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.

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.

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

  MDMA-assisted psychotherapy produced significantly greater CAPS reductions than placebo at all post-baseline time points, with 83% versus 25% clinical response and no drug-related serious adverse events.

  Synthesized October 22, 2026

• State of the evidence: MDMA for PTSD ↑Supports

  MDMA-assisted psychotherapy reduced CAPS scores significantly more than placebo at all post-baseline time points, with 83% versus 25% clinical response and no drug-related serious adverse events.

  Synthesized October 22, 2026

• State of the evidence: MDMA ↑Supports

  MDMA-assisted psychotherapy reduced PTSD symptom scores significantly more than placebo at all post-baseline time points, with 83% versus 25% clinical response and no drug-related serious adverse events.

  Synthesized October 19, 2026

• State of the evidence: PTSD ↑Supports

  MDMA-assisted psychotherapy produced significantly greater CAPS reductions than placebo at all post-baseline time points, with 83% versus 25% clinical response and no drug-related serious adverse events.

  Synthesized October 19, 2026

Comparable studies

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