Dataset Information

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

ABSTRACT: Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (3'-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance and a well-validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers.Treatment-seeking smokers (N = 69; 30 slow metabolizers and 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once after 24 hours of smoking abstinence.In whole-brain analysis, normal (compared with slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke.Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy.

SUBMITTER: Falcone M

PROVIDER: S-EPMC5625335 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

Falcone Mary M Cao Wen W Bernardo Leah L Tyndale Rachel F RF Loughead James J Lerman Caryn C

Biological psychiatry 20151126 3

<h4>Background</h4>Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (3'-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance and a well-validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers.<h4>Method ...[more]

PMID: 26805583

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Project description:IntroductionSmokers who use opioids smoke more cigarettes per day (CPD) than non-opioid users, which could be due to the effects of opioids on nicotine metabolism. Moreover, nicotine metabolism increases during pregnancy, potentially making quitting more difficult for pregnant smokers. We examined nicotine metabolism and its association with opioid use (OU) and CPD in pregnant smokers.MethodsWe recruited pregnant women who smoked at least 5 CPD for a clinical trial of smoking cessation. Plasma nicotine metabolite ratio (NMR; trans-3'-hydroxycotinine (3HC)/cotinine)-a biomarker of nicotine metabolism-OU (involving methadone, buprenorphine, fentanyl, oxycodone, or tramadol), and CPD were assessed at baseline. We used linear regression to examine the associations between log-transformed NMR, OU, and CPD, adjusting for race/ethnicity and menthol smoking.ResultsAmong 129 pregnant smokers, 25 (19%) were opioid users; most were maintained on methadone (n = 14). Compared to non-OU smokers, OU smokers had higher median CPD (10.0 vs. 7.0, p = .0007), serum 3HC (81.0 vs. 42.0 ng/mL, p = .0001), and NMR (0.63 vs. 0.43, p < .0001). In addition, methadone-maintained smokers had a higher median NMR than non-OU smokers (0.66 vs. 0.43, p = .0004). Adjusting for covariates, log-transformed NMR was greater in OU smokers (p = .012), specifically methadone-maintained smokers (p = .024), than non-OU smokers.ConclusionsOur preliminary results show that OU is associated with a higher NMR in pregnant smokers. A larger study sample is needed to replicate this finding, examine potential mechanisms, and determine its clinical significance.ImplicationsAmong pregnant smokers, we observed that nicotine metabolism was significantly faster among opioid users-the majority of whom were on methadone maintenance-compared to nonusers, which could have implications for smoking cessation. Further studies are needed to replicate this finding, evaluate potential mechanisms, and determine its clinical significance.

Dataset Information

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

Publications

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

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