Rate Of Nicotine Metabolism Research Articles

Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence.

This study investigated the influence of the rate of nicotine metabolism, as indicated by the nicotine metabolite ratio (NMR), on tobacco dependence. We stratified 136 smokers on the basis of saliva NMR as fast (n=65) and slow (n=71) metabolizers. Two "loading cigarettes" were smoked after overnight, and a "reward cigarette" was smoked after 6hours of daytime, abstinence. Blood nicotine concentrations, expired carbon monoxide, withdrawal/craving, and reward questionnaires were collected before/after smoking and during daytime abstinence. Compared with slow metabolizers, fast metabolizers had a shorter nicotine elimination half-life (P<0.001), lower plasma nicotine concentrations (P<0.001), and higher withdrawal/craving scores (P<0.05) for most times during daytime abstinence, indicating that fast metabolizers are likely smoking more to relieve withdrawal symptoms (negative reinforcement). Reward/satisfaction scores were similar in fast and slow metabolizers, suggesting that faster nicotine metabolism, assessed by NMR, is not associated with greater positive reinforcement. CYP2A6 normal (n=82) and reduced (n=42) genotype predicted plasma nicotine concentrations but not withdrawal symptoms.

Pregnancy-Induced Increases in the Nicotine Metabolite Ratio: Examining Changes During Antepartum and Postpartum.

Pregnancy-induced increases in nicotine metabolism may contribute to difficulties in quitting smoking during pregnancy. However, the time course of changes in nicotine metabolism during early and late pregnancy is unclear. This study investigated how pregnancy alters the nicotine metabolite ratio (NMR), a common biomarker of nicotine metabolism among nonpregnant smokers. Urinary NMR (trans-3'-hydroxycotinine [3HC]/cotinine [COT]) was assessed using total (free + glucuronide) and free compounds among women (N = 47) from a randomized controlled trial for smoking cessation who self-reported smoking and provided a urine sample during early pregnancy (M ± SD = 12.5 ± 4.5 weeks' gestation), late pregnancy (28.9 ± 2.0 weeks' gestation), and 6 months postpartum (24.7 ± 1.2 weeks since childbirth). Urine samples were analyzed using liquid chromatography-tandem mass spectrometry and NMR were calculated as Total 3HC/Free COT, Free 3HC/Free COT, and Total 3HC/Total COT. NMR was significantly higher during early and late pregnancy compared to postpartum and significantly increased from early to late pregnancy as measured by Total 3HC/Free COT (0.76, 0.89, 0.60; all p's < .05) and Free 3HC/Free COT (0.68, 0.80, 0.51; all p's < .05). Total 3HC/Total COT did not vary over time (p = .81). Total 3HC/Free COT and Free 3HC/Free COT increased in the first trimester and continued to increase throughout pregnancy, suggesting a considerable increase in nicotine metabolism over gestation. Future analyses are needed to interpret the changes in NMR in the context of nicotine pharmacokinetics, as well as its impact on changes in smoking behavior and cessation outcomes. We observed that the NMR was significantly higher as early as 12 weeks' gestation and increased further as a function of gestational age. Among nonpregnant smokers, elevated NMR is associated with smoking phenotypes such as smoking more cigarettes per day and poorer response to nicotine patch; therefore, pregnancy-induced increases in the NMR may contribute to smoking during the first trimester of pregnancy and reducing or quitting smoking may become more challenging as the rate of nicotine metabolism accelerates over the course of pregnancy.

Genetic Polymorphism of CYP2A6 and Its Relationship with Nicotine Metabolism in Male Bataknese Smokers Suffered from Lung Cancer in Indonesia.

BACKGROUND:Cytochrome P450 2A6 (CYP2A6) is known as an enzyme which is responsible for the metabolism of chemical compounds.AIM:This study aimed to analyse the relationship between CYP2A6 gene polymorphism with nicotine metabolism rates and lung cancer incidence among smokers of Batak ethnic group in Indonesia.METHODS:This study was a case-control study involving 140 research subjects through a purposive sampling technique from three hospitals in Medan, Indonesia. An examination of nicotine metabolism rates was conducted for all subjects using the 3HC/cotinine ratio parameter with LC-MS/MS technique. The examination of the CYP2A6 gene was performed with PCR-RFLP. Data were analysed with Conditional Logistic Regression test using Epi Info 7.0 software.RESULTS:The allele frequencies of CYP2A6*1A, CYP2A6*1B, and CYP2A6*4A found were 44.3%, 48.9%, and 6.8%, respectively. The *1B allele showed the highest metabolism rate. It is found that slow metabolizer individuals were 5.49 times more likely to develop lung cancer (P = 0.01, 95%CI 1.2-24.8).CONCLUSION:Among the Bataknese smokers studied, the CYP2A6*1B allele was found to be the most common allele and showed the highest rate of nicotine metabolism. However, the results show the insignificant relationship among CYP2A6 genetic polymorphism, nicotine metabolism, and lung cancer incidence.

