Clinical TrialPalliative & End-of-Life DistressPsilocybinPlaceboRecruiting

Psilocybin Microdose for Psychological and Existential Distress in Palliative Care (PSYCHED-PAL-RCT)

Phase III, randomized, quadruple-blind, placebo-controlled parallel-arm RCT (n=120) testing psilocybin microdosing (2–3 mg, 4 days/week for 2 weeks) versus placebo to reduce psychological and existential distress in patients receiving palliative care.

Target Enrollment
120 participants
Study Type
Phase III interventional
Design
Randomized, quadruple Blind

Detailed Description

Multi-site, randomized, double-blind, placebo-controlled parallel trial enrolling 120 patients with advanced illness and psychological distress to compare psilocybin microdosing with matched placebo; primary aim is reduction in psychological distress.

Intervention: oral psilocybin 2 mg if <55 kg or 3 mg if ≥55 kg taken Monday, Tuesday, Thursday and Friday for two consecutive weeks (8 dosing days). All participants are offered open-label microdosing after the 2-week follow-up, with an optional year-long extension.

Study Protocol

Preparation

sessions

Dosing

8 sessions

Integration

sessions

Study Arms & Interventions

Psilocybin microdose

experimental

Microdose psilocybin given 4 days/week for 2 weeks (weight‑based: 2 or 3 mg).

Interventions

  • Psilocybin2 - 3 mg
    via Oral• M,T,Th,F for 2 weeks• 8 doses total

    2 mg if <55 kg; 3 mg if ≥55 kg

Placebo

inactive

Matched placebo dosing schedule.

Interventions

  • Placebo2 - 3 mg
    via Oral• M,T,Th,F for 2 weeks• 8 doses total

    Matched placebo; 2 mg if <55 kg or 3 mg if ≥55 kg (matched)

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Patients >=18 years of age with advanced illness under palliative care management, defined as having an estimated 2 to 12 months life expectancy (in the judgment of the palliative care provider)
  • 2. 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-revised (ESAS-r)
  • 3. Living situation falls under one of two categories:
  • 1. Living in the community (i.e., receiving palliative care as an outpatient or through community home visits)
  • 2. Living in a chronic care inpatient facility (i.e., receiving long-term supportive care because care is unable to be provided in a community home - e.g., ALS) and have a family member who can administer the psilocybin/placebo medication to the patient
  • 4. Ability to understand and communicate in English or French
  • 5. For patients in community settings, patients must be able to have another individual present with them during and for 2 hours after they take their psilocybin/placebo dose for the first week of the intervention period

Exclusion Criteria

  • 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. Inability to complete assessments via telephone or video-conferencing platform
  • 7. Severe or unstable physical symptoms based on the judgment of the palliative care provider
  • 8. Palliative Performance Scale (PPS) <50%*
  • 9. Cancer with known central nervous system (CNS) involvement or other CNS disease
  • 10. Use of high-dose psychedelic substances in the past year
  • 11. Taking lithium at any dose
  • 12. Taking tramadol at any dose
  • 13. Taking tapentadol at any dose
  • 14. 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]
  • 15. Taking any atypical antipsychotic (aripiprazole, asenapine, brexpiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone)
  • a. Note: patients can be included if their atypical antipsychotic is stopped or, if appropriate, substituted with haloperidol 48 hours prior to the start and for the duration of the intervention period and follow-up.
  • 16. No enteral route of drug administration available
  • 17. Pregnancy or lactation
  • Does not apply to the open-label access or open-label extension phases (since participants are expected to decline in overall health and function from baseline due to natural disease progression towards the end of life).
  • Individuals with dementia (assessed at baseline by the treating team - no formal screening of dementia will be done during the intervention or follow-up period) or delirium are excluded. The use of selective serotonin reuptake inhibitors (SSRIs) and antipsychotic medications (other than atypical antipsychotics) is a relative contraindication; conditions for participation are described in protocol.

Study Details

Locations

William Osler Health System — Brampton, Ontario, Canada
Providence Care Hospital — Kingston, Ontario, Canada
St. Joseph's Healthcare — London, Ontario, Canada
South Lake Regional Health Centre — Newmarket, Ontario, Canada
Bruyere Health — Ottawa, Ontario, Canada
The Ottawa Hospital — Ottawa, Ontario, Canada
McGill University Health Centre — Montreal, Quebec, Canada

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