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Post Traumatic Stress DisorderPhase 2/3MAP VETSNCT07118839

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

A Phase 2/3 study testing Full Dose MDMA and MDMA-Assisted psychotherapy in people with Post Traumatic Stress Disorder and Alcohol Use Disorder, run by VA Office of Research and Development at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Full Dose MDMA and MDMA-Assisted psychotherapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
2 sitesUnited States
Study dates
18 May 2026to 30 May 2030
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Agree to inform the investigators within 48 hours of any medical conditions and procedures.
  • May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.
  • May have a history of or current Diabetes Mellitus (Type 2) if additional screening measures of Hemoglobin A1c levels are less than 7, identifying that the Type 2 diabetes is well controlled, if the condition is judged to be stable on effective management, and with approval by the study clinician.
  • May have hypothyroidism if taking adequate and stable thyroid replacement medication.
  • May have a history of, or current, glaucoma if approval for study participation is received from an ophthalmologist.

Who cannot join

  • 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.
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  • 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
  • Have engaged in a new form of psychiatric or mental health care within 12 weeks of enrollment, including Electroconvulsive Therapy (ECT) and ketamine-assisted therapy.
  • Are currently prescribed antidepressant medication (antidepressant pharmacotherapy use considered if assessed by physician and titrated down to 5 half-lives + 1 week washout).
  • Are currently prescribed antipsychotic medications. Note: off-label use of low dose quetiapine (<100 mg) for insomnia is not exclusionary. Quetiapine should be replaced by other treatment to control insomnia such as non-benzodiazepine sedative hypnotics (e.g., Zopiclone, Eszopiclone, Zolpidem).
  • Are likely, in the investigator's opinion and via observation during the Preparatory Period, to be re-exposed to their index trauma or other significant trauma directly during the study.
  • Have a current moderate (not in early remission in the 3 months prior to enrollment and meets at least 5 of 11 diagnostic criteria per DSM-5) or severe cannabis use disorder within the 12 months prior to enrollment (meets at least 6 of 11 diagnostic criteria per DSM-5).
  • a)May have current mild cannabis use disorder (meets 3 of 11 diagnostic criteria per DSM-5) or moderate cannabis use disorder in early remission for the 3 months prior to enrollment (meets 4 or 5 of 11 diagnostic criteria per DSM-5).
  • Have an active substance use disorder (other than cannabis) at any severity within 12 months prior to enrollment.
  • Have used MDMA or Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 12 months of the first Experimental Session
  • Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior, in the judgment of the investigator, will not be enrolled. Any participant presenting with the following on the Screening C-SSRS will be excluded:
  • Suicidal ideation score of 4 or greater within the last 6 months of the assessment at a frequency of once a week or more
  • Suicidal ideation score of 5 within the last 6 months of the assessment
  • Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment. Participants with non-suicidal self-injurious behavior may be included if approved by the study physician.
  • Would present a serious risk to others as established through clinical interview and contact with treating providers.
  • Prior/Concomitant Therapy
  • Require ongoing concomitant therapy with a psychiatric medication with exceptions described in protocol section on Concomitant Medications (refer to Appendix 3: Permitted and Prohibited Medications).
  • Current use of pharmacotherapies (i.e., naltrexone, acamprosate, or disulfiram) to treat alcohol use.
  • Require use of concomitant medications that could prolong the QT interval during Experimental Sessions.
  • Are currently engaged in trauma-focused psychotherapy or are currently in a treatment program for SUD (self-help programs are not an exclusion).
  • Prior/Concurrent Clinical Study Experience
  • Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research, unless approved by the study team.
  • Diagnostic Assessments
  • Have a history of or a current Schizophrenia Spectrum and other Psychotic Disorder according to the DSM-5, or a bipolar disorder type I or II, or DSM-5 category of Dissociative Identity Disorder, assessed via the DDIS and clinical interview.
  • Have a current eating disorder with compensatory behaviors.
  • Have current major depressive disorder with psychotic features.
  • Have current Personality Disorders (Cluster A or Cluster B) assessed via the SCID-5-PD. Diagnoses will be confirmed by clinical interview.
  • Other Exclusions
  • Are not able to provide adequate informed consent.
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Principal Investigator or study physician, contraindicates participation in the study.
  • Lack of social support or lack of a stable living situation since the inclusion of a support person to assist the participant following Experimental Sessions is important for ensuring participant safety. If a participant is not able to identify a support person whom the research team may contact, they will not be enrolled.
  • Previous participation in a MAPS/Lykos-sponsored MDMA clinical trial.
  • Employees (and their immediate family members) of MAPS, Lykos, or MAPS Europe B.V; or individuals in a personal relationship with the sponsor investigator.
  • Have any current problem which, in the opinion of the Principal Investigator or study clinician, might interfere with study participation.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Erica M Eaton, PhD contact

