MDMA-Assisted Massed Exposure Therapy for PTSD

NCT07288151 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025P012039TP240376
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate the efficacy of 3,4-methylenedioxy-methamphetamine hydrochloride (MDMA) combined with Massed Prolonged Exposure (PE) therapy for the treatment of posttraumatic stress disorder (PTSD) in adult participants diagnosed with PTSD. This randomized, placebo-controlled trial will enroll 95 participants. The main questions it aims to answer are:

• Does the combination of PE + MDMA lead to greater reduction in PTSD symptom severity from pre-treatment to one-month follow-up compared to PE + placebo?
• Does PE + MDMA improve response efficiency and durability of PTSD symptom improvement compared to PE + placebo?
• Does MDMA + PE enhance extinction retention and reduce amygdala threat reactivity, and are these changes associated with improved PTSD outcomes? Participants will:
• Receive 10 sessions of Massed Prolonged Exposure therapy over two weeks
• Be administered either 100 mg of MDMA or a placebo at Visit 2
• Undergo blinded independent evaluator assessments using the Clinician-Administered PTSD Scale for DSM-5-R (CAPS-5-R) at the one-month posttreatment follow-up

Conditions

Post Traumatic Stress Disorder

Keywords

MDMA; 3,4-Methylenedioxymethamphetamine; Massed prolonged exposure therapy; Pos traumatic stress disorder

Outcome Measures

Primary Outcomes (1)

• Changes in PTSD symptoms measured by CAPS-5-R

  The CAPS-5-R is a structured clinical interview used to assess PTSD symptoms based on DSM-5 criteria. Each symptom is rated on frequency and intensity * Combined into a severity score per item * Total score reflects overall PTSD symptom severity

  Baseline, 1 month post-treatment

Secondary Outcomes (2)

• Changes in PTSD symptoms measured by PCL-5

  Baseline, 1 month post treatment

• Change in PHQ questionnaire scores

  Baseline, 1 month post-treatment

Other Outcomes (2)

• Changes in fMRI-based neural activation patterns

  Day 1 of treatment, Day 10 of treatment

• Changes in fear extinction retention

  Day 4, Day 10 of treatment

Study Arms (2)

MDMA group

EXPERIMENTAL

Drug: 3,4-Methylenedioxymethamphetamine (MDMA); Behavioral: Massed Prolonged Exposure (PE)

Standard of Care

PLACEBO COMPARATOR

Drug: Placebo; Behavioral: Massed Prolonged Exposure (PE)

Interventions

Massed Prolonged Exposure (PE) BEHAVIORAL

Massed exposure therapy will be conducted for 11 sessions, 10 daily sessions and an additional therapy session during V2. They will consist of repeated exposures to trauma memories (imaginal exposure) consistent with the manualized protocol for massed exposure therapy. Also consistent with this treatment manual, participants will listen to imaginal exposures outside of PE sessions for "homework."

MDMA group; Standard of Care

3,4-Methylenedioxymethamphetamine (MDMA) DRUG

MDMA is a synthetic compound, commonly administered as MDMA hydrochloride (HCl). The drug will be administered in 100mg doses for a single session on Visit 2 out of 10- day study sessions over 2 weeks. MDMA is administered orally in capsule form and is taken under supervision in a controlled, therapeutic environment

Also known as: MDMA

MDMA group

Placebo DRUG

Placebos will visually match the 3 MDMA capsules (40mg, 40mg, and 20mg).

Standard of Care

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PTSD diagnosis as assessed by Clinician-Administered Posttraumatic Stress Scale for DSM-5 - Revised (CAPS-5-R).
• Able to speak and read English (due to standardization of outcome measures).
• Willing to sign a release for the investigators to communicate with their primary care or mental health providers if indicated.
• Able to swallow pills.
• Agree to have study visits video and/or audio recorded, including Experimental Session, assessments, and non-drug therapy sessions.
• Willing to provide a contact (relative, spouse, close friend, or another support person) who is willing and able to be contacted by the investigators.
• Agree to inform the investigators within 48 hours of any medical conditions and procedures.
• If able to become pregnant, must have a negative pregnancy test before study entry, at study entry, and before the Medicine Session. Must agree to use adequate birth control for a month before the Medicine session and through 10 days after the Medicine Session.
• Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications before the Medicine Session, and not participating in any other interventional clinical trials during the duration of the study, are driven home or to a hotel after the Medicine Session, and commit to medication dosing, therapy, and study procedures

You may not qualify if:

• Are not able to give adequate informed consent.
• Have previously participated in a Multidisciplinary Association for Psychedelic Studies (MAPS) sponsored MDMA clinical trial.
• Have any current problem which, in the opinion of the investigator or study physician, might interfere with participation.
• Have hypersensitivity to any ingredient of the Investigational Medicinal Product (IMP).
• Upon review of medical or psychiatric history and psychiatric assessment, have any current or past diagnosis that would be considered a risk to participating in the study
• Requires ongoing psychiatric medication use with certain exceptions. Individuals may decide to taper psychiatric medications under the guidance of their local provider.
• Have any unstable medical condition that would interfere with participation.
• Have uncontrolled hypertension) documented on three separate occasions.
• Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.
• Have a history of ever having ventricular arrhythmia or any other abnormal heart rhythm that the study physician believes would pose a significant risk of participation.
• Have an abnormal finding on electrocardiogram
• Have a history of additional risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Require the use of concomitant medications that could impact the effects or safety of MDMA during the Medicine Session.
• Have symptomatic liver disease or significant liver enzyme elevations.
• Have a history of hyponatremia or hyperthermia.

Sponsors & Collaborators

• Emory University: lead
• United States Department of Defense: collaborator

Study Sites (1)

Emory Brain Health Center

Atlanta, Georgia, 30329, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

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

• Jessica Maples-Keller, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica Maples-Keller, PhD

CONTACT

404-727-3662; patstudy@emory.edu

Syreese Fuller

CONTACT

patstudy@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 17, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)