Nicotine metabolite ratio predicts smoking topography: The Pennsylvania Adult Smoking Study

BackgroundThe nicotine metabolite ratio (NMR) as measured by the ratio of 3′hydroxycotinine to cotinine has been examined in relation to tobacco use patterns including cigarettes per day and quit success to determine its role in nicotine dependence. We examined the NMR in relation to smoking topography and tested the hypothesis that normal metabolizers have a greater total daily puff volume than slow metabolizers. MethodsThe Pennsylvania Adult Smoking Study (PASS) is a longitudinal study of 352 adults who smoked, on average, 17 cigarettes per day. Subjects used a portable smoking topography device over a two-day period at home and at work. We measured the ratio of 3′hydroxycotinine to cotinine in the saliva of the subjects. ResultsIn multiple linear regression analyses, a higher rate of nicotine metabolism was significantly associated with increased daily puffs and total daily puff volume. In a mediation analysis, a significant, indirect effect of race on the relationship between NMR and puff volume was observed, with 22% of the effect mediated by white race. A higher NMR was also associated with female gender, white race, cigarettes per day and nicotine dependence measures. ConclusionThe NMR was associated with tobacco use patterns including smoking topography. Faster nicotine metabolism was associated with greater total daily puffs and puff volume.

Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes

IntroductionAdherence to pharmacotherapies for tobacco dependence, such as varenicline, is necessary for effective treatment. The relationship between varenicline adherence, determined by commonly used indirect (i.e., self-reported pill counts) and infrequently used direct (i.e., varenicline levels) methods, and abstinence outcomes have not been previously examined, nor has their impact on the outcomes of a genetically randomized clinical trial been assessed. MethodsAt Week 1 following target quit date, self-reported pill count and salivary varenicline levels were obtained from participants (N = 376) in a smoking cessation clinical trial (NCT01314001). Point-prevalence abstinence was biochemically-verified by salivary cotinine at Week 1 and by exhaled carbon monoxide at Week 1, end-of-treatment, 6 and 12 months following treatment. Blood nicotine metabolite ratio (NMR) was obtained at baseline. ResultsAdherent individuals based on varenicline levels were significantly more likely to be abstinent than non-adherent individuals at Week 1 (odds ratios [ORs] 1.92–3.16, p’s≤0.006), end-of-treatment (OR = 2.53, p = .004), and six months following treatment (OR = 2.30, p = .03). In contrast, pill counts did not consistently predict abstinence. Including direct measures of adherence enhanced the association between rate of nicotine metabolism (NMR) and end-of-treatment abstinence; normal metabolizers (NMR ≥ 0.31) were significantly more likely than slow metabolizers (NMR < 0.31) to be abstinent at end-of-treatment (OR = 2.00, p = .005). ConclusionAdherence based on salivary varenicline, rather than on pill counts, is predictive of Week 1 abstinence, irrespective of the biomarker of abstinence assessed, and of long-term abstinence. Direct measures of adherence enhance the ability to assess the impact of a biomarker or genetic marker on abstinence outcomes.

Nicotine metabolite ratio and smoking outcomes using nicotine replacement therapy and varenicline among smokers with and without psychiatric illness.

