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Addictions and Polymorphism

A Focus on GRIN2B Gene and Ketamine Abuse

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Handbook of Substance Misuse and Addictions

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Abstract

Substance addiction is a chronic and relapsing brain disease with harmful consequences for both individual users and society. Following its approval as an anesthetic, ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, which mimics some of the symptoms of schizophrenia, has been used as a tool for psychiatric research. Recreational use of ketamine has been increasing in recent decades. There are now increasing concerns about the harmful physical and psychological consequences of repeated misuse of ketamine. However, little is known about the underlying molecular mechanisms responsible for ketamine-associated psychosis. Glutamate is a primary excitatory neurotransmitter in the brain, and both in vivo and in vitro experiments have implicated NMDA receptor, a glutamate receptor, as an element in various types of addiction. Recent findings from genetics-based approaches have demonstrated the significant association of NMDA receptor subunit genes such as GluN2B, GluN2A, and GluN3A with various addiction-related phenotypes. Of these genes, GluN2B has been one of the most studied, and it has been revealed to play crucial roles in the etiology of schizophrenia and addiction. In this chapter, we outline the abuse situation and adverse effects of ketamine abuse, the relationship between ketamine abuse and GRIN2B gene, and briefly review the role of GRIN2B polymorphism in schizophrenia and drug addiction, and provide an updated view of the research progress of GRIN2B polymorphism in ketamine users, especially in chronic ketamine users. To better understand the molecular mechanisms underlying ketamine-associated psychosis and to promote the development of specific strategies for the prevention and treatment of addiction, future studies focusing on identifying more variants of NMDA-related genes and other genes in diverse substance addiction are desired.

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Abbreviations

FDA:

The Food and Drug Administration

GABA:

γ-Aminobutyric acid

GRIN2B:

NMDA type subunit 2B gene

NMDA:

N-methyl-D-aspartate

SNPs:

Single nucleotide polymorphisms

SUDs:

Substance use disorders

US:

United States

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Authors and Affiliations

  1. The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China

    Ying Yan, Minling Zhang & Ni Fan

Authors
  1. Ying Yan
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  2. Minling Zhang
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  3. Ni Fan
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Corresponding author

Correspondence to Ni Fan .

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Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

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Yan, Y., Zhang, M., Fan, N. (2022). Addictions and Polymorphism. In: Patel, V.B., Preedy, V.R. (eds) Handbook of Substance Misuse and Addictions. Springer, Cham. https://doi.org/10.1007/978-3-030-92392-1_127

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