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Study of Psilocybin Under Anesthesia Controlled by EEG

ConditionMajor Depression
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age25-65
SponsorStanford University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

People 25 to 65 years of age at screening;

Able to read, understand, and provide dated, informed consent, either in writing or electronically, prior to screening. Patients will be deemed likely to comply with study protocol and communicate with study staff about adverse events and other clinically important information;

Fluent in English;

Able to commit to attend all study visits and participate in all remote data collection procedures;

Disqualifiers

Has any ongoing legal or disability claim such as Worker's Compensation

Is taking benzodiazepine medication such that patient cannot tolerate withholding doses 8 hours before through 6 hours after planned study intervention

Is taking agents that may interact with psilocybin metabolism effects such that the patient cannot tolerate withholding doses 8 hours before through 6 hours after planned study intervention.

Participation in a clinical trial within 30 days of entry into this trial, or during the trial, or treatment with another investigational drug or other intervention within 30 days or 5 half-lives, whichever is longer, that may interfere with psilocybin metabolism/effects.

Trial design

Design model

Crossover

Treatments tested in this trial

  • Psilocybin (Usona Institute)

    Drug

    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.

  • Propofol

    Drug

    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.

  • Placebo

    Drug

    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.

Treatment groups

10 Participants
are divided into 2 treatment groups
Group A: Sequence AExperimental treatment 3 interventions
Group B: Sequence BExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Blinding Success - Correct Identification of Psilocybin at Final Dosing Session

Percentage of participants who correctly guess whether they received a full dose of psilocybin during the final dosing session (Visit 20), assessed using the Blinding Survey at Visit 21.

Time frame
1 day after the final dosing session (Visit 21, Week 4)
2

Blinding Success - Accuracy of Guessed Psilocybin Dose at Final Dosing Session

The dose of psilocybin guessed by participants at Visit 21 compared to the dose actually received at Visit 20, assessed using the Blinding Survey.

Time frame
1 day after the final dosing session (Visit 21, Week 4)

Secondary outcomes

1

Acute Drug Effects by Dose - Drug Effects Questionnaire (DEQ)

Mean differences in acute subjective drug effects between psilocybin doses and placebo, assessed using the Drug Effects Questionnaire (DEQ; Morean et al., 2013) after emergence from anesthesia at each dosing session. The DEQ consists of 5 items rated on visual analog scales; scores are expressed as the mean across items. Minimum score: 0 (no drug effects); Maximum score: 100 (maximum drug effects). Higher scores indicate greater perceived drug effect.

Time frame
Immediately after emergence at each of the 4 dosing sessions (Visits 5, 10, 15, 20; Weeks 1-4)
2

Mystical-Type Experiences by Dose - Mystical Experiences Questionnaire (MEQ-30)

Mean changes in overall and subsection scores of the Mystical Experiences Questionnaire (MEQ-30; Maclean et al., 2012) compared between psilocybin doses and placebo, assessed after emergence from anesthesia at each dosing session. The MEQ-30 consists of 30 items rated on a 0-5 scale across four subscales: Mystical, Positive Mood, Transcendence of Time and Space, and Ineffability. Total scores are calculated by summing all individual items. Minimum score: 0 (no mystical-type experience); Maximum score: 150 (extreme mystical-type experience). Higher scores indicate greater mystical experience intensity.

Time frame
Immediately after emergence at each of the 4 dosing sessions (Visits 5, 10, 15, 20; Weeks 1-4)
3

Altered States of Consciousness by Dose - Three-Dimensional Altered States of Consciousness Scale (3D-ASCr)

Mean changes in overall and dimension scores of the Three-Dimensional Altered States of Consciousness Rating Scale - Revised (3D-ASCr; Stocker et al., 2025) compared between psilocybin doses and placebo, assessed after emergence from anesthesia at each dosing session. The 3D-ASCr consists of 42 items rated on visual analog scales, organized into three higher-order dimensions: Positive Effects (PosE), Distressing Effects (DisE), and Perceptual Effects (PerE). Dimension scores are calculated as means of their constituent subscale means. Minimum score: 0 (no alteration); Maximum score: 100 (maximum alteration). Higher scores indicate greater alteration of consciousness in each dimension; higher PosE scores reflect more positive experiential effects, higher DisE scores reflect more distressing effects, and higher PerE scores reflect greater perceptual effects.

Time frame
Immediately after emergence at each of the 4 dosing sessions (Visits 5, 10, 15, 20; Weeks 1-4)

Other outcomes

1

Feasibility - Challenging Experiences Questionnaire (CEQ)

Descriptive statistics of challenging experiences by dose of psilocybin versus placebo, assessed using the Challenging Experiences Questionnaire - 7 Item (CEQ-7; Strickland et al., 2024) after emergence from anesthesia at each dosing session. The CEQ-7 consists of 7 items rated on a 6-point scale (0 = none/not at all; 5 = extreme), one item per challenging experience domain (Fear, Grief, Physical Distress, Insanity, Isolation, Death, Paranoia). Total scores are calculated by summing all items. Minimum score: 0; Maximum score: 35. Higher scores indicate greater challenging experience severity.

Time frame
Immediately after emergence at Visits 5, 10, 15, and 20 (Weeks 1-4)
2

Safety - Incidence and Severity of Adverse Events

Incidence, severity, and CTCAE grade of adverse events, including CTCAE Grade 3 or higher cardiopulmonary, neurological, or psychiatric events, coded using MedDRA. Includes abnormal EKG and hemodynamic findings and clinically significant laboratory results.

Time frame
Continuously from Visit 1 through Visit 25 (up to 7 weeks)
3

Safety - PACU Discharge Readiness

Incidence of participants meeting post-anesthesia care unit (PACU) discharge readiness criteria within 4 hours of emergence from anesthesia at each dosing session.

Time frame
Within 4 hours of emergence at Visits 5, 10, 15, and 20 (Weeks 1-4)
4

Safety - Suicidal Ideation and Behavior (C-SSRS)

Incidence and severity of suicidal ideation and behavior assessed using the Columbia Suicide Severity Rating Scale (C-SSRS). Lifetime and Last 10 Years C-SSRS administered at screening (Visit 2); Since Last Visit C-SSRS administered at all subsequent visits.

Time frame
From Visit 2 through Visit 25 (Screening through Week 7)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Stanford University

Lead sponsor

Source ClinicalTrials.gov

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