Ignite Creation Date:
2026-03-26 @ 3:15 PM
Ignite Modification Date:
2026-03-30 @ 2:57 AM
Study NCT ID:
NCT07479550
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-18
First Post:
2026-03-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Anesthesia-Masked Psilocybin Therapy for Major Depression
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003865', 'term': 'Depressive Disorder, Major'}], 'ancestors': [{'id': 'D003866', 'term': 'Depressive Disorder'}, {'id': 'D019964', 'term': 'Mood Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D011562', 'term': 'Psilocybin'}, {'id': 'D015742', 'term': 'Propofol'}], 'ancestors': [{'id': 'D026121', 'term': 'Indole Alkaloids'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D014363', 'term': 'Tryptamines'}, {'id': 'D054836', 'term': 'Indolizidines'}, {'id': 'D007212', 'term': 'Indolizines'}, {'id': 'D010636', 'term': 'Phenols'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Participants are masked to treatment assignment through the use of general anesthesia - because they are unconscious during drug administration, they cannot detect the psychoactive effects of psilocybin. Outcomes assessors conducting blinded depression symptom ratings (MADRS) are kept unaware of treatment assignment throughout the study. The pharmacist preparing study drug is aware of treatment assignment for safety purposes but is otherwise not involved in outcome assessment.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'This is a within-subject, randomized sequence crossover design. Each participant receives all four dosing conditions - placebo (0 mg), psilocybin 10 mg, and psilocybin 25 mg administered across two separate sessions - in a randomized order. Dosing sessions are spaced one week apart.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 10}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-07', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-03', 'completionDateStruct': {'date': '2027-08', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-15', 'studyFirstSubmitDate': '2026-03-08', 'studyFirstSubmitQcDate': '2026-03-15', 'lastUpdatePostDateStruct': {'date': '2026-03-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Feasibility - Challenging Experiences Questionnaire (CEQ)', 'timeFrame': 'Immediately after emergence at Visits 5, 10, 15, and 20 (Weeks 1-4)', 'description': '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.'}, {'measure': 'Safety - Incidence and Severity of Adverse Events', 'timeFrame': 'Continuously from Visit 1 through Visit 25 (up to 7 weeks)', 'description': '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.'}, {'measure': 'Safety - PACU Discharge Readiness', 'timeFrame': 'Within 4 hours of emergence at Visits 5, 10, 15, and 20 (Weeks 1-4)', 'description': 'Incidence of participants meeting post-anesthesia care unit (PACU) discharge readiness criteria within 4 hours of emergence from anesthesia at each dosing session.'}, {'measure': 'Safety - Suicidal Ideation and Behavior (C-SSRS)', 'timeFrame': 'From Visit 2 through Visit 25 (Screening through Week 7)', 'description': '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.'}, {'measure': 'Safety - Positive Urine Drug Screens', 'timeFrame': 'Prior to each dosing session at Visits 5, 10, 15, and 20 (Weeks 1-4)', 'description': 'Incidence of positive urine drug screens prior to each dosing session.'}, {'measure': 'Pharmacokinetics of Psilocybin', 'timeFrame': 'During dosing session', 'description': 'Maximum measured serum concentration (Cmax) of psilocin, the active metabolite of psilocybin'}, {'measure': 'Pharmacokinetics of Psilocybin', 'timeFrame': 'During dosing sessions', 'description': 'Serum concentration of psilocin at the time of emergence.'}, {'measure': 'Clinician-Reported Depressive Symptoms - MADRS', 'timeFrame': 'Visits 2, 4, 9, 14, 19, and 25 (Screening through Week 7)', 'description': 'Changes in blinded clinician-reported depression symptoms across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Montgomery-Asberg Depression Rating Scale (MADRS; Montgomery and Asberg, 1979). The MADRS consists of 10 clinician-rated items, each scored from 0 to 6. Total scores are calculated by summing all items. Minimum score: 0 (no depressive symptoms); Maximum score: 60 (severe depression). Higher scores indicate greater depression severity.'