Clinical TrialPTSDMDMAPlaceboCompleted

A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP2)

This randomised, double-blind, placebo-controlled Phase III study (n=121) compares three sessions of MDMA-assisted psychotherapy (initial 80–120 mg with supplemental half-dose 40–60 mg) versus placebo with identical therapy in adults with moderate PTSD.

Target Enrollment
121 participants
Study Type
Phase III interventional
Design
Randomized, triple Blind

Detailed Description

This multi-site, randomized, triple-masked Phase III trial evaluates whether three sessions of MDMA-assisted psychotherapy reduce PTSD symptoms compared with identical psychotherapy plus an inactive placebo.

Each participant receives three preparatory non-drug therapy sessions, three experimental medication-assisted therapy sessions (initial 80 or 120 mg midomafetamine HCl followed 1.5–2 hours later by a supplemental half-dose of 40 or 60 mg unless contraindicated), and three integrative non-drug therapy sessions after each experimental session.

Primary outcome is change in CAPS-5 total severity from baseline to 18 weeks; key secondary outcomes include clinician-rated functional impairment (Sheehan Disability Scale items).

Study Protocol

Preparation

3 sessions
90 min each

Dosing

3 sessions
480 min each

Integration

9 sessions
90 min each

Therapeutic Protocol

maps

Study Arms & Interventions

MDMA-assisted therapy

experimental

Manualised non-directive psychotherapy combined with MDMA (initial 80–120 mg plus supplemental half-dose 40–60 mg) across three experimental sessions.

Interventions

  • MDMA80 - 180 mg
    via Oral• three sessions• 3 doses total

    Initial 80–120 mg followed 1.5–2 h later by a supplemental half-dose (40 or 60 mg); three monthly experimental sessions.

Placebo with therapy

inactive

Identical manualised psychotherapy with inactive placebo administered during three experimental sessions.

Interventions

  • Placebo
    via Oral• three sessions• 3 doses total

    Inactive placebo administered with therapy during three experimental sessions.

Participants

Ages
18 – 96
Sexes
Male & Female

Inclusion Criteria

  • Are at least 18 years old
  • Are fluent in speaking and reading the predominantly used or recognized language of the study site
  • Are able to swallow pills
  • Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions
  • Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable
  • Must agree to inform the investigators within 48 hours of any medical conditions and procedures
  • If of childbearing potential, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session
  • Must not participate in any other interventional clinical trials during the duration of the study
  • Must be willing to remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures
  • At baseline, have moderate PTSD diagnosis

Exclusion Criteria

  • Are not able to give adequate informed consent
  • Have uncontrolled hypertension
  • Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] in males and >460 ms in females corrected by Bazett's formula)
  • Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
  • Have evidence or history of significant medical disorders, such as myocardial infarction, cerebrovascular accident, or aneurysm
  • Have symptomatic liver disease
  • Have history of hyponatremia or hyperthermia
  • Weigh less than 48 kilograms (kg)
  • Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control
  • Have an active illicit or prescription drug use disorder
  • Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first Experimental Session; or have previously participated in a MAPS-sponsored MDMA clinical trial

Study Results

From: MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial

Key Outcomes

CAPS-5(Primary)
MDMA-assisted therapy @ Day 7:12 (±12)
Placebo with therapy @ Day 12:12 (±12)

Safety & Adverse Events

ArmnAnySevereSeriousDiscont.
MDMA-assisted therapy1212121212

* again here, include relevant notes

Study Details

  • Status
    Completed
  • Phase
    Phase III
  • Type
    interventional
  • Design
    Randomizedtriple Blind
  • Target Enrollment121 participants
  • Timeline
    Start: 2020-08-27
    End: 2023-03-05
  • Compounds
    MDMAPlacebo
  • Topic
    PTSD

Study Team

Sponsors & Collaborators

  • Primary Sponsor

Locations

New School Research — Los Angeles, California, United States
San Francisco Insight and Integration Center — San Francisco, California, United States
UCSF — San Francisco, California, United States
Aguazul Bluewater, Inc. — Boulder, Colorado, United States
Wholeness Center — Fort Collins, Colorado, United States
University of Connecticut — Farmington, Connecticut, United States
Ray Worthy Psychiatry LLC — New Orleans, Louisiana, United States
Trauma Research Foundation — Boston, Massachusetts, United States
New York University — New York, New York, United States
Nautilus Psychiatric Services — New York, New York, United States
Zen Therapeutic Solutions, LLC — Mt. Pleasant, South Carolina, United States
University of Wisconsin - Madison — Madison, Wisconsin, United States
Assaf Harofeh Research Fund — Beer Yaaqov, Israel
Sheba Fund for Health Services and Research — Tel Litwinsky, Israel

Related Publications

Paywallindividual

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial

This multi-site, randomised, double-blind, Phase IIIb trial (n=104) evaluated the efficacy and safety of MDMA-assisted therapy (MDMA-AT) for individuals with moderate to severe PTSD. The study found significant reductions in PTSD severity (CAPS-5 score) and functional impairment (SDS score) for the MDMA-AT group compared to placebo with therapy. Seven participants experienced severe treatment-emergent adverse events, but no deaths or serious adverse events were reported. The treatment was found to be generally well tolerated in a diverse population.

Published
Journal
Nature Medicine
Authors
Balliett, B., Bogenschutz, M. P., de Boer, A., Doblin, R., Gelfand, Y., Hamilton, S., Harrison, C., Kleiman, S., Mitchell, J., Mithoefer, A. T., Nicholas, C. R., Ot’alora G, M., Paleos, C., Parker-Guilbert, K., Quevedo, S., Shannon, S., Tzarfaty, K., van der Kolk, B., Yazar-Klosinski, B.

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