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Psilocybin for end-of-life distress

Studies whose primary subject is both Psilocybin and End-of-life distress, with an evidence synthesis read across the most-cited and most recent of them.

State of the evidence

Synthesized

Synthesized from 22 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Psilocybin, magic mushrooms, psilocin, psychedelic mushrooms, End-of-life distress, existential distress, then ranked by relevance.

The research consistently points toward psilocybin-assisted therapy reducing depression, anxiety, demoralization, and existential distress in people with life-threatening illness, with several trials reporting large effects and some follow-up data showing benefits sustained for months to several years. Evidence comes mainly from small trials and reviews, and durability, blinding, and generalizability remain uncertain. Implementation studies suggest that even where authorized, access is limited by logistical, regulatory, and training barriers.

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 22 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 responses.
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 baseline suicidal ideation, psilocybin-assisted psychotherapy was associated with within-group reductions in suicidal ideation apparent as early as 8 hours and persisting 6.5 months, plus large reductions in loss of meaning sustained to 4.5 years.
Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness. 2022 review Supports Reports 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 noting limited practical guidance for clinicians.
The Potential of Psychedelics for End of Life and Palliative Care. 2022 review Supports Argues that psychedelics may provide clinicians an additional psychopharmacological treatment for depression, existential distress, and well-being in end-of-life and palliative care.
Psilocybin in Palliative Care: An Update. 2023 review Supports Reports that psilocybin has significant and in some cases sustained anxiolytic, antidepressant, anti-inflammatory, and entheogenic effects with a favorable safety profile, while noting selection bias and short follow-up as limitations.
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 the end of life, and 84.8% agreed the public health system should cover its costs.
Exploring the Use of Psilocybin Therapy for Existential Distress: A Qualitative Study of Palliative Care Provider Perceptions 2021 qualitative descriptive study 5 Mixed Providers identified multiple barriers to addressing existential distress and expressed uncertainty about psilocybin's risks and benefits.
Psilocybin-assisted psychotherapy for existential distress: practical considerations for therapeutic application—a review 2024 narrative review Supports Reports that psilocybin and LSD combined with psychotherapy have shown rapid and sustained reductions in existential and psychiatric distress in patients facing life-threatening illness.
Evaluating the effectiveness of psilocybin in alleviating distress among cancer patients: A systematic review. 2025 systematic review 14 Supports Across 14 studies (3 RCTs, 5 open-label trials, 5 qualitative studies, 1 case report), psilocybin therapy consistently reduced depression, anxiety, and existential distress, with improvements sustained over several months and generally mild, transient adverse effects.
Psychedelics for the treatment of end-of-life distress in patients with a life-threatening disease. 2025 review Supports Reports that psychedelic-assisted therapy is associated with highly significant and sometimes sustained decreases in depression and death anxiety, along with improvements in meaning, spiritual well-being, optimism, and life satisfaction.
What do health professionals think about implementing psilocybin-assisted therapy in palliative care for existential distress? A World Café qualitative study. 2024 qualitative study 16 Mixed Professionals considered psilocybin-assisted therapy a treatment of interest but raised concerns about training, legalization, protocols, and eligibility criteria that need addressing for acceptability and access.
Palliative care patients’ attitudes and openness towards psilocybin-assisted psychotherapy for existential distress 2024 pilot survey study 31 Mixed 51.6% expressed interest in future psilocybin treatment, with belief in its therapeutic benefits correlating with interest, while concerns included risk of psychosis, lack of trained providers, and potential for exploitation.
Psilocybin-Assisted Early Palliative Care for Demoralization and Chronic Pain: An Open-Label Pilot Study. 2026 open-label pilot study 11 Supports A single 25 mg dose with multidisciplinary palliative care was safe and feasible, with 90% of dosed participants no longer meeting criteria for clinically significant demoralization and pain scores below the enrollment threshold by study endpoint.
The need for another tool: Australian healthcare professionals on the use of psilocybin for existential distress in people with cancer 2026 qualitative study 11 Mixed Professionals remained interested in psychedelic-assisted therapy for existential distress but identified knowledge gaps, barriers, and a need for more research, preferring multidisciplinary, culturally sensitive, and ethically rigorous delivery.
Bringing Psilocybin-Assisted Therapy to Palliative Oncology: Early Lessons from Real-World Implementation. 2026 single-case implementation study 10 Opposes Despite favorable views and modest estimated costs, no patients received psilocybin-assisted therapy after one year, indicating a gap between regulatory authorization and service uptake.
Implementing psilocybin-assisted therapy in palliative care settings: A survey of stakeholders 2026 cross-sectional survey 121 Supports 95% of physicians reported favorable attitudes toward psilocybin-assisted therapy, and 68% of stakeholders endorsed its introduction during early stages of illness; lack of trained providers was the primary barrier.
Meaning and Psychedelics in Palliative Care: A Narrative Review. 2026 narrative review Supports Reports that loss of meaning is a hallmark of demoralization and that psychedelic therapies show promise for existential distress and demoralization in palliative care.
Psilocybin-assisted psychotherapy for psycho-existential distress in advanced cancer: a narrative review 2026 narrative review Supports Argues that psilocybin-assisted psychotherapy is a compelling therapeutic option warranting further rigorous, interdisciplinary research for ethically grounded implementation in palliative settings.
Sense-Making Around Psilocybin in UK Women Experiencing Cancer-Related Existential Distress: An Interpretative Phenomenological Analysis 2026 qualitative study 7 Supports Participants considered psilocybin a much-needed alternative to traditional treatments for cancer-related depression and anxiety but felt its legal status was a significant barrier to access.
PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial 2026 open-label single-arm clinical trial 20 Supports Microdose psilocybin (1-3 mg over 3 weeks) was safe and feasible, with 69% of completers reporting meaningful global improvement and over half showing clinically significant reductions in depression and demoralization.
Psilocybin-assisted therapy for individuals with palliative care needs: A systematic review of safety and efficacy 2025 systematic review 74 Supports Across six studies, psilocybin-assisted therapy produced clinically significant reductions in depression and anxiety, with 57-79% achieving at least 50% symptom reduction and improvements sustained up to 4.5 years with no serious adverse events.
Supporting Meaningful Choices: A Decision Aid for Individuals Facing Existential Distress and Considering Psilocybin-Assisted Therapy 2025 descriptive study 10 Supports A decision aid for psilocybin-assisted therapy demonstrated satisfactory acceptability and usability, meeting IPDAS criteria for supporting shared decision-making.