}, {'measure': 'Participant-Reported Depressive Symptoms - QIDS-SR', 'timeFrame': 'Visits 3, 4, 9, 14, 19, 24, and 25 (Baseline through Week 7)', 'description': 'Changes in participant-reported depression symptoms across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR; Rush et al., 2003). The QIDS-SR consists of 16 items assessing 9 symptom domains; total scores are derived by summing the highest-rated item within each domain. Minimum score: 0 (no depressive symptoms); Maximum score: 27 (severe depression). Higher scores indicate greater depression severity.'}, {'measure': 'Anxiety Symptoms - Generalized Anxiety Disorder scale (GAD-7)', 'timeFrame': 'Visits 3, 4, 9, 14, 19, 24, and 25 (Baseline through Week 7)', 'description': 'Changes in participant-reported anxiety symptoms across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Generalized Anxiety Disorder scale (GAD-7; Spitzer et al., 2006). ). The GAD-7 consists of 7 self-reported items, each scored from 0 (not at all) to 3 (nearly every day). Total scores are calculated by summing all items. Minimum score: 0 (no anxiety symptoms); Maximum score: 21 (severe anxiety). Higher scores indicate greater anxiety severity.'}, {'measure': 'Global Mood - the Positive and Negative Affect Schedule (PANAS)', 'timeFrame': 'Daily from Visit 3 through Visit 25 (Baseline through Week 7)', 'description': 'Changes in participant-reported mood across placebo, 10mg, and 25mg psilocybin conditions, assessed daily using the Positive and Negative Affect Schedule (PANAS; Watson et al., 1988). The PANAS consists of 20 items rated on a 5-point scale (1 = very slightly or not at all; 5 = extremely), yielding a Positive Affect subscale (10 items; range 10-50) and a Negative Affect subscale (10 items; range 10-50). Higher Positive Affect scores indicate greater positive mood; higher Negative Affect scores indicate greater negative mood.'}, {'measure': 'Global Mood - 12-Point Affect Circumplex (12-PAC)', 'timeFrame': 'Daily from Visit 3 through Visit 25 (Baseline through Week 7)', 'description': 'Changes in participant-reported mood across placebo, 10mg, and 25mg psilocybin conditions, assessed daily using a subset of items from the 12-Point Affect Circumplex (12-PAC; Yik et al., 2011). From the 12-PAC, 8 items rated on a 5-point scale (1 = very slightly or not at all; 5 = extremely) are administered to assess low-arousal affect, yielding two mean subscale scores: low-arousal positive affect (4 items; mean range 1-5) and low-arousal negative affect (4 items; mean range 1-5). Higher scores indicate greater endorsement of the respective low-arousal affect dimension.'}, {'measure': 'Well-Being - Satisfaction With Life Scale (SWLS)', 'timeFrame': 'Visits 3, 9, 14, 19, and 24 (Baseline through Week 6)', 'description': 'Changes in participant-reported life satisfaction across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Satisfaction With Life Scale (SWLS; Diener et al., 1985). The SWLS consists of 5 self-reported items, each scored from 1 (strongly disagree) to 7 (strongly agree). Total scores are calculated by summing all items. Minimum score: 5 (lowest life satisfaction); Maximum score: 35 (highest life satisfaction). Higher scores indicate greater life satisfaction.'}, {'measure': 'Well-Being - Scales of Psychological Well-Being (SPWB)', 'timeFrame': 'Visits 3, 9, 14, 19, and 24 (Baseline through Week 6)', 'description': 'Changes in participant-reported psychological well-being across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Scales of Psychological Well-Being (SPWB; Ryff and Keyes, 1995). The SPWB 18-item version consists of 18 items rated on a 6-point scale (1 = strongly disagree; 6 = strongly agree), yielding six subscale scores - Autonomy, Environmental Mastery, Personal Growth, Positive Relations with Others, Purpose in Life, and Self-Acceptance - each ranging from 3 to 18, and a total score ranging from 18 to 108. Higher scores indicate greater psychological well-being.'