MDMA-Assisted Massed Exposure Therapy for PTSD

This Phase II, randomised, triple‑blind, parallel trial (n=200) will evaluate whether a single 100 mg oral dose of MDMA given adjunctively with massed Prolonged Exposure (PE) therapy improves PTSD symptom severity and related neural measures in adults with post‑traumatic stress disorder (age 21–70 years), with the primary outcome being change in Clinician‑Administered PTSD Scale for DSM‑5‑Revised (CAPS‑5‑R) score from baseline to one month post‑treatment. Participants will be randomised to MDMA + massed PE or placebo + massed PE; MDMA is administered as a 100 mg capsule under supervision at Visit 2 of a course of 10 daily PE sessions delivered over two weeks (11 therapy sessions total, including an additional session during Visit 2), and the placebo visually matches the three MDMA capsules (40mg, 40mg, and 20mg). The study will also assess response efficiency and durability of symptom improvement and explore extinction retention and amygdala threat reactivity (neuroimaging), with safety and blinded independent evaluator CAPS‑5‑R assessments at the one‑month post‑treatment follow‑up; the trial is sponsored by Emory University with an anticipated start in January 2026 and completion in January 2030.

Detailed Description

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

Participants

Ages

21 – 70

Sexes

Male & Female

BMI

Psychosis History

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

Company

Product

Legal

MDMA-Assisted Massed Exposure Therapy for PTSD

Detailed Description

Study Arms & Interventions

MDMA group

Interventions

Standard of Care

Locations

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators