- Phase 1 clinical trials of MDMA-assisted therapy for healthcare providers will measure development of self-compassion, professional quality of life, and professional burnout among clinicians delivering the treatment to patients
- The study, one of few legal means by which therapists can experience the treatment they provide in MDMA-assisted therapy for PTSD, was placed on clinical hold by the FDA for 20 months
- FDA’s Office of Neuroscience granted the appeal on the grounds of scientific merit, the absence of unreasonable risk to participants, and appropriate investigator qualifications
The U.S. Food and Drug Administration (FDA) Office of Neuroscience granted the Multidisciplinary Association of Psychedelic Studies (MAPS)’ appeal of the clinical hold on the Phase 1 study after almost two years of clinical hold. Initially placed on clinical hold by the FDA in 2019, the MT2 study protocol is a Phase 1, open-label, multi-site research study to assess the safety and psychological effects of MDMA-assisted therapy in healthy volunteer therapists undergoing training to treat patients suffering from posttraumatic stress disorder (PTSD) with MDMA-assisted therapy, developed by MAPS Public Benefit Corporation (MAPS PBC), a wholly-owned subsidiary of MAPS. Personal experience is widely considered to be an important element in preparation and training to deliver psychedelic-assisted therapies.
The hold, lifted on May 11, 2021, was placed by the FDA due to concerns about the scientific merit of the study, risk-to-benefit ratio for healthy therapist participants, and the credentials of clinical investigators. If MAPS’ appeal was not granted, the hold would have required that the Lead Facilitator in each two-person facilitator team hold an M.D., Ph.D., or equivalent degree and that the physician be on-site instead of on-call during the treatment sessions.
The evidence-based decision from the FDA Office of Neuroscience granting MAPS’ appeal notes that this study does not differ in risk or investigator qualifications from MT1, a prior, similarly designed Phase 1 study approved in 2009, and therefore the rationale for a clinical hold is not supported.
Though drug development is often thought of as a linear progression, Phase 1 and Phase 2 investigations can provide valuable data while Phase 3 trials are ongoing. “Even though we are in the midst of Phase 3 studies to treat PTSD, Phase 1 studies are an important area of scientific research and inquiry to generate exploratory and safety data to support new indications. We appreciate the Office of Neuroscience seeing the scientific merit of these data,” says Berra Yazar-Klosinski, Ph.D., Chief Scientific Officer for MAPS PBC. Other indications such as eating disorders and social anxiety are already in Phase 2 studies, and a number of reports suggest the potential for additional future indications.
While the MT1 and MT2 studies do not provide pivotal safety or efficacy data to support the PTSD treatment indication, they serve to increase understanding of MDMA’s clinical effects in a therapeutic setting as well as enhance therapist training, and may therefore prove beneficial in the treatment of patients. As is typical for therapeutic treatments, these studies serve as a vital part of the MDMA Therapy Training Program by providing therapists with personal knowledge of the treatment; the knowledge gained from firsthand experience is invaluable, difficult to replicate, and illegal outside a clinical trial. Participants in MT1 reported the experience was an invaluable part of their training that improved their ability to provide treatment to PTSD participants in Phase 3 clinical trials. “Allowing therapist trainees to enroll in MT2 will support the goals of the MDMA Therapy Training Program to provide comprehensive training to future providers. This work builds capacity to deliver quality, accessible care to patients, pending approval of MDMA-assisted therapy as a legal prescription treatment,” says MAPS PBC Director and Head of Training and Supervision Shannon Carlin, M.A., L.M.F.T.
“This is MAPS at its best, negotiating with the FDA in an evidence-based manner with existing and new data that we analyzed specifically for our response,” explains MAPS Executive Director Rick Doblin, Ph.D. “For three decades, we have sought to educate the FDA in our novel approach rather than simply accept FDA requirements that are unjustified by the evidence. The dedicated work and incisive strategy of our Clinical Development team continues to improve the regulatory landscape for all future patients of psychedelic-assisted medicines.”
MAPS PBC completed three requests to remove the clinical hold containing detailed information addressing the scientific benefit of the study, safety data from previous trial participants demonstrating positive risk-to-benefit ratio, and rationales for allowing licensed therapists with masters level, not doctoral level, degrees to serve as Lead Facilitator with a physician on-call. The successful dispute resolution comes after months of ongoing efforts and the engagement of the experienced legal team at Hyman, Phelps & McNamara, P.C. and lead attorney Josephine Torrente, J.D.
The Office of Neuroscience granting the appeal is encouraging for future negotiations with the FDA on requirements. “We choose to dispute MT2, not solely for its specific impact on MT2, but in an attempt to resolve an ongoing issue with the FDA regarding investigator qualifications across studies,” MAPS PBC Regulatory Affairs Manager, Allison Coker, Ph.D., notes. “The Office of Neuroscience’s agreement with our assessment establishes a precedent that can serve as guidance for developing requirements for investigators in future studies. Along with our clinical safety data, we hope this decision may also support our proposals for use guidelines post-approval.”
“While the term ‘dispute’ may seem adversarial, this process can actually strengthen the relationship and trust between us and our review Division and ensures the Division has support on this project from the Office of Neuroscience,” MAPS PBC Chief Executive Officer Amy Emerson explains. “This decision demonstrates how our strategic, data-driven strategy in challenging the FDA rulings can be successful.”
The safety and efficacy of MDMA-assisted therapy is currently under investigation. It has not yet been approved by the FDA, does not work for everyone, and carries risks even in therapeutic settings. These statements are no guarantee of future FDA approval or availability of MDMA-assisted therapy. These statements necessarily involve known and unknown risks and uncertainties, which may cause actual outcomes to differ materially from our projections.
Betty Aldworth, Director of Communications
Founded in 1986, MAPS is a 501(c)(3) non-profit research and educational organization that develops medical, legal, and cultural contexts for people to benefit from the careful uses of psychedelics and marijuana. MAPS is sponsoring the most advanced psychedelic therapy research in the world: Phase 3 clinical trials of MDMA-assisted therapy for PTSD. Since its founding, MAPS has raised over $100 million for psychedelic therapy and medical marijuana research and education and has earned the Guidestar Platinum Seal of Transparency.
MAPS Public Benefit Corporation (MAPS PBC) catalyzes healing and well-being through psychedelic drug development, therapist training programs, and sales of prescription psychedelics while prioritizing public benefit above profit. Founded in 2014, MAPS PBC is a wholly-owned subsidiary of the Multidisciplinary Association for Psychedelic Studies (MAPS), a 501(c)(3) non-profit organization.