MDMA-assisted Therapy Versus Cognitive Processing Therapy for Veterans With Severe Posttraumatic Stress Disorder
This randomized, interventional trial (n=30) will compare MDMA-assisted Cognitive Processing Therapy (three MDMA sessions plus preparatory and integration therapy) versus standard Cognitive Processing Therapy for Veterans with severe PTSD.
Detailed Description
Randomized, parallel-group trial comparing MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT) with standard Cognitive Processing Therapy (CPT) in U.S. military Veterans with severe PTSD to assess clinical effectiveness, implementation feasibility, and health economics.
MDMA-aCPT includes one 90-minute preparatory session, three ~8-hour experimental MDMA sessions (initial doses 80 mg with optional supplemental doses; later sessions 80 or 120 mg with optional supplements), and three 90-minute integration sessions, alongside 8–15 CPT sessions (average 12).
Outcomes include PTSD symptom reduction, feasibility and implementation metrics within the VA system, and economic assessments to inform potential deployment of MDMA-aCPT in VA settings.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
MDMA-aCPT
experimentalMDMA-assisted Cognitive Processing Therapy: CPT plus three MDMA experimental sessions with preparatory and integration sessions.
Interventions
- MDMA80 - 120 mgvia Oral• three sessions• 3 doses total
Session 1: 80 mg with optional 40 mg supplement 1.5–2 h later. Sessions 2–3: 80 or 120 mg initial dose with optional 40 or 60 mg supplement.
CPT
experimentalCognitive Processing Therapy alone (8–15 sessions, avg 12).
Interventions
- Compound• weekly• 12 doses total
8–15 CPT sessions (average 12), ~1–1.5 hours each; optional crossover to MDMA-aCPT after 6 months.
Participants
Inclusion Criteria
- Inclusion Criteria:
- 1. At least 18 years at time of informed consent
- 2. U.S. military veteran
- 3. Receiving services from VA Palo Alto, VA San Francisco, or VA NorCal Healthcare System
- 4. Fluent in spoken and written English
- 5. Agree to have study visits audio and/or video recorded
- 6. If assigned to MDMA-aCPT, able to identify appropriate support person(s) to stay with participant on evenings of MDMA sessions
- 7. Meet DSM-5 criteria for PTSD with symptom duration ≥6 months
- 8. Severe PTSD symptoms in the last month
- 9. Body weight ≥48 kg
- 10. Not pregnant, planning pregnancy, or breastfeeding
- 11. Capable of giving signed informed consent
Exclusion Criteria
- Exclusion Criteria:
- 1. History of any medical condition that could make receiving a sympathomimetic drug harmful
- 2. Current unstable medical illness
- 3. Cardiac conditions, including uncontrolled hypertension, prolonged QTc, and other cardiac conditions
- 4. Received ECT, ketamine-assisted therapy, or used ketamine within 12 weeks of enrollment
- 5. Moderate or severe alcohol or cannabis use disorder within last 12 months
- 6. Active illicit drug (other than cannabis) or prescription drug substance use disorder at any severity within last 12 months
- 7. Current serious suicide risk
- 8. Unable or unwilling to stop or safely taper prohibited medications
- 9. Prior use of MDMA (ecstasy)
- 10. Currently enrolled in any clinical study
- 11. Personal history of primary psychotic disorder, type I bipolar disorder, severe personality disorder, eating disorder with compensatory behaviours, or depressive disorder with psychotic features
- 12. Lack of social support or a stable living situation