Psilocybin prevented chemotherapy-related nerve injury in preclinical models by preserving mitochondrial energy delivery to nerves

Preclinical research from The University of Texas MD Anderson Cancer Center found that psilocybin given before chemotherapy prevented peripheral nerve injury and related symptoms across several models, including repeated treatment cycles with cisplatin, paclitaxel and docetaxel. The intervention reduced cold hypersensitivity, protected sensory nerve endings and preserved touch sensation without weakening chemotherapy's antitumor activity. Researchers linked the effect to serotonin 5-HT2A receptors and a signaling pathway that maintained the movement of mitochondria, the energy-producing structures inside nerve fibers, after chemotherapy-related damage. Blocking 5-HT2A reversed the protection, while a non-hallucinogenic compound acting on the same receptors produced similar results. The findings remain preclinical and do not establish efficacy or safety in patients. An upcoming Phase 2 NeuroGuard trial will test whether the mechanism reduces chemotherapy-induced peripheral neuropathy in people with cancer.