PSilocybin for psYCHological and Existential Distress in PALliative Care (PSYCHED-PAL)

Inclusion Criteria: 1. Patients \>/=18 years of age 2. Advanced illness under palliative care management, defined as having 1 to \<12 months life expectancy (in the judgment of the palliative care provider) 3. Experiencing psychological distress, defined as a score of 7 or greater on the Depression, Anxiety or Well-being item of the Edmonton Symptom Assessment System 4. Ability to understand and communicate in English or French Exclusion Criteria: 1. Current or previously diagnosed, or first-degree relative, with psychotic or bipolar disorder 2. Previously deemed eligible for MAiD with intention to proceed with MAiD regardless of study intervention effectiveness (this criteria is meant to exclude patients who would be unlikely to complete follow-up - those considering or being assessed for MAiD will still be eligible) 3. Documented or suspected delirium in the past 3 months without a clearly defined reversible cause (e.g. opioid toxicity, infection) and resolution 4. Documented moderate or severe dementia diagnosis 5. Inability to provide first-person informed consent 6. Severe or unstable physical symptoms based on the judgment of the palliative care provider 7. Palliative Performance Scale \<30% 8. Cancer with known central nervous system (CNS) involvement or other CNS disease 9. Use of high-dose psychedelic substances in the past year 10. Taking lithium at any dose 11. Taking tramadol at any dose 12. Taking any monoamine oxidase inhibitor at any dose \[American Hospital Formulary Service (AFHS) group 28:16.04.12 or 28:36.32, including, but not limited to, moclobemide, tranylcypromine, phenelzine, selegiline, rasagiline\] 13. Taking any atypical antipsychotic (aripiprazole, asenapine, brexpiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone) (patients can be included if their atypical antipsychotic is either stopped, or if appropriate, substituted with haloperidol 48 hours prior to the start and for the duration of the intervention period and follow-up) 14. Inability to ingest oral capsule 15. Pregnancy or lactation For participants taking either an SSRI or an antipsychotic medication, there are several conditions for participation: (1) the PC provider must approve their participation in the study; (2) the SSRI/anti-psychotic medication dose cannot change for the duration of the intervention trial and follow-up, and; (3) the patient must not be taking more than the maximum allowable trial dose for each SSRI. All trial participants must agree to not take any other psychedelic substance for the duration of the clinical trial and follow-up, and to notify the investigative team of any medication changes during intervention or follow-up. Participants must also agree not to take their benzodiazepine or antipsychotic medication, if applicable, within 12 hours (6 hours pre and 6 hours post) of taking their psilocybin dose (participants will be given detailed instructions about this in their Instruction Leaflet). Participants must also agree not to drive or operate any heavy machinery on any treatment day for the duration of the 4-week intervention.