Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor Modulation
Jules S Mitchell, Daniel Francis Hermens, Maxwell R. Bennett, Adem T. Can, Jim Lagopoulos
CNS Drugs January 22, 2023 DOI: 10.1007/s40263-022-00984-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Interventions | Zinc supplementation Ketamine |
| Dose | sub-anaesthetic doses of ketamine, low-dose ketamine |
| Topics | Esketamine Ketamine |
| Citations | 15 |
| Key findings | The authors argue that anorexia nervosa is associated with NMDA receptor-mediated excitatory and inhibitory neurometabolite dysfunction, supported by region-specific magnetic resonance spectroscopy findings linked to psychopathology. They propose that zinc supplementation and sub-anaesthetic ketamine may help normalise this dysfunction, and that combined low-dose ketamine plus zinc warrants future investigation to extend therapeutic benefits, with biological markers outlined for assessing and potentially predicting treatment response. |
Abstract
Anorexia nervosa is a disorder associated with serious adverse health outcomes, for which there is currently considerable treatment ineffectiveness. Characterised by restrictive eating behaviours, distorted body image perceptions and excessive physical activity, there is growing recognition anorexia nervosa is associated with underlying dysfunction in excitatory and inhibitory neurometabolite metabolism and signalling. This narrative review critically explores the role of N-methyl-D-aspartate receptor-mediated excitatory and inhibitory neurometabolite dysfunction in anorexia nervosa and its associated biomarkers. The existing magnetic resonance spectroscopy literature in anorexia nervosa is reviewed and we outline the brain region-specific neurometabolite changes that have been reported and their connection to anorexia nervosa psychopathology. Considering the proposed role of dysfunctional neurotransmission in anorexia nervosa, the potential utility of zinc supplementation and sub-anaesthetic doses of ketamine in normalising this is discussed with reference to previous research in anorexia nervosa and other neuropsychiatric conditions. The rationale for future research to investigate the combined use of low-dose ketamine and zinc supplementation to potentially extend the therapeutic benefits in anorexia nervosa is subsequently explored and promising biological markers for assessing and potentially predicting treatment response are outlined.
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 4
- Novel treatments for anorexia nervosa: Insights from neuroplasticity research European Eating Disorders Review October 12, 2023
- Ketamine as adjuvant treatment in eating disorders: an exploratory study of a case series and retrospective analysis. Journal of Eating Disorders March 17, 2025
- Psilocybin and ketamine affect novel neuropeptides gene expression in the rat hypothalamus Journal of Psychopharmacology April 17, 2025
- New Frontiers in Ketamine Research: From Mechanisms of Action to Novel Psychiatric Treatment Approaches American Journal of Psychiatry and Neuroscience August 17, 2023
Cites 30
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 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
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
and 25 more in the library