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BackgroundAdherence to nicotine patches relates to cessation. This is the first study to examine the validity of self-reported nicotine patch adherence relative to saliva cotinine.MethodsWe used data from 198 clinical trial participants who received 11 weeks of nicotine patches, self-reported patch use, had saliva cotinine 1-week after the start of treatment assessed, and were not smoking when saliva was collected (CO < 6). Self-reported patch adherence was defined as: 3-day (before saliva collection), 7-day (before saliva collection), 3-week use (7 days before, and 14 days after, saliva collection), and 11-week use (7 days before, and 10 weeks after, saliva collection). Analyses, including receiver operating characteristic curves, considered differences in nicotine metabolism. Sensitivity, specificity and positive (PPV) and negative predictive value (NPV) assessed optimal cotinine cut-point for adherence.ResultsSelf-reported 7-day (r = 0.13) and 3-week (r = 0.13) patch use marginally correlated with week 1 cotinine (p's = 0.08) but not 3-day or 11-week. Significant area under the curve (AUC) values of 0.67 (95 %CI: 0.55-0.79) and 0.72 (95 %CI: 0.57-0.88) were found using 7-day self-report for the overall sample and for slow metabolizers (p's

Smokers attempting to quit often attribute smoking relapse to negative affect, craving, and other nicotine withdrawal symptoms. In addition, there is evidence that smoking relapse can increase these symptoms, particularly negative affect. To address this issue, we analyzed data from an 11-week smoking cessation clinical trial in which smokers (n = 1,246) were randomized to receive either nicotine replacement therapy (NRT), varenicline, or placebo, combined with behavioral counseling. Using cross-lagged analyses, we examined the temporal bidirectional relationships between self-reported measures of affect, craving, and composite withdrawal symptoms and biochemically verified smoking abstinence. The relative strength of these temporal relationships was examined by comparing the explained variances of the models. The results showed that higher negative affect, craving, and composite withdrawal symptoms increased the likelihood of subsequent smoking relapse, and that smoking relapse led to subsequent increases in these same symptoms. A comparison of the explained variances found symptom predicting subsequent relapse models to be stronger than those where relapse predicted subsequent symptoms. Although the explained variance findings generally support a negative reinforcement conceptualization of nicotine dependence, the bidirectional relationship between symptoms and smoking relapse suggests that struggling with quitting smoking leads to significant negative affect, craving, and other withdrawal symptoms that do not quickly resolve. These findings highlight the importance of addressing specific symptoms within the context of smoking cessation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background and aimsThe activity of CYP2A6, the major nicotine-inactivating enzyme, is measurable in smokers using the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine). Due to its role in nicotine clearance, the NMR is associated with smoking behaviours and response to pharmacotherapies. The NMR is highly heritable (~80%), and on average lower in African Americans (AA) versus whites. We previously identified several reduce and loss-of-function CYP2A6 variants common in individuals of African descent. Our current aim was to identify novel genetic influences on the NMR in AA smokers using genome-wide approaches.DesignGenome-wide association study (GWAS).SettingMultiple sites within Canada and the United States.ParticipantsAA smokers from two clinical trials: Pharmacogenetics of Nicotine Addiction Treatment (PNAT)-2 (NCT01314001; n = 504) and Kick-it-at-Swope (KIS)-3 (NCT00666978; n = 450).MeasurementsGenome-wide SNP genotyping, the NMR (phenotype) and population substructure and NMR covariates.FindingsMeta-analysis revealed three independent chromosome 19 signals (rs12459249, rs111645190 and rs185430475) associated with the NMR. The top overall hit, rs12459249 (P = 1.47e-39; beta = 0.59 per C (versus T) allele, SE = 0.045), located ~9.5 kb 3' of CYP2A6, remained genome-wide significant after controlling for the common (~10% in AA) non-functional CYP2A6*17 allele. In contrast, rs111645190 and rs185430475 were not genome-wide significant when controlling for CYP2A6*17. In total, 96 signals associated with the NMR were identified; many were not found in prior NMR GWASs in individuals of European descent. The top hits were also associated with the NMR in a third cohort of AA (KIS2; n = 480). None of the hits were in UGT or OCT2 genes.ConclusionsThree independent chromosome 19 signals account for ~20% of the variability in the nicotine metabolite ratio in African American smokers. The hits identified may contribute to inter-ethnic variability in nicotine metabolism, smoking behaviours and tobacco-related disease risk.

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.

