MDMA-Assisted Therapy for Veterans With PTSD and Alcohol Use Disorder

Recruiting now · Phase 2/Phase 3 · Has a placebo group

Conditions studied: Post Traumatic Stress Disorder, Alcohol Use Disorder

In brief

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).

Key facts

Study ID

NCT07118839

Run by

VA Office of Research and Development

People needed

80

Starts

2026-05-18

Expected to finish

2030-05-30

Last updated by the study team

2026-06-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants are eligible to be included in the study if all the following criteria apply:
• Age
• Are at least 18 years old at the time of signing the informed consent.
• Type of Participant and Disease Characteristics
• 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.
• At Screening, Veterans must meet past 3-month criteria for Alcohol Use Disorder as measured by the SCID-5.
• Must have a desire to abstain or reduce alcohol use, per Veteran report.
• Able to safely abstain from alcohol for at least 48 hours without requiring medical detox.
• At Screening (V0) have a confirmed diagnosis of PTSD with symptom duration of at least 6 months and a total severity score of >28 per the CAPS-5.
• a.At Baseline (V3) must continue to have a confirmed diagnosis of PTSD per CAPS-5.
• Are able to swallow pills.
• Agree to have study visits recorded, including Experimental Sessions, assessments, and non-drug therapy sessions.
• Able to provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming unwell or unreachable.
• Able to identify an appropriate support person to stay with the participant on the evenings of the Experimental Sessions.
• Weight
• Body Mass Index (BMI) in the range of 18-35.
• Sex and Contraceptive/ Barrier Requirements
• For participants assigned female sex at birth:
• A participant is eligible to participate if not pregnant, not planning to become pregnant, or is not breastfeeding and one of the following conditions applies: oIs not able to become pregnant OR oIs a person able to be pregnant (PABP) and using a contraceptive method that is highly effective, with a failure rate of <1%. The investigator will evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first does of study intervention.
• A PABP must have a highly sensitive negative urine pregnancy test at study entry and prior to each Experimental Session, see Schedule of Activities.
• Informed Consent
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Other Inclusions

You may not qualify if…

• Participants are excluded from the study if any of the following criteria apply:
• Medical Conditions
• 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.
• a)Note: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B (e.g., the presence of hepatitis B surface antigen or positive hepatitis C antibody test result without evidence of active infection at screening or within 3 months prior to starting study intervention) is acceptable if the participant otherwise meets entry criteria.
• Moderate or severe chronic kidney disease, defined as Estimated Glomerular Filtration Rate (eGFR)<60 mL/min at screening or end stage renal disease on dialysis.
• Have a history of seizures or delirium tremens.
• Significant alcohol withdrawal symptoms, defined as a Clinical Institute Withdrawal Assessment of alcohol scale, revised (CIWA-Ar) >10.
• Have a recent history of clinically significant hyponatremia or hyperthermia.
• Have a marked Screening QTcF interval >450 ms demonstrated on repeated ECG assessments. Participants whose QTcF exceeds this value during screening may be initially enrolled if a pre-study concomitant medication is suspected to be prolonging the QT-interval.
• a)Note: The QTcF is the QT interval corrected for heart rate according to Fridericia's formula. It is either machine-read or manually over-read.
• Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, heart failure, severe coronary artery disease, or aneurysm.
• Participants with other mild, stable chronic medical problems may be enrolled if the study physician and principal investigators agree the condition would not significantly increase the risk of MDMA administration or be likely to produce significant symptoms during the study that could interfere with study participation or be confused with side effects of the study drug.
• Examples of stable medical conditions that could be allowed include, but are not limited to, Diabetes Mellitus (Type 2), Human Immunodeficiency Virus (HIV) infection, Gastroesophageal Reflux Disease (GERD), hypothyroidism (if taking adequate and stable thyroid replacement medication), glaucoma (if approval for study participation is received from an ophthalmologist).
• Acute Retention History (e.g., have needed a catheter in the last 6-12 months) or "Stage 4" BPH (kidney damage or chronic high residual urine)
• a.Note: BPH Stage 1-2 (Mild/Moderate) and BPH on Alpha Blockers could be included if study physician and principal investigator agree the condition would not significantly increase the risk of worsening the BPH symptoms.
• Have a diagnosis of uncontrolled hypertension, defined as repeated blood pressure readings of 140 millimeters of Mercury [mmHg] systolic or 90 mmHg diastolic. The diagnosis may be confirmed by repeated clinic measurements or home blood pressure monitoring if clinically indicated.
• Have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease.
• Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.
• Have a history of arrhythmia, other than premature atrial contractions (PACs) or occasional PVCs in the absence of ischemic heart disease, within 12 months of screening.
• a)Participants with a history of atrial fibrillation, atrial tachycardia, atrial flutter or paroxysmal supraventricular tachycardia or any other arrhythmia associated with a bypass tract may be enrolled only if they have been successfully treated with ablation and have not had recurrent arrhythmia for at least one year off all antiarrhythmic drugs or are under adequate and stable pharmacologic treatment for atrial fibrillation for at least a year, as confirmed by a cardiologist.
• Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Psychiatric Conditions

Where it is running

• VA Connecticut Healthcare System West Haven Campus, West Haven, CT — West Haven, Connecticut, United States (enrolling)
• Providence VA Medical Center, Providence, RI — Providence, Rhode Island, United States (enrolling)

Full record on ClinicalTrials.gov

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