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Licensed Unlicensed Requires Authentication Published by De Gruyter May 5, 2020

The neurophysiology of ketamine: an integrative review

  • Rebecca McMillan ORCID logo EMAIL logo and Suresh D. Muthukumaraswamy


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.


Dr Muthukumaraswamy is supported by a Rutherford Discovery Fellowship administered by the Royal Society of New Zealand. This work was supported by the Health Research Council of New Zealand.


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Received: 2019-09-10
Accepted: 2020-01-26
Published Online: 2020-05-05
Published in Print: 2020-07-28

©2020 Walter de Gruyter GmbH, Berlin/Boston

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