Journal of pain and symptom management • August 1, 2026 • Stefan Aguiar, Mary Makarious, Orly Lipsitz et al.
In adults with advanced cancer receiving palliative care, intranasal ketamine was associated with clinically meaningful improvements in existential distress, anxiety, symptom burden, and quality of life. Fifteen participants who completed three doses of ketamine showed improvements exceeding established minimal clinically important differences on measures of anxiety, death and dying distress, overall symptoms, and quality of life. Improvements in existential well-being were larger than those in physical symptoms. Changes in depression did not significantly correlate with changes in existential distress outcomes, suggesting ketamine may have independent effects on multiple dimensions of distress in this population.
BMC Medicine • July 6, 2026 • Hannah Adler, Rebecca Filipic, Dr Maria Gonzalez et al.
Healthcare professionals show interest in psychedelic-assisted therapy with psilocybin for existential distress in people with cancer, but face knowledge gaps, barriers, and a desire for more research. Interviews with 11 professionals from Australian cancer centers revealed four themes: varied knowledge about the therapy, conceptualizing its practical use, navigating complex provision and engagement, and envisioning future applications. Professionals preferred delivery by multidisciplinary teams that are culturally sensitive and ethically rigorous. Some saw it as a last resort, while others viewed it as another needed tool. The findings offer preliminary insights into implementation pathways for this therapy in oncology settings.
Current opinion in oncology • July 1, 2026 • Fatima Zohra Moujahid, Olivier Taymans
Psychedelic-assisted therapy (PAT) may offer a new approach to address the multidimensional nature of psychological and existential distress common across the cancer trajectory. PAT combines psychedelic compounds with structured psychotherapeutic support, including preparatory sessions, a supervised dosing experience, and post-session integration. Psychedelics are thought to enhance neuroplasticity and emotional flexibility, potentially supporting sustained psychological change. Recent trials in advanced cancer populations report improvements in anxiety, depression, pain-related distress, and quality of life following one or two dosing sessions. However, current evidence is limited by small and demographically narrow samples, variable treatment protocols, and potential expectancy effects, and implementation faces practical challenges such as training requirements and resource intensity.
Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists • June 5, 2026 • Osama Bhatti, Mohammad Qasim Latifi
Psychiatry has long held an ambivalent stance toward religion and spirituality, recognizing their importance but remaining cautious about integrating them into clinical practice. This article examines the historical, conceptual, and clinical tensions surrounding spirituality in psychiatry, particularly in light of renewed interest from contemporary psychedelic research. The authors discuss definitions, diagnostic categories, and evidence linking spirituality and meaning to mental health. They explore how psychedelic-assisted therapies highlight both therapeutic potential and ethical risks in addressing existential suffering. Psychiatry faces a challenging opportunity to incorporate spiritual dimensions of distress without undermining scientific integrity, which will shape its future relationship with the sacred.
Healthcare (Basel, Switzerland) • June 3, 2026 • Michel Dorval, Virginie Audet-croteau, Sue-Ling Chang et al.
After one year of offering psilocybin-assisted therapy (PAT) at a Canadian university-affiliated tertiary care center, no patients had received the treatment despite clinicians and managers viewing it favorably. Interviews with ten professionals identified administrative and regulatory procedures, along with logistical constraints, as key barriers, while perceived clinical relevance and institutional leadership were facilitators. The estimated cost of delivering a complete PAT intervention ranged from 2,648 to 5,827 Canadian dollars per patient, excluding the cost of psilocybin itself. The gap between regulatory authorization and actual service uptake highlights the need for structured implementation strategies, sustained institutional support, and alignment between regulatory frameworks and clinical workflows.
Healthcare (Basel) • June 2, 2026
Psychedelic-assisted therapies, including ketamine-assisted psychotherapy, show promise for reducing depression, anxiety, and existential distress in patients with life-limiting illness, primarily in early-phase oncology studies. A review of 22 studies found consistent improvements in quality of life and spiritual well-being, with generally favorable safety under controlled conditions. However, the evidence remains preliminary, drawn from small, methodologically diverse studies with limited blinding and highly selected populations. The incorporation of key therapeutic practices—such as preparation, integration, and clinician training—was uneven across the literature, revealing a gap between research evidence and emerging clinical recommendations.