}, {'measure': 'Well-Being - Peace of Mind Scale (PoMS)', 'timeFrame': 'Visits 3, 9, 14, 19, and 24 (Baseline through Week 6)', 'description': 'Changes in participant-reported peace of mind across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Peace of Mind Scale (PoMS; Lee et al., 2013). The PoMS is a 7-item self-report scale; each item is rated on a 5-point frequency scale from 1 (not at all) to 5 (all the time), with 2 items reverse-scored. The total score is the mean of all items. Minimum score: 1; Maximum score: 5. Higher scores indicate greater peace of mind.'}, {'measure': 'Loneliness - UCLA Loneliness Scale', 'timeFrame': 'Visits 3, 9, 14, 19, and 24 (Baseline through Week 6)', 'description': 'Changes in participant-reported loneliness across placebo, 10mg, and 25mg psilocybin conditions, assessed using the 3-item UCLA Loneliness Scale (Hughes et al., 2004). The scale consists of 3 self-reported items, each rated on a 3-point scale (1 = hardly ever; 3 = often). Total scores are calculated by summing all items. Minimum score: 3 (no loneliness); Maximum score: 9 (severe loneliness). Higher scores indicate greater loneliness.'}, {'measure': 'Psychological Flexibility - Psy-Flex Scale', 'timeFrame': 'Visits 3, 9, 14, 19, and 24 (Baseline through Week 6)', 'description': 'Changes in participant-reported psychological flexibility across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Psy-Flex scale (Gloster et al., 2021). The Psy-Flex consists of 6 self-reported items, each reflecting one of the six core processes of the ACT psychological flexibility model, rated on a 5-point scale (1 = very rarely; 5 = very often). Total scores are calculated by summing all items. Minimum score: 6 (lowest psychological flexibility); Maximum score: 30 (highest psychological flexibility). Higher scores indicate greater psychological flexibility.'}, {'measure': 'Subjective Sleep Quality and Quantity - Pittsburgh Sleep Quality Index (PSQI)', 'timeFrame': 'Visits 3, 9, 14, 19, and 24 (Baseline through Week 6)', 'description': 'Changes in participant-reported subjective sleep quality and quantity across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Pittsburgh Sleep Quality Index (PSQI; Buysse et al., 1989). The PSQI consists of 19 self-rated items generating 7 component scores (Subjective Sleep Quality, Sleep Latency, Sleep Duration, Habitual Sleep Efficiency, Sleep Disturbances, Use of Sleeping Medication, and Daytime Dysfunction), each scored 0-3. Component scores are summed to yield a global score. Minimum score: 0 (no sleep difficulties); Maximum score: 21 (severe sleep difficulties). Higher scores indicate worse sleep quality.'}, {'measure': 'Daily Subjective Sleep and Dream Quality - Sleep and Dream Log', 'timeFrame': 'Daily from Visit 3 through Visit 25 (Baseline through Week 7)', 'description': 'Changes in participant-reported daily sleep quality, quantity, and dream experiences across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Daily Sleep and Dream Log (Sikka et al., 2014, 2022, 2024).'}, {'measure': 'Nightmare Frequency and Dream Emotional Content - Mannheim Dream Questionnaire (MADRE)', 'timeFrame': 'Visits 3, 9, 14, 19, and 24 (Baseline through Week 6)', 'description': 'Changes in nightmare frequency and emotional content of dreams across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Mannheim Dream Questionnaire (MADRE; Schredl et al., 2014). The MADRE does not yield a total score; relevant items and their scales are as follows: nightmare frequency (Item 4) is rated on an 8-point ordinal scale (1 = never; 8 = several times a week), with higher scores indicating greater nightmare frequency; nightmare distress (Item 5) is rated on a 5-point scale (1 = not at all distressing; 5 = very distressing), with higher scores indicating greater distress; emotional intensity of dreams (Item 2) is rated on a 5-point scale (1 = not at all intense; 5 = very intense); and emotional tone of dreams (Item 3) is rated on a 5-point scale (1 = very negative; 5 = very positive), with higher scores indicating more positively toned dreams.'