Pathways to Psilocybin in Palliative Care

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The World Health Organization defines palliative care as an integral component of patient-centered health services, focused on relieving physical, social, psychological, and spiritual suffering.¹ For patients with serious or life-limiting illness, palliative care extends beyond symptom management to preserving quality of life, including the psychological and spiritual burden common in palliative populations. Conventional therapies such as antidepressants (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors) and anxiolytics (eg, benzodiazepines) are limited by delayed onset, variable efficacy, and tolerability concerns.

Consequently, interest in psychedelic-assisted therapy (PAT), particularly psilocybin, has increased to address these gaps. In the US, psilocybin has not yet been integrated into palliative care beyond the research setting, raising an important question about accessibility: Do existing regulatory structures adequately support access to investigational therapies?

Psilocybin Safety and Efficacy

Psilocybin is a naturally occurring tryptamine alkaloid (eg, dimethyltryptamine) and serotonergic psychedelic (eg, lysergic acid diethylamide) that exerts its effects primarily via 5-HT2A agonism.² Although commonly associated with “magic mushrooms” and recreational use, growing evidence suggests psilocybin’s clinical utility lies in its psychotherapeutic effects. In controlled therapeutic settings, single oral doses of psilocybin have demonstrated favorable effects on depression, anxiety, and demoralization-related aspects of life-limiting illness, including suicidal ideation and loss of meaning.³

Beyond efficacy, literature published over the last decade suggests psilocybin has the potential to produce sustained therapeutic effects⁴ with a favorable safety profile⁵ in patients with life-limiting disease. When administered under controlled conditions, psilocybin produced substantial and enduring improvements⁶ in mood and decreases in death anxiety. Despite favorable efficacy and safety findings, access to psilocybin outside clinical trials remains highly restricted, emphasizing the need to understand the mechanisms in place to facilitate the use of investigational therapies.

Expanded Access and ‘Right to Try’: Understanding the Regulatory Landscape

The 2 regulatory pathways for accessing investigational therapies outside of clinical trials are the FDA’s expanded access pathway⁷ and the federal Right to Try Act.⁸ Both options are intended for patients with life-threatening conditions who lack adequate treatment options, but each differs in terms of structure and oversight.

Expanded access requires FDA authorization and Institutional Review Board (IRB) approval,⁹ with requests submitted by the treating physician on the patient’s behalf after securing agreement from the drug manufacturer. The Right to Try Act allows eligible patients to seek access to investigational drugs that have completed phase 1 clinical testing through the manufacturer. The main difference is that the expanded access pathway provides regulatory oversight, while the Right to Try Act bypasses FDA oversight and IRB review.

Understanding the distinction between these processes is critical in evaluating whether an emerging therapy can be realistically accessed in palliative care settings.

Why ‘Right to Try’ Does Not Guarantee Access

Right to Try does not guarantee access to investigational therapies. It permits manufacturers to distribute eligible drugs upon request but does not obligate them to do so. More importantly, the Right to Try Act does not override other federal statutes, such as the Controlled Substances Act,¹⁰ nor does it eliminate Drug Enforcement Administration (DEA) requirements.

For Schedule I substances such as psilocybin, this distinction is particularly significant. While psilocybin may technically meet certain Right to Try criteria, its Schedule I designation is a barrier that cannot be overridden. As a result, the term “right to try” may imply a level of access that does not apply universally to all investigational products—namely, Schedule I drugs.

Can Psilocybin Be Accessed Through Right to Try?

The short answer is no. Although psilocybin meets Right to Try pathway requirements, to date, no patient in the US has been documented to legally access psilocybin outside of a clinical trial, as Schedule I restrictions continue to block access despite potential Right to Try eligibility. These barriers have prompted recent legislative efforts, including the Freedom to Heal Act, introduced in 2025,¹¹ which seeks to create a special registration pathway for Schedule I investigational drugs under the Right to Try law. The Freedom to Heal Act would create a DEA-regulated system allowing doctors to administer certain Schedule I substances (eg, psilocybin) to patients with life-threatening conditions. Such legislation reflects growing recognition that current frameworks do not align with emerging evidence supporting the use of psychedelics like psilocybin in palliative care settings.

Policy Considerations Moving Forward

As the specialty of palliative care evolves alongside interest in PAT, a need for supportive legislation is highlighted. Psychological and existential suffering have been identified as therapeutic targets that currently accepted treatments often struggle to address adequately. The gap between emerging clinical evidence in support of investigational therapies and existing regulatory pathways is particularly pronounced. While several countries offer regulated clinical access to psilocybin outside traditional research settings, including Health Canada’s Special Access Program¹² and Germany’s recent Compassionate Use Program,¹³ similar pathways remain limited in the US. For any Schedule I product to become available outside of research settings, sustained legislative efforts and engagement are required not only from policy makers but also from prescribers and pharmacists. This collaboration is crucial to ensuring that responsible yet accessible pathways are in place to address the full spectrum of needs of palliative care patients.

REFERENCES

1. World Health Organization. Palliative care. Accessed February 1, 2026. https://www.who.int/health-topics/palliative-care

2. Kim A, Halton B, Shah A, Seecof O, Ross S. Psilocybin-assisted psychotherapy for existential distress: practical considerations for therapeutic application - a review. Ann Palliat Med. 2024;30(6). doi:10.21037/apm-24-35

3. Whinkin E, Opalka M, Watters C, Jaffe A, Aggarwal S. Psilocybin in palliative care: an update. Curr Geriatr Rep. 2023;12(2):50-59. doi:10.1007/s13670-023-00383-7

4. Agin-Liebes GI, Malone T, Yalch MM, et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. 2020;34(2):155-166. doi:10.1177/0269881119897615

5. Ross S, Agin-Liebes G, Lo S, et al. Acute and sustained reductions in loss of meaning and suicidal ideation following psilocybin-assisted psychotherapy for psychiatric and existential distress in life-threatening cancer. ACS Pharmacol Transl Sci. 2021;4(2):553-562. doi:10.1021/acsptsci.1c00020

6. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197. doi:10.1177/0269881116675513

7. Expanded access. FDA. Updated September 8, 2025. Accessed February 1, 2026. https://www.fda.gov/news-events/public-health-focus/expanded-access

8. Right to Try. FDA. Updated December 12, 2024. Accessed February 1, 2026. https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try

9. Institutional Review Boards frequently asked questions: guidance for institutional review boards and clinical investigators. FDA. Updated February 5, 2025. Accessed February 1, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/institutional-review-boards-frequently-asked-questions

10. The Controlled Substances Act. FDA. Accessed February 1, 2026. https://www.dea.gov/drug-information/csa

11. Freedom to Heal Act of 2025, S.3346. 119th Cong (2025). Introduced December 12, 2025. Accessed February 1, 2026. https://www.congress.gov/bill/119th-congress/senate-bill/3346/text

12. Health Canada. Requests to the Special Access Program involving psychedelic-assisted psychotherapy. Government of Canada. Updated January 5, 2022. Accessed February 11, 2026.

13. Gründer G, Mertens LJ, Jungaberle A, Jungaberle H, Spangemacher M. Compassionate use of psilocybin for treatment-resistant depression in Germany. Lancet Psychiatry. 2026;13(2):91-93. doi:10.1016/S2215-0366(25)00277-9