Points of agreement

  • Multiple trials and reviews report reductions in depression, anxiety, demoralization, and existential distress after psilocybin-assisted therapy in life-threatening illness.
  • Several sources report that benefits can persist for months and, in some follow-ups, up to 4.5 years.
  • Adverse effects are generally described as mild and transient, with no serious adverse events reported in the reviewed trials.
  • Stakeholder surveys and qualitative studies generally show favorable attitudes toward psilocybin-assisted therapy among clinicians and patients.
  • Reviews consistently call for more rigorous research and standardized protocols.

Conflicts

  • Implementation findings contrast with attitudinal support: despite favorable views and regulatory authorization, one center reported no patients received therapy after one year.
  • Some qualitative studies emphasize provider uncertainty and concerns about risks, while surveys report high levels of favorable attitudes.

Gaps

  • Durability of benefits beyond 4.5 years is not established.
  • Blinding is difficult in psychedelic trials and few studies report adequate blinding.
  • Sample sizes are small and populations are often predominantly white, financially privileged, or from specific countries.
  • Optimal dosing (single high dose versus microdose) and protocol design are not settled.
  • Implementation barriers, training needs, and access equity are understudied.
  • Evidence in non-cancer life-threatening illnesses and diverse populations is limited.
Browse these studies in the library

