MDMA-Assisted Psychotherapy in Veterans With Combat-Related, Refractory PTSD

NCT04264026 | Completed Phase 2 FDA Drug

• 1 other identifier: 1311
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a single-site, open-label phase 2 study designed to test the feasibility of administering MDMA in conjunction with psychotherapy for combat-related treatment-resistant PTSD in US military veterans currently enrolled in VA. MDMA will be given in conjunction with structured psychotherapy in three single-dose psychotherapy sessions in a hospital setting over the course of 12 weeks, along with preparatory and integration psychotherapy sessions in-between each active-dose session. The overall objective of this study is to evaluate the risks, benefits, and feasibility of MDMA used in conjunction with manualized psychotherapy, on reduction of symptoms, or remission of PTSD, as evaluated by standard clinical measures, in a VA Healthcare System. The primary outcome measure for the study is the Clinician-Administered PTSD Scale (CAPS-5), a semi-structured interview used in the majority of clinical trials for PTSD, which will be assessed at baseline, primary endpoint, and at the long-term 12-month follow-up visit. Secondary safety and efficacy measures will also be collected. The planned duration of this study is 1-3 years, with each active treatment period lasting approximately 12 weeks, along with a long-term follow-up 12 months after the last active-drug session.

Conditions

Post Traumatic Stress Disorder; Combat Stress Disorders

Keywords

Veterans; Refractory PTSD; PTSD; MDMA

Outcome Measures

Primary Outcomes (1)

• Change in total score of CAPS-5

  The primary objective was amended in January 2024. The study will now aim to explore the feasibility of MDMA used in conjunction with manualized psychotherapy on reduction of symptoms, or remission of combat-related treatment resistant PTSD, as evaluated by standard clinical measures as a multiple case series.

  baseline, primary outcome (2 months after last experimental/MDMA session), 12-month follow-up

Secondary Outcomes (7)

• Changes in self-reported PTSD symptoms

  baseline, primary outcome (2 months after last experimental/MDMA session), 12-month follow up

• Depression Symptoms

  through study completion, an average of 1 year

• Changes in Alcohol Consumption

  through study completion, an average of 1 year

• Changes in Drug Consumption

  Baseline (screening) and long-term 12-month follow up (V18)

• Changes in self-reported sleep quality

  through study completion, an average of 1 year

Study Arms (1)

Open Label

EXPERIMENTAL

Participants will receive an initial dose of 80 mg of 3,4-methylenedioxymethamphetamine (MDMA) and an optional supplemental dose of 40 mg MDMA during the first Experimental Session. In the second and third Experimental Sessions, the participant will receive an initial dose of 120 mg MDMA and an optional supplemental dose of 40 mg MDMA.

Drug: 3,4-methylenedioxymethamphetamine

Interventions

3,4-methylenedioxymethamphetamine DRUG

Bottles are labeled with a unique container number, protocol number, IMP name, lot number, sponsor name and a statement that the IMP is restricted to clinical trial use only.

Also known as: MDMA

Open Label

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must be eligible for VA healthcare and currently being treated by VA Loma Linda Healthcare System or VA Long Beach providers
• Participants must meet DSM 5 criteria for combat-related PTSD (within the past 6 months). PTSD must be defined as treatment-resistant.
• Participants must have been exposed to combat in the current-era war.
• Participants must be 18-55 years old.

You may not qualify if:

• Participants must be willing to refrain from alcohol for 72 hours prior to each MDMA session and be deemed not at risk for significant alcohol withdrawal.
• Participants must be willing to refrain from taking any psychiatric medications during the study period, including gabapentin or any other anticonvulsants. If they are being treated with psychoactive medications during recruitment, participants must be willing and determined safe (by study physician(s)) to undergo medically-supervised withdrawal from these medications. The medications will be withdrawn in an appropriate fashion to minimize any withdrawal effects. The participants must be able to refrain from starting any new medications during the study period. The only exception to this will be in the case of rescue medications that may be administered in the event of a crisis during the experimental study sessions.
• Agree that, for one week preceding an MDMA session will refrain from:
• Taking any herbal supplement (except with prior approval of the research team);
• Taking any nonprescription medications (with the exception of non-steroidal anti-inflammatory drugs or acetaminophen unless with prior approval of the research team);
• Taking any prescription medications, with the exception of birth control pills, thyroid hormones or other medications approved by the research team.
• Are proficient in speaking and reading English.
• Must meet capacity and consent for treatment.
• Participants who are engaged in non-PTSD psychotherapy at the time of study screening, may continue to see their therapist during the course of the study. If seeing a non-VA therapist, participants must sign a release for the investigators to communicate directly with their therapist. Subjects may not change therapists, increase the frequency of therapy or commence any new type of therapy until after the evaluation session 2 months after the final experimental session.
• Participants of childbearing potential and age must have a negative pregnancy test and must agree to use an effective form of birth control during the study period.
• Participants must be willing to stay overnight at the hospital after each experimental session.
• Agree to have transportation other than driving themselves home on the day after an MDMA session.
• Are willing to follow restrictions and guidelines concerning medications, consumption of food, beverages, alcohol, nicotine, or illicit substances.
• 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.
• Must agree to inform the investigators within 48 hours of any medical conditions and procedures.

Sponsors & Collaborators

• VA Loma Linda Health Care System: lead
• Multidisciplinary Association for Psychedelic Studies: collaborator

Study Sites (1)

VA Loma Linda Health Care System

Loma Linda, California, 92357, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Combat Disorders

Interventions

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

Study Officials

• Shannon Remick, MD

  Staff Psychiatrist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single-site, open-label study

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 11, 2020
• Study Start: July 29, 2021
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)