ObjectivesLittle is known about the degree of nicotine replacement across first-generation e-cigarette brands, how e-cigarettes are used, and if there is variation across brands in relevant smoking phenotypes. The objective of this project was to collect data that are critical to better understanding, use, and exposure when using e-cigarettes, which may then inform clinical trials and tobacco regulatory policy.MethodsTwenty-eight cigarette smokers were randomized to use one of 5 popular brands of e-cigarettes for a 10-day study. Day 1 (own cigarette brand) data established baseline levels for cotinine, carbon monoxide (CO), topography, cigarette liking, withdrawal, and craving. Participants returned on Days 5 and 10 to reassess these measures while exclusively using e-cigarettes.ResultsCompared to cigarette smoking, e-cigarettes provided significantly lower nicotine levels (25%-50%), reduced CO exposure, and lower ratings of liking (p < .05). Topography significantly differed between cigarette and e-cigarette sessions (p < .05). All brands significantly reduced withdrawal and craving (p < .05). There were no significant brand differences in outcome measures associated with exposure or use.ConclusionsE-cigarettes are not liked as much as cigarettes, provide significantly lower nicotine replacement, reduce CO exposure, and mitigate withdrawal and craving. The patterns of use significantly differ compared to cigarette smoking.

Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism was a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step-down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers.

UnlabelledThe nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (α4β2* subtype) availability using PET imaging of the radiotracer 2-(18)F-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-(18)F-FA-85380, or 2-(18)F-FA).MethodsTwenty-four smokers-12 slow metabolizers (NMR < 0.26) and 12 normal metabolizers (NMR ≥ 0.26)-underwent 2-(18)F-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans.ResultsThalamic nAChR α4β2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability.ConclusionThe rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine.

BackgroundSubstantial variability exists in therapeutic response and adverse effects with pharmacotherapies for tobacco dependence. Biomarkers to optimise treatment choice for individual smokers might improve treatment outcomes. We tested whether a genetically informed biomarker of nicotine clearance, the nicotine metabolite ratio (NMR; 3'-hydroxycotinine:cotinine), predicts response to nicotine patch or varenicline for smoking cessation.MethodsWe undertook NMR-stratified multicentre, randomised, placebo-controlled clinical trial from Nov 16, 2010, to Sept 12, 2014, at four sites. Smokers seeking treatment were randomly assigned by baseline NMR status and study site, in blocks of 12 patients (1:1:1 ratio), to 11 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioural counselling. Participants and investigators were masked to group allocation and NMR status. An intention-to-treat analysis was done. Participants were followed up for 12 months after the target quit date. The primary endpoint was biochemically verified 7 day point prevalence abstinence at the end of treatment to estimate the pharmacological effect of treatment by NMR. The trial is registered at ClinicalTrials.gov, number NCT01314001.Findings1246 participants (662 slow metabolisers of nicotine, 584 normal metabolisers of nicotine) were enrolled and randomly assigned to the three interventions (408 placebo, 418 nicotine patch, 420 varenicline). At end of treatment, varenicline was more efficacious than nicotine patch in normal metabolisers (OR 2·17, 95% CI 1·38-3·42; p=0·001), but not in slow metabolisers (OR 1·13, 0·74-1·71; p=0·56). In the longitudinal model including all timepoints, the NMR-by-treatment interaction was significant (ratio of odds ratios [ORR] 1·96, 95% CI 1·11-3·46; p=0·02). An NMR-by-treatment interaction showed that slow (vs normal) metabolisers reported greater overall side-effect severity with varenicline versus placebo (β=-1·06, 95% CI -2·08 to -0·03; p=0·044).InterpretationTreating normal metabolisers with varenicline and slow metabolisers with nicotine patch could optimise quit rates while minimising side-effects.FundingNational Institutes of Health, Canadian Institutes of Health Research, Abramson Cancer Center, Centre for Addiction and Mental Health Foundation, and Pennsylvania Department of Health.

