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

An Open-Label, Multi-Site Phase 2 Study of the Safety and Effect of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder

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.

Study Overview

• Status: Completed
• Conditions: PTSD
• Intervention / Treatment: Drug: Midomafetamine; Behavioral: Manualized therapy

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).

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • North Hollywood, California, United States, 91601
      • New School Research LLC
    • San Francisco, California, United States, 94114
      • San Francisco Insight and Integration Center
    • San Francisco, California, United States, 94122
      • University of California San Francisco
  • Colorado
    • Boulder, Colorado, United States, 80302
      • Aguazul-Blue Water Inc.
    • Fort Collins, Colorado, United States, 80525
      • Wholeness Center
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut
  • Louisiana
    • New Orleans, Louisiana, United States, 70123
      • Ray Worthy Psychiatry LLC
  • Massachusetts
    • Brookline, Massachusetts, United States, 02446
      • Trauma Research Foundation
  • New York
    • New York, New York, United States, 10016
      • New York University
    • New York, New York, United States, 10024
      • Affective Care
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Zen Therapeutic Solutions, LLC
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin at Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Midomafetamine; 80 to 120 mg MDMA; Other Names: MDMA; 3,4-methylenedioxymethamphetamine; Behavioral: Manualized therapy; Non-directive therapy conducted during MDMA-assisted therapy session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores	The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.	Baseline to 18 weeks post-enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Visit 19 in Adapted SDS Total Score	The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.	Baseline to 18 weeks post-enrollment

Collaborators and Investigators

• Sponsor: Lykos Therapeutics
• Investigators: Study Director: Michael C Mithoefer, MD, MAPS Public Benefit Corp.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2017
• Primary Completion (Actual): August 10, 2019
• Study Completion (Actual): August 10, 2019

Study Registration Dates

• First Submitted: September 11, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: MDMA; therapy; methylenedioxymethamphetamine; midomafetamine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Adrenergic Agents; Neurotransmitter Uptake Inhibitors; Adrenergic Uptake Inhibitors; Serotonin Agents; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: MP-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will share outcome data appearing in any published reports upon request.
• IPD Sharing Time Frame: Data and study-related documents will be available wehn all participants have completed the study
• IPD Sharing Access Criteria: Interested persons should correspond with the central contact for the multi-site study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No