A Test of MDMA-Assisted Psychotherapy in People With Posttraumatic Stress Disorder
This Phase II, triple-blind, randomised, placebo-controlled study (n=23) evaluates MDMA-assisted therapy (125 mg + 62.5 mg) across two 8-hour sessions for chronic, treatment-resistant PTSD.
Detailed Description
Randomised, triple-blind, placebo-controlled trial comparing MDMA-assisted psychotherapy with psychotherapy plus inactive placebo in adults with chronic, treatment-resistant PTSD, including veterans.
Participants received two blinded 8-hour sessions (125 mg oral MDMA with a 62.5 mg supplemental dose, or matched placebo), with preparatory and integration therapy. Primary outcome: change in CAPS-IV two months post-treatment.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
MDMA-AT
experimentalTwo 8-hour MDMA-assisted psychotherapy sessions with a divided dose (125 mg + 62.5 mg).
Interventions
- MDMA125 mgvia Oral• two sessions• 2 doses total
Supplemental 62.5 mg 2–2.5 h after initial dose.
Placebo + therapy
inactiveTwo 8-hour psychotherapy sessions with inactive placebo.
Interventions
- Placebovia Oral• two sessions• 2 doses total
Participants
Inclusion Criteria
- Inclusion Criteria:
- Have current PTSD (within the past 6 months) in response to crime victimization, including childhood sexual or physical abuse, or meet criteria for PTSD in response to combat;
- Have a CAPS score showing moderate to severe PTSD symptoms;
- They must either:
- 1. Have had at least one unsuccessful attempt at treatment for PTSD with a SSRI and psychotherapy;
- 2. Be a veteran with PTSD symptoms that have endured for no less than one year but no more than five years
- Be at least 18 years old;
- Must be generally healthy;
- Willing to remain overnight at the study site;
- Agree to have transportation home the morning after experimental sessions;
- 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;
- Are proficient in reading English;
Exclusion Criteria
- Exclusion Criteria:
- Are pregnant or nursing, or are able to bear children and are not practicing an effective means of birth control;
- Weigh less than 50 kg or more than 105 kg;
- Are unable to give adequate informed consent;
- Prior use of Ecstasy (illicit drug preparations purported to contain MDMA) more than 5 times or at any time within the previous 6 months;
- Have a history of certain excluded medical disorders.
Primary Results(3 publications)
Participants
Response Rates
>30% reduction from baseline in CAPS total severity score (clinical response)
No longer met DSM-IV criteria for PTSD
Meaningful, sustained reductions in CAPS scores at long-term follow-up (exact reduction threshold not specified; reported as responder/non-responder based on relapse assumption in ITT analysis)
Participants who met the original study entry cutoff for relapse/non-relapse at long-term follow-up; relapse defined as CAPS scores above cutoff (≥50)
12
Adverse Events (from all publications)
| Arm / Group | n | Any TEAE | Severe | Serious | Discont. |
|---|---|---|---|---|---|
| MDMA-ATexperimental | 12 | — | — | 0(0.0%) | 2(16.7%) |
| Placebo + therapyinactive | 8 | — | — | 0(0.0%) | 0(0.0%) |
| MDMA-ATexperimental | 19 | 0(0.0%) | — | — | — |
| Active placebo (25 mg)active | 12 | 1(8.3%) | 1(8.3%) | 1(8.3%) | 1(8.3%) |
| Full dose (125 mg)experimental | 13 | 1(7.7%) | 2(15.4%) | 0(0.0%) | 2(15.4%) |
* The paper reports no drug-related serious adverse events and no serious drug-related adverse effects. Two MDMA-assigned subjects dropped out before the second experimental session, but the reasons given were resumption of medication for relapse of depression and travel/reimbursement issues, not clearly TEAE-related. Side effects were summarized as spontaneously reported AEs within 7 days, but no participant-level count of subjects with ≥1 TEAE or severe TEAEs was provided in the text.
* The paper reports no drug-related serious adverse events and no serious drug-related adverse effects. No participant-level count of subjects with ≥1 TEAE, severe TEAEs, or TEAEs of special interest was provided in the text.
* This paper is a prospective long-term follow-up of the original MDMA-assisted psychotherapy trial. It reports no subjects reporting harm from participation in the study and no evidence of substance abuse or neurocognitive decline, but does not provide treatment-emergent adverse event counts, severe/serious AE counts, discontinuations due to AEs, or TEAESI counts.
* Note on adverse effects here
* another adverse events note