Common questions

What does the research agree on about psilocybin for end-of-life distress?
  • Multiple trials and reviews report reductions in depression, anxiety, demoralization, and existential distress after psilocybin-assisted therapy in life-threatening illness.
  • Several sources report that benefits can persist for months and, in some follow-ups, up to 4.5 years.
  • Adverse effects are generally described as mild and transient, with no serious adverse events reported in the reviewed trials.
  • Stakeholder surveys and qualitative studies generally show favorable attitudes toward psilocybin-assisted therapy among clinicians and patients.
  • Reviews consistently call for more rigorous research and standardized protocols.
Where do studies on psilocybin for end-of-life distress conflict?
  • Implementation findings contrast with attitudinal support: despite favorable views and regulatory authorization, one center reported no patients received therapy after one year.
  • Some qualitative studies emphasize provider uncertainty and concerns about risks, while surveys report high levels of favorable attitudes.
What is still unknown about psilocybin for end-of-life distress?
  • Durability of benefits beyond 4.5 years is not established.
  • Blinding is difficult in psychedelic trials and few studies report adequate blinding.
  • Sample sizes are small and populations are often predominantly white, financially privileged, or from specific countries.
  • Optimal dosing (single high dose versus microdose) and protocol design are not settled.
  • Implementation barriers, training needs, and access equity are understudied.
  • Evidence in non-cancer life-threatening illnesses and diverse populations is limited.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Psilocybin for 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 Psilocybin for 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

37 articles · 22 from the last two years · 3,251 participants across 18 studies reporting sample size

Common study designs

review 10 commentary 2 narrative review 3 qualitative study 6 systematic review 2

Research volume by year

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37 studies whose primary subject is psilocybin for end-of-life distress since 2020

Studies about psilocybin for end-of-life distress per year, 2020 to 2026, peaking at 12 in 2025 Bar chart: one bar per year, taller where more studies were published that year. 0 10 20 2020 2025
2026 is partial
Show the numbers
Studies about psilocybin for end-of-life distress per year, 2020 to 2026, peaking at 12 in 2025
Year Studies
2020 1
2021 3
2022 4
2023 3
2024 6
2025 12
2026 8

Research

Synthesize the evidence →

Psilocybin-Assisted Early Palliative Care for Demoralization and Chronic Pain: An Open-Label Pilot Study.

medRxiv : the preprint server for health sciences July 14, 2026 Ali J Zarrabi, Tanja Mletzko, George H. Grant et al. preprint

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...

DOI: 10.64898/2026.07.11.26357570 (opens in new tab) Full text (opens in new tab)

The need for another tool: Australian healthcare professionals on the use of psilocybin for existential distress in people with cancer

BMC Medicine July 6, 2026 Hannah Adler, Rebecca Filipic, Dr Maria Gonzalez et al.

BACKGROUND: Existential distress is commonly experienced by people with cancer, yet there are limited treatment options. The therapeutic potential for psychedelic-assisted therapy (PAT) utilising psilocybin for this cohort is underexplored, with emerging literature showing clinical improvements in wellbeing. In Australia there is limited knowledge on healthcare professionals' (HCPs') attitudes,...

DOI: 10.1186/s12916-026-05024-2 (opens in new tab) Psilocybin Existentialism Distress Thematic analysis +12

Bringing Psilocybin-Assisted Therapy to Palliative Oncology: Early Lessons from Real-World Implementation.

Healthcare (Basel, Switzerland) June 3, 2026 Michel Dorval, Virginie Audet-Croteau, Sue-Ling Chang et al.

Background/Objectives: Psilocybin-assisted therapy (PAT) is a promising intervention to alleviate existential distress among patients with advanced cancer receiving palliative care. However, evidence on how to integrate PAT into routine oncology and palliative care services remains scarce. This study aimed to examine real-world PAT implementation, identify factors influencing adoption, and...

