Can Ketamine Treat Schizophrenia?
Journal of Biomedical Research & Environmental Sciences March 1, 2025 DOI: 10.37871/jbres2078 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Memantine Ketamine |
| Topics | Esketamine Ketamine |
| Key findings | Argues that NMDAR antagonists such as memantine and ketamine enhance 20S proteasome activity through the ubiquitin-independent 20S proteasome pathway, helping maintain protein homeostasis. The authors propose this explains how memantine reduces protein aggregation in Alzheimer's and Parkinson's disease, and suggest ketamine-induced synaptic protein changes within 2 hours may underlie its antidepressant effects. The review also discusses possible effects of these drugs on schizophrenia pathophysiology. |
Abstract
NMDAR antagonists, such as memantine and ketamine, have demonstrated efficacy in treating neurodegenerative diseases and major depression. Our recent findings reveal that these antagonists significantly enhance 20S proteasome activity, which is essential for degrading intrinsically disordered, oxidatively damaged, or misfolded proteins-key factors in neurodegenerative diseases like Alzheimer's and Parkinson's. Through the Ubiquitin-Independent 20S Proteasome pathway (UIPS), these drugs help maintain cellular protein homeostasis, a critical function that declines with age and contributes to protein aggregation and disease symptoms. Our findings provide a plausible explanation for how memantine alleviates symptoms of Alzheimer's and Parkinson's diseases by reducing or preventing protein aggregation in the brain. Furthermore, our data suggest that the dramatic changes in synaptic protein homeostasis induced by ketamine within 2 hours may contribute to its therapeutic effects in major depression. The etiology and mechanisms of schizophrenia are not well understood, arising from complex interactions between genetic and environmental factors. Its pathophysiology reflects this complexity, with abnormalities in multiple brain functions. This review discusses the potential effects of NMDAR antagonists on the pathophysiology of schizophrenia and their therapeutic impact, supported by our data.
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 5
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms Neuropsychopharmacology July 24, 2023
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- Enhancing proteasome activity by NMDAR antagonists explains their therapeutic effect in neurodegenerative and mental diseases. Scientific Reports January 13, 2025
- Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression. Pharmaceuticals May 12, 2023