It has been suggested that the effectiveness of nicotine replacement smoking cessation pharmacotherapy may be enhanced by assessing rates of nicotine metabolism using the nicotine metabolite ratio - which reflects differences in the activity of the CYP2A6 hepatic enzyme - and titrating doses appropriately. To date, supporting evidence is equivocal, with little information regarding the assessment and effectiveness of the nicotine metabolite ratio among smokers with psychiatric conditions. The nicotine metabolite ratio of 499 smokers from the FLEX trial was determined using urine samples obtained at baseline. They were randomized to receive either: standard transdermal nicotine (nicotine replacement therapy); extended nicotine replacement therapy + adjunct nicotine agent; or varenicline. Primary cessation outcomes were seven-day point prevalence at 5, 10, 22, and 52 weeks post-target quit date, comparing across treatment and psychiatric status. Our principal analysis employed logistic regression (outcome: abstinence), using slow metabolizers as the reference category. No differences were observed by nicotine metabolite ratio classification (slow, moderate, fast) with respect to any demographic or smoking-related variables. Nicotine metabolite ratio class did not predict smoking cessation in either the overall sample, or by treatment condition at any time-point (week 52 moderate metabolizers: odds ratio 1.34, 95% confidence interval (0.68-2.63), p=0.394; fast metabolizers: odds ratio 1.04 (0.56-1.91), p=0. 906). Our results did not find any associations between nicotine metabolite ratio and cessation outcomes among smokers using nicotine replacement therapy or varenicline with and without lifetime psychiatric conditions.

Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers.

BackgroundIdentifying the biological basis of smoking cessation success is of growing interest. The rate of nicotine metabolism, measured by the nicotine metabolite ratio, affects multiple aspects of nicotine dependence. Fast nicotine metabolizers tend to smoke more, experience more withdrawal and craving, and have lower cessation rates compared with slow metabolizers. The nicotine metabolite ratio predicts treatment response, and differences in brain activation between fast metabolizers and slow metabolizers have been reported in fMRI studies. As reinforcing/rewarding effects of tobacco are associated with dopamine transmission, the purpose of the present study was to study the dopaminergic system in human smokers based on their nicotine metabolite ratio.MethodsThe first aim of the study was to explore if there were differences in D2 and D3 receptor binding between fast metabolizers and slow metabolizers during abstinence. The second aim was to explore smoking-induced dopamine release in both groups. Participants underwent 2 [11C]-(+)-PHNO PET scans: one scan during abstinence and the other after smoking a tobacco cigarette. Subjective measures were recorded and blood was drawn for measurement of nicotine and cotinine levels.ResultsDuring abstinence, slow metabolizers (n = 13) had lower [11C]-(+)-PHNO binding potential than fast metabolizers (n = 15) restricted to the D2 regions of the associative striatum and sensorimotor striatum. After smoking a cigarette, [11C]-(+)-PHNO binding potential was decreased in the limbic striatum and ventral pallidum, suggestive of increases in dopamine, but there were no nicotine metabolite ratio differences.ConclusionsFurther studies are required to delineate if differences in [11C]-(+)-PHNO binding between slow metabolizers and fast metabolizers at abstinence baseline are preexisting traits or induced by prolonged tobacco use.

Novel CYP2A6 diplotypes identified through next-generation sequencing are associated with in-vitro and in-vivo nicotine metabolism.

Smoking patterns and cessation rates vary widely across smokers and can be influenced by variation in rates of nicotine metabolism [i.e. cytochrome P450 2A6 (CYP2A6), enzyme activity]. There is high heritability of CYP2A6-mediated nicotine metabolism (60-80%) owing to known and unidentified genetic variation in the CYP2A6 gene. We aimed to identify and characterize additional genetic variants at the CYP2A6 gene locus. A new CYP2A6-specific sequencing method was used to investigate genetic variation in CYP2A6. Novel variants were characterized in a White human liver bank that has been extensively phenotyped for CYP2A6. Linkage and haplotype structure for the novel single nucleotide polymorphisms (SNPs) were assessed. The association between novel five-SNP diplotypes and nicotine metabolism rate was investigated. Seven high-frequency (minor allele frequencies ≥6%) noncoding SNPs were identified as important contributors to CYP2A6 phenotypes in a White human liver bank (rs57837628, rs7260629, rs7259706, rs150298687 (also denoted rs4803381), rs56113850, rs28399453, and rs8192733), accounting for two times more variation in in-vitro CYP2A6 activity relative to the four established functional CYP2A6 variants that are frequently tested in Whites (CYP2A6*2, *4, *9, and *12). Two pairs of novel SNPs were in high linkage disequilibrium, allowing us to establish five-SNP diplotypes that were associated with CYP2A6 enzyme activity (rate of nicotine metabolism) in-vitro in the liver bank and in-vivo among smokers. The novel five-SNP diplotype may be useful to incorporate into CYP2A6 genotype models for personalized prediction of nicotine metabolism rate, cessation success, and response to pharmacotherapies.

