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 : the preprint server for health sciences 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.