Neurotoxicity mechanisms and clinical implications of six common recreational drugs.
Jing Wang, Yulei Hao, Di Ma, Liangshu Feng, Feng Yang, Pingxu An, Xingqi Su, Jiachun Feng
Frontiers in Pharmacology 2025 DOI: 10.3389/fphar.2025.1526270 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine |
| Keywords | Cocaine Heroin Methamphetamine Nervous system damage Nitrous oxide Synthetic cathinones Drug neurotoxicity Recreational drugs Substance-induced brain damage Neural pathways Addiction neuroscience |
| Citations | 14 |
| Key findings | Six commonly abused drugs converge on shared neurotoxic pathways, including oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. |
Abstract
The recreational abuse of addictive drugs poses considerable challenges to public health, leading to widespread neurotoxicity and neurological dysfunction. This review comprehensively examines the neurotoxic mechanisms, clinical manifestations, and treatment strategies associated with six commonly abused substances: methamphetamine, cocaine, synthetic cathinones, ketamine, nitrous oxide and heroin. Despite their diverse pharmacological properties, these drugs converge on shared neurotoxic pathways, including oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. Psychostimulants, such as methamphetamine, cocaine and synthetic cathinones, disrupt monoaminergic neurotransmission, causing cognitive impairment, psychiatric disturbances, and neurovascular damage. Dissociative anesthetics, including ketamine and nitrous oxide, impair glutamatergic transmission and mitochondrial function, thereby exacerbating excitotoxicity and neuronal apoptosis. Opioids, such as heroin, primarily target the brain's reward system and induce oxidative stress, neuroinflammation, and cerebrovascular complications. Treatment strategies remain limited, focusing on symptomatic management, neuroprotective interventions, and behavioral therapies. Emerging approaches, such as antioxidants, NMDA receptor modulators, and cognitive rehabilitation, show promise but require further validation. By highlighting the underlying mechanisms and therapeutic challenges, this review provides a foundation for developing targeted interventions and advancing research on drug-induced neurotoxicity.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cites 9
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics TIPS - Trends in Pharmacological Sciences September 24, 2021
- Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability. The Lancet Psychiatry November 1, 2022
- Subanaesthetic ketamine and altered states of consciousness in humans British Journal of Anaesthesia April 13, 2018
- Nitrous oxide-induced myeloneuropathy: a case series Journal of Neurology, Neurosurgery, and Psychiatry May 30, 2023
and 4 more in the library