MDMA-assisted Brief Cognitive Behavioral Conjoint Therapy for PTSD (MDMA-bCBCT)
Open-label single-group pilot (n=16 dyads, 8 PTSD+ veterans and their partners) testing MDMA-assisted bCBCT: 8-session therapy with two full-day MDMA sessions for PTSD+ veterans to evaluate preliminary effectiveness on PTSD and relationship functioning.
Detailed Description
Single-site, open-label pilot at VA San Diego Healthcare System evaluating MDMA-assisted Brief Cognitive Behavioral Conjoint Therapy (bCBCT) in veterans with chronic PTSD and their intimate partners; total N=16 (8 dyads), with therapy delivered over approximately 7–13 weeks and follow-up to study completion.
PTSD+ veterans receive two full-day oral MDMA sessions (Session 1: 80 mg + 40 mg supplemental; Session 2: 100 mg + 40 mg supplemental). Partners attend sessions but do not receive MDMA. Preparatory, integration, telephone follow-ups, and emotion-focused integrative sessions support safety and integration.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
bCBCT + MDMA
experimental8-session bCBCT for both partners with two full-day MDMA sessions for the PTSD+ veteran; partner present but not dosed.
Interventions
- MDMA120 - 140 mgvia Oral• two sessions• 2 doses total
PTSD+ veteran only; Session 1: 80 mg MDMA HCl + 40 mg supplemental (~120 mg total); Session 2: 100 mg MDMA HCl + 40 mg supplemental (~140 mg total). Partner present but not dosed.
- Compoundvia Other• 8 sessions• 8 doses total
Brief Cognitive Behavioral Conjoint Therapy (bCBCT) delivered to both partners; preparatory and integration sessions included.
Participants
Inclusion Criteria
- Inclusion Criteria:
- 1. Be a veteran (≥18 years) who meets criteria for PTSD on the CAPS-5 or be an intimate partner (≥18 years) of a veteran meeting PTSD criteria who is willing to participate and does not meet PTSD criteria on the PCL-5 (score ≤30).
- 2. Be in a committed relationship for ≥12 months and cohabiting.
- 3. Fluent in English.
- 4. Willing to commit to medication dosing, therapy sessions, follow-up, and telephone contact.
- 5. Able to swallow pills (PTSD+ veteran only).
- 6. Agree to study visit recording and Independent Rater assessments for bCBCT sessions.
- 7. Provide a local contact willing to be reached if participant becomes suicidal or unreachable (PTSD+ veteran only).
- 8. Agree to inform investigators of new medical conditions/procedures within 48 hours.
- 9. If able to become pregnant, have a negative pregnancy test at entry and prior to each MDMA session and use adequate birth control through 10 days after last MDMA session (PTSD+ veteran only).
- 10. Agree to fasting and medication restrictions prior to MDMA sessions (PTSD+ veteran only).
- 11. Not enroll in other interventional trials during study.
- 12. Both partners agree not to begin new mental healthcare during screening or treatment without PI approval; ongoing non-PTSD-focused care may continue if not increased in frequency.
- 13. At pre-screen, PTSD+ veteran: PCL-5 ≥40; at screening CAPS-5 total severity score ≥28.
- 14. May have well-controlled hypertension, treated HCV, stable diabetes type 2, or hypothyroidism with stable treatment if cleared by study physician.
- 15. May have alcohol or substance use disorder if not in withdrawal and with a realistic plan to reduce use agreed by investigators.
Exclusion Criteria
- Exclusion Criteria:
- 1. Unable to provide informed consent.
- 2. Currently engaged in compensation & pension litigation where financial gain could result from prolonged PTSD symptoms.
- 3. Likely to be re-exposed to index trauma, lack social support, or lack stable housing.
- 4. Ecstasy/MDMA use >10 times in past 10 years or any use within 6 months of first MDMA session (PTSD+ veteran only).
- 5. Any current problem that interferes with safe participation or adherence.
- 6. Hypersensitivity to any ingredient of the IMP (PTSD+ veteran only).
- 7. ECT within 12 weeks prior to enrollment (PTSD+ veteran only).
- 8. History or current primary psychotic disorder.
- 9. History or current Bipolar I/II or manic episode (PTSD+ veteran only).
- 10. Current eating disorder with active purging (PTSD+ veteran only).
- 11. Current MDD with psychotic features.
- 12. Current panic disorder (PTSD+ veteran only).
- 13. Current alcohol or substance use disorder (other than caffeine/nicotine) deemed a safety concern or likely to interfere with therapy; failure to agree to/manage use excludes enrollment.
- 14. Current serious suicide risk per C-SSRS or clinical interview; scores of 4+ on C-SSRS within last 6 months at weekly frequency or any suicidal behaviour/attempt within last 6 months exclude enrollment.
- 15. Reported intimate partner violence or severe relationship aggression meeting E-HITS ≥7 or 'severe' on CTS-2 psychological aggression (safety concern).
- 16. Present a serious risk to others per clinical interview.
- 17. Require ongoing psychiatric medication except protocol-allowed exceptions (PTSD+ veteran).
- 18. Medical conditions making sympathomimetic use unsafe (e.g., recent MI, stroke, aneurysm) unless cleared; uncontrolled hypertension (≥140/90), significant arrhythmia, WPW not ablated, marked QTc prolongation (>450 ms), symptomatic liver disease or significant enzyme elevations, history of hyponatraemia/hyperthermia.
- 19. Weigh <48 kg.
- 20. Pregnant or nursing or unwilling/unable to use effective contraception.
- 21. Ketamine-assisted therapy or ketamine use within 12 weeks of enrollment.
- 22. Preexisting conditions affecting renal function.
Study Protocol, Arms & Participants
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