Clinical TrialPTSDMDMAPlaceboRecruiting

MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder (MPATHY)

This Phase II interventional trial (n=120) explores the effectiveness of MDMA-assisted (80–160 mg per session, with possible supplemental doses) prolonged exposure therapy (COPE) versus niacin control in individuals with comorbid PTSD and alcohol use disorder.

Target Enrollment
120 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

Double-blind, randomised, placebo-controlled Phase II trial (n=120) comparing MDMA-assisted COPE (two oral MDMA dosing sessions, 80–160 mg per session with possible supplemental doses) to COPE with niacin control across 14 weeks including 12 COPE sessions.

Primary outcomes are change in PTSD symptom severity (CAPS-5) and heavy drinking; secondary outcomes include safety, tolerability, and functional measures. Investigators hypothesise greater reductions in PTSD symptoms and heavy drinking in MDMA-treated participants.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

cbt

Study Arms & Interventions

COPE + MDMA

experimental

COPE (prolonged exposure) plus MDMA-assisted dosing (two sessions)

Interventions

  • Compound

    Prolonged Exposure therapy (COPE): 12 individual 90-minute sessions (12 x 90 min). Delivered by clinical psychologist; integrated CBT for PTSD and AUD.

  • MDMA80 - 160 mg
    via Oral• two sessions• 2 doses total

    Per-session dosing delivered as initial 2x80mg capsules with optional supplemental 40mg (session 1) or 40–80mg (session 2); clinician-participant consensus; supplemental dose 60–90 minutes after initial dose.

COPE + Niacin (Control)

active comparator

COPE plus niacin active-control (niacin 250 mg or niacin-matched placebo)

Interventions

  • Compound

    Prolonged Exposure therapy (COPE): 12 individual 90-minute sessions.

  • Placebo250 mg
    via Oral• two sessions• 2 doses total

    Niacin 250 mg or niacin-matched placebo given to match dosing sessions.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion 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

  • 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

Study Details

  • Status
    Recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomizeddouble Blind
  • Target Enrollment120 participants
  • Timeline
    Start: 2023-09-19
    End: 2026-05-01
  • Compounds
    MDMAPlacebo
  • Topic
    PTSD

Locations

Drug Health Services, Royal Prince Alfred Hospital — Sydney, New South Wales, Australia
Turning Point — Richmond, Victoria, Australia

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