}, {'measure': 'Objective Sleep Quality and Quantity - Muse EEG Headband', 'timeFrame': 'Daily from Visit 3 through Visit 25 (Baseline through Week 7)', 'description': 'Changes in objective sleep measures (total sleep time, sleep onset latency, wake after sleep onset, sleep efficiency, sleep architecture, heart rate, oxygen saturation) across placebo, 10mg, and 25mg psilocybin conditions, measured daily using the Muse EEG headband (InteraXon Inc.).'}, {'measure': 'EEG Markers of Anesthesia Predicting Recall of Experiences', 'timeFrame': 'During each dosing session at Visits 5, 10, 15, and 20 (Weeks 1-4)', 'description': 'Changes in EEG markers associated with loss of responsiveness (e.g., frontal alpha power) across placebo, 10mg, and 25mg psilocybin dosing sessions, including dose-dependent effects and comparisons between participants who report recalled experiences during anesthesia versus those reporting no recall'}, {'measure': 'Sedation Levels During Anesthesia - Richmond Agitation-Sedation Scale (RASS)', 'timeFrame': 'During each dosing session at Visits 5, 10, 15, and 20 (Weeks 1-4)', 'description': 'Changes in sedation levels across placebo, 10mg, and 25mg psilocybin conditions, measured continuously during each dosing session using the Richmond Agitation-Sedation Scale (RASS; Sessler et al., 2002). The RASS is a 10-point clinician-rated scale ranging from -5 (unarousable) to +4 (combative), with 0 indicating an alert and calm state. Negative scores indicate increasing levels of sedation; positive scores indicate increasing levels of agitation. Minimum score: -5 (unarousable); Maximum score: +4 (combative). In the context of propofol anesthesia, lower scores reflect deeper sedation, which is the intended drug effect.'}, {'measure': 'Recall of Experiences During Anesthesia - Modified Brice Interview', 'timeFrame': 'Immediately after emergence at Visits 5, 10, 15, and 20 (Weeks 1-4)', 'description': 'Changes in awareness and dream recall across placebo, 10mg, and 25mg psilocybin conditions, assessed immediately upon emergence using the modified Brice structured interview (Brice et al., 1970; Noreika et al., 2011; Radek et al., 2018).'}, {'measure': 'Effect of Baseline Treatment Expectations on Depressive Symptom Change - Montgomery-Åsberg Depression Rating Scale', 'timeFrame': 'Visit 3 through Visits 9, 14, and 19 (Baseline through Week 5)', 'description': 'Change in clinician-rated depressive symptom severity across placebo, 10mg, and 25mg psilocybin conditions, evaluated as a function of pre-treatment expectations assessed at Visit 3 using the Stanford Expectations of Treatment Scale (SETS; Younger et al., 2012). The SETS is a 6-item self-report scale yielding two subscale scores: Positive Expectancy (mean of items 1, 3, and 5; range 1-7; higher = greater positive expectancy) and Negative Expectancy (mean of items 2, 4, and 6; range 1-7; higher = greater negative/fearful expectancy); all items rated 1 (strongly disagree) to 7 (strongly agree). Depressive symptoms are assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS; Montgomery \\& Åsberg, 1979), a 10-item clinician-rated scale; total score range: 0-60; higher scores indicate greater depression severity.'}, {'measure': 'Effect of Baseline Treatment Expectations on Depressive Symptom Change - Quick Inventory of Depressive Symptomatology - Self-Report', 'timeFrame': 'Visit 3 through Visits 9, 14, and 19 (Baseline through Week 5)', 'description': 'Change in self-reported depressive symptom severity across placebo, 10mg, and 25mg psilocybin conditions, evaluated as a function of pre-treatment expectations assessed at Visit 3 using the Stanford Expectations of Treatment Scale (SETS; Younger et al., 2012). The SETS is a 6-item self-report scale yielding two subscale scores: Positive Expectancy (mean of items 1, 3, and 5; range 1-7; higher = greater positive expectancy) and Negative Expectancy (mean of items 2, 4, and 6; range 1-7; higher = greater negative/fearful expectancy); all items rated 1 (strongly disagree) to 7 (strongly agree). Depressive symptoms are assessed using the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR; Rush et al., 2003), a 16-item self-report scale scored across 9 symptom domains; total score is the sum of the highest-rated item within each domain; range: 0-27; higher scores indicate greater depression severity.'