title: Rapid nicotine clearance is associated with greater reward and heart rate increases from intravenous nicotine.
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.
authors.affiliation: Department of Psychiatry and VA Connecticut Healthcare System, Yale University School of Medicine, West Haven, CT 06516, USA. Mehmet.Sofuoglu@yale.edu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sofuoglu
authors.forename: Aryeh I
authors.initials: AI
authors.lastname: Herman
authors.forename: Haleh
authors.initials: H
authors.lastname: Nadim
authors.forename: Peter
authors.initials: P
authors.lastname: Jatlow
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002248:Carbon Monoxide / Q000378:metabolism; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D003367:Cotinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage* / Q000097:blood*; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000097:blood*; D016037:Single-Blind Method; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D002248:Carbon Monoxide; D003367:Cotinine; D006854:Hydrocortisone