MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.
Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein, Charlotte Harrison, Sarah Kleiman, Kelly Parker-Guilbert, Marcela Ot'Alora G, Wael Garas, Casey Paleos, Ingmar Gorman, Christopher R. Nicholas, Michael C Mithoefer, Shannon Carlin, Bruce Poulter, Ann T Mithoefer, Sylvestre Quevedo, Gregory Wells, Sukhpreet Klaire, Bessel Van der Kolk, Keren Tzarfaty, Revital Amiaz, Ray Worthy, Scott Shannon, Joshua Woolley, Cole Marta, Yevgeniy Gelfand, Emma Hapke, Simon Amar, Yair Wallach, Randall Brown, Scott Hamilton, Julie B. Wang, Allison R. Coker, Rebecca Matthews, Alberdina De Boer, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin
FOCUS: The Journal of Lifelong Learning in Psychiatry July 1, 2023 DOI: 10.1176/appi.focus.23021011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 |
| Topics | MDMA PTSD |
| Citations | 97 |
| Registration | NCT03537014 |
| Key findings | 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.
Comparable studies
Other randomized controlled trials on MDMA for PTSD, most cited first.
Citations in the library
Cited by 73
- Updated cost-effectiveness of MDMA-assisted therapy for the treatment of posttraumatic stress disorder in the United States: Findings from a phase 3 trial PLoS One February 25, 2022
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- Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis BMJ August 21, 2024
- MDMA-assisted psychotherapy for the treatment of PTSD: A systematic review and meta-analysis of randomized controlled trials (RCTs). Neuropsychopharmacology Reports December 1, 2024
and 68 more in the library
Cites 12
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- MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology September 1, 2019
- MDMA enhances emotional empathy and prosocial behavior Social Cognitive and Affective Neuroscience October 4, 2013
- Oxytocin-dependent reopening of a social reward learning critical period with MDMA Nature April 3, 2019
- Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline Frontiers in Psychiatry September 12, 2019
and 7 more in the library