Psilocybin-Assisted Early Palliative Care for Demoralization and Chronic Pain: An Open-Label Pilot Study.
Ali J Zarrabi, Tanja Mletzko, George Grant, Caroline Peacock, Roman Palitsky, Tarrant Mcpherson, Isabelle Shub, Sarah Eisenacher, Jessica L Maples-Keller, Deanna Kaplan, Barbara O Rothbaum, Fayzan Rab, Nupur Dalal, Kimberly A Curseen, Charles Raison, Boadie W Dunlop
medRxiv : the preprint server for health sciences July 14, 2026 DOI: 10.64898/2026.07.11.26357570 (opens in new tab) via PubMed
Summary
AI-generated from the abstractIn an open-label pilot study, psilocybin-assisted therapy (PAT) was tested in cancer patients with demoralization and chronic pain within a multidisciplinary palliative care setting. Ten of eleven enrolled participants received a single 25 mg oral dose of psilocybin with preparation, monitoring, and integration. The intervention was safe and feasible, with no serious adverse events and complete retention. All dosed participants found it highly acceptable; 70% rated it among the five most meaningful experiences of their lives and 60% among the five most spiritually significant. By study endpoint, 90% no longer met criteria for clinically significant demoralization and had pain scores below the enrollment threshold.
Study at a glance
| Characteristics | Open-label pilot study Peer reviewed |
|---|---|
| Sample size | 11 |
| Population | Cancer patients across the illness trajectory with demoralization and chronic pain |
| Intervention | Psilocybin-assisted therapy |
| Dose | 25 mg |
| Key finding | 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.