Optimizing the number of MDMA-assisted therapy cycles for veterans with PTSD

A Dose Optimization Study of MDMA-Assisted Therapy for PTSD in U.S. Veterans

This program will try one to five cycles of MDMA-assisted therapy to see which number of cycles helps U.S. veterans with PTSD the most.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Bronx VA Medical Center (Federal)
• Locations: 1 site (The Bronx, New York)
• Trial ID: NCT06418178 on ClinicalTrials.gov

What this trial studies

This open-label, within-subjects Phase 2 trial enrolls U.S. military veterans with PTSD to determine the optimal number of MDMA-assisted therapy cycles. All participants receive three preparatory psychotherapy sessions, then at least one cycle consisting of one approximately eight-hour MDMA session with a two-therapist team followed by three 90-minute integration sessions, and they may continue up to five cycles. After each cycle, the participant and therapy team decide whether to continue based on symptom change, tolerability, and participant burden. Blood samples will be banked for future biomarker analyses and the design allows evaluation of both clinical response and tolerability across multiple cycles.

Who should consider this trial

Good fit: Ideal candidates are U.S. military veterans age 18 or older with a current PTSD diagnosis who can give written informed consent, swallow pills, commit to therapy dosing and multiple in-person sessions, and are not enrolled in other interventional trials.

Not a fit: Those unable to provide informed consent, with disqualifying medical or psychiatric conditions, or unwilling or unable to attend lengthy in-person sessions are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the study could identify how many MDMA-AT cycles produce the best symptom relief while minimizing burden and side effects for veterans with PTSD.

How similar studies have performed: Previous clinical trials of MDMA-assisted therapy for PTSD have reported promising symptom reductions, and this trial builds on those findings by focusing on optimizing the number of treatment cycles.

Eligibility criteria

Inclusion Criteria:

1. Are a U.S. military veteran at least 18 years old.
2. Are able to provide written, informed consent.
3. Are able to swallow pills.
4. Agree to have study visits recorded, including Experimental Sessions, psychological assessments, and non-drug therapy sessions.
5. Must provide a contact who is willing and able to be reached by the investigators in the event of a participant becoming unwell or unreachable.
6. If able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate contraceptive methods.
7. Must have a current PTSD diagnosis at screening and baseline.
8. Must not participate in any other interventional clinical trials for the duration of the study.
9. Must commit to medication dosing, therapy, and all study procedures.

Exclusion Criteria:

1. Are not able to give adequate informed consent.
2. Have a history of any medical condition, or any significant clinical finding on screening tests, that could make receiving a sympathomimetic drug harmful.
3. Have uncontrolled hypertension.
4. Have evidence or history of significant medical or psychiatric disorders.
5. Have symptomatic liver disease.
6. Have history of hyponatremia or hyperthermia.
7. Weigh less than 48 kilograms (kg).
8. Unable or unwilling to safely taper off prohibited psychiatric medication.
9. Abusing illegal drugs or alcohol.
10. Have received Electroconvulsive Therapy (ECT) or ketamine therapy within 12 weeks of enrollment.
11. Are pregnant or nursing or are able to become pregnant and are not practicing an effective means of contraception.

Where this trial is running

The Bronx, New York

• James J. Peters VA Medical Center — The Bronx, New York, United States (Recruiting)

Study contacts

• Principal investigator: Rachel Yehuda, PhD — James J. Peters VA Medical Center
• Study coordinator: Amy Lehrner, PhD

Conditions Posttraumatic Stress Disorder; MDMA-Assisted Therapy; Dose Optimization; Veterans