DOI: 10.3390/healthcare14111559 (opens in new tab) Full text (opens in new tab) Existential distress Cost analysis Implementation Palliative care +2

Implementing psilocybin-assisted therapy in palliative care settings: A survey of stakeholders

Palliative Medicine May 19, 2026 Louis Plourde, Sue-Ling Chang, Olivia Nguyen et al. 1 citation

BACKGROUND: While the adoption of psilocybin-assisted therapy for existential distress offers promising support for patients with life-threatening illnesses, implementing this intervention into palliative care settings presents significant real-world challenges. AIM: To examine palliative care stakeholders' knowledge and attitudes regarding psilocybin-assisted therapy, and identify barriers and...

DOI: 10.1177/02692163261446141 (opens in new tab)

Meaning and Psychedelics in Palliative Care: A Narrative Review.

Journal of Pain and Symptom Management March 1, 2026 William B Alexander, Eric D Hansen, Brian T Anderson et al. 1 citation

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...

DOI: 10.1016/j.jpainsymman.2025.10.015 (opens in new tab) Full text (opens in new tab) LSD Existential distress Palliative Psilocybin +3

Psilocybin-assisted psychotherapy for psycho-existential distress in advanced cancer: a narrative review

BMJ Supportive & Palliative Care February 18, 2026 Luca Magnani, Luca Ghirotto, Fabio Fesce et al.

psilocybin-assisted psychotherapy is a compelling therapeutic option warranting further investigation through rigorous, interdisciplinary research to promote an anthropologically/ethically grounded implementation in palliative settings, even beyond the oncology field.

DOI: 10.1136/spcare-2025-005689 (opens in new tab) Psychotherapist Narrative review Psycho-oncology Palliative care +6

Sense-Making Around Psilocybin in UK Women Experiencing Cancer-Related Existential Distress: An Interpretative Phenomenological Analysis

Qualitative Health Research February 17, 2026 Zaynab Khan, Sterre Weaver, Rachael V. Dando et al. 1 citation

People with cancer often experience anxiety and depression following a diagnosis and can face barriers to accessing treatment for their mental health. An increasing number of patients are considering alternative approaches to managing their mental health symptoms, such as the psychedelic, psilocybin. A growing number of clinical trials show significant and enduring improvements in mood and...

DOI: 10.1177/10497323261419338 (opens in new tab) Psilocybin Anxiety Mindfulness Interpretative phenomenological analysis +13

PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial

Palliative Medicine January 30, 2026 James Downar, Julie Lapenskie, Koby Anderson et al.

Background: Psychological distress is a common problem near the end of life, for which we lack effective, timely and scalable treatments. No previous study has assessed whether microdose psilocybin can improve symptoms in this population. Aim: To determine whether microdose psilocybin is safe, feasible and potentially efficacious in a palliative setting. Design: Open label, single-arm clinical...

DOI: 10.1177/02692163261416269 (opens in new tab) Psilocybin Palliative care Clinical trial Microdose +8

Psilocybin-assisted therapy for individuals with palliative care needs: A systematic review of safety and efficacy

Palliative Medicine December 18, 2025 Rita S. Matos, A. C. Silva, Licínio Rego et al. 1 citation

Background: Palliative Care is concerned with relieving suffering and improving the quality of life of patients and their families. Currently, questions arise about how to provide patients with good end-of-life care. There has been increasing interest in the beneficial effects of using psilocybin-assisted therapy in patients with severe chronic illnesses near the end of their lives and who...

DOI: 10.1177/02692163251383335 (opens in new tab) Anxiety Palliative care Health care Medline +4

Supporting Meaningful Choices: A Decision Aid for Individuals Facing Existential Distress and Considering Psilocybin-Assisted Therapy

Healthcare September 12, 2025 Ariane Bélanger, Sue-Ling Chang, Jean-François Stephan et al. 1 citation

Background/Objectives: Given the limitations of traditional approaches to treating existential distress in seriously ill patients, psilocybin-assisted therapy (PAT) has emerged as a promising treatment option. However, weighing up the potential risks and benefits of this approach can be challenging for both healthcare professionals and patients. Decision aids can play a key role in supporting...

DOI: 10.3390/healthcare13182290 (opens in new tab)

Clinical trials

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