Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials

This long-term follow-up study (n=107) examines the effects of MDMA-assisted psychotherapy on PTSD symptoms. It finds a significant reduction in PTSD symptoms both at treatment exit and at least 12 months post-treatment, with 67% of participants no longer meeting PTSD criteria at long-term follow-up.

Abstract of Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD

“Rationale: Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD.

Objectives: To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD.

Methods: Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire.

Results: There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = – 44.8 (2.82), p < .0001), with a Cohen’s d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = – 5.2 (2.29), p < .05), with a Cohen’s d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation.

Conclusions: PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD.”

Authors: Lisa Jerome, Allison A. Feduccia, Julie B. Wang, Scott Hamilton, Berra Yazar-Klosinski, Amy Emerson, Michael C. Mithoefer & Rick Doblin

Notes on Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD

β take: This article has been retracted (Aug '24). The main reason is that it includes data from at least one patient who had been abused by the (unlicenced) therapist in the MAPS' sponsored Phase II trial. In a reaction to the retraction, the authors argue that excluding the data wouldn't change the headline findings (they have appealed to retraction).

This article was one of the first to show the long-term durable effects of MDMA-assisted therapy (12 months, 100+ participants). We hope to see the long-term follow-up data from the Phase III trials to confirm this in an even larger sample (200+ participants).

This paper is included in our ‘Top 10 Articles on Psychedelics in the Year 2020‘

Summary of Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD