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

NCT04077437 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: MAPP2
• Study Type: interventional
• Target: 121
• Locations: 2 countries
• Sites: 14

Brief Summary

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with at least moderate 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 baseline post enrollment confirmation

Secondary Outcomes (1)

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

  Baseline to 18 weeks post enrollment confirmation

Study Arms (2)

Experimental: MDMA-assisted psychotherapy

EXPERIMENTAL

Administration of 80 to 120 mg midomafetamine HCl in combination with manualized psychotherapy, followed by a supplemental half-dose 1.5 to 2 hrs after the initial dose of 40 or 60 mg, respectively.

Behavioral: Therapy; Drug: Midomafetamine

Placebo Comparator: Placebo

PLACEBO COMPARATOR

Administration of inactive placebo in combination with manualized psychotherapy.

Behavioral: Therapy; Drug: Placebo

Interventions

Therapy BEHAVIORAL

Standardized non-directive therapy performed by therapist team.

Also known as: Manualized MDMA-assisted therapy

Experimental: MDMA-assisted psychotherapy; Placebo Comparator: Placebo

Midomafetamine DRUG

Administration of 80 to 120 mg midomafetamine HCl, followed by a supplemental half-dose 1.5 to 2 hrs after the initial dose of 40 or 60 mg, respectively, during three sessions of MDMA-assisted psychotherapy.

Also known as: 3,4-methylenedioxymethamphetamine, MDMA

Experimental: MDMA-assisted psychotherapy

Placebo DRUG

Administration of placebo with therapy during three experimental sessions

Also known as: Inactive placebo

Placebo Comparator: Placebo

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, have moderate PTSD diagnosis

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 (14)

New School Research

Los Angeles, California, 90004, United States

Location

San Francisco Insight and Integration Center

San Francisco, California, 94122, United States

Location

UCSF

San Francisco, California, 94122, United States

Location

Aguazul Bluewater, Inc.

Boulder, Colorado, 80304, United States

Location

Wholeness Center

Fort Collins, Colorado, 80525, United States

Location

University of Connecticut

Farmington, Connecticut, 06030, 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

Nautilus Psychiatric Services

New York, New York, 11012, United States

Location

Zen Therapeutic Solutions, LLC

Mt. Pleasant, South Carolina, 29464, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53705-2222, United States

Location

Assaf Harofeh Research Fund

Beer Yaaqov, Israel

Location

Sheba Fund for Health Services and Research

Tel Litwinsky, Israel

Location

Related Publications (3)

• Leon AC, Olfson M, Portera L, Farber L, Sheehan DV. Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med. 1997;27(2):93-105. doi: 10.2190/T8EM-C8YH-373N-1UWD.

  PMID: 9565717 BACKGROUND

• Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM. The development of a Clinician-Administered PTSD Scale. J Trauma Stress. 1995 Jan;8(1):75-90. doi: 10.1007/BF02105408.

  PMID: 7712061 BACKGROUND

• Mitchell JM, Ot'alora G M, van der Kolk B, Shannon S, Bogenschutz M, Gelfand Y, Paleos C, Nicholas CR, Quevedo S, Balliett B, Hamilton S, Mithoefer M, Kleiman S, Parker-Guilbert K, Tzarfaty K, Harrison C, de Boer A, Doblin R, Yazar-Klosinski B; MAPP2 Study Collaborator Group. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med. 2023 Oct;29(10):2473-2480. doi: 10.1038/s41591-023-02565-4. Epub 2023 Sep 14.

  PMID: 37709999 DERIVED

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

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 thirdparty 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: August 30, 2019
• First Posted: September 4, 2019
• Study Start: September 2, 2020
• Primary Completion: October 30, 2022
• Study Completion: November 2, 2022
• Last Updated: June 6, 2025
• Results First Posted: October 11, 2023

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 (12); IL (2)