NCT07332143

Psilocybin-Assisted Randomized Therapy

The Safety and Acceptability of Psilocybin With Support and With Massed Prolonged Exposure Therapy for PTSD

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This pilot study will examine the safety, tolerability, acceptability, and efficacy of combination psilocybin + psychotherapy to decrease PTSD symptoms. Participants will be randomized into two different treatment groups, allowing the investigators to directly compare PE augmented with psilocybin and psilocybin-assisted psychotherapy.

Detailed description

The Primary objective is to pilot and investigate tolerability, safety, and acceptability of psilocybin-assisted supportive therapy and psilocybin-assisted massed prolonged exposure (PE) therapy and conduct exploratory analyses related to comparative effectiveness of these treatments, including preliminary outcomes from pre-treatment to 1-month follow-up on post-traumatic stress disorder (PTSD) symptoms. Safety and tolerability of the treatment will be assessed and evaluated using the Swiss Psychedelic Side Effects Inventory (SPSI), Psychedelic-assisted Therapy After Effects (PATAE), and the Accessibility Questionnaire (AQ). The study will also evaluate the effect of psilocybin and massed exposure therapy using Subjective Units of Distress (SUDS) during imaginal exposure sessions; to assess self-reported PTSD and depression symptoms across treatment and investigate effect on fear extinction learning and fear extinction recall as assessed via fear potentiated startle. Given that this is a pilot study with small sample, analyses will be preliminary.

Conditions

• PTSD

Interventions

Type	Name	Description
DRUG	psilocybin	25 mg
BEHAVIORAL	Supportive Therapy	Treatment includes non-directive psychological support across the preparatory, dosing, and integration sessions. Preparatory sessions include psychoeducation regarding psilocybin's subjective effects and establish strategies for psilocybin related support, including boundaries around physical touch. Therapists encourage setting intention for dosing day, and practicing experiential exercises. Integration sessions include processing the participant's experience of their psilocybin administration session. Therapists will support participants in identifying activities for ongoing integration outside of sessions. The standard care for supportive therapy will be modeled in this study.
BEHAVIORAL	Prolonged Exposure Therapy	Prolonged Exposure (PE) Therapy will be conducted for 10 sessions. 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 and conduct in real life exposures outside of PE sessions for "homework". The standard care for PE therapy will be modeled in this study.

Timeline

• Start date: 2026-03-01
• Primary completion: 2027-03-01
• Completion: 2027-03-01
• First posted: 2026-01-12
• Last updated: 2026-01-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study