Treatment-Resistant Depression (TRD)Bipolar DisorderDepressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Chronic PainNeuroimaging & Brain MeasuresKetamine

Ketamine abuse potential and use disorder

This review (2016) contrasts the therapeutic potential of ketamine as a fast-acting antidepressant to its potential for substance abuse. It specifically examines the social harms, the psycho-physiological and neurochemical effects, reinforcement mechanisms, and the treatment of ketamine abuse. It concludes that ketamine elicits significant reinforcing and toxic effects, which must be weighed against its antidepressant potential, which needs to be investigated in greater depth.

Authors

  • Liu, Y.
  • Lin, D.
  • Wu, B.

Published

Brain Research Bulletin
meta Study

Abstract

Ketamine is a noncompetitive antagonist of N-methyl-d-asparate (NMDA) receptor and has been long used as an anesthetic agent in humans and veterinary medicine. The present article reviews the epidemiology, pharmacology, neurochemistry, and treatment of ketamine abuse. Ketamine has a unique mood controlling property and a number of studies have demonstrated a significant and rapid antidepressant effect of ketamine. However, the therapeutic value of ketamine to treat psychiatric disorders faces a major challenge that ketamine also owns significant reinforcing and toxic effects. Its abuse has posted severe harms on individuals and society. Disrupted learning and memory processing has long been related with ketamine use. It is hypothesized that ketamine blocks NMDA receptors on gamma-aminobutyric acid (GABA) neurons inside the thalamic reticular nucleus, which leads to disinhibition of dopaminergic neurons and increased release of dopamine. Currently, there is no specific treatment for treating every ketamine patient presenting peripheral toxicity. Interestingly, ketamine psychotherapy has been suggested to be a promising approach to treat addiction of other drugs. Future research can continue to develop creative ways to investigate potential mechanism and treatments related to ketamine abuse that have posted severe individual and social harms.

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Research Summary of 'Ketamine abuse potential and use disorder'

Introduction

Ketamine is a phencyclidine (PCP) derivative and a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor that has long been used as an anaesthetic in humans and veterinary medicine. Beyond anaesthesia, subanaesthetic doses produce rapid antidepressant effects and have been trialled for treatment-resistant depression, bipolar disorder, anxiety and chronic pain. At the same time, ketamine produces dissociative and reinforcing psychological effects and carries documented neurological, hepatic, renal and other peripheral toxicities, which have contributed to growing recreational use and public-health concerns. Liu and colleagues set out to review the epidemiology, pharmacology, neurochemistry and treatment of ketamine abuse, with particular focus on brain circuitry implicated in reinforcing effects. The paper synthesises findings from human epidemiological surveys, clinical reports, neuroimaging and biochemical studies, and animal models (for example self-administration and conditioned place preference paradigms) to characterise harms, mechanisms and therapeutic approaches reported in the literature.

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Study Details

References (7)

Papers cited by this study that are also in Blossom

Antidepressant effects of ketamine in depressed patients

Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)

The use of ketamine as an antidepressant: a systematic review and meta-analysis

Coyle, C. M., Laws, K. R. · Human Psychopharmacology (2015)

Therapeutic infusions of ketamine: do the psychoactive effects matter?

Dakwar, E., Anerella, C., Hart, C. L. et al. · Drug and Alcohol Dependence (2014)

Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up

Krupitsky, E. M., Burakov, A. M., Romanova, T. N. et al. · Journal of Substance Abuse Treatment (2002)

Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence

Krupitsky, E. M., Burakov, A. M., Dunaevsky, I. V. et al. · Journal of Psychoactive Drugs (2007)

154 cited
Ketamine psychedelic therapy (KPT): a review of the results of ten years of research

Krupitsky, E. M., Grinenko, A. Y. · Journal of Psychoactive Drugs (1997)

Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression

Romeo, B., Choucha, W., Fossati, P. et al. · Psychiatry Research (2015)

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Aicher, H. D., Mueller, M. J., Dornbierer, D. A. et al. · Frontiers in Psychiatry (2024)

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Neurocognitive effects of subanesthetic serial ketamine infusions in treatment resistant depression

Zavaliangos-Petropulu, A., Mcclintock, S. M., Khalil, J. et al. · Journal of Affective Disorders (2023)

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Davis, A. K., Streeter Barrett, F., Cosimano, M. P. et al. · Journal of Psychopharmacology (2022)

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Worrell, S. D., Gould, T. J. · Neuroscience and Biobehavioral Reviews (2021)

The History of Psychedelics in Psychiatry

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Greenway, K. T., Garel, N., Jerome, L. et al. · Expert Review of Clinical Pharmacology (2020)

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