{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:20:28Z","timestamp":1787026828783,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>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\u2019s 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\u2019s 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\u2019s 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.<\/jats:p>","DOI":"10.3389\/fneur.2026.1786249","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:12:48Z","timestamp":1774843968000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Ketamine as a potential cognitive enhancer in neurological disorders: evidence from preclinical and clinical studies"],"prefix":"10.3389","volume":"17","author":[{"given":"Jose E.","family":"Leon-Rojas","sequence":"first","affiliation":[{"name":"Cerebro, Emoci\u00f3n y Conducta (CEC) Research Group, School of Medicine, Universidad de Las Am\u00e9ricas (UDLA)","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Mascialino","sequence":"additional","affiliation":[{"name":"Health Sciences Department, Universidad P\u00fablica de Navarra","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizeth","family":"Vinueza Mera","sequence":"additional","affiliation":[{"name":"NeurALL Research Group","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario S.","family":"Hinojosa-Figueroa","sequence":"additional","affiliation":[{"name":"NeurALL Research Group","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina F.","family":"Navas Arias","sequence":"additional","affiliation":[{"name":"NeurALL Research Group","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefano D.","family":"Cadena Barberis","sequence":"additional","affiliation":[{"name":"NeurALL Research Group","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Sacks-Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"Acheron Psychiatry","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.jad.2020.09.007","article-title":"A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009-January 2019","volume":"277","author":"Marcantoni","year":"2020","journal-title":"J Affect Disord"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41398-023-02451-0","article-title":"Rapid neuroplasticity changes and response to intravenous ketamine: a 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