nctId: NCT06341426 id: 23-5872 briefTitle: Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: Comparing One Versus Two Doses of Psilocybin acronym: PSI-1V2 overallStatus: RECRUITING date: 2024-02-05 date: 2028-02-01 date: 2028-08-01 date: 2024-04-02 date: 2024-04-02 name: University Health Network, Toronto class: OTHER name: Centre for Addiction and Mental Health 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. conditions: Major Depressive Disorder conditions: Depression conditions: Treatment-Resistant Depression conditions: Mood Disorders studyType: INTERVENTIONAL phases: PHASE2 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 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 count: 92 type: ESTIMATED name: Single Psychedelic Dose Psilocybin name: Two Psychedelic Doses Psilocybin measure: Antidepressant Efficacy measure: Self-Reported Depression Symptoms measure: Anxiety Symptoms measure: Self-Reported Quality of Life measure: Subjective Functioning measure: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) measure: Cognitive Dysfunction measure: Psychomotor Performance measure: Phonemic Word Fluency measure: Psychomotor Speed, Visual search, and Attention measure: Verbal Learning and Memory measure: Working Memory, Attention and Executive Function measure: Effort-Based Decision Making measure: Participant Blinding Success measure: Expectancy Effects measure: Quality of Clinician-Patient Therapeutic Relationship measure: Qualitative Narrative Feedback measure: Percentage Restarting Antidepressants measure: EEG Predictors of Response sex: ALL minimumAge: 18 Years maximumAge: 65 Years stdAges: ADULT stdAges: OLDER_ADULT facility: Toronto Western Hospital status: RECRUITING city: Toronto state: Ontario zip: M5T 2S8 country: Canada name: Danica Johnson, BScH role: CONTACT email: danica.johnson@uhn.ca name: Zoe Doyle, RN role: CONTACT email: zoe.doyle@uhn.ca name: Joshua Rosenblat, MD, MSc role: PRINCIPAL_INVESTIGATOR lat: 43.70011 lon: -79.4163 hasResults: False