3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial

This Phase II clinical trial (n=26) finds that MDMA-assisted psychotherapy (75-125 mg) led to significant and sustained decreases in PTSD (CAPS-IV) scores as compared to an active placebo (30 mg). At the 12-month follow-up, the average CAPS-IV score had dropped from 87 to 39 (67% no longer qualified for PTSD diagnosis).


Background: Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population.

Methods: We did a randomised, double-blind, dose-response, phase 2 trial at an outpatient psychiatric clinic in the USA. We included service personnel who were 18 years or older, with chronic PTSD duration of 6 months or more, and who had a Clinician-Administered PTSD Scale (CAPS-IV) total score of 50 or greater. Using a web-based randomisation system, we randomly assigned participants (1:1:2) to three different dose groups of MDMA plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. We masked investigators, independent outcome raters, and participants until after the primary endpoint. MDMA was administered orally in two 8-h sessions with concomitant manualised psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second experimental session. Participants in the 30 mg and 75 mg groups subsequently underwent three 100–125 mg MDMA-assisted psychotherapy sessions in an open-label crossover, and all participants were assessed 12 months after the last MDMA session. Safety was monitored through adverse events, spontaneously reported expected reactions, vital signs, and suicidal ideation and behaviour.

Findings: Between Nov 10, 2010, and Jan 29, 2015, 26 veterans and first responders met eligibility criteria and were randomly assigned to receive 30 mg (n=7), 75 mg (n=7), or 125 mg (n=12) of MDMA plus psychotherapy. At the primary endpoint, the 75 mg and 125 mg groups had significantly greater decreases in PTSD symptom severity (mean change CAPS-IV total scores of −58·3 [SD 9·8] and −44·3 [28·7]; p=0·001) than the 30 mg group (−11·4 [12·7]). Compared with the 30 mg group, Cohen’s d effect sizes were large: 2·8 (95% CI 1·19–4·39) for the 75 mg group and 1·1 (0·04–2·08) for the 125 mg group. In the open-label crossover with full-dose MDMA (100–125 mg), PTSD symptom severity significantly decreased in the group that had previously received 30 mg (p=0·01), whereas no further significant decreases were observed in the group that previously achieved a large response after 75 mg doses in the blinded segment (p=0·81). PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 [SD 28·1] vs 87·1 [16·1]; p<0·0001). 85 adverse events were reported by 20 participants. Of these adverse events, four (5%) were serious: three were deemed unrelated and one possibly related to study drug treatment.

Interpretation: Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well-tolerated in reducing PTSD symptoms in veterans and first responders.”

Authors: Michael C. Mithoefer, Ann T. Mithoefer, Allison A. Feduccia, Lisa Jerome, Mark Wagner, Joy Wymer, Julie Holland, Scott Hamilton, Berra Yazar-Klosinski, Amy Emerson & Rick Doblin


A qualitative analysis (interviews) was done with 19 participants of this study by Barone and colleagues (2019).

Summary of MDMA-assisted psychotherapy for PTSD in military veterans, firefighters, and police officers


Post-traumatic stress disorder is a major public health problem, particularly among military veterans. It is associated with increased medical morbidity, occupational and relationship problems, and decreased quality of life.

Treatment options for PTSD include pharmacotherapy and psychotherapies. MDMA has shown promise as a psychotherapeutic adjunct, although high dropout occurs with trauma-focused psychotherapies.

MDMA-assisted psychotherapy showed large effect sizes with low dropout and durable improvements in military veterans, firefighters, and police officers with PTSD resulting from their service.


Authors associated with this publication with profiles on Blossom

Michael Mithoefer
Michael Mithoefer is a psychiatrist and a Clinical Investigator and acting Medical Director of MAPS Public Benefit Corporation.

Julie Holland
Julie Holland, M.D., is an American psychopharmacologist, psychiatrist, and author. Next to writing Ecstasy, she has written books about her experience working as an ER doctor in Bellevue Hospital in New York.

Rick Doblin
Rick Doblin Ph.D. is the founder of MAPS. His persistent work since 1986 has been one of the main drivers behind why psychedelics (including MDMA) are now coming back to therapy.


Institutes associated with this publication

MAPS stands for Multidisciplinary Association for Psychedelic Studies, it's the front runner in making psychedelics a legal way to use (and improve) in therapy.

Compound Details

The psychedelics given at which dose and how many times

MDMA 75 - 125
mg | 3x

Linked Research Papers

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Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder
This follow-up analysis (n=9), of fMRI data from veterans and first responders who underwent MDMA-assisted therapy (3x 100-125mg) for PTSD, finds a correlation between reductions in PTSD and 1) increased amygdala-hippocampal connectivity, and 2) reduced amygdala-precuneus connectivity during memory recall.

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Linked Clinical Trial

Study Comparing Three Doses of MDMA Along With Psychotherapy in Veterans With Posttraumatic Stress Disorder
This study is designed to provide information on whether psychotherapy ("talk therapy") combined with the drug MDMA is safe and helpful for subjects with posttraumatic stress disorder (PTSD).

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