Power Trip. Psymposia. Accessed January 14, 2025. https://www.psymposia.com/powertrip-2/
7. The Cut. Open-heart surgery. New York. March 2, 2022. Accessed January 14, 2025. https://www.thecut.com/2022/03/cover-story-podcast-open-heart-surgery.html
8. The Cut. Political science. New York. March 8, 2022. Accessed January 14, 2025. https://www.thecut.com/2022/03/cover-story-podcast-episode-7-political-science.html
9. Statement: public announcement of ethical violation by former MAPS-sponsored investigators. News release. MAPS. May 24, 2019. Updated March 25, 2022. Accessed January 14, 2025. https://maps.org/2019/05/24/statement-public-announcement-of-ethical-violation-by-former-maps-sponsored-investigators/
10. Manalac T. MDMA papers retracted for ‘unethical conduct’ on heels of Lykos’ FDA rejection. BioSpace. August 12, 2024. Accessed January 16, 2025. https://www.biospace.com/drug-development/mdma-papers-retracted-for-unethical-conduct-on-heels-of-lykos-fdarejection
11. Mithoefer MC, Feduccia AA, Jerome L, et al. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019;236(9):2735-2745. doi:10.1007/s00213-019-05249-5
12. Chacruna Institute Facebook page. Why does sexual abuse occur in ayahuasca healing contexts? March 26, 2021. Accessed January 16, 2025. https://www.facebook.com/photo. php?fbid=3658794740915995&id=658651994263633&set=a.658778960917603
