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End-of-life distress research: what the evidence shows

Research on easing psychological and existential suffering near the end of life, a landmark area for psilocybin therapy.

State of the evidence

Synthesized

Synthesized from 24 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for End-of-life distress, existential distress, palliative, terminal illness anxiety, then ranked by relevance.

The research on end-of-life distress centers mainly on psilocybin-assisted psychotherapy, which in small trials and long-term follow-ups has produced large, sustained reductions in anxiety, depression, demoralization, hopelessness, and death anxiety in people with life-threatening cancer, with some benefit persisting for years. Systematic reviews rate this evidence as promising but of low to very low certainty, citing small samples, unblinding, and short follow-up. Other approaches (ketamine, mindfulness, Buddhist spiritual care) show preliminary or mixed signals, and the durability, blinding, and generalizability of the psychedelic findings remain the main caveats.

Evidence by study

Direction is which way each study's own result points, not our rating of the study. All 25 matching studies were reviewed; the 24 that directly address the question are shown here.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
Study Design Sample size Direction Finding
Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer 2020 long-term within-subjects follow-up 15 Supports Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at 3.2 and 4.5 years, with 60–80% still meeting criteria for clinically significant antidepressant or anxiolytic response.
Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer 2021 RCT secondary analysis Supports Among participants with elevated suicidal ideation at baseline, psilocybin-assisted psychotherapy reduced suicidal ideation as early as 8 hours and produced large reductions in loss of meaning that persisted to 4.5 years.
Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases 2024 systematic review Supports Psilocybin or LSD-assisted therapy may be effective for anxiety, depression, and possibly existential distress, was well tolerated with no treatment-emergent serious adverse events, but certainty of evidence is low to very low.
Psilocybin in Palliative Care: An Update. 2023 review Supports Psilocybin showed significant and sometimes sustained anxiolytic, antidepressant, anti-inflammatory, and entheogenic effects with a favorable safety profile, though selection bias and short follow-up limit the evidence.
The Potential of Psychedelics for End of Life and Palliative Care. 2022 review Supports Argues that psychedelics may provide clinicians with an additional psychopharmacological treatment for depression, existential distress, and well-being at end of life.
Psychedelic-assisted psychotherapy to treat psychiatric and existential distress in life-threatening medical illnesses and palliative care. 2022 commentary Supports Argues that psychedelic-assisted psychotherapy warrants further rigorous research as a treatment for psychiatric and existential distress in life-threatening illness and palliative care.
Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness. 2022 review Supports Argues that one-time psychedelic-assisted therapy may lead to sustained reductions in anxiety, depression, and demoralization in seriously ill and end-of-life patients, while practical guidance for clinicians remains limited.
Psychedelic medicines for existential distress associated with life-threatening illnesses 2026 commentary Supports Argues that psychedelic-assisted therapy could alleviate existential distress and anxiety in patients facing life-threatening illness, where palliative care lacks an effective strategy.
Palliative Nursing and Sacred Medicine: A Holistic Stance on Entheogens, Healing, and Spiritual Care. 2019 theoretical paper Supports Proposes that entheogens can be integrated into holistic nursing care to promote presence, introspection, decreased fear, and increased joy and acceptance in advanced serious illness.
Psychedelic medicines for end-of-life care: Pipeline clinical trial review 2022. 2023 scoping review 25 Mixed Identified 25 pipeline trials (13 RCTs, 12 open-label) of psychedelics for end-of-life distress, but only three assessed expectancy and blinding effectiveness, and head-to-head comparisons are still needed.
Social acceptability of psilocybin-assisted therapy for existential distress at the end of life: A population-based survey 2024 cross-sectional survey 2800 Supports 79.3% considered psilocybin-assisted therapy a reasonable medical choice for existential distress at end of life and 84.8% supported public coverage.
