Psilocybin prevents chemotherapy-induced peripheral neuropathy through mitochondrial trafficking preservation.
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
Science (New York, N.Y.) September 3, 2026 DOI: 10.1126/science.aec6116 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Animal models (likely rodents) treated with platinum- and taxane-based chemotherapy |
| Intervention | Psilocybin |
| Dose | two doses (exact amount not specified) |
| Topics | Psilocybin |
| Key points | Two doses of psilocybin before chemotherapy durably prevented CIPN onset across platinum- and taxane-based models, including repeated cycles, without impairing antitumor efficacy. Peripherally, it maintained tactile sensitivity and intraepidermal nerve fibers via the TrkB-Akt-PAK5-MAP2-KIF5B pathway and mitochondrial remobilization; centrally, it normalized medial prefrontal cortical synaptic activity and alpha/beta EEG power. |
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.