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 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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cites 18
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
and 13 more in the library