Actively Recruiting

Open-Label Psilocybin Study in Transdiagnostic Population

PTSD • Depression • Anxiety • Substance Use

ClinicalTrials.gov

NCT06442423

Phase

Phase 1b · Open-Label

Enrollment

50 Participants

Intervention

Psilocybin (25 mg)

Sponsor

Yale University

PI

Benjamin Kelmendi, M.D.

This study is currently enrolling participants in New Haven, CT

Study Overview

This Phase 1b proof-of-concept trial investigates the safety, feasibility, and tolerability of psilocybin treatment in individuals with functional impairment due to psychiatric symptoms — including depression, PTSD, anxiety, OCD, and substance use disorders.

Unlike most psychedelic clinical trials, this study allows for diagnostic complexity and co-occurring conditions, mirroring how mental illness actually presents in clinical practice.

All participants receive a single dose of oral psilocybin with non-directive therapeutic support before, during, and after. Follow-up at 1, 4, and 6 weeks, with optional long-term follow-up at 3, 6, and 12 months.

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Primary Objective

Assess safety, feasibility, and tolerability of psilocybin in a transdiagnostic population — including screen failure rates, dropout rates, adverse events, and safety indices surrounding dosing.

Secondary objective

Determine whether participants experience statistically significant symptom reduction and functional improvement from baseline to 1-week, 4-week, and 6-week post-dosing assessments.

Initial psychiatric assessment, medical history review, lab work, and eligibility determination.
Standardized symptom rating scales administered. Baseline neuropsychological and functional assessments completed.
Meeting with the study therapist to prepare for the dosing experience. Includes orientation to the session environment, intention-setting, and safety review.
Single oral dose of psilocybin (25 mg in gelatin capsule) administered under non-directive therapeutic support. Continuous monitoring including vitals, C-SSRS, and adverse event documentation. Safe transportation arranged post-session.
Therapist-led session to process the dosing experience and integrate insights into daily life. Symptom re-assessment.
Symptom and functional assessments at 1, 4, and 6 weeks post-dosing. Safety monitoring continues throughout.
Optional check-ins at 3, 6, and 12 months for participants who consent to extended follow-up.

Important Considerations

Cost

All study procedures, therapy, and assessments are provided at no cost to participants.

Safety

Continuous monitoring during the dosing session including vitals, adverse events, and psychiatric safety assessments. Safe transportation arranged post-session.

FDA oversight

Conducted under FDA IND regulatory oversight at Yale School of Medicine with comprehensive safety protocols.

Medications

Participants may need to taper or adjust certain psychiatric medications prior to the study. This is discussed during screening and managed with physician oversight.

Confidentiality

All participant information is kept strictly confidential under Yale University's IRB-approved protocols.

Study Objectives

What to Expect: Protocol Timeline

Breakthrough: Psilocybin for Major Depression

Phase 2b trial shows 71% of participants experiencing significant symptom reduction

Oct 15, 2024

Breakthrough: Psilocybin for Major Depression

Phase 2b trial shows 71% of participants experiencing significant symptom reduction

Oct 15, 2024

Breakthrough: Psilocybin for Major Depression

Phase 2b trial shows 71% of participants experiencing significant symptom reduction

Oct 15, 2024

Breakthrough: Psilocybin for Major Depression

Phase 2b trial shows 71% of participants experiencing significant symptom reduction

Oct 15, 2024

What we Do

Beyond our direct research initiatives, ENACT serves as the operational foundation for the Yale Program for Psychedelic Science. We provide the structural support, methodological frameworks, and collaborative environment that enables the incubation of specialized research divisions. This catalytic role is central to what we do—transforming isolated expertise into interconnected knowledge networks that collectively advance the field."

At ENACT, research is not simply conducted—it is lived, activated, and set in motion. In this dynamic interplay of possibility and action, suspended potential transforms into living reality, where knowledge flows into practice and principles come alive through purpose. Here, ENACT catalyzes research that moves with intention, resonates with meaning, and brings knowledge to life in embrace of the whole person.

What we Do

Beyond our direct research initiatives, ENACT serves as the operational foundation for the Yale Program for Psychedelic Science. We provide the structural support, methodological frameworks, and collaborative environment that enables the incubation of specialized research divisions. This catalytic role is central to what we do—transforming isolated expertise into interconnected knowledge networks that collectively advance the field."

At ENACT, research is not simply conducted—it is lived, activated, and set in motion. In this dynamic interplay of possibility and action, suspended potential transforms into living reality, where knowledge flows into practice and principles come alive through purpose. Here, ENACT catalyzes research that moves with intention, resonates with meaning, and brings knowledge to life in embrace of the whole person.