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  5. Ketamine as a potential cognitive enhancer in neurological disorders: evidence from preclinical and clinical studies

Ketamine as a potential cognitive enhancer in neurological disorders: evidence from preclinical and clinical studies

File(s)
41982421.pdf (1.29 MB)
Permanent Link(s)
https://hdl.handle.net/1813/124351
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Department of Neurological Surgery
Author
Leon-Rojas, J.E.
Mascialino, G.
Vinueza Mera, L.
Hinojosa-Figueroa, M.S.
Navas Arias, C.F.
Cadena Barberis, E.D.
Sacks-Zimmerman, A.
Abstract

Subanesthetic ketamine shows rapid neuroplastic and antidepressant effects in psychiatric conditions, prompting interest in its potential relevance for cognitive dysfunction in neurological disorders. Cognitive deficits are widespread across traumatic brain injury, stroke, epilepsy, and neurodegenerative diseases, yet treatments remain primarily compensatory. Ketamine's actions on glutamatergic signaling, synaptogenesis, and neuroinflammation suggest possible cognitive implications, but its specific effects on cognition in neurological populations remain unclear. This systematic review evaluated evidence on the effects of ketamine on cognitive functioning in neurological diseases and injuries characterized by cognitive impairment. A systematic search of three databases through February 10, 2024, was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines, including animal or human studies administering ketamine or its derivatives with cognitive outcome measures. Twenty-two studies met inclusion criteria: twenty-one animal studies and one human study. In animal models of traumatic brain injury, epilepsy, cerebrovascular disease, Parkinson's disease, and infectious encephalopathy, a subject-level vote count in rodents indicated positive cognitive effects in 93.2% of subjects, particularly in working memory and spatial learning, while null effects appeared in 4.1% and negative effects in 2.7%. The only human study, conducted in patients with Huntington's disease, reported short-term, dose-dependent cognitive worsening after escalating intravenous ketamine. Overall, preclinical evidence indicates potential cognitive effects in animal models of neurological injury; however, human evidence remains extremely limited and does not currently support clinical cognitive enhancement. Further controlled clinical studies are needed to clarify safety, mechanisms, and translational relevance in neurological rehabilitation.

Journal / Series
Frontiers in neurology
Volume & Issue
17
Date Issued
2026-03-30
Publisher
Frontiers Media
Keywords
WCM Library Coordinated Deposit
•
cognitive function
•
ketamine
•
neurological disorders
•
neuroplasticity
•
traumatic brain injury
Related DOI
https://doi.org/10.3389/fneur.2026.1786249
Previously Published as
Leon-Rojas JE, Mascialino G, Vinueza Mera L, Hinojosa-Figueroa MS, Navas Arias CF, Cadena Barberis ED, Sacks-Zimmerman A. Ketamine as a potential cognitive enhancer in neurological disorders: evidence from preclinical and clinical studies. Frontiers in neurology. 2026;17:1786249. doi: 10.3389/fneur.2026.1786249. PMID: 41982421.
Rights
Attribution 4.0 International
Rights URI
https://creativecommons.org/licenses/by/4.0/
Type
article

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