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
Abstract
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 be…
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Mithoefer et al. (2018) showed significant reductions in PTSD symptoms with MDMA-assisted psychotherapy in chronic PTSD.
“Significant reductions in PTSD symptoms”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as Mithoefer et al. (2018)
Trials with ketamine and the trial with MDMA by Mithoefer et al. (2018) had the most important adverse reactions related to physiological distress, but these reactions were temporary and less meaningful than the overall benefits of the therapies.
“Trials with ketamine and the trial with MDMA by Mithoefer et al. (2018) had the most important adverse reactions related to physiological distress, but these reactions were temporary and less meaningful than the overall benefits of the therapies in which they were used.”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as Mithoefer et al. (2018)
In Mithoefer et al. (2018), 85 adverse events were reported by 20 participants, with four serious, three deemed unrelated and one possibly related to drug treatment.
“85 adverse events were reported by 20 participants, with four of them being serious, although three of them were deemed unrelated, and one possibly related to drug treatment.”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as Mithoefer et al. (2018)
In veterans and first responders with chronic PTSD, MDMA-assisted psychotherapy at 75 and 125 mg produced significantly greater decreases in PTSD symptom severity than the 30 mg group.
“the groups that received 75 and 125 mg of MDMA with adjunctive psychotherapy in a controlled setting had significantly greater decreases in PTSD symptom severity in contrast of the 30 mg group.”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as Mithoefer et al. (2018)
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“Trials with ketamine and the trial with MDMA by Mithoefer et al. (2018) had the most important adverse reactions related to physiological distress, but these reactions were temporary and less meaningful than the overall benefits of the therapies in which they were used.”
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- Authors
- Mithoefer, M. C., Mithoefer, A. T., Feduccia, A. A., Jerome, L., Wagner, M., Wymer, J., Holland, J., Hamilton, S., Yazar-Klosinski, B., Emerson, A., & Doblin, R.
- Affiliations
- Medical University of South Carolina (US)
- Multidisciplinary Association for Psychedelic Studies (US)
- Stanford Medicine (US)
- Corresponding author
- Feduccia, Allison A
- Venue
- The Lancet Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 5
- Issue
- 6
- Pages
- 486-497
- ISSN
- 2215-0366 (ISSN-L)
- OpenAlex
- W2799742551
- Cited by
- 439
- References
- 10
- Citations by year
- 2026: 27 · 2025: 40 · 2024: 73 · 2023: 51 · 2022: 55 · 2021: 70 · 2020: 62 · 2019: 38 · 2018: 20 · 2017: 1
- FWCI
- 55.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- MDMA-assisted psychotherapy, MDMA, post-traumatic stress disorder, chronic PTSD, military veterans, firefighters, police officers, first responders, dose-response relationship, psychotherapy, treatment-resistant PTSD, adverse events, suicidal ideation, open-label extension, long-term follow-up, PTSD symptom severity
- MeSH terms
- Adult, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Psychiatric Status Rating Scales, Psychotherapy, Stress Disorders, Post-Traumatic, Veterans, Police, Treatment Outcome, N-Methyl-3,4-methylenedioxyamphetamine, Young Adult, Firefighters
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