Casey Paleos, MD: Remaining Questions on MDMA-Assisted Therapy in PTSD

As the calendar turns from July to August, the psychiatry community’s gaze now finds itself affixed to August 11 and the US Food and Drug Administration’s decision surrounding Lykos Therapeutics’ application for 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of posttraumatic stress disorder (PTSD).

Despite backing from a pair of phase 3 randomized, double-blind, placebo-controlled trials in MAPP1 and MAPP2, MDMA-assisted therapy has encountered numerous hurdles on the way to this potential decision, including the historic stigma attached to use of MDMA as a result of its Schedule 1 controlled substance and, more recently, a negative outcome from a meeting convened by the FDA’s Psychopharmacologic Drugs Advisory Committee in early June.

As part of our ongoing coverage leading up to this historic FDA decision, we contacted leading subject matters in the field. In this video series, our audience can hear the perspective of Casey Paleos, MD, an adult psychiatrist in a New York-based private practice and the Chief Medical Officer of InnerMost PBC. In the following video series, Paleos, who also served as a principal investigator and study therapist for Lykos-sponsored phase 3 clinical trials of MDMA-assisted therapy in PTSD, offers his perspective on a group of 5 questions related to the upcoming August 11, 2024, PDUFA data for MDMA-assisted therapy in PTSD. The questions for each segment are as follows:

• Can you give a brief overview of current options and unmet need in PTSD?
• Can you discuss your interpretation of the data supporting MDMA-assisted therapy in PTSD, including concerns about safety?
• How can clinicians and researchers address the stigma associated with using MDMA in a therapeutic context to ensure broader acceptance and understanding?
• Regardless of the FDA decision on this one application, what is your outlook on the potential of psychedelic therapies in PTSD looking forward?
• What are the most pertinent unanswered questions surrounding MDMA-assisted therapy for PTSD?

In the video segment featured above, Paleos tackles the fifth and final question. In his response, Paleos delves into the uncertainties surrounding MDMA-assisted therapy, including when it will receive FDA approval and what the Risk Evaluation and Mitigation Strategies (REMS) will entail. He also raises important questions about ensuring proper training and oversight for psychotherapists involved in this treatment. While the REMS will likely require a licensed and trained psychotherapist to administer the drug, the specifics of psychotherapy regulation remain unclear. Paleos introduces the International Alliance of MDMA Practitioners, a new organization aiming to be a resource for expert information and guidance on this emerging therapy.

Relevant disclosures of interest for Paleos include Lykos Therapeutics, Fluency, Mindbloom, Nautilus Sanctuary, Nautilus Psychiatric Services, InnerMost PBC, and Journey Clinical.

References:

1. Lykos Therapeutics. Lykos Therapeutics announces FDA Advisory Committee meeting to review investigational MDMA-Assisted therapy for PTSD. Lykos Therapeutics - News Release Archive. May 6, 2024. Accessed August 5, 2024. https://news.lykospbc.com/2024-05-06-Lykos-Therapeutics-Announces-FDA-Advisory-Committee-Meeting-to-Review-Investigational-MDMA-Assisted-Therapy-for-PTSD.
2. Kunzmann K. FDA Psychopharmacologic Advisory Committee votes against supporting effectiveness of MDMA FOR PTSD. HCP Live. June 4, 2024. Accessed August 05, 2024. https://www.hcplive.com/view/live-updates-fda-psychopharmacologic-advisory-committee-meeting-mdma-ptsd.