Clinical Trial of MDMA-Assisted Therapy for Military Service Members With Posttraumatic Stress Disorder

This Phase 2, randomized, double-blind, active-controlled, single-site clinical trial evaluates the safety, tolerability, and efficacy of MDMA-Assisted Therapy (MDMA-AT) for Service Members with moderate-to-severe Post-Traumatic Stress Disorder (PTSD) within a Military Health System (MHS) setting. The study integrates Acceptance and Commitment Therapy (ACT) as the core therapeutic modality, comparing full-dose MDMA against an active-control low-dose MDMA among 86 randomized participants. To test the feasibility of a regional referral center model, participants are recruited both locally from the National Capital Region and non-locally throughout the MHS. Additionally, the trial begins with an open-label lead-in training cohort of five participants receiving full-dose MDMA-AT to establish protocol fidelity and train therapists prior to the randomized phase. The primary goal of this trial is to evaluate the therapeutic efficacy, safety, and tolerability of MDMA-AT for Service Members with PTSD, with the primary endpoint assessed one month after the final dosing session. The secondary goal is to evaluate the feasibility, tolerability, and acceptability of the regional referral center model for non-local recruitment and treatment, which will be measured at the secondary endpoint three months after the final dosing session. Additionally, the trial's preparatory goal is to ensure therapist adherence to the treatment protocol through the initial open-label training cohort. For each participant, the trial progresses sequentially through five clinical phases, beginning with a Screening Phase to confirm eligibility and obtain informed consent. This is followed by a Preparation Phase, which includes medication tapering and three 90-minute preparatory sessions to confirm enrollment. The 12-week Intervention Phase consists of three month-long cycles, with each cycle containing a single 6-to-8-hour dosing session followed by three 90-minute non-drug integration sessions. Finally, participants enter the Follow-up Phase, which involves primary endpoint assessments at one month, monthly safety follow-up calls, and secondary endpoint assessments leading to Study Completion three months after the final dosing session.