NCT06442423

Open-Label Psilocybin Study in Transdiagnostic Population

Safety, Feasibility, and Tolerability of Psilocybin Treatment for Individuals With Functional Impairment Related to Mood, Anxiety, Trauma and/or Addiction Symptoms: An Open-label Proof-of-concept Study

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

The primary objective of this study is to investigate the safety, feasibility, and tolerability of psilocybin treatment in individuals with functional impairment due to psychiatric symptoms. The secondary objective of this study is to determine whether individuals with functional impairments due to psychiatric symptoms will experience statistically significant symptom reduction and functional improvement from baseline symptom measurements (Visit 3) to 1-week (Visit 7), 4-weeks (Visit 8), and 6-weeks (Visit 9) post dosing. The investigators will recruit individuals with mood, anxiety, trauma, addictive, or related symptomatology, and who have functional impairment associated with these symptoms. A DSM-5 diagnosis is not required (nor is it an exclusion). The investigators will allow for comorbidity and only exclude based on psychological and physiological safety considerations. Critically, this approach will allow us to assess the tolerability of our interventions in individuals who would typically be excluded from efficacy studies due to various comorbid DSM-5 conditions. The investigators will employ an open-label study where participants will be given one dose of oral psilocybin 25mg. The investigators will also have follow-up visits at 1, 4, and 6 weeks and an optional long-term follow-up at 3, 6, and 12 months.

Detailed description

In this Phase 1b proof-of-concept clinical trial, the investigators aim to investigate the safety, feasibility, and tolerability of treatment of oral psilocybin in participants with functional impairment due to depressive, anxiety, trauma addictive, or other psychiatric symptomatology, allowing for comorbidity and diagnostic complexity to mirror potential real-world clinical scenarios. Secondarily, The investigators will assess improvement in functional status and symptomatology. The investigators will employ an open-label study design, with participants receiving one dose of oral psilocybin. This is an open-label clinical trial with a single treatment arm and no blinding. All participants will receive 25 mg of oral psilocybin. All dosing will be accompanied by non-directive support before, during, and after treatment sessions.The rationale for conducting this study lies in recognizing that the narrow inclusion and exclusion criteria commonly employed in clinical trials may raise issues of external validity. While previous research has predominantly focused on specific diagnostic categories, our study aims to address these limitations by exploring the safety, feasibility, and tolerability of psilocybin in a heterogeneous population. This study also recognizes the importance of symptom-related functional impairment as a cross-cutting construct relevant to all diagnostic categories.This is a Phase 1b open-label clinical trial to determine the feasibility, tolerability and safety of psilocybin to reduce psychiatric symptoms in participants experiencing functional impairment. Participants will receive one dose of oral psilocybin (25mg). Follow-up visits for assessments and measures at 1-week, 4-week, and 6-week post psilocybin dosing. Long-term follow-up visits assessments and measures for participants who consent to long-term follow-up (reassessments of study measures) for 3-month, 6-month, and 12-month post dosing. Psilocybin (4-hydroxy-N,N-dimethyltryptamine) occurs in nature in many species of mushrooms, including the genera Psilocybe, Conocybe, Gymnopilus, Panaeolus, and Strophparia. Its chemical formula is C12H17N2O4P. Psilocybin is a potent agonist at 5-HT2A/C receptors; potency of binding by related compounds to these receptors correlates with human potency as hallucinogens. Psilocybin is currently a Schedule I substance. Psilocybin will be orally administered in this study. Psilocybin will be administered in an opaque, size 2 gelatin capsule with approximately 180 ml of water to be orally ingested at Visit 5. The dose of psilocybin will be 25 mg. Descriptives for all safety measures (e.g., C-SSRS total and subscale scores, vitals, documented adverse events) will be compiled at all assessment intervals. Classification of adverse events will follow institute and regulatory body guidelines. Subsequent summary descriptives may focus on safety indices surrounding the dosing session and 1-week, 4 weeks, and 6-weeks after dosing. In addition, The investigators will perform descriptives and non-parametric analysis screen failure rates (including analysis of ineligibility), drop out rates pre and post dosing to determine feasibility and tolerability.

Conditions

• Transdiagnostic
• Depression - Major Depressive Disorder
• Anxiety
• PTSD Symptoms
• PTSD
• Substance Use
• Substance Use Disorder (SUD)
• OCD

Interventions

Type	Name	Description
DRUG	Psilocybin	Psilocybin will be administered in an opaque, size 2 gelatin capsule with approximately 180 ml of water to be orally ingested at Visit 5. The dose of psilocybin will be 25 mg.This is an open-label clinical trial with a single treatment arm. This is an open-label clinical trial with no blinding.

Timeline

• Start date: 2024-10-17
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2024-06-04
• Last updated: 2026-03-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study