}, {'measure': 'Psychological Insight - Psychological Insight Scale (PIS)', 'timeFrame': 'Visits 6, 11, 16, 21, 24, and 25 (Weeks 1-7)', 'description': 'Changes in psychological insight across placebo, 10mg, and 25mg psilocybin conditions, assessed using the Psychological Insight Scale (PIS; Peill et al., 2022). The PIS-6 is a 6-item self-report scale in which each item is rated on a Visual Analogue Scale from 0 (not at all) to 100 (entirely or completely); the total score is the mean of all 6 items. Minimum score: 0; Maximum score: 100. Higher scores indicate greater psychological insight following the session (better outcome). A supplementary single item (PIS item 7) assessing insight-motivated behavioral change is rated on the same 0-100 VAS and analyzed separately.'}], 'primaryOutcomes': [{'measure': 'Blinding Success - Correct Identification of Psilocybin at Final Dosing Session', 'timeFrame': '1 day after the final dosing session (Visit 21, Week 4)', 'description': '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.'}, {'measure': 'Blinding Success - Accuracy of Guessed Psilocybin Dose at Final Dosing Session', 'timeFrame': '1 day after the final dosing session (Visit 21, Week 4)', 'description': 'The dose of psilocybin guessed by participants at Visit 21 compared to the dose actually received at Visit 20, assessed using the Blinding Survey.'}], 'secondaryOutcomes': [{'measure': 'Acute Drug Effects by Dose - Drug Effects Questionnaire (DEQ)', 'timeFrame': 'Immediately after emergence at each of the 4 dosing sessions (Visits 5, 10, 15, 20; Weeks 1-4)', 'description': '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.'}, {'measure': 'Mystical-Type Experiences by Dose - Mystical Experiences Questionnaire (MEQ-30)', 'timeFrame': 'Immediately after emergence at each of the 4 dosing sessions (Visits 5, 10, 15, 20; Weeks 1-4)', 'description': '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.'}, {'measure': 'Altered States of Consciousness by Dose - Three-Dimensional Altered States of Consciousness Scale (3D-ASCr)', 'timeFrame': 'Immediately after emergence at each of the 4 dosing sessions (Visits 5, 10, 15, 20; Weeks 1-4)', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['psilocybin', 'major depressive disorder', 'anesthesia', 'propofol', 'psychedelic-assisted therapy', 'blinding', 'masking'], 'conditions': ['Major Depression']}, 'referencesModule': {'references': [{'pmid': '41451514', 'type': 'BACKGROUND', 'citation': 'Stocker K, Hartmann M, Schmid Y, Vogt SB, Becker AM, Ley L, Straumann I, Arikci D, Klaiber A, Erne L, Vizeli P, Holze F, Liechti ME. The 3D-ASCr scale: A revalidation of the core dimensions of the Altered States of Consciousness Rating Scale 5D(11)-ASC for psychedelic research. J Psychopharmacol. 2025 Dec 26:2698811251397328. doi: 10.1177/02698811251397328. Online ahead of print.'}, {'pmid': '23316089', 'type': 'BACKGROUND', 'citation': 'Maclean KA, Leoutsakos JM, Johnson MW, Griffiths RR. Factor Analysis of the Mystical Experience Questionnaire: A Study of Experiences Occasioned by the Hallucinogen Psilocybin. J Sci Study Relig. 2012 Dec;51(4):721-737. doi: 10.1111/j.1468-5906.2012.01685.x.'}, {'pmid': '38598236', 'type': 'BACKGROUND', 'citation': 'Yerubandi A, Thomas JE, Bhuiya NMMA, Harrington C, Villa Zapata L, Caballero J. Acute Adverse Effects of Therapeutic Doses of Psilocybin: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2024 Apr 1;7(4):e245960. doi: 10.1001/jamanetworkopen.2024.5960.'}, {'pmid': '18593734', 'type': 'BACKGROUND', 'citation': 'Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6):603-20. doi: 10.1177/0269881108093587. Epub 2008 Jul 1.'}, {'pmid': '38188539', 'type': 'BACKGROUND', 'citation': 'Lii TR, Smith AE, Flohr JR, Okada RL, Nyongesa CA, Cianfichi LJ, Hack LM, Schatzberg AF, Heifets BD. Randomized trial of ketamine masked by surgical anesthesia in patients with depression. Nat Ment Health. 2023 Nov;1(11):876-886. doi: 10.1038/s44220-023-00140-x. Epub 2023 Oct 19.'}, {'pmid': '38387698', 'type': 'BACKGROUND', 'citation': 'Szigeti B, Heifets BD. Expectancy Effects in Psychedelic Trials. