Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD

NCT ID: NCT03282123

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-16
• Study Completion Date: 2019-08-10

Brief Summary

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people diagnosed with at least severe PTSD.

The main question it aims to answer is: Do three open-label sessions of MDMA-assisted therapy reduce PTSD symptoms?

Participants will receive three non-drug preparatory sessions followed by three sessions of MDMA-assisted therapy. Each MDMA-assisted therapy session is followed by three non-drug integrative therapy sessions.

Detailed Description

This multi-site, open-label, Phase 2, lead-in study assesses the safety and efficacy of MDMA-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study.

This study will compare the effects of three open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to Primary Endpoint (Visit 19).

Conditions

PTSD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MDMA-assisted therapy

Three sessions of MDMA-assisted therapy with flexible dose of midomafetamine HCl from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later

Group Type: EXPERIMENTAL

Midomafetamine

Intervention Type: DRUG

80 to 120 mg MDMA

Manualized therapy

Intervention Type: BEHAVIORAL

Non-directive therapy conducted during MDMA-assisted therapy session

Interventions

Midomafetamine

80 to 120 mg MDMA

Intervention Type: DRUG

Manualized therapy

Non-directive therapy conducted during MDMA-assisted therapy session

Intervention Type: BEHAVIORAL

Other Intervention Names

3,4-methylenedioxymethamphetamine; MDMA

Eligibility Criteria

Inclusion Criteria

• Are at least 18 years old
• Are fluent in speaking and reading the predominantly used or recognized language of the study site
• 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
• Meet DSM-5 Criteria for Severe PTSD

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] 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
• 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.
• Meet DSM-5 criteria for active substance use disorder for any substance other than caffeine or nicotine
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lykos Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael C Mithoefer, MD

Role: STUDY_DIRECTOR

MAPS Public Benefit Corp.

Locations

New School Research LLC

North Hollywood, California, United States

San Francisco Insight and Integration Center

San Francisco, California, United States

University of California San Francisco

San Francisco, California, United States

Aguazul-Blue Water 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

Brookline, Massachusetts, United States

New York University

New York, New York, United States

Affective Care

New York, New York, United States

Zen Therapeutic Solutions, LLC

Mt. Pleasant, South Carolina, United States

University of Wisconsin at Madison

Madison, Wisconsin, United States

Countries

United States

References

Christie D, Yazar-Klosinski B, Nosova E, Kryskow P, Siu W, Lessor D, Argento E. MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder. Front Psychiatry. 2022 Nov 3;13:939302. doi: 10.3389/fpsyt.2022.939302. eCollection 2022.

Reference Type: DERIVED

PMID: 36405923 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

MP-16

Identifier Type: -

Identifier Source: org_study_id