Ketamine's Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review.
Gustavo N Silva, Virna G A Brandão, Kenneth Blum, Kai-Uwe Lewandrowski, Rossano K A Fiorelli
Pharmaceuticals August 29, 2025 DOI: 10.3390/ph18091298 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Nmda receptors Brain injury Ketamine ketamine Neuroprotection neuroprotection Protective agent Neuroinflammation neuroinflammation Cellular damage Excitotoxicity |
| Citations | 7 |
| Key findings | Ketamine reduces excitotoxicity and inflammation, which may contribute to neuroprotection in acute neurological injuries. |
Abstract
Ketamine, a widely used anesthetic with emerging evidence suggesting neuroprotective and anti-inflammatory properties across various neurological disorders, is recognized for its NMDA receptor antagonism. It has been postulated to play a role in neuroprotection, due to its anti-inflammatory properties, and decrease microglial activation, as well as cytokines TNF and IL-6. Despite its established role, the extent of ketamine's effects on neuroinflammation and neuroprotection remains to be fully elucidated. Here, we conducted a narrative review synthesizing current knowledge on ketamine's operating mechanisms, including its modulation of synaptic plasticity, excitotoxicity, and cytokine release, alongside its therapeutic applications in traumatic brain injury, neurodegenerative diseases, psychiatric disorders, and pain management. For this narrative review, we searched the Medline, Embase, Scopus, Web of Science, and PubMed databases. Our findings indicate that ketamine reduces excitotoxicity and inflammation, which may contribute to neuroprotection in acute neurological injuries. These insights underscore ketamine's potential as an adjunctive neuroprotective agent, warranting further clinical investigation to optimize its therapeutic utility across neurological and psychiatric contexts.
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
Cited by 3
- A review of the therapeutic and neuroprotective properties of ketamine Medical Science of Ukraine June 30, 2026
- Effect of ketamine/esketamine on postoperative delirium and cognitive dysfunctions: A systematic review and meta-analysis of randomised trials Indian Journal of Anaesthesia November 18, 2025
- Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics. Molecular Psychiatry July 28, 2026
Cites 21
- Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review BJPsych Open December 23, 2021
- Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. Journal of Psychiatric Research May 1, 2022
- Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial. American Journal of Psychiatry March 3, 2021
- Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine Journal of Neuroinflammation September 15, 2021
- Ketamine as a therapeutic agent for depression and pain: mechanisms and evidence. Journal of Neurological Sciences 2022
and 16 more in the library