PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial
James Downar, Julie Lapenskie, Koby Anderson, Gaelle Parsons, Nadia Polskaia, Genevieve Lalumiere, Peter G. Lawlor
Palliative Medicine January 30, 2026 DOI: 10.1177/02692163261416269 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open label, single-arm clinical trial Open-label Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Adults with advanced, incurable illness and estimated prognosis of 1–12 months, experiencing severe psychological distress |
| Intervention | Psilocybin |
| Dose | 1 mg daily in week 1, increased to 2 mg in week 2 and 3 mg in week 3 |
| Duration | 3-week intervention |
| Topics | Psilocybin End-of-life distress |
| Keywords | Palliative care Clinical trial Microdose Psychological distress Cancer Medline Psychotherapist Clinical psychology Existentialism Depression economics Hallucinogen |
| Registration | NCT04754061 |
| Key findings | Microdose psilocybin was safe and feasible, with 69% of completers reporting meaningful global improvement and over half showing clinically significant reductions in depression and demoralization. |
Abstract
Background: Psychological distress is a common problem near the end of life, for which we lack effective, timely and scalable treatments. No previous study has assessed whether microdose psilocybin can improve symptoms in this population.
Aim: To determine whether microdose psilocybin is safe, feasible and potentially efficacious in a palliative setting.
Design: Open label, single-arm clinical trial of a 3-week oral psilocybin intervention, starting with 1 mg daily in week 1, increased to 2 mg in week 2 and 3 mg in week 3. ClinicalTrials.gov NCT04754061. Setting/participants: Two-center study in Ottawa, Canada of adults with advanced, incurable illness and an estimated prognosis of 1–12 months, experiencing severe psychological distress.
Results: We enrolled 20 participants (59% of those screened) between January 2024 and April 2025, of which 17 began and 13/17 (76%) completed the intervention. Participants were 40–84 years old, 53% female, and 82% had cancer. There were no serious adverse events reported, and nine mild or moderate adverse events. Four participants withdrew due to disease progression or poor response. Of the 13 remaining participants, nine (69%) reported a meaningful global improvement (Patient Global Impression of Change ⩾ 5); 8 (62%) reported >50% improvement in Hamilton Depression Rating Scale scores, 7 (54%) reported >50% improvement in Hospital Anxiety and Depression Scale scores and 9 (72%) reported a meaningful improvement in Demoralization Scale II scores.
Conclusions: Microdose psilocybin is a safe, feasible and potentially efficacious treatment for psychological distress in people with advanced illness.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Microdose psilocybin (1-3 mg over 3 weeks) was safe and feasible, with 69% of completers reporting meaningful global improvement and over half showing clinically significant reductions in depression and demoralization.
Synthesized
Comparable studies
Other non-randomized and open-label trials on psilocybin for end-of-life distress, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Press Release - Clinical Trial into Psilocybin Therapy for Psychological Distress in Palliative Care, PsyPal, Receives Medical Ethical Authorisation, with Conditions Patients with progressive, incurable diseases including COPD, multiple sclerosis, ALS,... | 2024 | Clinical trial | |
| Psilocybin-Assisted Early Palliative Care for Demoralization and Chronic Pain: An Open-Label Pilot Study. Cancer patients across the illness trajectory with demoralization and chronic pain | 2026 | Open-label pilot study | n = 11 |