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The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study.

Michael C Mithoefer, Mark T Wagner, Ann T Mithoefer, Lisa Jerome, Rick Doblin

Journal of Psychopharmacology July 19, 2010 DOI: 10.1177/0269881110378371 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Open-label Pilot study Peer reviewed
Sample size 20
Population Patients with chronic post-traumatic stress disorder refractory to both psychotherapy and psychopharmacology
Interventions MDMA psychotherapy
Duration Two 8-hour experimental psychotherapy sessions; primary outcome assessed at baseline, 4 days after each session, and 2 months after the second session
Measures Clinician-Administered PTSD Scale (CAPS)
Topics Psychedelic-assisted therapy MDMA PTSD
Keywords Trauma therapy PTSD Management Mental health treatment Psychiatric intervention MDMA-Assisted Psychotherapy MDMA Therapy Entactogen-assisted therapy Drug-assisted psychotherapy Novel PTSD Treatment Clinical research Pilot study Medical investigation Therapeutic trials Drug development Efficacy study Safety profile
Citations 672
Key findings MDMA-assisted psychotherapy produced significantly greater reductions in Clinician-Administered PTSD Scale scores than placebo at all post-baseline time points, with 83% (10/12) of the MDMA group versus 25% (2/8) of the placebo group showing clinical response. No drug-related serious adverse events, adverse neurocognitive effects, or clinically significant blood pressure increases were observed, and the authors suggest MDMA-assisted psychotherapy may be useful in patients refractory to other treatments.

Abstract

Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as 'Ecstasy' resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.

In the evidence

This study is part of the evidence base for 4 syntheses in the library. Here is how each one recorded it.

  • MDMA-assisted psychotherapy reduced PTSD symptoms more than placebo therapy.

    Synthesized

  • MDMA-assisted psychotherapy reduced PTSD symptoms more than placebo therapy in people with chronic, treatment-resistant PTSD.

    Synthesized

  • MDMA-assisted psychotherapy reduced PTSD symptoms more than placebo therapy in people with chronic, treatment-resistant PTSD.

    Synthesized

  • MDMA-assisted psychotherapy reduced PTSD symptoms more than placebo therapy in people with chronic, treatment-resistant PTSD.

    Synthesized

Comparable studies

Other randomized controlled trials on MDMA and psychedelic-assisted therapy, most cited first.

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