Slower nicotine metabolism among postmenopausal Polish smokers.

A non-invasive phenotypic indicator of the rate of nicotine metabolism is nicotine metabolite ratio (NMR) defined as a ratio of two major metabolites of nicotine - trans-3'-hydroxycotinine/cotinine. The rate of nicotine metabolism has important clinical implications for the likelihood of successful quitting with nicotine replacement therapy (NRT). We conducted a study to measure NMR among Polish smokers. In a cross-sectional study of 180 daily cigarette smokers (42% men; average age 34.6±13.0), we collected spot urine samples and measured trans-3'-hydroxycotinine (3-HC) and cotinine levels with LC-MS/MS method. We calculated NMR (molar ratio) and analyzed variations in NMR among groups of smokers. In the whole study group, an average NMR was 4.8 (IQR 3.4-7.3). The group of women below 51 years had significantly greater NMR compared to the rest of the population (6.4; IQR 4.1-8.8 vs. 4.3; IQR 2.8-6.4). No differences were found among group ages of male smokers. This is a first study to describe variations in nicotine metabolism among Polish smokers. Our findings indicate that young women metabolize nicotine faster than the rest of population. This finding is consistent with the known effects of estrogen to induce CYP2A6 activity. Young women may require higher doses of NRT or non-nicotine medications for most effective smoking cessation treatment.

Measures and predictors of varenicline adherence in the treatment of nicotine dependence

IntroductionWhile adherence to medication in smoking cessation clinical trials is strongly associated with clinical outcome, very few studies have evaluated the validity of pill count as a measure of adherence relative to a biological assay, and evaluated a broad range of correlates of adherence. MethodsIn a smoking cessation clinical trial of varenicline, we compared pill counts collected over 4 different time periods to varenicline salivary levels taken after 2weeks of treatment, as well as evaluated predictors of adherence to varenicline. ResultsUsing a binary measure of adherence based on salivary varenicline levels, adherence was higher among older, white, and more educated participants. Relative to 3, 7, and 14-day pill count, 12-week pill count was the only significant measure able to discriminate adherence as defined by salivary varenicline levels (assessed by area under the receiver operating characteristic curve; AUC=0.59, p=0.004). Seventy-two percent of participants who indicated adherence on 12-week pill count were classified as adherent based on varenicline saliva levels (sensitivity=0.80; specificity=0.40). There was modest variability in the relationship between 12-week pill count and varenicline levels across race and rate of nicotine metabolism. Lastly, General Estimating Equation models demonstrated that longitudinal changes in withdrawal, craving, negative and positive affect, and side effect count and severity were not related to adherence based on salivary varenicline levels. ConclusionsThese results indicate that 12-week pill count was the best, albeit a relatively weak, measure of varenicline adherence; additional factors associated with treatment adherence need to be identified.

Does coffee consumption impact on heaviness of smoking?

Background and AimsCoffee consumption and cigarette smoking are strongly associated, but whether this association is causal remains unclear. We sought to: (1) determine whether coffee consumption influences cigarette smoking causally, (2) estimate the magnitude of any association and (3) explore potential mechanisms.DesignWe used Mendelian randomization (MR) analyses of observational data, using publicly available summarized data from the Tobacco and Genetics (TAG) consortium, individual‐level data from the UK Biobank and in‐vitro experiments of candidate compounds.SettingThe TAG consortium includes data from studies in several countries. The UK Biobank includes data from men and women recruited across England, Wales and Scotland.ParticipantsThe TAG consortium provided data on n ≤ 38 181 participants. The UK Biobank provided data on 8072 participants.MeasurementsIn MR analyses, the exposure was coffee consumption (cups/day) and the outcome was heaviness of smoking (cigarettes/day). In our in‐vitro experiments we assessed the effect of caffeic acid, quercetin and p‐coumaric acid on the rate of nicotine metabolism in human liver microsomes and cDNA‐expressed human CYP2A6.FindingsTwo‐sample MR analyses of TAG consortium data indicated that heavier coffee consumption might lead to reduced heaviness of smoking [beta = −1.49, 95% confidence interval (CI) = −2.88 to −0.09]. However, in‐vitro experiments found that the compounds investigated are unlikely to inhibit significantly the rate of nicotine metabolism following coffee consumption. Further MR analyses in UK Biobank found no evidence of a causal relationship between coffee consumption and heaviness of smoking (beta = 0.20, 95% CI = –1.72 to 2.12).ConclusionsAmount of coffee consumption is unlikely to have a major causal impact upon amount of cigarette smoking. If it does influence smoking, this is not likely to operate via effects of caffeic acid, quercetin or p‐coumaric acid on nicotine metabolism. The observational association between coffee consumption and cigarette smoking may be due to smoking impacting on coffee consumption or confounding.

