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Meaning and Psychedelics in Palliative Care: A Narrative Review.

William B Alexander, Eric D Hansen, Brian T Anderson, Ali John Zarrabi, Andrew H Rogers, Gregory Loewen, Zachary R Ficarro, Margaret H Alexander, Dylan Schaefer, Amy A Case

Journal of pain and symptom management March 1, 2026 DOI: 10.1016/j.jpainsymman.2025.10.015 via PubMed

Summary

AI-generated from the abstract

Loss of meaning is a hallmark of demoralization syndrome, a prevalent condition in palliative care linked to diminished quality of life, increased symptom burden, and higher suicide risk. Existential psychological interventions improve psychosocial outcomes, but evidence for their effect on demoralization is limited. Psychedelic therapies, which enhance meaning-making and integrate existential approaches, show promise for existential distress and demoralization in early clinical trials. Novel combined pharmacological and psychological interventions like psychedelic therapy warrant further investigation.

Study at a glance

Characteristics Narrative review Peer reviewed
Population Patients with advanced illnesses in palliative care
Topics End-of-life distress LSD Psilocybin
Keywords Demoralization Meaning
Citations 1
Key finding Loss of meaning is a hallmark of demoralization syndrome, and psychedelic therapies show promise for existential distress and demoralization in palliative care.

Abstract

Meaning is a primary existential concern in those with advanced illnesses and functions as an important coping mechanism. Loss of meaning contributes to existential distress, and, in particular, may manifest as demoralization, a syndrome of poor coping that is associated with negative outcomes. Psychedelics are unique psychoactive compounds that, among other properties, are proposed to enhance meaning. In the palliative setting, psychedelic therapies are under investigation for existential distress, including demoralization. To synthesize the literature on meaning in palliative care, including the clinical impact of loss of meaning, particularly demoralization, and evidence for proposed interventions including existential psychological interventions and psychedelic therapies. We conducted a narrative review based on a structured search within Pubmed. Articles were screened for those addressing prespecified questions derived from our objectives, and results were synthesized in narrative format. Loss of meaning is a hallmark feature of demoralization syndrome, a prevalent and distinct condition linked with diminished quality of life, increased symptom burden, and increased suicide risk. Existential psychological interventions improve numerous psychosocial outcomes, although evidence for their efficacy in demoralization is limited. In psychedelic therapy, meaning-making is a typical feature, and existential interventions are commonly integrated. Finally, early clinical trial data indicate that psychedelic therapies show promise for existential distress, including demoralization. Novel approaches are needed to address existential distress, especially when manifested as demoralization. Psychedelic therapy is a promising combined pharmacologic and psychological intervention that promotes meaning-making and shows potential for improving demoralization, warranting further investigation.

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