Open Label Study of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people diagnosed with at least severe PTSD. The main question it aims to answer is: Do two open-label sessions of MDMA-assisted therapy reduce PTSD symptoms? Participants will receive three non-drug preparatory sessions followed by two sessions of MDMA-assisted therapy. Each MDMA-assisted therapy session is followed by three non-drug integrative therapy sessions.

This multi-site, open-label, Phase 2, lead-in study conducted in Europe assesses the safety and efficacy of MDMA-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). This study additionally provides an opportunity for clinical supervision to planned Phase 3 therapy teams. Select sites will also participate in an optional fMRI (brain imaging) sub-study. This study compares the effects of two open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA HCl. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA HCl, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This \~8-week Treatment Period is preceded by three non-drug Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. The primary endpoint is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to 13 weeks post-baseline (Visit 14). The secondary endpoint is the change in Sheehan Disability Scale (adapted SDS) item scores from Baseline to 13 weeks post-baseline (Visit 14).