Study of Psilocybin Under Anesthesia Controlled by EEG

Starting soon · Phase 2 · Has a placebo group

Conditions studied: Major Depression

In brief

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.

Key facts

Study ID

NCT07479550

Run by

Stanford University

People needed

10

Starts

2026-07-01

Expected to finish

2027-08-01

Last updated by the study team

2026-05-06

Who can join

Age: 25 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• A participant will be eligible for inclusion when all of the following criteria are met:
• 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;
• Be stable in background psychotherapy for at least 4 weeks prior to enrollment outside of the study and able to access mental healthcare for the duration of the study;
• Body mass index between 17-35 kg/m2.
• Participant has a current diagnosis of MDD during a current Major Depressive Episode (MDE) (single or recurrent episode as defined by DSM-5-TR [if single episode, duration of ≥4 weeks] and verified after evaluation by a qualified member of the investigative team using the QuickSCID-5 (Quick Structured Clinical Interview for DSM-5 Disorders).
• Able to physically tolerate general anesthesia, as determined by American Society of Anesthesiologists (ASA) Physical Status Class I or II. ASA Class III participants whose functional impairment is directly related to a psychiatric diagnosis (depression) will be included.
• Agree that for one week preceding the psilocybin sessions and throughout the study, they will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study staff. Exceptions will be evaluated by the study staff and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
• Agree not to consume any food or drink after midnight preceding dosing days.
• Agree not to consume alcoholic beverages for 48 hours prior to and 24 hours following the dosing sessions.
• Agree not to use cannabis in any form for the duration of the study.
• Non-smoker, or abstained at least 6 weeks.
• For people who can become pregnant: agree to use highly effective contraception from entry into the trial through the end of the study.
• a. A person with a uterus is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterilized (i.e. has had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy).
• b. A person with a uterus who is not of childbearing potential is considered to be postmenopausal after at least 12 months without menstruation.
• c. Highly effective contraception (typical use failure rate of less than 1%) is defined i. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
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• oral
• intravaginal
• Transdermal
• Double-barrier method ii. progestogen-only hormonal contraception associated with inhibition of ovulation:
• oral 2. injectable 3. implantable iii. intrauterine device (IUD) iv. intrauterine hormone-releasing system (IUS) v. bilateral tubal occlusion vi. vasectomized partner vii. sexual abstinence
• d. Periodic abstinence (i.e., calendar, symptothermal, or postovulation methods, and tubal ligation/occlusion) are not an acceptable form of contraception for this study.

You may not qualify if…

• A potential participant will NOT be eligible for participation in this study if any of the following criteria are met:
• Has any ongoing legal or disability claim such as Worker's Compensation
• Is taking a medication belonging to any of the following classes:
• a. TCAs, MAOIs, SSRIs, SNRIs. (Other antidepressants including mirtazapine, nefazodone, trazodone, vilazodone, vortioxetine, and bupropion are allowed.) b. Typical or atypical antipsychotics c. Anticonvulsants such as valproate, topiramate, oxcarbazepine, carbamazepine. (Gabapentinoids and lamotrigine are allowed.) d. Other agents that may be associated with serotonin syndrome: i. St. John's Wort ii. S-adenosyl-methionine (SAM-e) iii. 5-Hydroxytryptophan (5-HTP) iv. Lithium v. Dextromethorphan vi. Linezolid vii. Buspirone viii. Efavirenz ix. Lorcaserin e. Agents that may interact with psilocybin metabolism/effects: i. Modulators of uridine diphosphate (UDP) or glucuronosyltransferase (UGT) (e.g., COMT inhibitors, ethinyl estradiol, valproate, diclofenac, mefenamic acid, verapamil, ketoconazole, itraconazole, probenecid, phenobarbital, protease inhibitors) ii. L-Methylfolate (>/= 7.5mg/day) iii. Alcohol or aldehyde dehydrogenase inhibitors
• 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.
• For individuals who can become pregnant:
• a. Currently pregnant (confirmed or suspected) b. Currently breastfeeding c. Positive urinary pregnancy test at screening or immediately before dosing d. Unwilling or unable to use highly effective contraception (defined as methods with failure rate <1% per year) from the time of consent through 30 days following the last dosing session e. Planning to become pregnant within 30 days following the psilocybin or placebo administration sessions
• 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.
• Currently receiving electroconvulsive therapy (ECT). Previous treatment with ECT is permitted; last treatment must be at least 30 days prior to entry into this trial.
• History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms, mania, or bipolar affective disorder
• A positive urine toxicology screen including amphetamines, cocaine, MDMA, cannabis, opioids, ketamine, and benzodiazepines at screening visit and on the morning of the dosing session.
• Use of psychedelics in the previous 6 months prior to screening (psilocybin, LSD, DMT, 5-Meo-DMT, MDMA, Ibogaine).
• History of meeting DSM-5 criteria for Hallucinogen Use Disorder (Moderate or Severe) or Hallucinogen Persisting Perception Disorder (HPPD),or has ever had a negative reaction to or experience with a psychedelic (e.g., "bad trip").
• Current diagnosis of a Substance Use Disorder over the last 12 months (SUD; Abuse or Dependence, as defined by DSM-V) per QuickSCID-5. Participants who are at risk of alcohol or cannabis withdrawal will be excluded (e.g. those who endorse tolerance or who have experienced previous withdrawal). The following categories of SUD will NOT be excluded: nicotine dependence; alcohol or cannabis substance use disorder rated "mild".
• Current diagnosis of a psychiatric disorder or mental health status that in the judgement of the study staff increases the risk of the intervention or would interfere with the patient's ability to engage in the intervention at any time within the six months prior to screening.
• History of suicide attempt requiring hospitalization or suicidal ideation with intent in the last 10 years.
• In the judgment of the study staff, the participant is at significant risk for suicidal behavior during the course of their participation in the study per Columbia Suicide Severity Rating Scale (C-SSRS), rated 'High Risk'.
• A neurological disorder including:
• Dementia, delirium, amnestic, or any other cognitive disorder.
• Lifetime history of surgical procedures involving the brain or meninges,
• Encephalitis, meningitis, degenerative central nervous system disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation
• Any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system (CNS),
• History of significant head trauma within the past two years.
• A cardiovascular disorder including:

Where it is running

• Stanford University — Stanford, California, United States

Full record on ClinicalTrials.gov

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