Randomized Placebo-controlled Study of MDMA-assisted Psychotherapy in People With PTSD – Israel
Randomised, triple-blind Phase II trial (n=12) comparing two sessions of full-dose MDMA-assisted psychotherapy (125 mg + 62.5 mg supplemental) versus low-dose active placebo MDMA (25 mg + 12.5 mg) for chronic PTSD.
Detailed Description
Participants are randomised to receive two day-long MDMA-assisted psychotherapy sessions given two to four weeks apart, either full therapeutic dose or low active placebo dose, with preparatory and integration therapy sessions.
The full dose regimen is 125 mg orally with a supplemental 62.5 mg 2–2.5 hours later; the low dose regimen is 25 mg with a 12.5 mg supplement. PTSD symptoms are measured at baseline and at 2, 6 and 12 months after the second experimental session.
Participants who received low dose may enter an open-label continuation receiving two additional full-dose sessions with follow-up assessments at 6 and 12 months.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Full dose MDMA
experimentalTwo day-long MDMA-assisted psychotherapy sessions with full therapeutic dose (initial 125 mg + supplemental 62.5 mg).
Interventions
- MDMA125 mgvia Oral• two sessions• 2 doses total
Initial 125 mg followed 2–2.5 h later by 62.5 mg; two 6–8 hour therapy sessions.
Low dose MDMA
active comparatorTwo day-long MDMA-assisted psychotherapy sessions with low active placebo dose (initial 25 mg + supplemental 12.5 mg).
Interventions
- MDMA25 mgvia Oral• two sessions• 2 doses total
Initial 25 mg followed 2–2.5 h later by 12.5 mg; two 6–8 hour therapy sessions.
Participants
Inclusion Criteria
- Diagnosis of posttraumatic stress disorder (PTSD) remaining after at least one treatment (psychotherapy or pharmacotherapy); at least two-thirds of participants will have PTSD due to war or terrorism.
- May meet criteria for a mood disorder.
- Age ≥18 years.
- Able to stop psychiatric medication from study start until the two-month follow-up.
- May continue seeing an outside therapist but cannot increase length or frequency of treatments.
- Able to follow rules/instructions for experimental sessions, including food and substance restrictions.
- Willing to stay overnight in clinic after each experimental session until the non-drug session the next morning.
- Willing to be contacted daily for a week after each experimental session.
- Women of childbearing potential must have a negative pregnancy test and agree to use effective birth control.
- Able to speak and read Hebrew.
Exclusion Criteria
- History of or current psychotic disorder or bipolar I disorder.
- Diagnosis of dissociative identity disorder, an eating disorder with active purging, or borderline personality disorder.
- Significant hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder (stable treated hypothyroidism allowed).
- Uncontrolled hypertension, peripheral vascular disease, hepatic disease, history of hyponatraemia or hyperthermia.
- Weight <50 kg or >105 kg.
- Lifetime use of "Ecstasy" >5 times or use within past 6 months.
- Serious suicide risk or likely to require hospitalisation during study.
- Requirement for ongoing concomitant psychotropic therapy.
- DSM-IV substance abuse or dependence (except caffeine or nicotine) in past 60 days.
- Unable to give adequate consent.