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 May;9(5):512-521. doi: 10.1016/j.bpsc.2024.02.004. Epub 2024 Feb 20.'}, {'pmid': '35359159', 'type': 'BACKGROUND', 'citation': 'Aday JS, Heifets BD, Pratscher SD, Bradley E, Rosen R, Woolley JD. Great Expectations: recommendations for improving the methodological rigor of psychedelic clinical trials. Psychopharmacology (Berl). 2022 Jun;239(6):1989-2010. doi: 10.1007/s00213-022-06123-7. Epub 2022 Apr 1.'}, {'pmid': '27210031', 'type': 'BACKGROUND', 'citation': 'Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.'}, {'pmid': '36636296', 'type': 'BACKGROUND', 'citation': 'von Rotz R, Schindowski EM, Jungwirth J, Schuldt A, Rieser NM, Zahoranszky K, Seifritz E, Nowak A, Nowak P, Jancke L, Preller KH, Vollenweider FX. Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine. 2022 Dec 28;56:101809. doi: 10.1016/j.eclinm.2022.101809. eCollection 2023 Feb.'}, {'pmid': '36322843', 'type': 'BACKGROUND', 'citation': "Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Palenicek T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443."}, {'pmid': '37651119', 'type': 'BACKGROUND', 'citation': "Raison CL, Sanacora G, Woolley J, Heinzerling K, Dunlop BW, Brown RT, Kakar R, Hassman M, Trivedi RP, Robison R, Gukasyan N, Nayak SM, Hu X, O'Donnell KC, Kelmendi B, Sloshower J, Penn AD, Bradley E, Kelly DF, Mletzko T, Nicholas CR, Hutson PR, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis MC, Nelson-Douthit C, Wilson S, Brown C, Linton W, Ross S, Griffiths RR. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):843-853. doi: 10.1001/jama.2023.14530."}]}, 'descriptionModule': {'briefSummary': '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.\n\nThis study 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.\n\nParticipants 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.', 'detailedDescription': '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.\n\nAll 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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '25 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'INCLUSION CRITERIA:\n\nA participant will be eligible for inclusion when all of the following criteria are met:\n\n1. People 25 to 65 years of age at screening;\n2. 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;\n3. Fluent in English;\n4. Able to commit to attend all study visits and participate in all remote data collection procedures;\n5. 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;\n6. Body mass index between 17-35 kg/m2.\n7. 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).\n8. 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.\n9. 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.\n10. Agree not to consume any food or drink after midnight preceding dosing days.\n11. Agree not to consume alcoholic beverages for 48 hours prior to and 24 hours following the dosing sessions.\n12. Agree not to use cannabis in any form for the duration of the study.\n13. Non-smoker, or abstained at least 6 weeks.\n14. For people who can become pregnant: agree to use highly effective contraception from entry into the trial through the end of the study.\n\n 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).\n\n b. A person with a uterus who is not of childbearing potential is considered to be postmenopausal after at least 12 months without menstruation.\n\n 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\n\n<!-- -->\n\n1. oral\n2. intravaginal\n3. Transdermal\n4. Double-barrier method ii. progestogen-only hormonal contraception associated with inhibition of ovulation:\n\n1\\. 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\n\nd. Periodic abstinence (i.e., calendar, symptothermal, or postovulation methods, and tubal ligation/occlusion) are not an acceptable form of contraception for this study.\n\ne. The PI will use his judgement and familiarity with the participant\'s preferred and usual lifestyle to understand if reporting of abstinence may be trusted to achieve 100% effectiveness.\n\n15\\. Negative urinary pregnancy test at screening and again immediately before dosing sessions.