Randomized, Double-blind, Active Placebo-Controlled Pilot Study of MDMA-assisted Psychotherapy in People With Chronic PTSD
This randomised, double-blind, active placebo‑controlled Phase II pilot (n=10) compared low (25 mg) versus full (125 mg) MDMA‑assisted psychotherapy across two experimental sessions in people with chronic, treatment‑resistant PTSD.
Detailed Description
Participants received preparatory psychotherapy sessions, followed by two MDMA‑assisted psychotherapy sessions scheduled 3–5 weeks apart; each experimental session lasted approximately 6–8 hours and included psychotherapeutic support.
Stage 1 randomised participants received either an active placebo (25 mg, optional 12.5 mg supplemental) or full dose MDMA (125 mg, optional 62.5 mg supplemental); an open‑label lead‑in of full dose MDMA was conducted for the first two subjects, and participants who received active placebo could opt into an open‑label Stage 2 of full dose MDMA.
Outcomes included CAPS assessment at baseline and two months after the second session, safety measures, vital signs and measures of psychological distress during experimental sessions.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Open‑label lead‑in
experimentalOpen‑label full dose MDMA-assisted therapy lead‑in for first two participants.
Interventions
- MDMA125 mgvia Oral• two sessions• 2 doses total
Initial 125 mg with optional supplemental 62.5 mg 1.5–2.5 hours later; two experimental psychotherapy sessions (open‑label lead‑in).
Active placebo (25 mg)
activeActive placebo MDMA-assisted therapy (low dose) during two psychotherapy sessions.
Interventions
- MDMA25 mgvia Oral• two sessions• 2 doses total
Initial 25 mg with optional supplemental 12.5 mg 1.5–2.5 hours later; adjunct to psychotherapy.
Full dose (125 mg)
experimentalFull dose MDMA-assisted therapy during two psychotherapy sessions.
Interventions
- MDMA125 mgvia Oral• two sessions• 2 doses total
Initial 125 mg with optional supplemental 62.5 mg 1.5–2.5 hours later; adjunct to psychotherapy.
Participants
Inclusion Criteria
- Inclusion Criteria:
- Diagnosed with chronic PTSD with a duration of 6 months or longer.
- Have a CAPS score showing moderate to severe symptoms.
- Had at least one unsuccessful attempt at treatment for PTSD, either with talk therapy or with drugs, or stopped treatment because of inability to tolerate psychotherapy or drug therapy.
- Are at least 18 years old.
- Generally healthy.
- Must sign a medical release for the investigators to communicate directly with their therapist and doctors.
- Are willing to refrain from taking any psychiatric medications during the study period.
- One week before the MDMA session, will refrain from taking herbal supplements and nonprescription medications (with the exception of NSAIDs or acetaminophen) unless approved by the research team; some prescription medications (with exceptions such as birth control pills or thyroid hormone) may also be restricted.
- Are willing to follow restrictions and guidelines concerning consumption of food, beverages, and nicotine the night before and just prior to each experimental session.
- Are willing to remain overnight at the study site.
- Are willing to be contacted via telephone for all necessary telephone contacts.
- Must have a negative pregnancy test if able to bear children, and agree to use an effective form of birth control.
- Agree not to participate in any other clinical trial for the duration of this clinical trial, including the follow-up period.
- Are proficient in speaking and reading Hebrew.
- Agree to have all psychotherapy sessions recorded to audio/video.
Exclusion Criteria
- Exclusion Criteria:
- Are pregnant or nursing, or if they can have children and are not practicing an effective means of birth control.
- Weigh less than 48 kg.
- Are abusing illegal drugs.
- Have used "Ecstasy" (material represented as containing MDMA) more than five times or at least once within 6 months of the MDMA session.
- Are unable to give adequate informed consent.
- Upon review of past and current drugs/medication must not be on or have taken a medication that is exclusionary.
- Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation in the study.
Study Results
From: Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials
Key Outcomes
Safety & Adverse Events
| Arm | n | Any | Severe | Serious | Discont. |
|---|---|---|---|---|---|
| Active placebo (25 mg) | 12 | 1 | 1 | 1 | 1 |
| Full dose (125 mg) | 13 | 1 | 2 | 0 | 2 |
* Note on adverse effects here
Study Details
- StatusCompleted
- PhasePhase II
- Typeinterventional
- DesignRandomizedtriple Blind
- Target Enrollment10 participants
- TimelineStart: 2013-01-03End: 2017-01-09
- Compounds
- Topic
Study Team
Sponsors & Collaborators
- Primary Sponsor
Investigators
- MKMoshe Kotler