A Randomized, Double-Blind, Placebo Controlled Phase 3 Study Assessing Efficacy and Safety of MDMA-Assisted Therapy for the Treatment of Severe PTSD

Background: Posttraumatic stress disorder (PTSD) presents significant unmet medical need that affects the lives of millions of people each year, despite available medications and psychotherapy. Results will be presented from the first pivotal Phase 3 trial of the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for treatment of severe, chronic PTSD. Methods: The study was a double-blind, placebo-controlled, multi-site Phase 3 trial of three 8-hour MDMA sessions and 12 psychotherapy sessions. Randomization was stratified by sites in the U.S., Israel, and Canada. Change in PTSD (CAPS-5) and functional impairment (SDS) were assessed by central blinded Independent Raters. Modified intent to treat efficacy analyses were conducted using a mixed-effect repeated measure model (MMRM). Adverse events and suicidality were tracked throughout the study (NCT03537014). Results: Of 131 participants, 91 were randomized to MDMA (n=46 treated, 91.3% completed) or placebo (n=44, 84.0% completed). Participants were 59% female and 27% LGBTQI. MDMA robustly reduced PTSD symptoms (Mean (SD) CAPS-5 MDMA = -24.5 (11.6), n=42 vs. Placebo = -12.7 (11.5), n=37, p < 0.0001; d=0.91) and significantly improved function (Mean (SD) SDS MDMA = -3.1 (2.6), n=42 vs. Placebo = -2.0 (2.5), n=37; p=0.0209; d=0.42). Three SAEs of suicidality were reported in the placebo arm. Adverse events were transient and mild to moderate in severity, including decreased appetite, muscle tightness, and hyperhidrosis. Conclusions: These data indicate that MDMA-assisted therapy is highly efficacious in treating severe PTSD and improves safety compared to psychotherapy alone despite comorbidities. MDMA presents a breakthrough treatment that merits rapid clinical development. Funding Source: Multidisciplinary Association for Psychedelic Studies Keywords: Neuroplasticity, MDMA, Psychotherapy, PTSD Research, Collaboration, Drug Development