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Catechol-O-Methyltransferase Effects on Smoking: a Review and Proof of Concept of Sex-Sensitive Effects

  • Addictions (M Potenza and E DeVito, Section Editors)
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Abstract

Purpose of Review

This article reviews recent research on how catechol-O-methyltransferase (COMT) may impact cigarette smoking behavior, and how effects may be sex-sensitive. Preliminary data are presented on sex-sensitive effects of COMT on response to short-term abstinence in individuals who smoke.

Recent Findings

Although research is mixed, functional variants in the COMT gene have been linked with smoking behavior, cessation outcomes, and nicotine abstinence-related symptoms. Our proof-of-concept preliminary data from a human laboratory study of individuals who smoke cigarettes found that those with the high COMT enzyme activity genotype (Val/Val) reported more severe smoking urges and withdrawal symptoms following overnight abstinence than Met carriers. These effects were present in women, but not in men and were abstinent dependent, in that they dissipated following nicotine administration.

Summary

The preliminary data showing sex-sensitive pharmacogenetic effects may shed light on mechanisms contributing to sex differences in barriers to smoking cessation or potential sex-specific treatment options.

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Acknowledgements

The authors would like to thank Stacy Minnix, Lance Barnes, Katherine Barrett, Christopher Cryan, and Ellen Mitchell, R.N., for their valuable contributions to subject recruitment and data collection, and thank members of Dr. Joel Gelernter’s laboratory for help with genoty**. We also thank the participants for their time.

Funding

The collection of the data (which was used for the secondary analysis) was supported by the National Institute on Drug Abuse (NIDA) (R01 DA12690, R01 DA12849, R03 DA027474) and the Veterans Administration Mental Illness Research, Education and Clinical Center (MIRECC); EED received support from K12 DA031050 from NIDA, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Office of Research on Women’s Health (ORWH), and NIH Office of the Director (OD) and 5R21DA038253-02 from NIDA. The funding bodies had no role in the collection, analysis, or the decision to publish these data.

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  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA

    Elise E. DeVito & Mehmet Sofuoglu

  2. VA Connecticut Healthcare System, West Haven, CT, USA

    Mehmet Sofuoglu

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Correspondence to Elise E. DeVito.

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DeVito, E.E., Sofuoglu, M. Catechol-O-Methyltransferase Effects on Smoking: a Review and Proof of Concept of Sex-Sensitive Effects. Curr Behav Neurosci Rep 9, 113–123 (2022). https://doi.org/10.1007/s40473-022-00251-2

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