Dose Optimization of MDMA-Assisted Therapy for PTSD (DosOp)
Open-label, within-subjects dose optimisation trial (n=60) in U.S. veterans with PTSD investigating the optimal number of MDMA-Assisted Therapy cycles (one MDMA session + three integration sessions).
Detailed Description
Open-label, single-group dose-optimisation study in U.S. veterans with PTSD. All participants receive three preparatory psychotherapy sessions and at least one MDMA-assisted therapy cycle; participants may receive up to five cycles.
Each cycle comprises one approximately eight-hour MDMA dosing session (120 mg initial dose with optional 60 mg supplemental dose) followed by three 90-minute integrative psychotherapy sessions with a two-therapist team.
After each cycle participants and therapists jointly decide whether to continue based on symptom change, tolerability, and burden; blood samples are collected and banked for future biomarker analyses.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Treatment Arm
experimentalOpen-label, within-subjects treatment arm. Participants receive 120 mg + optional 60 mg supplement MDMA; one to five dosing sessions three to five weeks apart; each dosing session followed by three integration psychotherapy sessions.
Interventions
- MDMA120 - 180 mgvia Oral• single dose• 5 doses total
120 mg initial dose with optional 60 mg supplemental dose; 1–5 MDMA-assisted therapy sessions per participant.
- Compoundvia Other• per cycle
Standardised psychotherapy by a team of two therapists: three preparatory sessions before first dosing and three 90-minute integrative sessions after each dosing session.
Participants
Inclusion Criteria
- Inclusion Criteria:\n\n1. Are a U.S. military veteran at least 18 years old.\n2. Are able to provide written, informed consent.\n3. Are able to swallow pills.\n4. Agree to have study visits recorded, including Experimental Sessions, psychological assessments, and non-drug therapy sessions.\n5. Must provide a contact who is willing and able to be reached by the investigators in the event of a participant becoming unwell or unreachable.\n6. If able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate contraceptive methods.\n7. Must have a current PTSD diagnosis at screening and baseline.\n8. Must not participate in any other interventional clinical trials for the duration of the study.\n9. Must commit to medication dosing, therapy, and all study procedures.
Exclusion Criteria
- Exclusion Criteria:\n\n1. Are not able to give adequate informed consent.\n2. Have a history of any medical condition, or any significant clinical finding on screening tests, that could make receiving a sympathomimetic drug harmful.\n3. Have uncontrolled hypertension.\n4. Have evidence or history of significant medical or psychiatric disorders.\n5. Have symptomatic liver disease.\n6. Have history of hyponatremia or hyperthermia.\n7. Weigh less than 48 kilograms (kg).\n8. Unable or unwilling to safely taper off prohibited psychiatric medication.\n9. Abusing illegal drugs or alcohol.\n10. Have received Electroconvulsive Therapy (ECT) or ketamine therapy within 12 weeks of enrollment.\n11. Are pregnant or nursing or are able to become pregnant and are not practicing an effective means of contraception.