Nicotine biomarkers and rate of nicotine metabolism among cigarette smokers taking buprenorphine for opioid dependency

BackgroundIndividual differences in the rate of nicotine metabolism contribute to differences in tobacco use, dependence, and efficacy of smoking cessation treatments and can be assessed using the nicotine metabolite ratio (NMR), a validated biomarker for CYP2A6 activity. Despite the high cigarette smoking rates observed in opioid users, no data have been reported on NMR among this population as they has been largely excluded from previous studies that have examined the relationship between tobacco use characteristics and rate of nicotine metabolism. MethodsA linear regression model was used to examine the relationship between tobacco use characteristics and NMR among smokers taking buprenorphine for opioid dependency (N=141). The relationship between buprenorphine dose and NMR was also examined. All participants were enrolled in an intervention designed to promote cigarette-smoking cessation, though participants did not need to stop smoking to enroll. Results and conclusionsRate of nicotine metabolism assessed using the NMR was positively associated with cigarettes smoked in the past 24h, but was not related to time to first cigarette or past year quit attempts. Dose of buprenorphine was not associated with NMR, suggesting no association with rate of nicotine metabolism. Our results suggest that NMR is related to tobacco use among persons enrolled in opioid treatment, as reported in general population smokers and may be a useful biomarker to include in future research assessing efficacy of tobacco cessation interventions in this population.

Nicotine Metabolite Ratio (NMR) Prospectively Predicts Smoking Relapse: Longitudinal Findings From ITC Surveys in Five Countries.

The ratio of trans 3'-hydroxycotinine (3HC) to cotinine (nicotine metabolite ratio [NMR]) is a biomarker of the rate of nicotine metabolism, with higher NMR indicating faster metabolism. Higher NMR has been found to be associated with higher daily cigarette consumption and less success stopping smoking in cessation trials. This study examines differences in NMR among population-based samples of smokers in the five countries and explores the relationship between NMR and smoking abstinence. Participants (N = 874) provided saliva samples during International Tobacco Control (ITC) surveys in the United States, United Kingdom, Mauritius, Mexico, and Thailand conducted in 2010/2011 with follow-up surveys in 2012/2013. When all samples were received, they were sent to a common laboratory for analysis using liquid chromatography and tandem mass spectroscopy. There was significant variation in NMR across countries (F = 15.49, p < .001). Those who reported smoking at follow-up had a mean NMR of 0.32, compared to a mean NMR of 0.42 in participants who reported that they had stopped (F = 8.93; p = .003). Higher mean NMR values were also associated with longer quit duration (p = .007). There was no substantial difference in NMR between current smokers who made a failed quit attempt and those who made no attempt-both had significantly lower NMR compared to those who quit and remained abstinent. Smokers with a higher NMR were more likely to report that they stopped smoking compared to those with a lower NMR (odds ratio = 2.67; 95% confidence interval: 1.25 to 5.68). These results suggest faster nicotine metabolizers may be less likely to relapse following a quit attempt. This finding differs from results of clinical trials testing stop smoking medications, where slower metabolizers have been found to be more likely to maintain abstinence from smoking. Results of this study suggest faster nicotine metabolizers may be less likely to relapse following a quit attempt. This finding differs from results of clinical trials testing stop smoking medications, where slower metabolizers have been found to be more likely to maintain abstinence from smoking.