Palliative Medicine • May 19, 2026 • 1 citation
Most palliative care stakeholders in Canada view psilocybin-assisted therapy favorably, with 95% of physicians reporting positive attitudes. A cross-sectional online survey of 121 adults involved in palliative care found that the lack of trained healthcare providers is the primary barrier to implementation, while further research and standardized protocols are key facilitators. Sixty-eight percent of stakeholders support introducing this therapy early in the illness trajectory. The findings highlight significant divergence in perspectives between clinical and non-clinical groups, suggesting tailored interprofessional education could build shared understanding. The study's Canadian context may limit transferability to other regulatory frameworks.
Journal of pain and symptom management • March 1, 2026 • William B Alexander, Eric D Hansen, Brian T Anderson et al. • 1 citation
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.
Journal of palliative medicine • March 1, 2026 • Robert K Horowitz, William E Rosa, Ali John Zarrabi et al.
Psychospiritual distress causes profound suffering in people with serious illness, yet treatment options are few. A palliative care-embedded ketamine-assisted psychotherapy (KAP) program called Pal-KAP was developed and delivered at an academic medical center. Between May 2023 and September 2025, 59 patients were referred for screening; 43 met eligibility criteria, and 30 elected to participate. Patients (age 19-76, mean 53) completed a median of 1.5 medicine sessions (range 1-5). Most had cancer (80%) or neurological disease (13.3%). Ketamine dose averaged 0.93 mg/kg intramuscularly, with minor adverse effects and no serious adverse events. This experience suggests that KAP can be delivered safely and ethically in palliative care.
BMJ Supportive & Palliative Care • February 18, 2026 • Luca Magnani, Luca Ghirotto, Fabio Fesce et al.
Psilocybin-assisted psychotherapy shows promise as a therapeutic option for palliative care, and further rigorous, interdisciplinary research is needed to ensure its implementation is grounded in anthropological and ethical considerations, extending its potential beyond oncology to other palliative settings.
PloS one • January 1, 2025 • Eirini K Argyri, Jules Evans, David Luke et al. • 27 citations
Psychedelic experiences can sometimes trigger long-lasting existential distress, marked by confusion about existence and purpose, alongside cognitive, emotional, social, and bodily difficulties. Interviews with 26 people who experienced such distress revealed that ontological challenges—struggles with understanding reality—were common. Participants alleviated distress primarily through 'grounding' practices: embodiment, social connection, and cognitive normalization of their experience. The findings suggest psychedelic experiences act as pivotal mental states that can facilitate transformative learning, challenging and expanding meaning-making. This work contributes to understanding how people reestablish coherence and grow after ontologically challenging psychedelic experiences.
Journal of Psychopharmacology • December 10, 2024 • Mattia Marchi, Riccardo Farina, Karim Rachedi et al. • 13 citations
A systematic review and network meta-analysis of nine randomized controlled trials involving 606 participants with terminal illnesses found that psychedelic compounds—psilocybin, ketamine, MDMA, and LSD—significantly reduced depression (standardized mean difference −0.80) and anxiety (standardized mean difference −0.84) compared to control conditions. Psilocybin appeared most effective for depression, and LSD for anxiety, though direct comparisons between psychedelics did not show statistically significant differences. Rates of treatment discontinuation and adverse events were similar between psychedelic and control groups. The findings suggest psychedelics, particularly psilocybin and LSD, may help alleviate existential distress in end-of-life care, but limitations include few trials, blinding challenges, and a lack of head-to-head comparisons.