Exploring the Use of Psilocybin Therapy for Existential Distress: A Qualitative Study of Palliative Care Provider Perceptions 2021 qualitative descriptive study 5 Unclear Providers described multiple barriers to addressing existential distress and expressed uncertainty about the risks and benefits of psilocybin therapy.
Navigating groundlessness: An interview study on dealing with ontological shock and existential distress following psychedelic experiences. 2025 qualitative interview study 26 Opposes Participants reported persistent existential struggle and confusion after psychedelic experiences, alleviated mainly through grounding practices of embodiment and social and cognitive normalization.
A Phase II, Open-Label Clinical Trial of Intranasal Ketamine for Depression in Patients with Cancer Receiving Palliative Care (INKeD-PC Study) 2023 single-arm open-label phase II trial 20 Supports Intranasal ketamine produced 70% antidepressant response and 45% remission by day 8, with mean depression scores falling from 31 to 11, and effects partially sustained into the second week.
A rapid systematic review of palliative uses of ketamine for depression and pain in people living with advanced cancer. 2026 systematic review Mixed Ketamine may alleviate refractory cancer pain and depression, but findings are inconsistent, and a cost-effectiveness analysis of the only adequately powered RCT found no analgesic benefit and greater toxicity among inpatients near end of life.
Effects of embedded micro-mindfulness on psychological symptoms in patients with advanced cancer receiving palliative care: a prospective controlled study. 2026 prospective non-randomized observational study 243 Supports An embedded micro-mindfulness program produced greater reductions over four weeks in anxiety, depressive symptoms, psychological distress, and sleep problems than usual care, with no difference in pain intensity.
Mindfulness and Existential Healing Interventions in Palliative Care for Patients with Advanced Cancer:A Scoping Review 2026 scoping review Supports Mindfulness-based and existential healing interventions both show potential for reducing emotional distress and death anxiety and improving meaning, spiritual well-being, and quality of life, though integrated programs remain underdeveloped.
Mindfulness and compassion-oriented practices at work reduce distress and enhance self-care of palliative care teams: a mixed-method evaluation of an “on the job“ program 2017 observational mixed-method pilot 28 Supports A 10-week mindfulness and compassion training significantly improved emotional exhaustion, personal accomplishment, anxiety, stress, emotion regulation, and joy at work.
Effect of mindfulness-based stress reduction on nursing interns' death anxiety, stress, and palliative care self-efficacy during oncology end-of-life training. 2026 quasi-experimental pre-post study 120 Supports An 8-week MBSR program significantly reduced death anxiety and perceived stress and improved attitudes toward caring for dying patients.
The DSC Triangle Model of Buddhist Palliative Care: Doctrine, Spiritual Pillar, and Community at Wat Kham Pramong 2026 qualitative case study 10 Supports Describes qualitative patterns of movement from fear, anxiety, and isolation toward acceptance, inner peace, and relational connection through Buddhist doctrine, spiritual practice, and community support, with responses varying by patient factors.
Sensory perceptions during near-death experiences in palliative care excluding pathological causes or artificial induction. 2026 review Unclear Found no direct evidence on sensory perceptions during near-death experiences in palliative care excluding pathological causes, but notes end-of-life dreams and visions are common and usually comforting in hospice.
How do near-death experiences in palliative care differ from typical hallucinations? 2026 commentary Supports Argues that near-death experiences in palliative care are predominantly distinct from typical hallucinations because they are comforting, meaningful, and spiritual, and that proper recognition can enhance end-of-life care.
Mindfulness as the missing link in spiritual care: Reframing palliative care practice through presence. 2026 theoretical paper Supports Argues that mindfulness as presence is a crucial but overlooked component of spiritual care in palliative care and proposes reframing practice around presence.
How is caregiver involvement conceptualized across oncology, palliative care, and psychedelic-assisted therapy literature, and which relational mechanisms can inform its use in oncology-based psychedelic care? 2026 review Unclear Argues that caregiver involvement is important in oncology and palliative care but that no direct evidence exists for psychedelic-assisted therapy in oncology, highlighting a need for research on caregiver roles.