CYP2A6 Genetic Variation Alters Striatal-Cingulate Circuits, Network Hubs, and Executive Processing in Smokers

BackgroundVariation in the CYP2A6 gene alters the rate of nicotine metabolic inactivation and is associated with smoking behaviors and cessation success rates. The underlying neurobiological mechanisms of this genetic influence are unknown. MethodsIntrinsic functional connectivity strength, a whole-brain, data-driven, graph theory–based method, was applied to resting-state functional magnetic resonance imaging data in 66 smokers and 92 nonsmokers. A subset of subjects (n = 23/20; smokers/nonsmokers) performed the monetary incentive delay task, probing reward anticipation, and a go/no-go task, probing response inhibition, on two occasions, in the presence and absence of a nicotine patch. ResultsA significant CYP2A6 genotype × smoking effect was found in the dorsal anterior cingulate cortex and ventral striatum, such that the normal (vs. slow) genotype individuals showed greater functional connectivity strength among smokers but not nonsmokers. Functional connectivity strength was negatively associated with severity of nicotine dependence in slow metabolizers. Both hubs were biased by inputs from the insula identified from seed-based connectivity. Similar gene × environment interactions were seen in ventral striatum during smoking abstinence when subjects performed the monetary incentive delay task and in dorsal anterior cingulate cortex when they performed the go/no-go task; both reductions were “normalized” in smokers (and increased in nonsmokers) after acute nicotine administration. ConclusionsBecause the CYP2A6 effect was seen only in smokers, these data suggest that the rate of nicotine metabolism—and thus the concentration of nicotine presented to the brain over the course of nicotine addiction—shapes brain circuits that, among other functions, compute reward and impulsivity processes.

Study the influence of licorice and pomegranate drinks on nicotine metabolism in human urine by LC-orbitrap MS

Nicotine-diet interactions have a particular importance on human health. Some food substances are subject to change hepatic CYP2A6 metabolism rate for nicotine and its levels in smokers consequently. This study investigates the effect of pomegranate and licorice drinks on nicotine metabolism, by a new developed and validated method for simultaneous determination of nicotine with its major metabolites (cotinine and nicotine N-oxide) in human urine, utilizing LC ESI-orbitrap-MS. Twenty-four Jordanian healthy and smoker volunteers were participated in two equal groups, crossover design for each of pomegranate and licorice test drink. In the study periods each group assigned either to drink test juice three times a day or to be avoided from test drink for 7 successive days, and then both groups switched their drink treatment in subsequent period. Early morning urine samples were collected from all volunteers after each period. Nicotine metabolism rate was evaluated from nicotine/cotinine and nicotine/nicotine N-oxide ratios in urine. A consistent trend of increase in metabolism rate for nicotine was observed from urine analysis under pomegranate or licorice drink conditions compared to control conditions. Pomegranate and licorice drinks are increasing the metabolism rate for nicotine in terms of induction effect for hepatic cytochrome p450 enzymes.

Disposition kinetics and metabolism of nicotine and cotinine in African American smokers: impact of CYP2A6 genetic variation and enzymatic activity.

The rate of nicotine metabolism, determined primarily by CYP2A6 activity, influences tobacco dependence and smoking-induced disease risk. The prevalence of CYP2A6 gene variants differs by race, with greater numbers in African Americans compared with Caucasians. We studied nicotine disposition kinetics and metabolism by the CYP2A6 genotype and enzymatic activity, as measured by the nicotine metabolite ratio (NMR), in African American smokers. Participants were administered intravenous infusions of deuterium-labeled nicotine and cotinine. Plasma and urine concentrations of nicotine and metabolites were measured and pharmacokinetic parameters were estimated. Pharmacokinetic parameters and urine metabolite excretion data were analyzed by CYP2A6 genotype and by NMR. A number of gene variants were associated with markedly reduced nicotine and cotinine clearances. NMR was strongly correlated with nicotine (r=0.72) and cotinine (r=0.80) clearances. Participants with higher NMR excreted significantly greater nicotine C-oxidation and lower non-C-oxidation products compared with lower NMR participants. CYP2A6 genotype, NMR, and nicotine pharmacokinetic data may inform studies of individual differences in smoking behavior and biomarkers of nicotine exposure.

