Two pre-chemotherapy doses of psilocybin prevented nerve damage in mice through a peripheral mitochondrial-trafficking pathway

A study led by MD Anderson researchers found that two doses of psilocybin given before platinum-based chemotherapy completely prevented pain and cold sensitivity in mice through six treatment cycles. The proposed mechanism is peripheral: activation of the serotonin receptor 5-HT2A preserved mitochondrial movement and positioning within nerve fibers, rather than increasing total mitochondrial energy production. The same pathway was functional in human donor sensory neurons and skin tissue, strengthening its translational relevance. Psilocybin did not reduce chemotherapy's ability to kill tumor cells in the study. Researchers also observed normalized cortical activity in treated mice, but have not shown that these central changes caused the protection or determined the relative contribution of central and peripheral mechanisms. The findings remain preclinical: a registered Phase 2 trial, NeuroGuard, will test whether the approach reduces neuropathy in cancer patients. Human efficacy, dosing, and management of psychedelic effects during chemotherapy remain unproven.