MDMA-Assisted Massed Exposure Therapy for PTSD

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

Interventions

DRUG

3,4-Methylenedioxymethamphetamine (MDMA)

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

DRUG

Placebo

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

BEHAVIORAL

Massed Prolonged Exposure (PE)

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."

Sponsors & Collaborators

• United States Department of Defense

  collaborator FED

• Emory University

  lead OTHER

Principal Investigators

• Jessica Maples-Keller, PhD · Emory University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-30

Primary Completion

2030-01-31

Completion

2030-01-31

FDA Drug

Yes

Countries

• United States

Study Locations