Cochrane Database of Systematic Reviews • September 11, 2024 • Sivan Schipper, Kabir Nigam, Yasmin Schmid et al. • 34 citations
Psychedelic-assisted therapy using psilocybin or LSD may help treat anxiety, depression, and existential distress in people with life-threatening diseases, and appears well tolerated with no serious adverse events reported in reviewed studies. However, the evidence is low to very low certainty, meaning results are uncertain and could change with future research. As of 2024, these drugs remain illegal in many countries. Blinding issues and small sample sizes limit confidence; more rigorous studies with active placebos and larger samples are needed. Research is restricted in the US due to Schedule I classification but is increasing.
Palliative Medicine • January 22, 2024 • Louis Plourde, Sue-Ling Chang, Houman Farzin et al. • 22 citations
A survey of 2,800 adults in four Canadian provinces found high social acceptability of psilocybin-assisted therapy for existential distress at the end of life. 79.3% considered it a reasonable medical choice, 84.8% agreed public health insurance should cover it, and 63.3% would support legalization for medical purposes. More favorable attitudes were linked to prior psilocybin use, exposure to palliative care, and progressive political orientation. The findings suggest public support is strong enough to help mobilize resources and improve access to this emerging therapy in palliative and end-of-life care.
Palliative & supportive care • August 1, 2023 • Xuepeng Jing, Nicholas R Hoeh, David B Menkes • 18 citations
A scoping review of pipeline clinical trials identified 25 studies of psychedelic treatment for depression, anxiety, and existential distress at end of life, including 13 randomized controlled trials and 12 open-label trials. Investigational drugs included ketamine (11 trials), psilocybin (10), MDMA (2), and LSD (2); three trials involved microdosing, and fifteen incorporated psychotherapy. Only three trials assessed expectancy and blinding effectiveness beyond randomization. The review expects ongoing trials to extend evidence for psychedelic-assisted group therapy and microdosing, but head-to-head comparisons of different psychedelics and more rigorous studies controlling expectancy are still needed.
Neuropharmacology • April 2, 2023 • Farah Z Zia, Michael H Baumann, Sean J Belouin et al. • 28 citations
Chronic pain is a leading cause of disability and opioid overdose in the United States. While many people manage pain with existing medicines and psychosocial treatments, others find these options ineffective or unacceptable due to side effects and risks. Preliminary evidence suggests psychedelics may improve quality of life, functionality, and reduce disability and distress for people whose pain may never be completely relieved. This commentary calls for more basic research and clinical trials to explore psychedelics' potential in chronic pain management, and to determine whether effects stem from direct antinociceptive or anti-inflammatory mechanisms, or from increased tolerability, acceptance, and spirituality that mediate therapeutic effects seen in psychiatric disorders.
Current geriatrics reports • January 1, 2023 • Emily Whinkin, Moira Opalka, Conor Watters et al. • 26 citations
Psilocybin, a tryptamine psychedelic found in certain mushrooms, shows promise for alleviating emotional and spiritual distress in palliative care patients. A review of recent research and field reports indicates that psilocybin has significant and sometimes sustained anxiolytic, antidepressant, anti-inflammatory, and entheogenic effects with a favorable safety profile. However, the research has limitations, including selection bias toward healthy, white, financially privileged individuals and follow-up periods too short to assess long-term psychospiritual benefits and quality of life. Major legal, ethical, and financial barriers to access exist, likely worsened for geriatric and palliative care patients. More large-scale controlled trials are needed.
Neuropharmacology • September 15, 2022 • S Ross, M Agrawal, R R Griffiths et al. • 69 citations
Psychiatric and existential distress are common in advanced cancer and other life-threatening illnesses, yet current treatments—including medication and psychotherapy—have limited effectiveness, especially for existential distress. This commentary reviews the rationale for developing psychedelic-assisted psychotherapy as a novel intervention, summarizing efficacy data from first and second waves of psychedelic research. The authors conclude that more rigorous, government-funded research is needed to assess effectiveness and mechanisms of action. If approved and prescribable, psychedelic-assisted treatments could have significant clinical and public health impact internationally.
