MDMA Plus Exposure Therapy for PTSD

NCT05746572 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY000001272025P013168
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Posttraumatic stress disorder (PTSD) is a debilitating disorder. While effective treatments exist, some patients fail to receive the full benefits. Alternative treatment approaches are needed. 3,4-methylenedioxymethamphetamine (MDMA) is a medicine associated with feelings of closeness and love for others, empathy, insightfulness, and feelings of peace or well-being. Recent research combining one or two doses of MDMA with psychotherapy has shown improvements in PTSD symptoms. For the present study, the researchers will investigate MDMA in combination with Prolonged Exposure therapy (PE), a gold-standard treatment for PTSD. All participants receive MDMA on the second day of a 10-day PE treatment program in which a PE therapy session occurs each day. This study will occur at the Emory Brain Health Center. Potential participants will be recruited via community advertising and mental health referrals. The research team will also collect psychophysiological data for exploratory analyses regarding how MDMA may improve PE treatment for PTSD. This is an important study as it is the first time MDMA will be combined with an evidence-based existing PTSD treatment. The study population will consist of people who meet the criteria for PTSD and are medically appropriate for MDMA administration.

Conditions

PTSD

Keywords

MDMA; Massed Exposure Therapy

Outcome Measures

Primary Outcomes (1)

• Effect of MDMA-assisted massed exposure therapy on clinician-rated PTSD symptoms

  Measured by the change in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score from baseline to 1-month post-treatment. The CAPS-5 is a structured clinician-administered measure that assesses the presence and severity of PTSD per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. All the DSM-5 symptoms of PTSD are assessed and rated on a scale from 0 (Absent) to 4 (Extremely Severe), with clear anchors provided to clinicians to assist with accurate ratings.

  Baseline (day 1) and day 42 (+/- 2 days)

Secondary Outcomes (1)

• Effect of MDMA on massed exposure therapy on self-reported PTSD symptoms.

  Baseline (day 1) and day 42 (+/- 2 days)

Study Arms (1)

Medicine Session

EXPERIMENTAL

3,4-methylenedioxymethamphetamine (MDMA) in combination with massed exposure therapy for PTSD

Drug: MDMA

Interventions

MDMA DRUG

Participants will receive MDMA HCl (100 mg, 84 mg MDMA) in combination with massed exposure therapy for PTSD.

Also known as: MDMA-assisted massed exposure therapy, MDMA + PE

Medicine Session

Eligibility Criteria

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

You may qualify if:

• Meet criteria for PTSD
• Willingness of the participant to sign a release for the investigators to communicate with their primary care or mental health providers if indicated
• Are able to visually read and understand the English language and give written informed consent.
• Are able to swallow pills.
• Agree to have study visits and treatment sessions video and/or audio recorded,
• Must provide a contact (relative, spouse, close friend, or another support person) who is willing and able to be reached by the investigators.
• Must 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 prior to study entry, at study entry, and prior to the Medicine Session. Must agree to use adequate birth control for a month prior to 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 prior to Medicine Session, and not participate in any other interventional clinical trials during the duration of the study and 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 assessment, have any current or past diagnosis that would be considered a risk to participating in the study
• Current or past substance abuse that would be considered a risk for 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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory Brain Health Center

Atlanta, Georgia, 30329, United States

Location

Related Publications (1)

• Maples-Keller JL, Dunlop BW, Rothbaum BO. The METEMP protocol: Massed exposure therapy enhanced with MDMA for PTSD. Contemp Clin Trials Commun. 2024 Nov 24;43:101400. doi: 10.1016/j.conctc.2024.101400. eCollection 2025 Feb.

  PMID: 39895858 DERIVED

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

• Barbara O Rothbaum, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: February 27, 2023
• Study Start: February 13, 2024
• Primary Completion (Estimated): May 29, 2026
• Study Completion (Estimated): May 29, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)