MDMA with intensive prolonged exposure therapy for PTSD

MDMA-Assisted Massed Exposure Therapy for PTSD

This trial will test whether adding a single dose of MDMA to a two-week course of intensive prolonged exposure therapy helps adults with PTSD reduce their symptoms more than therapy with a placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 21 Years to 70 Years
• Sex: All
• Sponsor: Emory University (Academic / other)
• Locations: 1 site (Atlanta, Georgia)
• Trial ID: NCT07288151 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 trial enrolling 95 adults with PTSD to test one dose of MDMA given during the second of ten massed Prolonged Exposure (PE) therapy sessions delivered over two weeks. Participants are randomized to receive either 100 mg MDMA or placebo alongside identical PE therapy, with blinded independent evaluators measuring PTSD symptoms before treatment and at one-month follow-up using standardized interviews. The study also includes mechanistic measures of extinction retention and amygdala threat reactivity to explore how MDMA may alter fear-related brain responses. Results will compare symptom reduction magnitude, speed of response, and durability between the MDMA and placebo groups.

Who should consider this trial

Good fit: Adults diagnosed with PTSD who can commit to an intensive two-week therapy schedule, are medically eligible to take MDMA (including negative pregnancy tests and agreed contraception where applicable), and are willing to undergo medication sessions and video or audio recording are ideal candidates.

Not a fit: Patients who cannot safely take MDMA for medical or pregnancy-related reasons, who cannot commit to the intensive two-week therapy schedule, or who are unwilling to accept medication or recording of sessions may not receive benefit from this protocol.

Why it matters

Potential benefit: If effective, adding MDMA to intensive PE could produce faster, larger, and more durable reductions in PTSD symptoms for some patients.

How similar studies have performed: Early pilot data and other MDMA-assisted PTSD research have reported large symptom reductions, but this is among the first randomized trials combining MDMA specifically with massed PE to test those effects formally.

Eligibility criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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 a history of any medical condition that could make receiving MDMA dangerous because of increases in blood pressure and heart rate or any medical condition the study physician believes would pose a safety risk or interfere with the effects of the treatment. Any medical disorder judged by the investigator to significantly increase the risk of MDMA administration by any mechanism is exclusionary.
* 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.
* Weigh less than 48 kilograms (105 lbs.).
* Are pregnant or nursing
* Have engaged in ketamine-assisted therapy or used ketamine within 12 weeks of enrollment

Where this trial is running

Atlanta, Georgia

• Emory Brain Health Center — Atlanta, Georgia, United States (Recruiting)

Study contacts

• Principal investigator: Jessica Maples-Keller, PhD — Emory University
• Study coordinator: Jessica Maples-Keller, PhD

Conditions Post Traumatic Stress Disorder; MDMA; 3,4-Methylenedioxymethamphetamine; Massed prolonged exposure therapy; Pos traumatic stress disorder