Psilocybin and Chronic Pain: A New Perspective for Future Pain Therapists?
Medical Sciences November 20, 2025 Silvia Natoli, Arturo Cuomo, Maurizio Marchesini et al.
Psilocybin, a serotonergic psychedelic compound, shows promise as a multidimensional therapy for chronic pain, which affects nearly one in five adults worldwide and remains a major healthcare burden. Preclinical studies demonstrate that psilocybin promotes synaptogenesis via BDNF-TrkB signalling, modulates 5-HT2A receptor activity, and reduces neuroinflammatory processes, leading to persistent analgesic and anxiolytic effects. Animal models of chemotherapy-induced neuropathy and inflammatory pain showed long-lasting antinociceptive responses. Clinical studies, though limited, reported improvements in depression, anxiety, resilience, and quality of life in patients with advanced cancer and chronic conditions, with preliminary evidence of analgesic benefit. Ethical issues, safety concerns, and regulatory barriers necessitate careful management, and robust randomized controlled trials are essential to confirm efficacy.