protocolSection identificationModule nctId: NCT06341426, orgStudyIdInfo id: 23-5872, briefTitle: Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: Comparing One Versus Two Doses of Psilocybin, acronym: PSI-1V2, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-02-05, primaryCompletionDateStruct date: 2028-02-01, completionDateStruct date: 2028-08-01, studyFirstPostDateStruct date: 2024-04-02, lastUpdatePostDateStruct date: 2024-04-02, sponsorCollaboratorsModule leadSponsor name: University Health Network, Toronto, class: OTHER, collaborators name: Centre for Addiction and Mental Health, descriptionModule briefSummary: The purpose of this study is to see if one or two doses of psilocybin is more effective in relieving depressive symptoms in patients with treatment-resistant depression (TRD). Researchers also want to know if a second dose of psilocybin is safe and well-tolerated. This study will see if psilocybin is effective, safe, and well-tolerated by tracking changes in depressive symptoms, suicidality, and side effects. This study will also see if a second dose of psilocybin has an effect on quality of life, functioning, cognition (thinking, reasoning, remembering), and how long depressive symptoms improve (or worsen) after psilocybin is administered., conditionsModule conditions: Major Depressive Disorder, conditions: Depression, conditions: Treatment-Resistant Depression, conditions: Mood Disorders, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Participants will be randomized to two groups for the first dosing session in a 1:1 allocation: 1) non-psychedelic/placebo dose (psilocybin 1mg) or 2) psychedelic dose (psilocybin 25mg). All participants will receive a psychedelic dose (psilocybin 25mg) for their second dosing session., primaryPurpose: TREATMENT, maskingInfo masking: QUADRUPLE, maskingDescription: The first dose will be randomized and blinded (1mg psilocybin versus 25mg psilocybin), while the second dose will be open-label (25mg psilocybin)., whoMasked: PARTICIPANT, whoMasked: CARE_PROVIDER, whoMasked: INVESTIGATOR, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 92, type: ESTIMATED, armsInterventionsModule interventions name: Single Psychedelic Dose Psilocybin, interventions name: Two Psychedelic Doses Psilocybin, outcomesModule primaryOutcomes measure: Antidepressant Efficacy, secondaryOutcomes measure: Self-Reported Depression Symptoms, secondaryOutcomes measure: Anxiety Symptoms, secondaryOutcomes measure: Self-Reported Quality of Life, secondaryOutcomes measure: Subjective Functioning, secondaryOutcomes measure: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability), secondaryOutcomes measure: Cognitive Dysfunction, secondaryOutcomes measure: Psychomotor Performance, secondaryOutcomes measure: Phonemic Word Fluency, secondaryOutcomes measure: Psychomotor Speed, Visual search, and Attention, secondaryOutcomes measure: Verbal Learning and Memory, secondaryOutcomes measure: Working Memory, Attention and Executive Function, secondaryOutcomes measure: Effort-Based Decision Making, otherOutcomes measure: Participant Blinding Success, otherOutcomes measure: Expectancy Effects, otherOutcomes measure: Quality of Clinician-Patient Therapeutic Relationship, otherOutcomes measure: Qualitative Narrative Feedback, otherOutcomes measure: Percentage Restarting Antidepressants, otherOutcomes measure: EEG Predictors of Response, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 65 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Toronto Western Hospital, status: RECRUITING, city: Toronto, state: Ontario, zip: M5T 2S8, country: Canada, contacts name: Danica Johnson, BScH, role: CONTACT, email: danica.johnson@uhn.ca, contacts name: Zoe Doyle, RN, role: CONTACT, email: zoe.doyle@uhn.ca, contacts name: Joshua Rosenblat, MD, MSc, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 43.70011, lon: -79.4163, hasResults: False