\n\nEXCLUSION CRITERIA:\n\nA potential participant will NOT be eligible for participation in this study if any of the following criteria are met:\n\n1. Has any ongoing legal or disability claim such as Worker\'s Compensation\n2. Is taking a medication belonging to any of the following classes:\n\n 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\n3. Is taking benzodiazepine medication such that patient cannot tolerate withholding doses 8 hours before through 6 hours after planned study intervention\n4. 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.\n5. For individuals who can become pregnant:\n\n 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\n6. 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.\n7. 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.\n8. History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms, mania, or bipolar affective disorder\n9. 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.\n10. Use of psychedelics in the previous 6 months prior to screening (psilocybin, LSD, DMT, 5-Meo-DMT, MDMA, Ibogaine).\n11. 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").\n12. 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".\n13. 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.\n14. History of suicide attempt requiring hospitalization or suicidal ideation with intent in the last 10 years.\n15. 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\'.\n16. A neurological disorder including:\n\n 1. Dementia, delirium, amnestic, or any other cognitive disorder.\n 2. Lifetime history of surgical procedures involving the brain or meninges,\n 3. Encephalitis, meningitis, degenerative central nervous system disorder (e.g., Alzheimer\'s or Parkinson\'s Disease), epilepsy, mental retardation\n 4. Any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system (CNS),\n 5. History of significant head trauma within the past two years.\n17. A cardiovascular disorder including:\n\n a. Elevated blood pressure defined as systolic blood pressure (SBP) \\>140 or diastolic blood pressure (DBP) \\>90 averaged over two separate measurements taken during the screening period b. Tachycardia defined as heart rate (HR) \\>90 beats per minute averaged over two separate measurements taken during the screening period c. Bradycardia defined as heart rate (HR) \\<50 beats per minute averaged over two separate measurements taken during the screening period d. Angina e. Clinically significant EKG abnormality (e.g., atrial fibrillation, QTcF \\>450 ms for males or \\>470 ms for females) f. Any other significant current or history of a cardiovascular condition that would preclude safe participation in the study based on the clinical judgment of the investigators.\n18. Clinically significant pulmonary/respiratory disorder including\n\n a. History of difficult airway or difficult mask ventilation, or predictors of difficult airway such as Mallampati Score 3 or 4, limited mouth opening, thyromental distance \\<6cm, restricted neck mobility, or significant retrognathia.\n\n b. COPD requiring systemic steroid use. c. Obstructive Sleep Apnea, moderate or severe (Apnea-Hypopnea Index \\>=15), or requiring regular CPAP use\n19. Clinically significant liver disease, determined by Liver Function Tests (LFTs) within the past 6 months: Hepatic dysfunction as indicated by any of the following values:\n\n 1. AST \\> 3 x upper limit of normal\n 2. ALT \\> 3 x upper limit of. Normal\n 3. Total bilirubin \\> 3.0 mg/dl\n20. Known allergy or hypersensitivity to propofol or any of its components (unless they have a documented propofol exposure without complication), including:\n\n 1. Eggs or egg products\n 2. Soybeans, soy products, or soy lecithin\n 3. Peanuts or other legumes\n 4. History of anaphylaxis, angioedema, bronchospasm, or other serious allergic reaction to any of the above substances.\n21. Known allergy or hypersensitivity to psilocybin or its metabolites.\n22. History of severe lipid disorder or recent pancreatitis\n23. Is taking a GLP-1 agonist class drug like tirzepatide, or has taken a dose within the past 7 days prior to propofol dosing.\n24. Has symptomatic gastroesophageal reflux disease, or other delayed gastric emptying conditions.