Points of agreement

  • Psilocybin-assisted psychotherapy is consistently associated with reductions in anxiety, depression, demoralization, and death anxiety in people with life-threatening cancer.
  • Benefits in several trials and follow-ups appear sustained for months to years, with large within-group effect sizes.
  • Psychedelic-assisted therapy is generally described as well tolerated, with no treatment-emergent serious adverse events reported in reviewed trials.
  • Reviewers agree that the evidence base is limited by small samples, unblinding, and low certainty.
  • Mindfulness-based interventions also show promise for reducing distress and death anxiety in palliative patients and staff.

Conflicts

  • Psychedelic literature is largely positive, whereas a qualitative study documents persistent existential distress and ontological shock following psychedelic experiences.
  • Ketamine evidence is mixed: an open-label trial reports high antidepressant response rates, while a systematic review notes inconsistent findings and a negative adequately powered RCT for pain near end of life.
  • Some reviews describe sustained benefit, while others emphasize that follow-up is too short to judge durability.

Gaps

  • Blinding and expectancy effects are rarely assessed in psychedelic trials.
  • Sample sizes are small and populations skew toward healthier, white, financially privileged participants.
  • Long-term durability beyond a few years is largely unstudied.
  • Head-to-head comparisons between different psychedelics are lacking.
  • Little research addresses caregiver roles and integration into palliative care settings.
  • Adverse or difficult psychedelic experiences and their management are understudied.
Browse these studies in the library

Common questions

What does the research agree on about end-of-life distress?
  • Psilocybin-assisted psychotherapy is consistently associated with reductions in anxiety, depression, demoralization, and death anxiety in people with life-threatening cancer.
  • Benefits in several trials and follow-ups appear sustained for months to years, with large within-group effect sizes.
  • Psychedelic-assisted therapy is generally described as well tolerated, with no treatment-emergent serious adverse events reported in reviewed trials.
  • Reviewers agree that the evidence base is limited by small samples, unblinding, and low certainty.
  • Mindfulness-based interventions also show promise for reducing distress and death anxiety in palliative patients and staff.
Where do studies on end-of-life distress conflict?
  • Psychedelic literature is largely positive, whereas a qualitative study documents persistent existential distress and ontological shock following psychedelic experiences.
  • Ketamine evidence is mixed: an open-label trial reports high antidepressant response rates, while a systematic review notes inconsistent findings and a negative adequately powered RCT for pain near end of life.
  • Some reviews describe sustained benefit, while others emphasize that follow-up is too short to judge durability.
What is still unknown about end-of-life distress?
  • Blinding and expectancy effects are rarely assessed in psychedelic trials.
  • Sample sizes are small and populations skew toward healthier, white, financially privileged participants.
  • Long-term durability beyond a few years is largely unstudied.
  • Head-to-head comparisons between different psychedelics are lacking.
  • Little research addresses caregiver roles and integration into palliative care settings.
  • Adverse or difficult psychedelic experiences and their management are understudied.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is End-of-life distress, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when End-of-life distress or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

The full method, including what a person does and does not review, is on the methods page.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: September 2026 →

391 articles · 177 from the last two years · 213,196 participants across 129 studies reporting sample size

Common study designs

review 79 narrative review 18 qualitative study 29 systematic review 32 theoretical or philosophical paper 53

Research volume by year

Compare topics →

126 studies whose primary subject is end-of-life distress since 2005

Studies about end-of-life distress per year, 2005 to 2026, peaking at 37 in 2026 Bar chart: one bar per year, taller where more studies were published that year. 0 20 40 2005 2010 2015 2020 2025
2026 is partial
Show the numbers
Studies about end-of-life distress per year, 2005 to 2026, peaking at 37 in 2026
Year Studies
2005 1
2006 0
2007 0
2008 1
2009 1
2010 0
2011 1
2012 0
2013 0
2014 0
2015 0
2016 0
2017 3
2018 3
2019 5
2020 2
2021 5
2022 9
2023 11
2024 15
2025 32
2026 37

Research

Synthesize the evidence → Search all →

Psilocybin-Assisted Therapy for Cancer-Related Psychological and Existential Distress in Adults with Cancer: An Integrative Systematic Review

Journal of Pain & Palliative Care Pharmacotherapy November 3, 2026 Athanasios Pitis, Maria Nikoloudi, Nikos C. Stefanis et al.

Psilocybin-assisted therapy has reemerged as a promising intervention for distress associated with cancer and life-threatening illness. This integrative systematic review evaluated evidence on the safety, efficacy, and therapeutic impact of psilocybin-assisted therapy in adults with cancer experiencing depression, anxiety and existential distress. Following PRISMA guidelines, PubMed, Scopus,...

DOI: 10.1080/15360288.2026.2756950 (opens in new tab)

The DSC Triangle Model of Buddhist Palliative Care: Doctrine, Spiritual Pillar, and Community at Wat Kham Pramong

Journal of International Buddhist Studies September 23, 2026 Yin Li, Asst. Prof. Dr. Phramaha Nantakorn Piyabhani, Asst. Prof. Dr. Phramaha Anon Anando

This qualitative case study examines Buddhist spiritual care for terminal cancer patients through the case of Wat Kham Pramong in Sakon Nakhon Province, Thailand. It addresses three objectives: to examine how the temple responds to patients’ spiritual needs, to identify the Buddhist teachings and practices relevant to those needs, and to assess the approach’s qualitative impact in terminal...

