Meaning and Psychedelics in Palliative Care: A Narrative Review

Context: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.