\n25. Clinically significant kidney disease determined by creatinine/glomerular filtration rate within the past 6 months. Renal insufficiency (creatinine clearance \\< 40 ml/min using Cockraft and Gault equation)\n26. Any endocrine disorder or any thyroid disorder treated (medically or surgically) within the past 6 months prior to screening:\n\n 1. Uncontrolled diabetes, type 1 or 2 (well-controlled diabetes is allowed).\n 2. Hyperthyroidism or hypothyroidism diagnosed within the past six months prior to screening (stable treatment with a thyroid hormone replacement therapy is allowed).\n27. Other medical condition(s) or diagnosis, physical exam finding, EKG or laboratory abnormality that precludes participation in study procedures due to safety concerns at the discretion of the study staff.\n\n \\-'}, 'identificationModule': {'nctId': 'NCT07479550', 'acronym': 'SPACE', 'briefTitle': 'Anesthesia-Masked Psilocybin Therapy for Major Depression', 'organization': {'class': 'OTHER', 'fullName': 'Stanford University'}, 'officialTitle': 'A Phase 2 Randomized Study Examining the Safety, Feasibility, and Effectiveness of Masking Psilocybin Therapy With General Anesthesia in Major Depressive Disorder', 'orgStudyIdInfo': {'id': '72097'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Sequence A', 'description': 'Participants are randomized 1:1 to one of two dosing sequences. All participants receive all four dosing conditions across weekly sessions: placebo (0 mg), psilocybin 10 mg, and psilocybin 25 mg administered in two separate sessions. Sequences differ only in the order of the first two sessions. Specific sequence assignments are not disclosed to preserve blinding.', 'interventionNames': ['Drug: Psilocybin (Usona Institute)', 'Drug: Propofol', 'Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Sequence B', 'description': 'Participants are randomized 1:1 to one of two dosing sequences. All participants receive all four dosing conditions across weekly sessions: placebo (0 mg), psilocybin 10 mg, and psilocybin 25 mg administered in two separate sessions. Sequences differ only in the order of the first two sessions. Specific sequence assignments are not disclosed to preserve blinding.', 'interventionNames': ['Drug: Psilocybin (Usona Institute)', 'Drug: Propofol', 'Drug: Placebo']}], 'interventions': [{'name': 'Psilocybin (Usona Institute)', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['Sequence A', 'Sequence B']}, {'name': 'Propofol', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['Sequence A', 'Sequence B']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['Sequence A', 'Sequence B']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94304', 'city': 'Stanford', 'state': 'California', 'country': 'United States', 'contacts': [{'name': 'Dr. Pilleriin Sikka, PhD', 'role': 'CONTACT', 'email': 'sikka@stanford.edu', 'phone': '6506808801'}, {'name': 'Dr. Boris Heifets, MD, PhD', 'role': 'CONTACT', 'email': 'bheifets@stanford.edu'}, {'name': 'Dr. Boris Heifets, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Dr. Pilleriin Sikka, PhD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Stanford University', 'geoPoint': {'lat': 37.42411, 'lon': -122.16608}}], 'centralContacts': [{'name': 'Dr. Boris Heifets, MD, PhD', 'role': 'CONTACT', 'email': 'bheifets@stanford.edu', 'phone': '4157161585'}, {'name': 'Dr. Pilleriin Sikka, PhD', 'role': 'CONTACT', 'email': 'sikka@stanford.edu'}], 'overallOfficials': [{'name': 'Dr. Boris Heifets, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Stanford University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Individual participant data will not be shared due to the small sample size (N=10) and the sensitive nature of the data collected, including psychiatric diagnoses, psychedelic drug administration, and detailed psychological assessments. Sharing IPD could compromise participant confidentiality. Aggregate findings will be reported in peer-reviewed publications.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Stanford University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'Boris D. Heifets', 'investigatorAffiliation': 'Stanford University'}}}}