Heles, Mario, Pasvolsky, Lilach, Sathishkumar, Hinduja, Naara, Shorook, Vu, Yen, Stewart, Caitlyn L, Xie, Tongxin, Gleber-Netto, Frederico O, McCarthy, William, Yaniv, Dan, Kamal, Shashank S, Elahi, Hajira, Zhu, Pengyu, Uhelski, Megan L, Chatwin, Jordan, Lara, Andrew, Stolley, Danielle L, Migden, Michael R, Lee, Z-Hye, Thevasagayampillai, Shiyanth, Gunaratne, Preethi H, Ait-Ahmad, Kaoutar, Kuykendall, MJ, Eksi, Sebnem Ece, Cohen, Lorenzo, Borniger, Jeremy C, Gottlieb, Eyal, Jones, Gregory H, Dougherty, Patrick M, Amit, Moran (September 2026) Psilocybin prevents chemotherapy-induced peripheral neuropathy through mitochondrial trafficking preservation. Science, 393 (6815). eaec6116. ISSN 0036-8075
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.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders organism description > animal diseases & disorders > cancer > drugs and therapies > chemotherapy diseases & disorders > cancer > drugs and therapies organism description > animal > mammal organism description > animal > mammal > rodent > mouse organism description > animal > mammal > rodent |
| CSHL Authors: | |
| Communities: | CSHL labs > Borniger lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 3 September 2026 |
| Date Deposited: | 21 Sep 2026 13:47 |
| Last Modified: | 21 Sep 2026 13:47 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/42319 |
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