NCT07288151

MDMA-Assisted Massed Exposure Therapy for PTSD

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 21 Years – 70 Years
• Healthy volunteers: Not accepted

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

Detailed description

Posttraumatic stress disorder (PTSD) affects many individuals, including military veterans and civilians exposed to trauma. While trauma-focused therapies like Prolonged Exposure (PE) are effective, many people do not fully recover, and current medications often have limited success. This study will test whether combining PE therapy with a single dose of MDMA (a psychoactive drug) can improve PTSD treatment outcomes. Ninety-five participants with PTSD will be randomly assigned to receive either MDMA or a placebo during the second of ten PE therapy sessions, which are delivered over two weeks. Researchers will measure PTSD symptoms one month after treatment using a standardized interview. The study will also explore how MDMA affects brain responses related to fear and emotional memory, which may help explain how it works. Early results from a pilot study suggest this combination may lead to large reductions in PTSD symptoms. This is the first clinical trial to formally test MDMA with PE therapy, and it may lead to new, more effective treatment options for PTSD.

Conditions

• Post Traumatic Stress Disorder

Interventions

Type	Name	Description
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."

Timeline

• Start date: 2026-04-01
• Primary completion: 2030-01-01
• Completion: 2030-01-01
• First posted: 2025-12-17
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study