A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD (MAPP1)

NCT03537014 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: MAPP1
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 15

Brief Summary

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with at least severe PTSD. The main question it aims to answer is: Do three sessions of MDMA-assisted therapy reduce PTSD symptoms? Researchers will compare three sessions of MDMA-assisted therapy with an initial dose of 80 to 120 mg to three sessions of placebo with therapy. Participants will undergo three preparatory sessions without any study drug, followed by three MDMA-assisted therapy or placebo with therapy sessions. Each medication session will be followed by three integrative therapy sessions without study drug.

Conditions

Posttraumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-V (CAPS-5)

  The CAPS-5 is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.

  Baseline to 18 weeks post enrollment confirmation

Secondary Outcomes (1)

• Change From Baseline to Primary Endpoint in Sheehan Disability Scale (SDS) Total Score

  Baseline to 18 weeks post enrollment confirmation

Study Arms (2)

MDMA-assisted therapy

EXPERIMENTAL

Administration of 80 or 120 mg midomafetamine HCl with a supplemental dose 1.5 to 2 hours later of 40 or 60 mg midomafetamine HCl, respectively, in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart.

Behavioral: Therapy; Drug: midomafetamine HCl

Placebo with therapy

PLACEBO COMPARATOR

Administration of inactive placebo in combination with therapy during 3 experimental sessions scheduled 3-5 weeks apart

Behavioral: Therapy; Drug: Placebo

Interventions

Therapy BEHAVIORAL

Non-directive therapy performed by therapist team

Also known as: Manualized therapy

MDMA-assisted therapy; Placebo with therapy

midomafetamine HCl DRUG

Administration of 80 to 120 mg midomafetamine HCl, followed by a supplemental dose 1.5 to 2 hrs later of 40 or 60 mg midomafetamine HCl, respectively, during three experimental sessions

Also known as: 3,4-methylenedioxymethamphetamine, MDMA, midomafetamine, MDMA HCl

MDMA-assisted therapy

Placebo DRUG

Administration of placebo during three experimental sessions

Also known as: Inactive placebo

Placebo with therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, meet DSM-5 criteria for current severe PTSD

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lykos Therapeutics: lead

Study Sites (15)

New School Research LLT

North Hollywood, California, 91601, United States

Location

San Francisco Insight and Integration Center

San Francisco, California, 94114, United States

Location

University of California San Francisco

San Francisco, California, 94122, United States

Location

Aguazul-Blue Water Inc.

Boulder, Colorado, 80302, United States

Location

Wholeness Center

Fort Collins, Colorado, 80525, United States

Location

Ray Worthy Psychiatry LLC

New Orleans, Louisiana, 70123, United States

Location

Trauma Research Foundation

Boston, Massachusetts, 02446, United States

Location

New York University

New York, New York, 10016, United States

Location

New York Private Practice

New York, New York, 10024, United States

Location

Zen Therapeutic Solutions, LLC

Mt. Pleasant, South Carolina, 29464, United States

Location

University of Wisconsin at Madison

Madison, Wisconsin, 53705, United States

Location

Providence Health Center

Vancouver, British Columbia, V5R 5H3, Canada

Location

Dr. Simon Amar, Inc.

Montreal, Quebec, H2W1Y9, Canada

Location

Assaf Harofeh Research Fund

Be’er Ya‘aqov, Israel

Location

Sheba Fund for Health Services and Research

Tel Litwinsky, Israel

Location

Related Publications (1)

• Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021 Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub 2021 May 10.

  PMID: 33972795 RESULT

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Therapeutics; N-Methyl-3,4-methylenedioxyamphetamine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Lykos Therapeutics

trialdata@lykospbc.com

877-627-7722

Study Officials

• Casey Paleos, MD

  Affective Care

  PRINCIPAL INVESTIGATOR

• Bessel van der Kolk, MD

  Trauma Research Foundation

  PRINCIPAL INVESTIGATOR

• Emma Hapke, MD

  Dr. Simon Amar, Inc.

  PRINCIPAL INVESTIGATOR

• Revital Amiaz, MD

  The Chaim Sheba Medical Center, Tel Hashomer Hospital

  PRINCIPAL INVESTIGATOR

• Michael Bogenschutz, MD

  New York University/Langone Medical Center/Bellevue Hospital

  PRINCIPAL INVESTIGATOR

• Randall Brown, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Sylvestre Quevedo, MD

  San Francisco Insight and Integration Center

  PRINCIPAL INVESTIGATOR

• Josh Woolley, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Ray Worthy, MD

  Ray Worthy Psychiatry, LLC

  PRINCIPAL INVESTIGATOR

• Cole Marta, MD

  New School Research, LLC

  PRINCIPAL INVESTIGATOR

• Scott Shannon, MD

  Wholeness Center

  PRINCIPAL INVESTIGATOR

• Wael Garas, MD

  Aguazul-Bluewater, Inc.

  PRINCIPAL INVESTIGATOR

• Yevgeniy Gelfand, MD

  Zen Therapeutics Solutions, LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Use of separate databases for outcome measures and safety data. Assessment made by pool of independent raters. Randomization will be managed via an Interactive Web Randomization System (IWRS) based on a centralized randomization schedule developed by an independent third-party vendor to maintain blinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, between-group comparison of change in PTSD symptoms

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: May 25, 2018
• Study Start: November 21, 2018
• Primary Completion: August 11, 2020
• Study Completion: August 21, 2020
• Last Updated: June 6, 2025
• Results First Posted: September 16, 2021

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data and study-related documents will be available when the database has been locked and data has been unblinded.
• Access Criteria: Interested persons should correspond with the central contact for the multisite study.

Locations

US (11); CA (2); IL (2)