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

NCT07063862 | Recruiting Phase 3 DMC

• 1 other identifier: 7745629246728
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 7

Brief Summary

About 30-50% of patients with advanced illness experience depression, anxiety, or decreased sense of purpose and autonomy. Together, these are called psychological distress. Treatment options such as medication and therapy are available; however, they do not always work and can be time-consuming and expensive. We need treatments that work well, quickly, and can be available to all patients with advanced illness who have psychological distress. Psilocybin, a psychedelic medication (commonly called 'magic mushrooms') works well for improving psychological distress in people with cancer or chronic illness when given in high doses with specific forms of therapy. However, psilocybin has not been well-studied among people with advanced illness, and there are concerns about safety and side effects in people approaching the end of life. However, reports on psilocybin microdosing, which involves taking small doses that do not cause hallucinations and do not require therapy, suggest that this may be effective, safer, and more acceptable for people with advanced illness. We recently completed a small study of psilocybin microdosing. Our results showed psilocybin microdose improved psychological distress in most participants with advanced illness, without serious side effects. Our next step is to do a randomized clinical trial where some patients receive psilocybin microdose and some receive placebo (a drug that contains no medicinal ingredients). By comparing these two groups, we can remove the possibility that improvements in symptoms are only because patients thought they were getting treatment. We will enroll 120 patients from inpatient, outpatient, and community care settings across seven sites. Participants in the microdose psilocybin group will receive 2 or 3 mg of psilocybin daily, 4 days per week, for two consecutive weeks. The placebo group will receive placebo with the same treatment schedule. All participants will be offered microdose psilocybin after 2-week follow-up. If this study is successful, we have the potential to change how psychological distress is managed in patients with advanced illness.

Conditions

Psychological Distress

Keywords

Psychological distress; psilocybin; microdosing

Outcome Measures

Primary Outcomes (1)

• Change in Psychological Distress - Patient Global Impression of Change

  Measured using the Patient Global Impression of Change (PGIC) scale (score 1-7 on one item; higher scores indicate greater positive change)

  Weekly (every Friday) during intervention (2 weeks) and 2-week follow-up

Secondary Outcomes (15)

• Change in Psychological Distress - Anxiety, Depression, and Well-being

  Baseline, weekly (every Friday) during intervention (2 weeks), and 2-week follow-up

• Change in Psychological Distress - Depression and Anxiety

  Baseline, weekly (every Friday) during intervention (2 weeks), and 2-week follow-up

• Change in Psychological Distress - Depression

  Baseline, weekly (every Friday) during intervention (2 weeks), and 2-week follow-up

• Psychological Distress - Change in Existential Distress

  Baseline, weekly (every Friday) during intervention (2 weeks), and 2-week follow-up

• Change in Quality of Life

  Baseline, weekly (every Friday) during intervention (2 weeks), and 2-week follow-up

Study Arms (2)

Psilocybin Microdosing

EXPERIMENTAL

Drug: Psilocybin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Psilocybin DRUG

Participants randomized to the psilocybin microdosing intervention will take 2mg (if participant weighs \<55kg) or 3mg (if participant weighs ≥55 kg) of psilocybin daily on Monday, Tuesday, Thursday, and Friday for two consecutive weeks.

Psilocybin Microdosing

Placebo DRUG

Participants randomized to the placebo intervention will take 2mg (if participant weighs \<55kg) or 3mg (if participant weighs ≥55 kg) of placebo daily on Monday, Tuesday, Thursday, and Friday for two consecutive weeks.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)
• Living situation falls under one of two categories:
• Living in the community (i.e., receiving palliative care as an outpatient or through community home visits)
• 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
• Ability to understand and communicate in English or French
• 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

You may not qualify if:

• Current or previously diagnosed, or first-degree relative with, psychotic or bipolar disorder
• 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)
• Documented or suspected delirium in the past 3 months without a clearly defined reversible cause (e.g. opioid toxicity, infection) and resolution
• Documented moderate or severe dementia diagnosis
• Inability to provide first-person informed consent
• Inability to complete assessments via telephone or video-conferencing platform
• Severe or unstable physical symptoms based on the judgment of the palliative care provider
• Palliative Performance Scale (PPS) \<50%\*
• Cancer with known central nervous system (CNS) involvement or other CNS disease
• Use of high-dose psychedelic substances in the past year
• Taking lithium at any dose
• Taking tramadol at any dose
• Taking tapentadol at any dose
• Taking any monoamine oxidase inhibitor at any dose \[American Hospital Formulary Service (AFHS) group 28:16.04.12 or 28:36.32, including, but not limited to, moclobemide, tranylcypromine, phenelzine, selegiline, rasagiline\]
• Taking any atypical antipsychotic (aripiprazole, asenapine, brexpiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone)

