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

NCT07118839 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: D5603-R
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

The study investigators are conducting the first randomized placebo-controlled trial of MDMA-assisted therapy (MDMA-AT) 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-AT 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).

Conditions

Alcohol Use Disorder; Post Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• 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 0) to Visit 16 (approximately 22 weeks post-baseline). The CAPS-5 total severity score ranges from 0 to 80 with higher scores reflecting worse PTSD symptom severity.

  from Baseline (Visit 0) to Visit 16 (approximately 22 weeks post-baseline)

Secondary Outcomes (4)

• Timeline Follow-Back (TLFB): Drinks per drinking day (past 90 days)

  from Baseline (Visit 0) to Visit 16 (approximately 22 weeks post-baseline

• Timeline Follow-Back (TLFB): Number of heavy drinking days (past 90 days)

  from Baseline (Visit 0) to Visit 16 (approximately 22 weeks post-baseline

• Timeline Follow-Back (TLFB): Percent days abstinent (past 90 days)

  from Baseline (Visit 0) to Visit 16 (approximately 22 weeks post-baseline

• Inventory of Psychosocial Functioning (IPF) total average score

  from Baseline (Visit 0) to Visit 16 (approximately 22 weeks post-baseline

Study Arms (2)

Full dose MDMA-Assisted Therapy

EXPERIMENTAL

Initial dose of 80 mg MDMA HCl administered orally at the start of each of three dosing sessions, possibly followed by a supplemental dose of 40 mg MDMA HCl 1.5 to 2 hours later. At dosing sessions 2 and 3, participants will be offered the option of taking a higher dose, 120 mg MDMA HCl, possibly followed by a supplemental dose of 60 mg MDMA HCl 1.5 to 2 hours later.

Drug: Full Dose MDMA; Behavioral: MDMA-AT

Active Placebo dose MDMA-Assisted Therapy

ACTIVE COMPARATOR

During the three Experimental Sessions, participants will receive the active placebo dose (one capsule) consisting of 40 mg MDMA HCl plus a second capsule containing an inactive placebo (indistinguishable weight placebo comprised entirely of mannitol and magnesium stearate), followed 1.5-2 hours later by the inactive placebo. The number of capsules comprising the initial dose (two) is consistent across both conditions.

Behavioral: MDMA-AT; Drug: Active Placebo Dose MDMA

Interventions

Full Dose MDMA DRUG

3 MDMA dosing (Experimental) sessions: Session 1 - 80mg to 120mg MDMA HCl; Session 2 - 80mg to 180mg MDMA HCl; Session 3 - 80mg to 180mg MDMA HCl

Full dose MDMA-Assisted Therapy

MDMA-AT BEHAVIORAL

inner-directive psychotherapy will be conducted throughout the study; Lykos Therapeutics MDMA-AT Manual

Active Placebo dose MDMA-Assisted Therapy; Full dose MDMA-Assisted Therapy

Active Placebo Dose MDMA DRUG

3 MDMA dosing (Experimental) sessions in which participants will receive 40mg MDMA HCl max at each session.

Active Placebo dose MDMA-Assisted Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 Baseline, meet past-year criteria for Alcohol Use Disorder as measured by the SCID-5.
• Able to safely abstain from alcohol for at least 48 hours without requiring medical detox.
• At Baseline meet DSM-5 criteria for current PTSD with a symptom duration of at least 6 months per the 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

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.
• 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 Baseline 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.
• a)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).

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, 06516-2770, United States

Location

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908-4734, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Alcoholism

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Erica M. Eaton, PhD

  Providence VA Medical Center, Providence, RI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erica M Eaton, PhD

CONTACT

(401) 273-7100; Erica.Eaton@va.gov

Christy Capone, PhD

CONTACT

(401) 273-7100; christy.capone@va.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This is a randomized study. Participants will be 1:1 randomized to receive either MDMA-AT or identical psychotherapy with active placebo.

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: August 12, 2025
• Study Start: April 15, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 30, 2030
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)