NCT06512194

Investigation to Understand and Optimize Psilocybin

An Investigation of Strategies to Understand and Optimize the Antidepressant Effects of Psilocybin (The OPTIMIZE Study)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 141 (estimated)
• Sponsor: Charles Raison · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This study will examine the effects of a single dose of psilocybin, administered with psychological support, on symptoms of depression. It will also assess whether different post-dosing interventions, including a non-invasive technique called transcutaneous auricular Vagus Nerve Stimulation (taVNS), influence various psychological and behavioral outcomes. In addition, the study will explore objective measures of real-world social behavior and identify early behavioral responses that may be associated with long-term treatment outcomes.

Detailed description

One hundred forty-one adults ages 18 to 70 experiencing a major depressive episode of at least 60 days duration of moderate or greater severity at screening will be enrolled to obtain evaluable data on approximately 120 subjects. All subjects will receive a single 25 mg dose of psilocybin using a "set and setting" therapeutic approach that will include 1) several hours of preparatory sessions prior to dosing and 2) the presence of two facilitators throughout the dosing session; and 3) several post dosing integration sessions with a facilitator. Following the psilocybin dosing session, subjects will be randomized to 1) taVNS (7 days of twice daily taVNS), 2) sham taVNS (7 days of twice daily sham taVNS), or 3) no taVNS. Both taVNS and sham sessions will include guided prompts encouraging participants to reflect on key aspects of their psychedelic experience, accompanied by music previously used during the psilocybin dosing session. Participants will complete assessments at multiple time points to evaluate depression, anxiety, well-being, functional disability, quality of life, social behavior, suicidal ideation, and adverse events before and after psilocybin dosing.

Conditions

• Depression

Interventions

Type	Name	Description
DRUG	Psilocybin	The psilocybin used in this study is synthesized under Good Manufacturing Practice (GMP) guidelines and is provided in a capsule containing 25 mg of synthetic psilocybin.
DEVICE	Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)	Participants will be provided with a taVNS device and trained on its use. The device delivers gentle stimulation to the left ear.
DEVICE	Sham taVNS	Participants will be provided with a taVNS device and trained on its use. The device delivers gentle stimulation to the left ear. In the sham condition, the device will simulate the sensations of active taVNS without delivering therapeutic stimulation.

Timeline

• Start date: 2025-05-13
• Primary completion: 2029-05-01
• Completion: 2029-05-01
• First posted: 2024-07-22
• Last updated: 2025-05-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study