The Effects of MDMA-Assisted Therapy on Alcohol and Substance Use in a Phase 3 Trial for Treatment of Severe PTSD
This trial (n=90) assessed patterns of alcohol and substance use in patients receiving MDMA-assisted therapy. MDMA was associated with a significant reduction in Alcohol Use Disorder Identification Test (AUDIT) scores when compared to placebo. Changes in Drug Use Disorder Identification Test (DUDIT) scores did not significantly differ between groups.
Authors
- Rick Doblin
- Berra Yazar-Klosinski
- Amy Emerson
Published
Abstract
Background
Post-traumatic stress disorder (PTSD) is commonly associated with alcohol and substance use disorders (ASUD). A randomized, placebo-controlled, phase 3 trial demonstrated the safety and efficacy of MDMA-assisted therapy (MDMA-AT) for the treatment of severe PTSD. This analysis explores patterns of alcohol and substance use in patients receiving MDMA-AT compared to placebo plus therapy (Placebo+Therapy).
Methods
Adult participants with severe PTSD (n = 90) were randomized to three blinded trauma-focused therapy sessions with either MDMA-AT or Placebo+Therapy. Eligible participants met DSM-5 criteria for severe PTSD and could meet criteria for mild (current) or moderate (early remission) alcohol or cannabis use disorder; other SUDs were excluded. The current analyses examined outcomes on standardized measures of hazardous alcohol (i.e., Alcohol Use Disorder Identification Test; AUDIT) and drug (i.e., Drug Use Disorder Identification Test; DUDIT) use at baseline prior to randomization and at study termination.
Results
There were no treatment group differences in AUDIT or DUDIT scores at baseline. Compared to Placebo+therapy, MDMA-AT was associated with a significantly greater reduction (improvement) in mean (SD) AUDIT change scores (Δ = -1.02 (3.52) as compared to placebo (Δ = 0.40 (2.70), F (80, 1) = 4.20, p = 0.0436; Hedge’s g=.45). Changes in DUDIT scores were not significantly different between treatment groups.
Conclusions
MDMA-AT for severe PTSD may also lead to subclinical improvements in alcohol use. MDMA-AT does not appear to increase risk of illicit drug use. These data provide preliminary evidence to support the development of MDMA-AT as an integrated treatment for co-occurring PTSD and ASUD.
Research Summary of 'The Effects of MDMA-Assisted Therapy on Alcohol and Substance Use in a Phase 3 Trial for Treatment of Severe PTSD'
Introduction
PTSD is frequently comorbid with alcohol and substance use disorders (ASUD), with prior research estimating co-occurrence between 17% and 46%. This comorbidity is commonly attributed to self-medication, since PTSD symptoms often precede substance use, though bidirectional and more nuanced interactions have also been proposed. MDMA-assisted therapy (MDMA-AT) was recently shown in a multi-site, randomized, placebo-controlled Phase 3 trial to reduce severe PTSD symptoms substantially, with 88% showing a clinically significant response and 67% in the MDMA-AT arm no longer meeting diagnostic criteria for PTSD by study end; measures of functioning and depression also improved in that trial, suggesting potential downstream effects on comorbid conditions. Nicholas and colleagues set out to examine whether MDMA-AT for severe PTSD is associated with changes in alcohol and drug use. The present analysis uses data from that Phase 3 trial to compare changes from baseline to study termination on standard screening instruments for hazardous alcohol use (AUDIT) and drug use (DUDIT) in participants randomised to MDMA-AT versus placebo plus therapy, with an emphasis on whether MDMA-AT might reduce or increase alcohol/substance use in this population. The analysis is exploratory and focused on screening-level changes rather than diagnostic outcomes.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Nicholas, C. R., Wang, J. B., Coker, A., Mitchell, J. M., Klaire, S. S., Yazar-Klosinski, B., Emerson, A., Brown, R. T., & Doblin, R. (2022). The Effects of MDMA-Assisted Therapy on Alcohol and Substance Use in a Phase 3 Trial for Treatment of Severe PTSD. Drug and Alcohol Dependence, 233, 109356. https://doi.org/10.1016/j.drugalcdep.2022.109356
References (3)
Papers cited by this study that are also in Blossom
Jerome, L., Feduccia, A. A., Wang, J. B. et al. · Psychopharmacology (2020)
Mitchell, J., Bogenschutz, M. P., Lilienstein, A. et al. · Nature Medicine (2021)
Sessa, B., Higbed, L., Durant, C. et al. · Journal of Psychopharmacology (2021)
Cited By (6)
Papers in Blossom that reference this study
Thurgur, H., Sessa, B., Higbed, L. et al. · Alcohol and Alcoholism (2025)
Sicignano, D., Hernandez, A. V., Schiff, B. et al. · Current Medical Research and Opinion (2023)
Mitchell, J., Ot’alora G, M., van der Kolk, B. et al. · Nature Medicine (2023)
Van Vugt, A. S., Zijlmans, J., Lindauer, R. et al. · Drug Science Policy and Law (2023)
Kangaslampi, S., Zijlmans, J. · European Child and Adolescent Psychiatry (2023)
Jones, J. L. · Frontiers in Psychiatry (2023)
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