(401) 273-7100

Erica.Eaton@va.gov

Christy Capone, PhD contact

(401) 273-7100 ext. 6169

christy.capone@va.gov

United States2 sites, 2 recruiting

  • Providence VA Medical Center, Providence, RI

    Providence, Rhode Island, 02908-4734

    Erica M Eaton, PhD, (401) 273-7100, Erica.Eaton@va.gov

    Erica M. Eaton, PhD

    Recruiting

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

    West Haven, Connecticut, 06516-2770

    Candice Presseau, PhD, Candice.Presseau@va.gov

    Recruiting

Other trials in United States

About this study

Official title: MDMA-Assisted Therapy for Veterans With PTSD and Alcohol Use Disorder: A Randomized Controlled 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).

Read the detailed description

The study will use a longitudinal design to conduct a randomized controlled trial of MDMA-AT for Veterans with PTSD-AUD. Eligible participants will complete an in-person baseline assessment, engage in MDMA-assisted therapy or identical psychotherapy with low dose ("active placebo") MDMA with trained therapist dyads, and complete assessments at post-treatment, 3-, and 6-month follow-ups. For complete description of the investigational plan, please the attached Clinical Protocol.

Being tested
Full Dose MDMA, MDMA-Assisted psychotherapy, Active Placebo Dose MDMA
Medical subject headings
Stress Disorders, Post-Traumatic, Alcoholism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Full Dose MDMADrug

    During 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 psychotherapyBehavioural

    inner-directive psychotherapy will be conducted throughout the study; Integrative MDMA-Assisted Psychotherapy (IMAP) for PTSD Therapy Manual.

  • Active Placebo Dose MDMADrug

    During 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]).

Study groups in NCT07118839
Study groupRoleWhat they receive
Full dose MDMA-Assisted TherapyExperimentalDuring 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).
Receives: Drug: Full Dose MDMA; Behavioral: MDMA-Assisted psychotherapy
Active Placebo dose MDMA-Assisted TherapyActive comparatorDuring 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]).
Receives: Behavioral: MDMA-Assisted psychotherapy; Drug: Active Placebo Dose MDMA

What is being measured

The primary outcome is the main question the study is designed to answer.

  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 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.

    Measured: from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline)

Secondary outcomes (4)

  1. 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).

    Measured: from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline)

  2. 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).

    Measured: from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline)

  3. 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).

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

  4. 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).

    Measured: from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2025
  2. Study start18 May 2026
  3. Primary completion1 May 2030 (estimated)
  4. Study completion30 May 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a randomized study. Participants will be 1:1 randomized to receive either MDMA-assisted therapy or identical psychotherapy with active placebo.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07118839
Sponsor's protocol ID
D5603-R
Acronym
MAP VETS
Status last verified
Jun 2026
First submitted
5 Aug 2025
Last updated
2 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Full Dose MDMA and MDMA-Assisted psychotherapy in people with Post Traumatic Stress Disorder and Alcohol Use Disorder, run by VA Office of Research and Development at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 57 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Erica M Eaton, PhD ((401) 273-7100, Erica.Eaton@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score (time frame: from Baseline (Visit 3) to Visit 16 (approximately 16 weeks post-baseline)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07118839.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.

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