Study of 3,4-Methylenedioxymethamphetamine-assisted Psychotherapy in People With Posttraumatic Stress Disorder
Randomised, triple-blind, placebo-controlled Phase II trial (n=14) of MDMA-assisted psychotherapy for PTSD comparing full dose (125 mg + optional 62.5 mg booster) versus low active placebo (25 mg + optional 12.5 mg booster) across three 8-hour therapy sessions.
Detailed Description
Randomised, triple-blind, parallel-group Phase II study in adults with PTSD resistant to at least one prior treatment, evaluating whether three 8-hour MDMA-assisted psychotherapy sessions reduce PTSD symptoms compared with a low (active placebo) MDMA dose.
Each experimental session includes administration of oral MDMA (125 mg or 25 mg) with an optional booster dose ~2.5 hours later, paired with non-directive psychotherapy by two co-therapists; assessments occur acutely and at 2, 6 and 12 months follow-up, with an open-label rollover offered to low-dose participants.
Safety monitoring included overnight observation after sessions, daily contact for one week post-session, and exclusion of participants with significant medical or psychiatric comorbidity.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Full dose MDMA
experimentalThree 8-hour MDMA-assisted psychotherapy sessions (125 mg + optional 62.5 mg booster) with non-directive therapy by two co-therapists.
Interventions
- MDMA125 mgvia Oral• three sessions• 3 doses total
125 mg initial dose each session; optional 62.5 mg booster ~2.5 h after initial dose if agreed.
- Compoundvia Other
Non-directive therapy performed by two co-therapists during each dosing session and in integration/follow-up.
Low (active placebo) MDMA
active comparatorThree 8-hour MDMA-assisted psychotherapy sessions (25 mg + optional 12.5 mg booster) with same therapy.
Interventions
- MDMA25 mgvia Oral• three sessions• 3 doses total
25 mg initial dose each session; optional 12.5 mg booster ~2.5 h after initial dose if agreed.
- Compoundvia Other
Non-directive therapy performed by two co-therapists during each dosing session and in integration/follow-up.
Participants
Inclusion Criteria
- Diagnosed with posttraumatic stress disorder (PTSD).
- PTSD still remains after one or more prior treatment, with treatment including psychotherapy (talk therapy) or drug therapy.
- May meet criteria for a mood disorder.
- Must be at least 18 years old.
- Must be able to stop taking psychiatric medication during the course of the study, from the start of the study to the follow-up two months after experimental session 3.
- Must agree to follow all rules and instructions relating to the experimental session, including restrictions on food and substance (alcohol and drug) consumption.
- Must be willing to stay overnight at the researcher's office after each experimental session until the non-drug session occurring the next morning.
- Must be willing to be contacted by one of the researchers on a daily basis for a week after each experimental session.
- Female participants of childbearing potential must have a negative pregnancy test and must agree to use an effective form of birth control.
- Participants must have sufficient proficiency in speaking the German language to participate in MDMA-assisted psychotherapy. Participants must be able to read documents in German.
Exclusion Criteria
- Cannot have history of or current primary psychotic disorder or bipolar affective disorder-1.
- Dissociative identity disorder, or an eating disorder with active purging or borderline personality disorder.
- Evidence or history of significant hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder. (People with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded).
- Uncontrolled hypertension, peripheral vascular disease, hepatic disease (with or without abnormal liver enzymes), or history of hyponatremia or hyperthermia.
- Being pregnant or lactating (nursing), or not practicing an effective method of birth control.
- Weight of less than 50 or more than 105 kg.
- Patients reporting prior use of "Ecstasy" more than 5 times or at any time within the previous 6 months.
- People who would present a serious suicide risk or who are likely to require hospitalization during the course of the study.
- People who need ongoing concomitant therapy with a psychotropic drug.
- Meeting DSM-IV criteria for substance abuse or dependence for any substance save caffeine or nicotine in the past 60 days.
- People who cannot give adequate consent.