MDMA-Assisted Therapy for Veterans with Comorbid Posttraumatic Stress Disorder and Alcohol Use Disorder: Clinical Outcomes from the First Open-Label Pilot Trial.
Erica Eaton, Christy Capone, Brian J Gully, Lewis Nunez Severino, Mollie A Monnig, Michael S Worden, Robert M Swift, Carolina L Haass-Koffler
Alcohol October 30, 2026 DOI: 10.1016/j.alcohol.2026.107464 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label trial Randomized Pilot study Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | U.S. Veterans with co-occurring posttraumatic stress disorder and alcohol use disorder |
| Intervention | MDMA-assisted therapy |
| Duration | 11 therapy sessions (three preparatory, two MDMA-assisted therapy sessions, six integration), followed by a 4-week follow-up |
| Measures | Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), Timeline Follow-Back (TLFB) |
| Topics | Addiction MDMA PTSD |
| Keywords | Comorbidity MDMA-Assisted Therapy Posttraumatic stress disorder Veterans |
| Key findings | MDMA-assisted therapy was associated with significant reductions in PTSD symptom severity (CAPS-5, p = 0.006, d = 1.241) and descriptive but non-clinically-significant reductions in alcohol consumption (31% fewer drinks per drinking day, 54% fewer heavy drinking days). No serious adverse events were reported, and 90% of participants completed treatment. |
Abstract
Co-occurring posttraumatic stress disorder and alcohol use disorder (PTSD-AUD) are highly prevalent among U.S. Veterans and associated with greater symptom severity, functional impairment, and poorer outcomes than either disorder alone. Existing treatments demonstrate modest effectiveness, with persistent challenges in engagement, retention, and sustained improvement. To evaluate the feasibility, safety, tolerability, and preliminary clinical outcomes of investigational 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for Veterans with comorbid PTSD-AUD. We conducted the first open-label trial of MDMA-assisted therapy in Veterans (N = 10) with PTSD-AUD. The intervention included 11 therapy sessions (three preparatory, two MDMA assisted therapy sessions, and six integration), followed by a 4-week follow-up. Primary outcomes were PTSD symptom severity and alcohol consumption, measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and Timeline Follow-Back (TLFB). Secondary outcomes assessed safety and tolerability. Exploratory outcomes included alcohol craving and substance misuse. Recruitment and retention were strong with 90% of enrolled participants completing treatment. MDMA-assisted therapy was associated with significant reductions in PTSD symptoms (p = 0.006, d = 1.241). Descriptive reductions were observed in alcohol consumption, including a 31% reduction in drinks per drinking day and a 54% reduction in heavy drinking days, although these changes did not reach clinical significance. No serious adverse events were reported. Treatment-emergent adverse events were non-serious and consistent with expected acute MDMA effects under protocol monitoring. Substance-use measures did not indicate systematic increases in alcohol or other substance use; one participant reported an isolated recurrence of cocaine use. Findings support the safety, feasibility, and tolerability of MDMA-assisted therapy and provide preliminary descriptive evidence of improvement in PTSD symptoms and alcohol-related outcomes. Larger randomized controlled trials are needed to evaluate efficacy, durability, and benefit-risk profile in this population.
Comparable studies
Other non-randomized and open-label trials on MDMA for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| First study of safety and tolerability of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in patients with alcohol use disorder. Patients with alcohol use disorder (AUD) following community alcohol detoxification | 2021 | Open-label safety and tolerability proof-of-concept study | n = 14 |
| First study of safety and tolerability of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with alcohol use disorder: preliminary data on the first four participants. Patients with alcohol use disorder | 2019 | Open-label safety and tolerability proof of concept study | n = 4 |
| Design and methodology of the first open-label trial of MDMA-assisted therapy for veterans with post-traumatic stress disorder and alcohol use disorder: Considerations for a randomized controlled trial. Military veterans with PTSD and alcohol use disorder | 2024 | Open-label trial | n = 12 |
Citations in the library
Cites 18
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- 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. Journal of Psychopharmacology July 19, 2010
- A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD) Journal of Psychopharmacology October 31, 2012
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
- Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology 2013
and 13 more in the library