Introduction: This article presents a narrative review of psilocybin-assisted psychotherapy as a promising intervention for addressing anxiety, depression and psycho-existential distress in patients with advanced cancer. This group of disorders, often resistant to conventional treatments, significantly impacts patients’ quality of life and autonomy, as well as illness trajectories. Psilocybin, when administered in high doses within a structured therapeutic framework, seems to alleviate these symptoms safely and effectively, with potential additional benefits on pain and systemic inflammation.

Methods and analysis: A targeted literature search was conducted across major scientific databases—including PubMed, Scopus, PsycINFO, Cochrane Library and Embase—supervised by experts from various relevant disciplines to identify sources of particular importance.

Results: The process also led to the acquisition of highly cited scientific works to compose a coherent theoretical framework through which to interpret the evidence initially collected. Emerged key themes include: the complex and treatment-resistant nature of psycho-existential disorders in cancer; the importance of set, setting and peak experiences for psilocybin efficacy, as well as the consequent therapeutic value of integrated approaches that include psychotherapy; and the methodological limitations in more recent experimental trials. The article also identifies palliative care as a uniquely appropriate context for psilocybin-assisted psychotherapy.

Conclusion: 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.