The MPATHY study: MDMA therapy for the challenging combination of PTSD and alcohol dependence

An Australian research team, comprising researchers from the University of Sydney, Monash University and Eastern Health, amongst others, has in BMJ Open the study protocol published for the MPATHY study (MDMA-assisted PTSD and Alcohol Therapy Trial).
This double-blind, randomised, controlled trial is investigating whether MDMA can enhance the effectiveness of existing, proven therapies for people who have both PTSD and alcohol dependence, a combination that is notoriously difficult to treat.
As with the psiAN and New Mexico protocols discussed earlier, this too does not yet involve the publication of results, but rather a pre-defined research design.

Why this combination is so difficult

The treatment of co-occurring PTSD and alcohol use disorder (AUD) is considerably more challenging than the treatment of either condition on its own.
Even with current gold-standard treatments, the success rate is only around half A clinically significant improvement was observed in the participants in clinical trials.
The researchers suggest that adjunctive pharmacotherapy, such as MDMA, may enhance these existing treatments.

Study design

This is described as a world first: the first double-blind trial specifically testing MDMA as an adjunct to integrated exposure therapy for this comorbidity.
In total, there are 100 participants with PTSD and AUD, randomised into two groups.
Both groups will receive COPE (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure), an existing, evidence-based therapy protocol comprising 12 sessions.
One group is given MDMA (80–160 mg, divided into 2 dosing sessions plus 2 integration sessions), whilst the other group receives a active monitoring 250 mg of niacin, also divided into 2 dosing sessions and 2 integration sessions.
All participants also receive regular medical support throughout the programme.

What exactly is being measured?

The primary PTSD outcome measure is the clinically administered CAPS-5 (Clinician-Administered PTSD Scale for DSM-5).
The primary drinking outcome is the number of heavy drinking days per week, as objectively measured using the biomarker phosphatidylethanol in the blood, rather than relying solely on self-reporting.
Secondary outcome measures include, amongst others, the PCL-5 self-report questionnaire, the proportion of participants without heavy drinking days, the average number of standard glasses per drinking day, and changes in depression, sleep problems and post-traumatic thought patterns.
In addition, the study looks at patient satisfaction, engagement, side effects and, notably, cost-effectiveness, something that is by no means taken into account in every psychedelic trial.

Ethics and registration

The study is being conducted in accordance with the Declaration of Helsinki and international Good Clinical Practice guidelines, and has received ethical approval from the Sydney Local Health District Ethics Review Committee.
The trial has been registered under number NCT05709353, and the researchers emphasise that the results will provide the world’s first data on the safety, efficacy and cost-effectiveness of MDMA for this specific comorbidity.

Addition

This study is clinically relevant because PTSD and alcohol dependence very often co-occur in clinical practice – for example, among veterans, victims of domestic or sexual violence, and people with a history of early-life trauma; and because clinicians usually treat these two problems one after the other or in isolation from one another, even though they can actually reinforce each other.
The use of the phosphatidylethanol biomarker As an objective measure of alcohol consumption, this is a methodological strength, as self-reports of drinking behaviour can be notoriously unreliable, particularly among people who are still in the midst of an addiction or recovery process.
The emphasis on cost-effectiveness It is striking that many MDMA and psilocybin trials focus almost exclusively on clinical outcomes, whilst the actual scaling up of these treatments within healthcare systems ultimately depends on whether they can be organised in a cost-effective manner.
Should this study yield positive results, it would be a significant indication that MDMA-assisted therapy is effective not only for "pure" PTSD, but also for the more complex, common cases involving comorbid conditions, where most existing treatments currently fall short.

Source: Morley KC, Arunogiri S, Mills K, et al. "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." BMJ Open. 6 July 2026;16(7):e114896. doi: 10.1136/bmjopen-2025-114896. Clinical trial: NCT05709353.