Phase 3 Trials of MDMA-Assisted Therapy for PTSD: Publication in Nature Medicine and Major Media Coverage

On May 3, 2021, we announced that the first Phase 3 trial of MDMA-assisted therapy for posttraumatic stress disorder (PTSD) which replicated and expanded on Phase 2 results indicates that MDMA-assisted therapy may be an effective and cost-saving treatment for PTSD. On May 10, Nature Medicine published the peer-reviewed paper detailing the results of the study. In this first Phase 3 trial of any psychedelic-assisted therapy, participants who received MDMA-assisted therapy reported a significant reduction in PTSD symptoms compared to those who received placebo with therapy (p<0.0001), successfully achieving the prespecified primary endpoint for the trial. In fact, 67% of the group who received MDMA, compared to 32% of the group who received placebo, no longer qualified for a PTSD diagnosis after three treatment sessions. In addition, participants treated with MDMA-assisted therapy had statistically significant reductions for the key secondary endpoint of functional impairment relative to placebo with therapy (p=0.0116).

This exciting accomplishment led to news coverage by major media outlets. Articles about the Nature Medicine publication appeared in The New York Times, BBC, Scientific American, Newsweek, CNBC, and more.

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study | Nature Medicine
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder.
MAPS’ Phase 3 Trial of MDMA-Assisted Therapy for PTSD Achieves Successful Results for Patients with Severe, Chronic PTSD – Multidisciplinary Association for Psychedelic Studies – MAPS
The highly statistically significant results and excellent safety record suggest MDMA-assisted therapy will be approved as effective treatment for severe, chronic PTSD in 2023. 67% of participants who received three MDMA-assisted therapy sessions no longer qualified for a PTSD diagnosis and 88% experienced a clinically meaningful reduction in symptoms The pivotal Phase 3 trial treated 90 patients with severe, chronic PTSD with an average duration of 14 years. Study participants included those with PTSD caused by combat-related events, accidents, abuse, and sexual harm; 84% have a history of developmental trauma.