End-of-life distress

Psilocybin-assisted psychotherapy produced sustained reductions in anxiety, depression, hopelessness, demoralization, and death anxiety at 3.2 and 4.5 years after administration, with 60–80% of participants still meeting criteria for clinically significant antidepressant or anxiolytic responses.

long-term within-subjects follow-up analysis Sample size: 15

Mindfulness and compassion-oriented meditation training significantly improved emotional exhaustion, personal accomplishment, anxiety, stress, and two emotional regulation competences in palliative care staff.

observational mixed-method pilot evaluation Sample size: 28

Psilocybin-assisted psychotherapy reduced suicidal ideation and loss of meaning in cancer patients with elevated baseline suicidal ideation, with effects persisting up to 4.5 years.

randomized controlled trial

Argues that psychedelic-assisted psychotherapy warrants further research as a treatment for psychiatric and existential distress in life-threatening medical conditions and palliative care.

commentary

Intranasal ketamine produced high rates of antidepressant response (70%) and remission (45%) by day 8 in patients with advanced cancer and major depressive disorder.

single-arm, open-label phase II trial Sample size: 20

Psychedelic-assisted therapy can safely and effectively reduce anxiety, depression, and demoralization in seriously ill and end-of-life patients, but practical guidance for palliative care clinicians remains limited.

review

Psychedelic-assisted therapy with psilocybin or LSD may be effective for anxiety, depression, and possibly existential distress, but the certainty of evidence is low to very low.

systematic review

Psychedelics may provide clinicians with an additional psychopharmacological treatment in the context of end-of-life and palliative care.

review

Argues that preliminary evidence suggests psychedelics may improve quality of life and functionality in chronic pain patients, and calls for more research to clarify mechanisms.

commentary

Participants experienced persistent existential struggle and confusion following psychedelic experiences, alleviated primarily through grounding practices of embodiment and social and cognitive normalization.

qualitative study Sample size: 26

Proposes that entheogens can be integrated into spiritual and holistic nursing care to help patients with advanced serious illness achieve integrative experiences that promote presence, introspection, decreased fear, and increased joy and acceptance.

theoretical or philosophical paper

Psilocybin has significant and in some cases sustained anxiolytic, antidepressant, anti-inflammatory and entheogenic effects with a favorable safety profile for palliative care patients, though major barriers to access exist.

review

79.3% of respondents considered psilocybin-assisted therapy a reasonable medical choice for existential distress at the end of life.

cross-sectional survey Sample size: 2800

25 pipeline clinical trials of psychedelic treatment for end-of-life distress were identified, but only three assessed expectancy and blinding effectiveness, and head-to-head comparisons of different psychedelics are still needed.

scoping review Sample size: 25

Palliative care providers identified multiple barriers to addressing existential distress and expressed uncertainty about psilocybin's risks and benefits.

qualitative descriptive study Sample size: 5

Argues that psychedelic-assisted therapy could serve as a powerful tool to alleviate existential distress and anxiety in patients with life-threatening illnesses, and that current palliative care lacks an effective strategy for this distress.

commentary

Intranasal ketamine was associated with clinically meaningful improvements in existential distress, anxiety, symptom burden, and quality of life in individuals with advanced cancer being treated for depression.

secondary analysis of a clinical trial Sample size: 15

The review aims to determine the extent to which spiritual, existential, religious, and theological components are a focus of screening and treatment protocols in psychedelic-assisted therapies for seriously ill individuals.

narrative review

Psychedelics can produce rapid and long-lasting antidepressant and anxiolytic effects with a low risk of serious adverse events in end-of-life patients.

review

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.

open-label pilot study Sample size: 11

Healthcare professionals are interested in psychedelic-assisted therapy for existential distress in cancer patients but identify knowledge gaps, barriers, and a need for more research, with preferences for multidisciplinary, culturally sensitive, and ethically rigorous delivery.

qualitative study Sample size: 11

Argues that Canada's evolving psychedelic drug policy trajectory aligns with international trends toward cautious medicalization and regulated access to psychedelic therapies, while offering an instructive case for how end-of-life frameworks and federal-provincial governance shape policy development.

theoretical or philosophical paper

Psychedelic-assisted therapy shows promise for improving anxiety, depression, pain-related distress, and quality of life in advanced cancer patients, but evidence is limited by small sample sizes and other methodological constraints.

review

Psychiatry faces a challenging opportunity to integrate spiritual dimensions of distress without compromising scientific integrity, shaping its future relationship with the sacred.

review

Despite favorable views and modest estimated costs, no patients received psilocybin-assisted therapy after one year, indicating a gap between regulatory authorization and effective service uptake.

single-case implementation study Sample size: 10