Longitudinal changes in smoking abstinence symptoms and alternative reinforcers predict long-term smoking cessation outcomes

BackgroundTransdermal nicotine, with behavioral counseling, is among the most popular approaches used to quit smoking. Yet, 6-month cessation rates rarely exceed 20–25%. Identifying factors associated with cessation success may help researchers and clinicians develop enhanced interventions that can improve quit rates. This study examined longitudinal changes in withdrawal, craving, depression and anxiety symptoms, and alternative reinforcers, from a baseline assessment to a 6-month outcome, as predictors of 6-month smoking cessation outcomes following 8 weeks of nicotine patch treatment and counseling. MethodsA sample of 180 smokers, who completed an effectiveness trial that provided counseling and 8 weeks of 21mg nicotine patches, was analyzed. Generalized estimating equations evaluated changes in withdrawal and craving, depression and anxiety symptoms, and alternative reinforcers over time, between participants who were smoking at 6-months and participants who were abstinent (confirmed with carbon monoxide) at 6-months. Multiple logistic regression assessed changes in these variables as predictors of relapse. ResultsControlling for covariates associated with cessation (i.e., nicotine dependence, patch adherence, and rate of nicotine metabolism), participants who were abstinent at 6 months showed significantly lower craving and withdrawal and significantly higher substitute reinforcers from baseline to 6 months, vs. those who were smoking at 6 months (p<0.001). An increase in craving predicted relapse to smoking (p<0.05). ConclusionsThese results support continued efforts to strengthen interventions that reduce withdrawal and craving and the development of interventions to address alternative reinforcers in order to promote long-term smoking abstinence following nicotine patch treatment.

The Nicotine Metabolite Ratio is Associated With Early Smoking Abstinence Even After Controlling for Factors That Influence the Nicotine Metabolite Ratio

The decrease in smoking rates in North America has plateaued, underscoring the need for new approaches to treat nicotine dependence. Inter-individual differences in smoking behavior result, in part, from variation in the rate of CYP2A6-mediated nicotine metabolism. A phenotypic measure of CYP2A6 activity is the nicotine metabolite ratio (NMR), the ratio of 3'hydroxycotinine/cotinine. The NMR is associated with smoking cessation. However, the NMR is also associated with genetic (eg, CYP2A6 genotype) and other (eg, sex and ethnicity) factors. Here we aimed to determine if previously identified non-CYP2A6 sources of variation in the NMR mitigated the association between the NMR and short-term abstinence. The NMR was determined from blood samples collected at intake from daily smokers aged 18-65. Biochemically-verified point prevalence abstinence (exhaled carbon monoxide level ≤ 8 ppm) was measured at 1 week following the target quit date in participants from a smoking cessation clinical trial (NCT01314001). Analyses were restricted to N = 462 blacks and N = 693 whites in the intent-to-treat sample. Lower NMR (<0.31) was associated with a higher likelihood of 1-week abstinence (OR = 1.43; 95% CI = 1.12, 1.84). NMR was associated with abstinence even after controlling for treatment arm (nicotine patch or varenicline) and factors previously associated with NMR variation including sex, ethnicity, estrogen-containing hormonal therapy, body mass index, alcohol, and cigarette consumption. NMR was associated with 1-week smoking abstinence; NMR may be a useful addition to medication screening approaches evaluating treatments for nicotine dependence.

The Influence of Puff Characteristics, Nicotine Dependence, and Rate of Nicotine Metabolism on Daily Nicotine Exposure in African American Smokers.

African American (AA) smokers experience greater tobacco-related disease burden than Whites, despite smoking fewer cigarettes per day (CPD). Understanding factors that influence daily nicotine intake in AA smokers is an important step toward decreasing tobacco-related health disparities. One factor of interest is smoking topography, or the study of puffing behavior. (i) to create a model using puff characteristics, nicotine dependence, and nicotine metabolism to predict daily nicotine exposure, and (ii) to compare puff characteristics and nicotine intake from two cigarettes smoked at different times to ensure the reliability of the puff characteristics included in our model. Sixty AA smokers smoked their preferred brand of cigarette at two time points through a topography device. Plasma nicotine, expired CO, and changes in subjective measures were measured before and after each cigarette. Total nicotine equivalents (TNE) was measured from 24-hour urine collected during ad libitum smoking. In a model predicting daily nicotine exposure, total puff volume, CPD, sex, and menthol status were significant predictors (R(2) = 0.44, P < 0.001). Total puff volume was significantly greater and inter-puff intervals were significantly shorter after ad lib smoking compared with the first cigarette of the day, but puffing behaviors for both cigarettes were highly correlated (r range = 0.69-0.89, P < 0.001) within-subjects. This is the first study, to our knowledge, to show that puff characteristics of individual cigarettes are predictive of daily nicotine intake. These findings enhance our understanding of the relationship between smoking behavior and nicotine intake in AA smokers. Cancer Epidemiol Biomarkers Prev; 25(6); 936-43. ©2016 AACR.

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296).