Abstract
The ratio of nicotine metabolites (trans-3′-hydroxycotinine (3HC) to cotinine) correlates with nicotine clearance. In previous studies, high nicotine metabolite ratio (NMR) predicted poor outcomes for smoking cessation treatment with nicotine patch. The underlying mechanisms that associate NMR with treatment outcomes have not been fully elucidated. A total of 100 smokers were divided into quartiles based on their baseline plasma NMR. Following overnight abstinence, smokers received saline followed by escalating intravenous doses of nicotine (0.5 and 1.0 mg/70 kg) given 30 min apart. The effects of nicotine on subjective, plasma cortisol, heart rate, and systolic and diastolic blood pressure measures were obtained. Smokers in the first NMR quartile (slower metabolizers) had lower Fagerstrom Test for Nicotine Dependence (FTND) scores, suggesting lower levels of dependence. In contrast, smokers in the fourth NMR quartile (faster metabolizers) reported greater craving for cigarettes following overnight abstinence from smoking and reported greater ratings of nicotine-induced good drug effects, drug liking, and wanting more drug. Higher NMR was also associated with greater heart rate increases in response to nicotine. These results suggest that enhanced nicotine reward and cigarette craving may contribute to the poor treatment response in smokers with high NMR. These findings warrant further investigation, especially in treatment-seeking smokers undergoing cessation treatment.
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Acknowledgements
We would like to thank Ellen Mitchell, RN, Lance Barnes, Stacy Minnix, and Kathy Barrett for excellent technical assistance. This research was supported by the Veterans Administration Mental Illness Research, Education and Clinical Center (MIRECC) and grants R03-DA 027474, K12 DA000167-20 (AH), and K02-DA021304 (MS) from the National Institute on Drug Abuse (NIDA).
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Dr Sofuoglu serves as an expert witness on behalf of Pfizer in lawsuits related to varenicline. The other authors declare no conflict of interest.
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Sofuoglu, M., Herman, A., Nadim, H. et al. Rapid Nicotine Clearance is Associated with Greater Reward and Heart Rate Increases from Intravenous Nicotine. Neuropsychopharmacol 37, 1509–1516 (2012). https://doi.org/10.1038/npp.2011.336
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DOI: https://doi.org/10.1038/npp.2011.336
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