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Peer-reviewed article

Psilocybin prevents chemotherapy-induced peripheral neuropathy through mitochondrial trafficking preservation.

Heles MiD, Pasvolsky LiD, Sathishkumar HiD, Naara SiD, Vu Y, Stewart CL, Xie T, Gleber-Netto FOiD, McCarthy WiD, Yaniv DiD, Kamal SSiD, Elahi HiD, Zhu P, Uhelski MLiD, Chatwin J, Lara AiD, Stolley DLiD, Migden MRiD, Lee ZHiD, Thevasagayampillai SiD, Gunaratne PHiD, Ait-Ahmad KiD, Kuykendall MJiD, Eksi SEiD, Cohen LiD, Borniger JCiD, Gottlieb EiD, Jones GHiD, Dougherty PMiD, Amit MiD

Science (New York, N.Y.)Sep 3, 2026United States, Israel2 citationsDOI: 10.1126/science.aec6116

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling, often irreversible toxicity that affects millions of patients, limits life-saving cancer therapy, and lacks proven treatment. In this work, we show that as little as two doses of psilocybin before chemotherapy durably prevented the onset of CIPN across platinum- and taxane-based models, including repeated chemotherapy cycles, without impairing antitumor efficacy. Peripherally, psilocybin maintained tactile sensitivity and intraepidermal nerve fiber endings through axonal mitochondrial trafficking and distribution preservation, through the TrkB-Akt-PAK5-MAP2-KIF5B pathway and remobilization of syntaphilin-anchored mitochondria. Centrally, it normalized medial prefrontal cortical synaptic activity and cortical alpha and beta electroencephalography power. This stabilization of peripheral axonal energy balance establishes psilocybin as a first-in-class prophylactic agent for CIPN while also preserving central neural function. Given psilocybin's established safety, these discoveries support clinical evaluation as a strategy to prevent CIPN.

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Psilocybin

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