MDMA-assisted PTSD and Alcohol Therapy Trial (MPATHY): study protocol for a double-blind, randomised, controlled outpatient trial of MDMA-assisted integrated exposure-based therapy for comorbid post-traumatic stress disorder and alcohol use disorder
Kirsten Morley, Shalini Arunogiri, Katherine L. Mills, Joshua Watt, M Teesson, A Baillie, Y Y Lee, Alyssa R Morse, S E Back, Dan I Lubman, Paul Haber
BMJ Open July 1, 2026 DOI: 10.1136/bmjopen-2025-114896 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 100 |
| Population | Adults with comorbid post-traumatic stress disorder and alcohol use disorder |
| Interventions | MDMA Niacin |
| Dose | 80-160 mg MDMA; 250 mg niacin |
| Topics | Addiction Depression MDMA PTSD |
| Keywords | Dosing Randomized controlled trial Clinical trial Comorbidity Checklist Regimen Cognitive behavioral therapy Protocol science Pharmacotherapy Gold standard test Adverse effect Medline Substance abuse |
| Registration | NCT05709353 |
| Key findings | The trial will test whether MDMA-assisted integrated exposure therapy improves PTSD and alcohol use outcomes compared to active control-assisted integrated exposure therapy in comorbid PTSD and AUD. |
Abstract
Introduction: The treatment of comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) is significantly more challenging than the treatment of either disorder alone. While gold standard evidence-based treatments exist for this comorbidity, clinically significant improvements are only observed in approximately half of clinical trial participants. The use of adjunctive pharmacotherapies, such as 3,4-methylenedioxymethamphetamine (MDMA), may serve to optimise gold standard interventions. The primary aim of the MDMA-assisted PTSD and Alcohol Therapy Trial study is to examine the therapeutic and cost-effectiveness of combining MDMA with evidence-based integrated care for comorbid PTSD+AUD. Specifically, we will examine MDMA-assisted integrated exposure therapy versus active control-assisted integrated exposure therapy in improving treatment outcomes for PTSD+AUD.
Methods: AND ANALYSIS: This world-first double-blind trial will aim to randomise 100 participants with PTSD+AUD to a regimen of Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) (12 sessions)+MDMA (80-160 mg: 2 dosing and 2 integration sessions) or COPE (12 sessions)+active control (niacin 250 mg: 2 dosing sessions and 2 integration sessions). All participants will receive medical management. The primary PTSD outcome will be the clinician-administered PTSD Scale for DSM-5. The primary drinking outcome will be the number of heavy drinking days (HDDs) per week, validated by phosphatidylethanol. Secondary PTSD and alcohol-related outcomes will include PTSD checklist for DSM-5 scores, absence of any HDDs and standard drinks per drinking day. We will also examine change in other clinical conditions and symptoms including depression, sleep disturbances and post-traumatic cognitions; treatment satisfaction and engagement; adverse events; and cost-effectiveness. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and the International Conference on Harmonisation-Good Clinical Practice guidelines. Ethical approval has been granted by the Sydney Local Health District Ethics Review Committee (X22-0121 & 2022/ETH00773). The results of this study will provide world-first data regarding safety, efficacy and cost-effectiveness of MDMA to optimise integrated exposure-based therapy for comorbid AUD and PTSD and will be disseminated to ensure wide accessibility and to support further research and clinical application.
Trial Registration: NUMBER: NCT05709353.