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

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, Google Scholar, and CINAHL databases were searched from 10 August 2025 to 31 October 2025. Eleven eligible reports derived from six independent clinical cohorts met inclusion criteria. Psilocybin was generally administered as a single supervised moderate-to-high dose (25-30 mg/70 kg), within structured preparation, dosing, and integration. Across all designs, psilocybin produced rapid and enduring reductions in depression, anxiety, existential distress, and fear of death, with benefits lasting 2-6 months and, in some cases, up to 4.5 years. Qualitative findings highlighted enhanced emotional clarity, acceptance, spiritual well-being, and reconnection with meaning. Five of the 11 reports met Mixed Methods Appraisal Tool (MMAT) criteria; concerns in others involved assessor blinding, representativeness, confounding control, or mixed-methods integration. No psilocybin-related serious adverse events were reported; transient cardiovascular changes, headache, nausea, anxiety or emotional distress, and occasional brief psychotic-like symptoms occurred. Psilocybin-assisted therapy may be promising but still investigational palliative pharmacotherapy-related intervention for cancer-related psychological and existential distress.