About this trial
The study investigators are conducting the first randomized placebo-controlled trial of MDMA-assisted therapy with a comorbid sample of military Veterans with a co-occurring diagnosis of Alcohol Use Disorder (AUD) and Post-Traumatic Stress Disorder (PTSD). 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. The primary objective of the proposed project is to evaluate safety and clinical outcomes of MDMA-assisted therapy compared to identical psychotherapy with low dose ("active placebo") MDMA for the treatment of PTSD-AUD in military Veterans. The Primary Outcome measures, the Clinician Administered PTSD Scale (CAPS-5) and Inventory of Psychosocial Functioning (IPF), will evaluate changes in PTSD symptoms and psychosocial outcomes over time. Changes in drinking outcomes will also be evaluated (via the Timeline Followback, TLFB).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Are at least 18 years old at the time of signing the informed consent.
Are currently enrolled in VA care.
Veterans must have initiated and discontinued (or completed) at least one first-line evidence-based treatment (EBT) for PTSD alone, for PTSD and AUD together, or for a dual-diagnosis condition, as documented in CPRS.
Are fluent in speaking and reading English.
Disqualifiers
Have symptomatic liver disease or have significant liver enzyme elevations.
Alanine transaminase (ALT) or aspartate transaminase (AST) > 3 x upper limit of normal (ULN).
Total bilirubin > 1.5 x ULN or direct bilirubin < 35%.
Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
Trial design
Parallel
Treatments tested in this trial
Full Dose MDMA
DrugDuring the three Experimental Sessions, participants will receive a split dose of 180 mg midomafetamine hydrochloride salt (MDMA HCl) administered orally (2 × 60 mg midomafetamine HCl capsules, followed approximately 1.5 to 2 hours later by 1 × 60 mg midomafetamine HCl capsule).
MDMA-Assisted psychotherapy
Behavioralinner-directive psychotherapy will be conducted throughout the study; Integrative MDMA-Assisted Psychotherapy (IMAP) for PTSD Therapy Manual.
Active Placebo Dose MDMA
DrugDuring the three Experimental Sessions, participants will receive a split dose of 40 mg midomafetamine HCl administered orally (1 × 40 mg midomafetamine HCl capsules and 1 x placebo capsule \[0 mg midomafetamine HCl\], followed 1.5 to 2 hours later by 1 × placebo capsule \[0 mg midomafetamine HCl\]).
Treatment groups
Trial outcomes
Primary outcomes
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score
To evaluate the efficacy of MDMA-assisted therapy (MDMA-AT) in reducing PTSD symptom severity in participants with co-occurring PTSD and Alcohol Use Disorder (AUD), as measured by the change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score (past 30 days) from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline). The CAPS-5 total severity score ranges from 0 to 80 with higher scores reflecting worse PTSD symptom severity.
Secondary outcomes
Timeline Follow-Back (TLFB): Drinks per drinking day (past 90 days)
To evaluate the efficacy of MDMA-assisted therapy in reducing alcohol use in participants with co-occurring PTSD and Alcohol Use Disorder (AUD), as measured by the change in drinks per drinking day on the Timeline Follow-Back (TLFB; past 90 days) from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline).
Timeline Follow-Back (TLFB): Number of heavy drinking days (past 90 days)
To evaluate the efficacy of MDMA-assisted therapy in reducing alcohol use in participants with co-occurring PTSD and Alcohol Use Disorder (AUD), as measured by the change in the number of heavy drinking days on the Timeline Follow-Back (TLFB; past 90 days) from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline).
Timeline Follow-Back (TLFB): Percent days abstinent (past 90 days)
To evaluate the efficacy of MDMA-assisted therapy in reducing alcohol use in participants with co-occurring PTSD and Alcohol Use Disorder (AUD), as measured by the change in percent days abstinent on the Timeline Follow-Back (TLFB; past 90 days) from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline).
Inventory of Psychosocial Functioning (IPF) total average score
To assess the impact of MDMA-assisted therapy on psychosocial functioning in participants with co-occurring PTSD and Alcohol Use Disorder (AUD), as measured by the change in Inventory of Psychosocial Functioning (IPF) total score (past 30 days) from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline). Items on the IPF are rated on a 1-7 scale with scales averaged across items; total score range is 1-7. Higher scores reflect worse psychosocial functioning (i.e., greater impairment).
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