ORCID

0000-0001-6575-9729 (Sanders)

Document Type

Article

Publication Date

2026

DOI

10.3389/fncel.2026.1899553

Publication Title

Frontiers in Cellular Neuroscience

Volume

20

Pages

1899553

Abstract

Substance use disorders (SUDs) remain major public health concerns worldwide, particularly in developed countries. SUDs are characterized by persistent neuroinflammation and synaptic dysfunction in the brain. Despite decades of extensive investigation, the detailed mechanisms underlying SUDs remain elusive. Ferroptosis is a highly regulated cell death process deeply affected by iron metabolism, lipid peroxidation, reactive oxygen species (ROS) production, and antioxidant systems. It has been implicated in multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ischemic stroke. Recently, emerging evidence has highlighted the role of ferroptosis in drug-induced pathological changes. Various types of abused substances including alcohol, cocaine, methamphetamine (METH) nicotine, cannabis, and opioids have been shown to disrupt ferroptosis-relevant pathways, leading to microglial activation and neuronal injury. Inhibition of ferroptosis could mitigate these pathological changes in preclinical models. Here, we summarize current evidence demonstrating the effects of abused drugs on ferroptosis pathways. Collectively, these findings underscore the potential role of ferroptosis in the pathophysiology of SUDs. Targeting ferroptosis may represent a promising therapeutic strategy for alleviating drug-induced neurological damage and improving recovery outcomes such as cognitive and memory deficiency in individuals with addiction.

Rights

© 2026 Bouchard, Russell, Guo, Nguyen, Cheng, Sanders and Guo. 

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License. The use, distribution or reproduction in other forums is permitted, provided the original authors and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Original Publication Citation

Russell, B., Bouchard, T., Guo, L. L., Nguyen, T., Cheng, Y., Sanders, Y. Y., & Guo, M. (2026). The effects of abused drugs on ferroptosis pathways: Potential therapeutic targets for substance use disorders. Frontiers in Cellular Neuroscience, 20, Article 1899553. https://doi.org/10.3389/fncel.2026.1899553

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