Journal of palliative medicine • August 1, 2022 • William E Rosa, Zachary Sager, Megan Miller et al. • 49 citations
Psychedelic-assisted therapy (PAT) is a promising treatment for conditions like treatment-resistant depression, substance use disorder, and PTSD. In palliative care, a single PAT session can produce lasting reductions in anxiety, depression, and demoralization—symptoms that harm quality of life for seriously ill and end-of-life patients. Although interest in psychedelics has revived, few resources exist for applying PAT in hospice and palliative care. This article provides 10 evidence-informed tips for palliative care clinicians, developed with international experts, to help familiarize teams with PAT, address legal and logistical barriers, discuss therapeutic competencies, and highlight approaches to maximize safety and benefits for patients and caregivers.
Current topics in behavioral neurosciences • January 1, 2022 • David B Yaden, Sandeep M Nayak, Natalie Gukasyan et al. • 31 citations
End-of-life and palliative care have improved, but psychopharmacological options for depression, existential distress, and well-being remain limited. This review examines recent clinical research on psychedelics for patients with life-threatening diagnoses and proposes that psychedelics could offer clinicians an additional treatment option in end-of-life and palliative care settings.
Journal of Psychoactive Drugs • July 16, 2021 • Coryn E. Mayer, Virginia Lebaron, Kimberly Acquaviva • 17 citations
Palliative care providers see multiple barriers—cultural, institutional, relational, and individual—to addressing existential distress in their patients. They describe the power and duality of being present with suffering, view suffering as inherently subjective, and express uncertainty about the risks and benefits of psilocybin therapy. These findings come from interviews with five interdisciplinary hospital-based palliative care team members. The authors call for more research to guide safe, inclusive integration of psilocybin into palliative care for existential distress.
ACS Pharmacology & Translational Science • March 18, 2021 • Stephen Ross, Gabrielle Agin-Liebes, Sharon L. Lo et al. • 133 citations
People with advanced cancer face elevated risks of desire for hastened death, suicidal ideation, and completed suicide. Loss of meaning, a component of demoralization, predicts these outcomes. In a randomized controlled trial, psilocybin-assisted psychotherapy produced rapid and sustained improvements in depression, demoralization, and hopelessness. Secondary analyses showed that among participants with elevated suicidal ideation at baseline, reductions in suicidal ideation appeared as early as 8 hours and persisted for 6.5 months. Large reductions in loss of meaning emerged 2 weeks after treatment and remained significant at 6.5 months and at 3.2 and 4.5 year follow-ups. The findings suggest psilocybin-assisted psychotherapy may be an effective antisuicidal intervention for cancer patients due to its positive impact on hopelessness and meaning-making.
Journal of Psychopharmacology • January 9, 2020 • Gabrielle Agin-Liebes, Tara C. Malone, Matthew M. Yalch et al. • 353 citations
A long-term follow-up of a randomized trial found that psilocybin-assisted psychotherapy produced lasting reductions in anxiety, depression, hopelessness, demoralization, and death anxiety in people with cancer-related psychiatric distress. At an average of 3.2 and 4.5 years after psilocybin administration, 60–80% of participants still showed clinically significant antidepressant or anxiolytic responses. Most participants (71–100%) attributed positive life changes to the therapy and rated it among the most personally meaningful and spiritually significant experiences of their lives. The study's conclusions are limited by the crossover design of the original trial, but the results suggest psilocybin-assisted therapy may promote long-term relief from cancer-related distress.
Journal of holistic nursing : official journal of the American Holistic Nurses' Association • March 1, 2019 • William E Rosa, Stephanie Hope, Marianne Matzo • 27 citations
Entheogens—medicines that induce experiences of the sacred—show promise in helping patients with advanced serious illness find meaning, reduce fear, and increase joy and acceptance. Clinical trials have yielded impressive preliminary findings on their healing potential, yet nursing literature has not engaged with these advancements. The article introduces scholarly dialogue on integrating entheogens into spiritual and holistic nursing care, provides a brief history of their global use, and includes a case study. Evidence-based knowledge on this sensitive topic is needed to foster understanding, advance scientific knowledge, and create healing environments for patients, nurses, and researchers.