NCT07479550

Anesthesia-Masked Psilocybin Therapy for Major Depression

A Phase 2 Randomized Study Examining the Safety, Feasibility, and Effectiveness of Masking Psilocybin Therapy With General Anesthesia in Major Depressive Disorder

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Stanford University · Academic / Other
• Sex: All
• Age: 25 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Major depressive disorder (MDD) affects millions of Americans and remains difficult to treat. Psilocybin, a psychedelic compound, has shown promise for reducing depression symptoms, but a key challenge in psychedelic research is that participants can usually tell whether they received the active drug - making it hard to conduct fully blinded studies. This study (Studying Psilocybin with Anesthesia Controlled by EEG \[SPACE\]) tests a new approach: administering psilocybin while participants are under general anesthesia, so that the noticeable psychological effects of psilocybin are masked. This allows both participants and outcome assessors to remain unaware of whether psilocybin or placebo was given, improving the scientific rigor of the research. Participants with MDD will be randomly assigned to receive either psilocybin or placebo across four dosing sessions conducted under general anesthesia. The study will assess whether this approach is safe and feasible, and will collect early data on whether it may reduce depression symptoms.

Detailed description

Participants will receive four dosing sessions spaced one week apart. Each session involves taking an oral capsule containing either psilocybin (10 mg or 25 mg) or placebo, followed by general anesthesia with propofol. All sessions take place at Stanford Hospital under the supervision of a board-certified anesthesiologist. Between and after sessions, participants complete questionnaires about mood, sleep, wellbeing, and anxiety. Participants may also wear a consumer-grade EEG headband at home to track sleep patterns. The total study duration per participant is approximately 7 weeks, across around 25 visits, most of which are conducted remotely. Psilocybin is not FDA-approved and is administered under an FDA Investigational New Drug (IND) authorization for research purposes only.

Conditions

• Major Depression

Interventions

Type	Name	Description
DRUG	Psilocybin (Usona Institute)	Oral psilocybin capsules administered at doses not disclosed to participants to preserve blinding. Each dose is administered approximately 30 minutes prior to induction of general anesthesia with propofol. Participants receive psilocybin or placebo across four weekly dosing sessions.
DRUG	Propofol	Intravenous propofol administered by a board-certified anesthesiologist to induce and maintain general anesthesia during each of the four dosing sessions. Propofol is co-administered with psilocybin or placebo to mask the psychoactive effects of psilocybin and enable participant blinding.
DRUG	Placebo	Oral placebo capsule identical in appearance to the psilocybin capsules, administered prior to induction of general anesthesia with propofol during one of the four dosing sessions.

Timeline

• Start date: 2026-07-01
• Primary completion: 2027-07-01
• Completion: 2027-08-01
• First posted: 2026-03-18
• Last updated: 2026-04-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study