A Randomised, Double-Blind, Active Placebo-Controlled Phase 2 Pilot Study of MDMA-Assisted Manualised Psychotherapy in Australian War Veterans with Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)
Double-blind, randomised Phase II pilot study (n=14; includes 2-person open-label lead-in) comparing two MDMA-assisted psychotherapy sessions (125 mg vs 30 mg active placebo) plus 10 non-drug psychotherapy sessions in Australian war veterans with chronic, treatment-resistant PTSD.
Detailed Description
Randomised, double-blind Phase II pilot: Stage 1 compares full-dose MDMA (125 mg with optional 62.5 mg supplement) versus a low-level active placebo (30 mg with optional 15 mg supplement) delivered as two supervised drug-assisted psychotherapy sessions within a 12-session manualised program.
Treatment comprises two ~8-hour drug sessions spaced 3–5 weeks apart plus 10 non-drug psychotherapy sessions (preparatory, integrative and follow-up). An open-label lead-in (n=2) verifies therapist adherence; Stage 2 offers optional open-label full-dose treatment to eligible participants initially receiving active placebo.
Primary outcome: change in CAPS scores; secondary outcomes include BDI-II and 12-month follow-up assessments.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
MDMA 125 mg
experimentalFull-dose MDMA-assisted psychotherapy (two drug sessions) with optional supplemental dose; part of 12-session manualised therapy.
Interventions
- MDMA125 mgvia Oral• two sessions• 2 doses total
Optional supplemental 62.5 mg at ~2.5 h (per session); capsules; two experimental drug-assisted psychotherapy sessions ~8 hours each.
Active placebo 30 mg
activeLow-level active placebo MDMA (30 mg) with optional supplemental 15 mg; identical psychotherapy schedule to maintain blinding.
Interventions
- MDMA30 mgvia Oral• two sessions• 2 doses total
Optional supplemental 15 mg at ~2.5 h (per session); intended to provide physiological effects without therapeutic benefit.
Open-label lead-in
experimentalTwo-participant open-label lead-in using full-dose MDMA to verify therapist adherence prior to Stage 1.
Interventions
- MDMA125 mgvia Oral• two sessions• 2 doses total
N=2 open-label participants; optional supplemental 62.5 mg at ~2.5 h; same psychotherapy sequence.
Participants
Inclusion Criteria
- 1. Meet DSM-IV criteria for chronic PTSD with a duration of at least six months.
- 2. Have a CAPS score of 50 or higher, indicating moderate to severe PTSD symptoms.
- 3. Have had at least one unsuccessful attempt at treatment for PTSD using drugs (SSRI, SNRI or MAOI) and/or psychotherapy; OR who discontinued treatment due to either: inability to tolerate psychotherapy for PTSD, or inability to tolerate psychopharmacology for PTSD due to treatment emergent side effects.
- 4. May have a concurrent affective disorder, excepting bipolar affective disorder 1.
- 5. Are war veterans.
- 6. If female and of childbearing potential, must have negative pregnancy test results, be willing to have pregnancy tests and must agree to use an effective form of birth control during throughout the treatment period.
- 7. Are proficient in speaking and reading English.
Exclusion Criteria
- 1. Are pregnant or nursing, or of child bearing potential and not practising an effective method of birth control.
- 2. Have a personal or immediate family history of or current primary psychotic disorder, bipolar affective disorder type 1, or borderline personality disorder.
- 3. Are diagnosed with dissociative identity disorder or an eating disorder with active purging.
- 4. Have evidence or history of significant (controlled or uncontrolled) haematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder, or any other medical disorder judged by the investigator to significantly increase the risk of MDMA administration (participants with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded).
- 5. Have hypertension using the standard criteria of the American Heart Association (values of 140/90 or higher assessed on three separate occasions) unless their hypertension has been successfully treated and is currently well-controlled on antihypertensive medicines. In this case participants with well-controlled hypertension may be enrolled if they pass additional screening to rule out underlying cardiovascular disease.
- 6. Have liver disease.
- 7. Have a history of Diabetes Type I or II.
- 8. Have a history of hyponatraemia or hyperthermia.
- 9. Weigh less than 48 kg.
- 10. Would present a serious suicide risk or who are likely to require hospitalisation during the course of the study.
- 11. Have used “Ecstasy” (material represented as containing MDMA) more than five times in the past 3 years or at any time within 6 months of the MDMA session.
- 12. Require ongoing concomitant therapy with a psychiatric drug, including but not limited to SSRIs, SNRIs, or MAOIs.
- 13. Meet DSM-IV criteria for substance abuse or dependence for any substance save caffeine or nicotine in the past 60 days.
- 14. Have glaucoma, significant atherosclerosis or hyperthyroidism.
- 15. Have any current problem, which in the opinion of the investigator or medical monitor, might interfere with participation in the study.