The effects of psilocybin on psychological distress in cancer patients: a systematic review and meta-analysis

INTRODUCTION: Psilocybin may effectively treat psychological distress in cancer patients. A meta-analysis assessed its safety and effectiveness in this context. METHODS: A comprehensive search across six databases (Scopus, PsycINFO, PubMed, Cochrane, CINAHL Complete, and Web of Science) was conducted to identify studies on psilocybin's effects on mental health in cancer patients up to November 2024. Both randomized and non-randomized trials were included, assessing anxiety, depression, and other mental outcomes at short-term (2-5 weeks) and long-term (6 months) follow-ups. Study quality was assessed using Cochrane tools, and statistical analyses were performed with Stata version 17. RESULTS: In randomized controlled trials (RCTs), psilocybin significantly reduced depressive symptoms, with the Beck Depression Inventory (BDI) (standardized mean difference [SMD] = - 2.87, 95% confidence interval [CI]: - 3.99 to - 1.76, p < 0.001) and the Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) (SMD = - 2.97, 95% CI: - 3.60 to - 2.33, p < 0.001) showing strong effects. Anxiety outcomes were mixed: the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) was not significant (SMD = - 3.63, p = 0.11), while the State-Trait Anxiety Inventory (STAI) also showed inconsistent results. Short-term analyses (2-5 weeks) revealed significant improvements in the BDI (SMD = - 1.17), HADS-D (SMD = - 1.58), and HADS-A (SMD = - 1.99), all p < 0.001. Long-term analyses (6 months) demonstrated sustained benefits on the BDI (SMD = - 2.60, p = 0.04) and HADS-D (SMD = - 3.56, p = 0.01). Measures of quality of life (QOL) and spiritual well-being using the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) scale also improved significantly after psilocybin treatment. CONCLUSION: Psilocybin may reduce depressive symptoms in cancer patients, with mixed effects on anxiety and time-dependent improvements in spiritual well-being and (in single-arm data) quality of life. Given the small number of studies, high heterogeneity, challenges with blinding/expectancy, and frequent co-intervention with psychotherapy, these findings are preliminary. Larger, rigorously blinded trials are needed to determine clinical effectiveness and safety.