NCT06308653

Psilocybin for Major Depressive Disorder (MDD)

A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Psilocybin in Adults With Major Depressive Disorder (MDD)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: Usona Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Participants will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo. The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the difference between groups in change in depressive symptoms from Baseline to Day 43 post-dose, and to characterize the durability of initial treatment effect and subsequent response to optional Psilocybin 25 mg re-administration(s) during the 1-year Follow-up Period.

Detailed description

Double-blind Period: Participants who show stable depression symptoms between Screening and Trial Baseline will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo. Investigational Product (IP) will be administered in the context of a "Set and Setting" (SaS) Protocol for psychosocial support, comprised of 1) a period of preparation with Facilitators prior to dosing; 2) administration of IP in an aesthetically pleasing room under the supervision of two Facilitators; and 3) post-dose integration sessions during which participants will discuss their dosing experience with the Facilitators. Trial outcome measures will assess depressive symptoms, functional disability, health-related quality of life, and clinical global impression of disease severity. Long-term Follow-up Period: After the initial 6-week Double-blind Period and completion of the post-dosing Trial Day 43 assessments, all participants will proceed into a 1-year Follow-up Period. During the 1-year Follow-up Period, participants will be followed regularly by clinic staff to assess MDD symptom severity, functional disability, and health-related quality of life; long-term safety data will also be collected. In addition to scheduled clinic visits, clinic staff will contact participants by telephone every two weeks to assess for changes in MDD symptom severity, concomitant medications, adverse events (AEs), and suicidal ideation and behavior. Participants who meet the pre-defined MDD severity criteria and meet all re-administration eligibility criteria may be offered re-administration(s) of open-label Psilocybin 25 mg administered under a "Set and Setting" (SaS) Protocol. Psychosocial support, including psychoeducation, is also incorporated in the long-term Follow-up Period.

Conditions

• Depressive Disorder, Major

Interventions

Type	Name	Description
DRUG	Psilocybin 25 mg	The Psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of Psilocybin.
DRUG	Inactive Placebo	The inactive placebo is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of Microcrystalline Cellulose (MCC). The MCC is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use.
DRUG	Psilocybin 5 mg	The Psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active comparator is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 5 mg of Psilocybin.
BEHAVIORAL	Psychosocial Support	Psychosocial Support, including psychoeducation, begins after the Double-blind Period and continues throughout the 1-year Follow-up Period in order to enhance participant safety and maximize retention for the entire trial duration.

Timeline

• Start date: 2024-03-13
• Primary completion: 2026-01-05
• Completion: 2027-01-30
• First posted: 2024-03-13
• Last updated: 2026-04-14

Locations

29 sites across 1 country: United States

Regulatory

• FDA-regulated drug study