MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.
Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein, Charlotte Harrison, Sarah Kleiman, Kelly Parker-Guilbert, Marcela Ot'Alora G, Wael Garas, Casey Paleos, Ingmar Gorman, Christopher Nicholas, Michael Mithoefer, Shannon Carlin, Bruce Poulter, Ann Mithoefer, Sylvestre Quevedo, Gregory Wells, Sukhpreet S Klaire, Bessel Van der Kolk, Keren Tzarfaty, Revital Amiaz, Ray Worthy, Scott Shannon, Joshua D Woolley, Cole Marta, Yevgeniy Gelfand, Emma Hapke, Simon Amar, Yair Wallach, Randall Brown, Scott Hamilton, Julie B Wang, Allison Coker, Rebecca Matthews, Alberdina De Boer, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin
Focus (American Psychiatric Publishing) July 1, 2023 DOI: 10.1176/appi.focus.23021011 via PubMed
Summary
AI-generated from the abstractA phase 3 clinical trial tested MDMA-assisted therapy for severe PTSD. In 90 participants randomized to receive either MDMA or placebo alongside therapy, those receiving MDMA showed a significantly larger reduction in PTSD symptoms, with an average decrease of 24.4 points on the CAPS-5 scale compared to 13.9 points in the placebo group. Functional impairment also improved more with MDMA. No serious safety issues like abuse potential or suicidality were observed. The treatment was effective even for patients with common co-occurring conditions such as depression or substance use history. The authors conclude MDMA-assisted therapy is a safe and highly effective treatment for severe PTSD.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 90 |
| Population | Patients with severe PTSD, including those with comorbidities such as dissociation, depression, history of alcohol and substance use disorders, and childhood trauma |
| Intervention | MDMA-assisted therapy |
| Duration | 2 months after the last experimental session |
| Citations | 97 |
| Registration | NCT03537014 |
| Key finding | MDMA-assisted therapy produced significantly greater reductions in PTSD symptoms and functional impairment than placebo-assisted therapy, with a large effect size and no major safety concerns. |
Abstract
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. Appeared originally in Nat Med 2021; 27:1025-1033.