Using psilocybin to help patients with psychological distress in palliative care

PSilocybin for psYCHological and Existential Distress in PALliative Care (PSYCHED-PAL): A Multi-site, Open-label, Single Arm Phase I/II Proof-of-concept, Dose-finding, and Feasibility Clinical Trial

Phase1; Phase2 Interventional Ottawa Hospital Research Institute · NCT04754061

This study is testing if small doses of psilocybin can help people with serious illnesses feel less anxious and depressed while improving their overall well-being.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment20 (estimated)
Ages18 Years and up
SexAll
SponsorOttawa Hospital Research Institute Academic / other
Locations2 sites (Ottawa, Ontario and 1 other locations)
Trial IDNCT04754061 on ClinicalTrials.gov

What this trial studies

This multi-centre phase I/II open-label study aims to evaluate the safety, feasibility, therapeutic dose, and preliminary efficacy of psilocybin microdosing for treating psychological distress in patients with advanced illness. Over four weeks, forty participants will take oral capsules containing 1-3mg of psilocybin daily, Monday through Friday. The study will assess feasibility through recruitment and follow-up rates, safety by monitoring adverse events, and preliminary efficacy by measuring changes in depression, anxiety, and overall well-being. The goal is to provide a rapid and effective therapeutic approach for patients experiencing existential distress.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced illness under palliative care management experiencing significant psychological distress.

Not a fit: Patients with a history of psychotic or bipolar disorders, or those who are actively pursuing medical assistance in dying, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly alleviate psychological distress and improve quality of life for patients in palliative care.

How similar studies have performed: While the use of psilocybin in palliative care is a novel approach, preliminary studies have shown promise in addressing psychological distress.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Ottawa, Ontario and 1 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Depression, AnxietyDistress, Emotionalexistential distresspsychological distresspsilocybinmicrodosing
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.