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3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial.

Marcela Ot'Alora G, Jim Grigsby, Bruce Poulter, Joseph W Van Derveer, Sara Gael Giron, Lisa Jerome, Allison A. Feduccia, Scott Hamilton, Berra Yazar-Klosinski, Amy Emerson, Michael C Mithoefer, Rick Doblin

Journal of psychopharmacology (Oxford, England) December 1, 2018 DOI: 10.1177/0269881118806297 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Open-label Peer reviewed
Sample size 28
Population People with chronic posttraumatic stress disorder
Intervention MDMA-assisted psychotherapy
Dose 100 mg, 125 mg, 40 mg
Duration Two eight-hour psychotherapy sessions, one additional open-label session for active dose groups, three open-label active dose sessions for low dose group, 12-month follow-up after final MDMA session
Topics Depression MDMA PTSD Serotonin Psychedelic-assisted therapy
Keywords 3,4-Methylenedioxymethamphetamine MDMA Oxytocin Posttraumatic stress disorder Sleep disturbance PTSD Treatment Standard therapies Innovative treatment MDMA-Assisted Psychotherapy MDMA-Assisted Sessions Active MDMA Doses Low dose Mental health outcomes PTSD Symptoms Severe depression Diagnostic criteria Relief Well-tolerated Neurochemical mechanisms Brain chemicals
Citations 232
Key findings Active doses of MDMA (100 mg and 125 mg) combined with psychotherapy produced larger reductions in PTSD symptoms than a low dose (40 mg), and 76% of participants no longer met PTSD criteria at 12-month follow-up.

Abstract

Posttraumatic stress disorder often does not resolve after conventional psychotherapies or pharmacotherapies. Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms. This pilot dose response trial assessed efficacy and safety of MDMA-assisted psychotherapy across multiple therapy teams. Twenty-eight people with chronic posttraumatic stress disorder were randomized in a double-blind dose response comparison of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA administered during eight-hour psychotherapy sessions. Change in the Clinician-Administered PTSD Scale total scores one month after two sessions of MDMA served as the primary outcome. Active dose groups had one additional open-label session; the low dose group crossed over for three open-label active dose sessions. A 12-month follow-up assessment occurred after the final MDMA session. In the intent-to-treat set, the active groups had the largest reduction in Clinician-Administered PTSD Scale total scores at the primary endpoint, with mean (standard deviation) changes of -26.3 (29.5) for 125 mg, -24.4 (24.2) for 100 mg, and -11.5 (21.2) for 40 mg, though statistical significance was reached only in the per protocol set ( p=0.03). Posttraumatic stress disorder symptoms remained lower than baseline at 12-month follow-up ( p<0.001) with 76% ( n=25) not meeting posttraumatic stress disorder criteria. There were no drug-related serious adverse events, and the treatment was well-tolerated. Our findings support previous investigations of MDMA-assisted psychotherapy as an innovative, efficacious treatment for posttraumatic stress disorder.

In the evidence

This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.

  • State of the evidence: MDMA and psychedelic-assisted therapy Supports

    Active MDMA doses (100 and 125 mg) produced larger PTSD symptom reductions than a 40 mg dose, with 76% no longer meeting PTSD criteria at 12-month follow-up.

    Synthesized

  • State of the evidence: MDMA for PTSD Supports

    Active MDMA doses (100 and 125 mg) produced larger CAPS reductions than a 40 mg low dose, reaching significance only in the per-protocol set (p = 0.03), with 76% no longer meeting PTSD criteria at 12-month follow-up.

    Synthesized

  • State of the evidence: MDMA for depression Supports

    Active doses of MDMA (100 mg and 125 mg) with psychotherapy produced larger reductions in PTSD symptoms than a low dose (40 mg), with statistical significance only in the per-protocol set, and 76% no longer met PTSD criteria at 12-month follow-up.

    Synthesized

Comparable studies

Other randomized controlled trials on MDMA for depression, most cited first.

Study Year Design Participants
Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users homozygous for the l-allele of the serotonin transporter Polydrug ecstasy users 2018 Pooled analysis of four placebo-controlled, within-subject studies n = 63
Self-compassion mediates treatment effects in MDMA-assisted therapy for posttraumatic stress disorder. Adults diagnosed with severe PTSD 2025 Secondary analysis of a randomized controlled trial n = 82
Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial. Participants with advanced-stage cancer and associated depression and anxiety 2024 Randomized controlled trial n = 32
MDMA-assisted PTSD and Alcohol Therapy Trial (MPATHY): study protocol for a double-blind, randomised, controlled outpatient trial of MDMA-assisted integrated exposure-based therapy for comorbid post-traumatic stress disorder and alcohol use disorder Adults with comorbid post-traumatic stress disorder and alcohol use disorder 2026 Randomized controlled trial n = 100

Related reading

Explore topics

Depression MDMA PTSD Serotonin Psychedelic-assisted therapy

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MDMA and psychedelic-assisted therapy MDMA for PTSD MDMA for depression