The neurophysiology of ketamine: an integrative review
Rebecca McMillan, Suresh Muthukumaraswamy
Reviews in the Neurosciences May 5, 2020 DOI: 10.1515/revneuro-2019-0090 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Neurophysiology Neuroimaging Neurology Psychosis |
| Citations | 53 |
| Key findings | Ketamine's acute effects on the resting brain are complex and vary across species, doses, and methodologies, highlighting the need for standardized approaches in future research. |
Abstract
The drug ketamine has been extensively studied due to its use in anaesthesia, as a model of psychosis and, most recently, its antidepressant properties. Understanding the physiology of ketamine is complex due to its rich pharmacology with multiple potential sites at clinically relevant doses. In this review of the neurophysiology of ketamine, we focus on the acute effects of ketamine in the resting brain. We ascend through spatial scales starting with a complete review of the pharmacology of ketamine and then cover its effects on in vitro and in vivo electrophysiology. We then summarise and critically evaluate studies using EEG/MEG and neuroimaging measures (MRI and PET), integrating across scales where possible. While a complicated and, at times, confusing picture of ketamine's effects are revealed, we stress that much of this might be caused by use of different species, doses, and analytical methodologies and suggest strategies that future work could use to answer these problems.
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 26
- Ketamine and the Future of Rapid-Acting Antidepressants Annual Review of Clinical Psychology February 9, 2021
- A qualitative and quantitative account of patient's experiences of ketamine and its antidepressant properties. Journal of Psychopharmacology August 1, 2021
- The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression Frontiers in Psychiatry September 19, 2023
- Digital twin brain simulator for real-time consciousness monitoring and virtual intervention using primate electrocorticogram data. NPJ Digital Medicine February 10, 2025
- Anterior default mode network and posterior insular connectivity is predictive of depressive symptom reduction following serial ketamine infusion. Psychological Medicine September 1, 2022
and 21 more in the library
Cites 71
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
and 66 more in the library