Authors
Mario Heles, Lilach Pasvolsky, Hinduja Sathishkumar, Shorook Naara, Yen Vu, Caitlyn L Stewart, Tongxin Xie, Frederico O Gleber-Netto, William McCarthy, Dan Yaniv, Shashank S Kamal, Hajira Elahi, Pengyu Zhu, Megan L Uhelski, Jordan Chatwin, Andrew Lara, Danielle L Stolley, Michael R Migden, Z-Hye Lee, Shiyanth Thevasagayampillai, Preethi H Gunaratne, Kaoutar Ait-Ahmad, M J Kuykendall, Sebnem Ece Eksi, Lorenzo Cohen, Jeremy C Borniger, Eyal Gottlieb, Gregory H Jones, Patrick M Dougherty, Moran Amit
Published in
Science (New York, N.Y.). Volume 393. Issue 6815. Pages eaec6116. Sep 03, 2026. Epub Sep 03, 2026.
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.
PMID:
42691184
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.
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