A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder
In the first Phase 3 randomized, double-blind, placebo-controlled study of MDMA-assisted therapy, participants with severe PTSD were recruited and randomized to receive either manualized therapy with MDMA (n=46) or with placebo (n=44) at one of fifteen study sites across the United States, Canada, and Israel. Participants underwent three 8-hour experimental sessions spaced four weeks apart with a single divided dose of 80 to 180 mg MDMA or placebo, in addition to three preparatory and nine integrative therapy sessions. In the first experimental session, participants received an initial dose of 80 mg followed by a supplemental half-dose of 40 mg, 1.5 to 2.5 hours later. In the second and third experimental sessions, participants received an initial dose of 120 mg followed by a supplemental half-dose of 60 mg. Each experimental session was followed by three 90-minute integrative sessions spaced one week apart in order to allow participants to incorporate their experiences.
“At the primary endpoint, 67% of participants in the MDMA group no longer met diagnostic criteria for PTSD, compared with 32% of participants in the placebo group.”
At the primary endpoint (18 weeks post-baseline), participants in the MDMA group showed a significant reduction in PTSD severity, as assessed by CAPS-5 total severity scores (mean change=-24.4, SD=11.6, n=42) compared to participants in the placebo group (mean change=-13.9, SD=11.5, n=37, d=0.91, p < .0001). At the primary endpoint, 67% of participants in the MDMA group no longer met diagnostic criteria for PTSD, compared with 32% of participants in the placebo group. Across the same time period, there was also a significant decrease in functional impairment, as assessed by SDS scores in the MDMA group (mean change=-3.1, SD=2.6) compared to the placebo group (mean change=-2.0, SD=2.4, p=0.0116).
MDMA was generally well-tolerated with transient increases in vital signs and adverse events that were generally rated mild to moderate including muscle tightness, decreased appetite, nausea, hyperhidrosis, and feeling cold. There was no increase in suicidality adverse events in the MDMA group and serious suicidal ideation was minimal and occurred mostly in the placebo group.
“Three sessions of MDMA-assisted therapy significantly reduced PTSD symptoms and functional impairment, compared to placebo.”
The results of this first Phase 3 trial of MDMA-assisted therapy in people with severe PTSD indicate that three sessions of MDMA-assisted therapy significantly reduced PTSD symptoms and functional impairment, compared to placebo. The effect size (d=0.91) shown in this study between MDMA-assisted therapy and placebo was larger than effect sizes shown for any other previously identified PTSD pharmacotherapy.