MDMA-assisted therapy for PTSD and alcohol use disorder

A Randomised, Controlled Trial of MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder

This study is testing if therapy combined with MDMA can help people with PTSD and alcohol use problems feel better and drink less.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Sydney (Academic / other)
• Locations: 2 sites (Sydney, New South Wales and 1 other locations)
• Trial ID: NCT05709353 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of MDMA-assisted prolonged exposure therapy in treating individuals with both post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD). The study employs a double-blind, randomized, placebo-controlled design, comparing the effects of MDMA to a control substance (niacin) over 14 weeks. Participants will undergo 12 sessions of COPE therapy and 2 dosing sessions with either MDMA or niacin. The goal is to assess improvements in PTSD symptoms and heavy drinking behaviors.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of both PTSD and alcohol use disorder for at least six months.

Not a fit: Patients with current or lifetime psychotic disorders, bipolar disorder, or major depression with psychotic features may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly enhance treatment outcomes for patients suffering from both PTSD and alcohol use disorder.

How similar studies have performed: Emerging evidence suggests that MDMA-assisted therapy has shown promise for PTSD, indicating potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Both AUD and current PTSD according to the DSM-5 criteria, for 6 months or longer with at least moderate severity, according to investigator judgement and CAPS-5
2. Aged ≥18 years old
3. Adequate cognition and English language skills to give valid consent and complete research interviews assessments
4. Willing to give written informed consent
5. Received prior treatment for PTSD or AUD (not including study interventions)
6. Stable housing
7. Able to identify a significant other (such as a family/friend/partner) who could accompany them from clinic/provide transport and/or be contacted by the study team if required

Exclusion Criteria:

1. History of, or currently meeting, DSM-5 criteria for:

   * current or lifetime psychotic or bipolar disorders, or
   * major depression with psychotic features Assessed via Structured Clinical Interview for DSM-5 - Research Version (SCID-5-RV). Potential participants will be screened for personality disorders but suitability will then be confirmed by clinical interview given the prevalence of high scores in this comorbid population
2. Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing)
3. Significant alcohol withdrawal (current Clinical Institute Withdrawal Assessment for Alcohol \[CIWA-Ar\] score ≥10, including history of delirium tremens or alcohol withdrawal seizures).
4. Concurrent use of psychotropic medication (antidepressants and alcohol pharmacotherapy use considered if assessed by physician and titrated down with 5 half-lives + 1 week washout)
5. Use of, and unable or unwilling to cease, any medications likely to interact with MDMA in the opinion of the physicians and investigators during the trial (low dose opiates are permitted for pain management but not the night before or after MDMA sessions)
6. Substance use disorder other than tobacco (e.g. benzodiazepines, cannabis)
7. Abnormal clinical findings including a history of, or current: cardiac disease and/or dysrhythmia, uncontrolled hypertension or severe hypotension, abnormal electrocardiogram findings, stroke, liver disease, a history of epilepsy, hyponatraemia, or malignant hyperthermia (controlled hypertension and diabetes type II may be permitted)
8. Suicide risk according to clinician judgement and responses to Columbia Suicide Severity Rating Scale-Lifetime (C-SSRS-L) and SCID-5-RV.

   • Details surrounding any previous attempts \>6 months ago will be gathered whereby attempts related to their trauma/PTSD and/or associated with the use of psychostimulants will contribute to risk assessment and guide trial safety measures if enrolled
9. Clinically unstable systemic medical (e.g., cancer) or psychiatric disorder or condition that might require hospitalisation that precludes trial participation
10. Regular use of ecstasy (e.g. at least twice in last 6 months, or \>10 times within the last 5 years)
11. Enrolled in any other interventional clinical trials in the previous two months or over the duration of the study

Where this trial is running

Sydney, New South Wales and 1 other locations

• Drug Health Services, Royal Prince Alfred Hospital — Sydney, New South Wales, Australia (Recruiting)
• Turning Point — Richmond, Victoria, Australia (Not_yet_recruiting)

Study contacts

• Principal investigator: Kirsten C Morley, PhD — University of Sydney
• Study coordinator: Kirsten C Morley, PhD

Conditions PTSD; Alcohol Use Disorder; Alcohol Dependence; Post-traumatic Stress Disorder; Comorbidities and Coexisting Conditions; MDMA-assisted therapy; Randomised-Controlled Trial; Comorbid PTSD and AUD