Psilocybin FCR Early-Stage Breast Cancer

This trial is designed to evaluate efficacy and psychological mechanisms of single-dose psilocybin-assisted psychotherapy (PAP) to treat fear of cancer recurrence (FCR), psychiatric (anxiety, depression) distress and quality-of-life (QOL), in 100 outpatients with early-stage breast cancer. The study will assess the strength and durability of therapeutic effects in a double-blind, parallel-design, placebo-controlled, two-center randomized controlled trial (RCT) comparing a single 25mg oral 'high' dose of psilocybin to a single 5mg oral 'low dose psilocybin (active placebo), both delivered in conjunction with a psychotherapy platform.

Inclusion Criteria: * Aged ≥ 21 * Females * Diagnosis of Stage 1 or 2 Estrogen/Progesterone Receptor-Positive (ER/PR +), Human Epidermal growth factor Receptor 2 negative (HER2-) breast cancer * Having completed initial treatment (e.g. surgery, chemotherapy, radiotherapy) for breast cancer (ongoing adjuvant endocrine, and/or HER2 therapy allowed) * At least 1 year after completing initial treatment * Clinically significant Fear of Cancer Recurrence (FCR) defined as Fear of Cancer Recurrence Inventory (FCRI) \> 20 at Screening * Have an identified support person * Agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing * Participants of childbearing potential must agree to practice an effective means of birth control throughout the duration of the study. Exclusion Criteria: * Unstable medical conditions or serious abnormalities of complete blood count, chemistries, or ECG that in the opinion of the study physician would preclude safe participation in the trial. * Risk for hypertensive crisis defined as Screening, Baseline, and Medication Session (prior to dosing) BP \>160/100, HR \>110 bpm * Significant central nervous system (CNS) pathology. * Primary psychotic or affective psychotic disorders. * Family history of first-degree relative with psychotic or serious bipolar spectrum illnesses. * Clinically significant suicidality or high risk of completed suicide. * History of hallucinogen persisting perception disorder (HPPD) * Pregnancy/lactation * Concurrent Medications * Psychotherapy * Have any psychological or physical symptom, medication or other relevant finding prior to randomization, based on the clinical judgment of the PI or relevant clinical study staff that would make a participant unsuitable for the study. * Be enrolled in another clinical trial assessing intervention(s) for anxiety, depression, and/or existential distress (e.g., pharmacologic or psychotherapeutic interventions)