MDMA-Assisted Therapy for Veterans with PTSD and Alcohol Use Disorder: A Randomized Controlled Trial

Across veterans of all eras, the co-occurrence of posttraumatic stress disorder and alcohol use disorder and (PTSD-AUD) contributes to greater decreases in health functioning and difficulties readjusting to civilian life. The Veterans Administration (VA) health care system estimates that 63% of veterans with substance use disorder (SUD) also receive a PTSD diagnosis, making comorbidity the rule rather than the exception. Veterans with PTSD-AUD experience more severe symptomatology, increased risk of suicidality, and poorer response to treatments than veterans with either disorder alone. Treatments targeting PTSD-AUD among veterans are needed. There is modest evidence to support the use of medications to treat AUD among those with comorbid PTSD and results are contradictory. Current evidence-based behavioral approaches, including trauma-focused psychotherapies such as prolonged exposure (PE) and cognitive processing therapy (CPT) are considered gold standard treatments for PTSD. However, upon completion many patients continue to report clinically significant PTSD symptoms. This is further complicated by low engagement and retention, particularly among those with comorbid substance use. These findings underscore the need to address this comorbidity more effectively and efficiently in Veterans. The combined neurobiological effects of 3,4-methylenedioxymethamphetamine assisted therapy (MDMA-AT) increase compassion, reduce defenses, and fear of emotional injury, and enhance communication and introspection, making MDMA-AT especially useful for treating PTSD-AUD. This application proposes the first placebo-controlled randomized clinical trial of MDMA-AT with a comorbid sample of military veterans (N = 80). This novel experimental treatment package consists of three once-monthly Experimental Sessions of therapy combined with a divided-dose of MDMA HCl, along with non-drug preparatory and integrative therapy. Follow-up data will be collected at post-treatment, 3-, and 6-month follow-up. We will focus on both symptom reductions and functional outcomes. We hypothesize that Veterans who receive MDMA-AT will endorse a) greater reductions in PTSD symptoms, b) greater improvements in psychosocial functioning, c) greater reductions in alcohol consumption, and d) greater decreases in depressive symptoms than those in the active placebo condition. This study will begin to address a gap in the field’s knowledge about MDMA-AT and its role in the treatment of PTSD- AUD in Veterans. Project Number: 1I01RX005603-01 | Fiscal Year: 2026 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Erica Eaton | Institution: PROVIDENCE VA MEDICAL CENTER, PROVIDENCE, RI | Activity Code: I01 | Study Section: Behavioral Health & Social Reintegration[RRD4] View on NIH RePORTER: https://reporter.nih.gov/project-details/11106125