Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action.
Eric A Maltbie, Gopinath S Kaundinya, Leonard L. Howell
Behavioural Pharmacology December 2017 DOI: 10.1097/fbp.0000000000000354 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Key findings | Ketamine exerts robust and consistent effects on whole-brain functional connectivity that are highly conserved across humans and nonhuman primates. The authors propose that ketamine's therapeutic potential may derive from strengthening executive control circuitry, suggesting it as a candidate treatment for drug abuse. Important questions about its mechanism of action and therapeutic potential remain unresolved. |
Abstract
Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and the therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional MRI studies have yielded at a systems level focused on brain circuitry. Multiple analytic approaches show that ketamine exerts robust and consistent effects at the whole-brain level. These effects are highly conserved across human and nonhuman primates, validating the use of nonhuman primate models for further investigations with ketamine. Regional analysis of brain functional connectivity suggests that the therapeutic potential of ketamine may be derived from a strengthening of executive control circuitry, making it an intriguing candidate for the treatment of drug abuse. There are still important questions about the mechanism of action and the therapeutic potential of ketamine that can be addressed using appropriate functional neuroimaging techniques.
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 7
- Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network NeuroImage: Clinical 2018
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
- The ketamine chameleon: history, pharmacology, and the contested value of experience. Expert Review of Clinical Pharmacology March 1, 2025
- The effects of esketamine and treatment expectation in acute major depressive disorder (Expect): study protocol for a pharmacological fMRI study using a balanced placebo design Trials August 13, 2023
- Ketamine Alters Tuning of Neural and Behavioral Spatial Working Memory Precision bioRxiv Preprint Server February 10, 2025
and 2 more in the library
Cites 24
- 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
- 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
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
and 19 more in the library