Sponsors & Collaborators

• Bruyère Health Research Institute.: lead

Study Sites (7)

William Osler Health System

Brampton, Ontario, Canada

NOT YET RECRUITING

Providence Care Hospital

Kingston, Ontario, Canada

RECRUITING

St. Joseph's Healthcare

London, Ontario, Canada

NOT YET RECRUITING

South Lake Regional Health Centre

Newmarket, Ontario, Canada

RECRUITING

Bruyere Health

Ottawa, Ontario, Canada

RECRUITING

The Ottawa Hospital

Ottawa, Ontario, Canada

NOT YET RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

NOT YET RECRUITING

Related Publications (15)

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  PMID: 15621359 BACKGROUND

• Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967 Dec;6(4):278-96. doi: 10.1111/j.2044-8260.1967.tb00530.x. No abstract available.

  PMID: 6080235 BACKGROUND

• Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.

  PMID: 6880820 BACKGROUND

• Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6):603-20. doi: 10.1177/0269881108093587. Epub 2008 Jul 1.

  PMID: 18593734 BACKGROUND

• Anderson T, Petranker R, Christopher A, Rosenbaum D, Weissman C, Dinh-Williams LA, Hui K, Hapke E. Psychedelic microdosing benefits and challenges: an empirical codebook. Harm Reduct J. 2019 Jul 10;16(1):43. doi: 10.1186/s12954-019-0308-4.

  PMID: 31288862 BACKGROUND

• Siegel JS, Subramanian S, Perry D, Kay B, Gordon E, Laumann T, Reneau R, Gratton C, Horan C, Metcalf N, Chacko R, Schweiger J, Wong D, Bender D, Padawer-Curry J, Raison C, Raichle M, Lenze EJ, Snyder AZ, Dosenbach NUF, Nicol G. Psilocybin desynchronizes brain networks. medRxiv [Preprint]. 2023 Aug 24:2023.08.22.23294131. doi: 10.1101/2023.08.22.23294131.

  PMID: 37701731 BACKGROUND

• Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.

  PMID: 27909165 BACKGROUND

• Reiche S, Hermle L, Gutwinski S, Jungaberle H, Gasser P, Majic T. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:1-10. doi: 10.1016/j.pnpbp.2017.09.012. Epub 2017 Sep 22.

  PMID: 28947181 BACKGROUND

• Byock I. Taking Psychedelics Seriously. J Palliat Med. 2018 Apr;21(4):417-421. doi: 10.1089/jpm.2017.0684. Epub 2018 Jan 22.

  PMID: 29356590 BACKGROUND

• Faller H, Schuler M, Richard M, Heckl U, Weis J, Kuffner R. Effects of psycho-oncologic interventions on emotional distress and quality of life in adult patients with cancer: systematic review and meta-analysis. J Clin Oncol. 2013 Feb 20;31(6):782-93. doi: 10.1200/JCO.2011.40.8922. Epub 2013 Jan 14.

  PMID: 23319686 BACKGROUND

• Lo C, Hales S, Jung J, Chiu A, Panday T, Rydall A, Nissim R, Malfitano C, Petricone-Westwood D, Zimmermann C, Rodin G. Managing Cancer And Living Meaningfully (CALM): phase 2 trial of a brief individual psychotherapy for patients with advanced cancer. Palliat Med. 2014 Mar;28(3):234-42. doi: 10.1177/0269216313507757. Epub 2013 Oct 29.

  PMID: 24170718 BACKGROUND

• Salt S, Mulvaney CA, Preston NJ. Drug therapy for symptoms associated with anxiety in adult palliative care patients. Cochrane Database Syst Rev. 2017 May 18;5(5):CD004596. doi: 10.1002/14651858.CD004596.pub3.

  PMID: 28521070 BACKGROUND

• Kissane DW. Psychospiritual and existential distress. The challenge for palliative care. Aust Fam Physician. 2000 Nov;29(11):1022-5.

  PMID: 11127057 BACKGROUND

MeSH Terms

Interventions

Psilocybin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Central Study Contacts

James Downar, MDCM, MHSc

CONTACT

613-562-6262; jdownar@toh.ca

Julie Lapenskie, MSc

CONTACT

613-562-6262; jlapenskie@bruyere.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist; Head, Division of Palliative Care, University of Ottawa

Model Details: This study is a multi-site, randomized, double-blind, placebo-controlled, parallel-arm clinical trial with an optional open-label access and extension phase.

Study Record Dates

• First Submitted: July 3, 2025
• First Posted: July 14, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)