Psilocybin-Assisted Early Palliative Care for Demoralization and Chronic Pain: An Open-Label Pilot Study.
Ali J Zarrabi, Tanja Mletzko, George H. Grant, Caroline Peacock, Roman Palitsky, Tarrant Mcpherson, Isabelle Shub, Sarah Eisenacher, Jessica L Maples-Keller, Deanna M Kaplan, Barbara O Rothbaum, Fayzan Rab, Nupur Dalal, Kimberly A Curseen, Charles L. Raison, Boadie W Dunlop
medRxiv July 14, 2026 preprint DOI: 10.64898/2026.07.11.26357570 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pilot study |
|---|---|
| Sample size | 11 |
| Population | Cancer patients across the illness trajectory with demoralization and chronic pain |
| Intervention | Psilocybin-assisted therapy |
| Dose | 25 mg |
| Topics | End-of-life distress Psilocybin |
| Key points | Psilocybin-assisted therapy with multidisciplinary palliative care was safe, feasible, and acceptable, with 90% of dosed participants no longer meeting criteria for clinically significant demoralization and having pain scores below the enrollment threshold by study endpoint. |
Abstract
Demoralization, a syndrome of helplessness, hopelessness, and loss of meaning and chronic pain are common sources of distress in early palliative care. Psilocybin-assisted therapy (PAT) is an emerging intervention with preliminary data suggesting improvements in pain and demoralization. To date, PAT has not been studied among people living with both demoralization and chronic pain nor has it been studied as part of routine multidisciplinary outpatient palliative care. We conducted an open-label pilot study assessing the safety, feasibility, and acceptability of PAT delivered with multidisciplinary palliative care support in cancer patients across the illness trajectory living with demoralization and chronic pain. Participants received a single 25 mg oral dose of psilocybin with preparation, monitoring, and integration provided by a mental health clinician and spiritual health clinician, alongside multidisciplinary palliative care support. Outcomes included safety, feasibility, acceptability, and exploratory self-report measures assessing for demoralization and pain intensity pre- and post-dosing. Eleven participants were enrolled, ten of whom received psilocybin. The intervention was safe and feasible, with no serious adverse events and complete study visit retention among dosed participants. All 10 dosed participants reported the intervention as highly acceptable. Among dosed participants, 70% rated the experience among the five most meaningful and educational of their lives, and 60% among their five most spiritually significant experiences. By study endpoint, 90% no longer met criteria for clinically-significant demoralization syndrome and had pain scores below the trial enrollment threshold. PAT delivered with multidisciplinary palliative care support was safe, feasible, and acceptable in demoralized cancer patients with chronic pain. Psilocybin-assisted therapy delivered within multidisciplinary outpatient palliative care was safe, feasible, and acceptable among demoralized cancer patients with chronic pain.
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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A single 25 mg dose with multidisciplinary palliative care was safe and feasible, with 90% of dosed participants no longer meeting criteria for clinically significant demoralization by study endpoint.
Synthesized
Comparable studies
Other non-randomized and open-label trials on end-of-life distress, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A Phase II, Open-Label Clinical Trial of Intranasal Ketamine for Depression in Patients with Cancer Receiving Palliative Care (INKeD-PC Study) Patients with advanced cancer and moderate to severe major depressive disorder | 2023 | Single-arm, open-label phase II trial | n = 20 |
| Mindfulness and compassion training on daily work with patients and within the multiprofessional palliative care team: a retrospective self-assessment study Employees of a university-based specialized palliative care unit | 2023 | Observational cohort (pre-post self-assessment) | n = 24 |
| Intranasal Ketamine for Existential Distress in Advanced Cancer. Patients with advanced cancer receiving palliative care | 2026 | Secondary analysis of a clinical trial | n = 15 |
| PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial Adults with advanced, incurable illness and estimated prognosis of 1–12 months,... | 2026 | Open label, single-arm clinical trial | n = 20 |
| Effect of mindfulness-based stress reduction on nursing interns' death anxiety, stress, and palliative care self-efficacy during oncology end-of-life training. Final-year Bachelor of Science in nursing interns at Prince Sattam Bin Abdulaziz... | 2026 | Quasi-experimental pre-post study | n = 120 |