DOI: 10.65680/95161722026 (opens in new tab)

Sensory perceptions during near-death experiences in palliative care excluding pathological causes or artificial induction.

Zenodo (CERN European Organization for Nuclear Research) September 11, 2026 preprint

No direct evidence for sensory perceptions during near-death experiences in palliative care specifically excluding pathological causes was identified. However, end-of-life dreams and visions are common and usually comforting in hospice settings, emphasizing the need for sensitive interpretation by healthcare professionals.

DOI: 10.5281/zenodo.22707463 (opens in new tab)

Effect of mindfulness-based stress reduction on nursing interns' death anxiety, stress, and palliative care self-efficacy during oncology end-of-life training.

Palliative & Supportive Care September 11, 2026 Donia Elsaid Fathi Zaghamir, Ateya Megahed Ibrahim, Hala Samir Ahmed El-Husseiny

Objectives: Nursing interns often experience high levels of death anxiety and stress, which can reduce their comfort and confidence in caring for dying patients. This study evaluated the effects of an 8-week Mindfulness-Based Stress Reduction (MBSR) program on death anxiety, perceived stress, and attitudes toward care of the dying among nursing interns during palliative and oncology rotations....

DOI: 10.1017/s1478951526103447 (opens in new tab) Humans Palliative care Terminal care Attitude to death +12

A rapid systematic review of palliative uses of ketamine for depression and pain in people living with advanced cancer.

Annals of Palliative Medicine September 3, 2026 Danielle B Tometich, Christina L Hersh, Matthew A Murphy et al.

Background: Given the growing population of patients living with metastatic cancer, palliative care providers need every available tool for symptom management. We conducted a rapid review of the literature on palliative uses of ketamine for pain and depression in people with cancer. Methods: We systematically searched for studies published since 2015 that examined palliative uses of ketamine in...

DOI: 10.21037/apm-2026-0032 (opens in new tab) Depression Ketamine Cancer Pain +1

Effects of embedded micro-mindfulness on psychological symptoms in patients with advanced cancer receiving palliative care: a prospective controlled study.

Frontiers in Oncology August 26, 2026 Qin Zhang, Qianer Li, Aiping Deng et al.

Objective: To evaluate changes in psychological distress, anxiety and depressive symptoms, sleep problems, and pain intensity associated with participation in an embedded micro-mindfulness program among patients with advanced cancer receiving palliative care, and to explore factors associated with psychological symptom response. Methods: This single-center, prospective, non-randomized...

DOI: 10.3389/fonc.2026.1916107 (opens in new tab) Full text (opens in new tab) Advanced cancer Palliative care Anxiety and depression Psychological symptoms +1

Mindfulness and Existential Healing Interventions in Palliative Care for Patients with Advanced Cancer:A Scoping Review

Research Square August 18, 2026 Shenghuan Yang, Yan Lou, Tingting Chen et al. preprint

Abstract Background: Patients with advanced cancer frequently experience multidimensional suffering,including psychological distress,existential distress,and concerns related to death and dying.Mindfulness-based interventions and existential healing interventions have increasingly been applied in palliative care;however,the current evidence regarding their integration,intervention...

DOI: 10.21203/rs.3.rs-10302533/v1 (opens in new tab) Full text (opens in new tab)

How is caregiver involvement conceptualized across oncology, palliative care, and psychedelic-assisted therapy literature, and which relational mechanisms can inform its use in oncology-based psychedelic care?

Zenodo (CERN European Organization for Nuclear Research) August 12, 2026 preprint

Current evidence highlights the importance of caregiver involvement in oncology and palliative care, emphasizing communication and decision-making. No direct evidence exists for psychedelic-assisted therapy in oncology, highlighting a need for research exploring caregiver roles in this context.

DOI: 10.5281/zenodo.21906477 (opens in new tab)

Psychedelic medicines for existential distress associated with life-threatening illnesses

International Journal of Whole Person Care August 9, 2026 Houman Farzin

This presentation will review the history of scientific research into the use of psychedelic medicines for the treatment of existential distress due to life-threatening illnesses, it will then outline the current state of affairs in North America, and conclude with exploring the implications it will have on the future of palliative care. Despite the significant advances in the field of...

DOI: 10.26443/ijwpc.v9i1.332 (opens in new tab) Full text (opens in new tab)

Clinical trials

All End-of-life distress trials →