Introduction: Smoking among adults with major depressive disorder (MDD) is at least double that of the general US population. More effective smoking cessation interventions for depressed smokers may be facilitated through a better understanding of the smoking and depression-related characteristics of this population.Methods: We used baseline data from 300 participants enrolled in randomized clinical trial for smokers with current or past MDD. We described history of smoking cessation behaviors (ie, quit attempts, quit motivation, and cessation treatment utilization) and used multivariate regression to identify demographic and depression-related correlates of these behaviors.Results: Sixty-eight percent of participants reported at least one quit attempt in the past year, nearly 51% reported motivation to quit in the subsequent 30 days, and 83% reported prior use of a nicotine replacement therapy. A greater readiness to quit smoking was associated with increased age (p = .04) and lower cigarettes per day (p = .01). Greater use of smoking cessation medication was associated with greater education and nicotine dependence, minority race, and greater use of complementary reinforcers (eg, activities associated with increased reinforcing value of smoking; p's < .05).Conclusions: These data indicate that smokers with current or past MDD are highly motivated to quit smoking and have a history of engaging in efforts to quit. Interventions to promote smoking cessation behaviors should address younger and lighter smokers, who may perceive less risk from tobacco use, and efforts to promote smoking cessation medications and counseling should address minority smokers who are engaging in complementary reinforcers.Implications: These data are inconsistent with the assumption that smokers with serious mental illness are not willing to quit smoking and suggest the need for studies that test behavioral interventions that address complementary reinforcers to treat tobacco use in this community. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with psychiatric conditions smoke at higher rates than the general population and may need more intensive treatment to quit. We examined whether or not extended treatment with nicotine patch, combined with behavior counseling, would disproportionally benefit smokers with versus without a lifetime psychiatric condition.Methods: We conducted a secondary analysis of data from an effectiveness trial of treatment with 12 counseling sessions (48 weeks) and 21-mg nicotine patch (8, 24, or 52 weeks) among 525 adult daily smokers. A structured clinical interview assessed past and current psychiatric disorders (major depression, generalized anxiety disorder, alcohol abuse and/or dependence, and substance abuse and/or dependence), as described in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Abstinence was bioverified at week 52. Logistic regression evaluated the effect of the psychiatric status × treatment duration interaction on abstinence at week 52, covarying for sociodemographics, baseline psychological symptoms, and treatment adherence.Results: At baseline, 115 (21.9%) participants were diagnosed with one or more psychiatric conditions. The psychiatric status × treatment duration interaction was significant for week 52 abstinence (p = .027). Abstinence rates between smokers with versus without a psychiatric condition in the 24-week treatment arm (9.3% vs. 31.5% abstinent) significantly differed from the 8-week treatment arm (18.8% vs. 22.3%), p = .017. Abstinence rates for smokers with (22.5%) versus without a psychiatric condition (19.7%) in the 52-week treatment arm did not differ from those in the 8-week arm.Conclusions: Targeted smoking cessation treatment, rather than extending treatment duration, may be especially warranted to optimize treatment for smokers with comorbid mood, anxiety, and substance use disorders.Implications: Individuals with psychiatric conditions smoke at higher rates and have greater difficulty quitting compared to those in the general population, but little is known about how to best optimize treatment for this high tobacco burden population. The present study found that cessation response to extended duration treatment with the transdermal nicotine patch did not differ for smokers with versus without comorbid anxiety, mood, and substance use disorders in a large-scale clinical effectiveness trial. Development of targeted behavioral treatments may be required to optimize abstinence outcomes for this high-risk population, rather than simply extending the duration of pharmacotherapy treatments. [ABSTRACT FROM AUTHOR]

Introduction: Adherence 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.Methods: At 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.Results: Adherent 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).Conclusion: Adherence 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. [ABSTRACT FROM AUTHOR]

Background: Continuing to smoke after a cancer diagnosis can adversely influence the prognosis for patients with cancer. However, remarkably few studies have carefully examined the use of first-line FDA-approved medications for nicotine dependence in patients with cancer. This study evaluated the feasibility, safety, and effect on cessation of varenicline for smoking cessation in patients with cancer.Methods: Data from 132 treatment-seeking smokers who received 12 weeks of open-label varenicline and five brief behavioral counseling sessions were used to evaluate the feasibility, safety, and impact on cessation of varenicline. The effects of abstinence on cognitive function and affect were also explored.Results: Of 459 patients screened, 306 were eligible for the study (66.7%) and 132 entered treatment (43.1%). Retention was 84.1% over 12 weeks. The rate of biochemically verified abstinence at week 12 was 40.2%. Expected side effects were reported (e.g. sleep problems, nausea), but there were no reports of elevated depressed mood, suicidal thoughts, or cardiovascular events. Abstinence was associated with improved cognitive function and reduced negative affect over time (p < 0.05).Conclusions: Although many patients with cancer who smoke did not enroll in treatment, the side effect profile of varenicline and its effect on short-term cessation converge with what is seen in the general population. Further, as with the general population, abstinence while taking varenicline may lead to improved cognitive function and reduced negative affect. The present data support the use of varenicline to help patients with cancer to quit smoking. [ABSTRACT FROM AUTHOR]

Introduction: Anhedonia has been recognized as a major risk factor for smoking persistence. Potential gender differences in the effect of anhedonia on smoking cessation have not been studied. Using data from a completed clinical trial of maintenance nicotine patch therapy, we hypothesized that gender would moderate the effect of anhedonia on short-term abstinence, such that anhedonic women would be less likely to achieve abstinence.Methods: Participants (N = 525; 50% female, 48.2% Black/African American, average age: 46 years) received 21mg/day nicotine patch and four brief behavior counseling sessions over 8 weeks. Participants were classified at baseline using the Snaith-Hamilton Pleasure Scale as anhedonic (scores > 2) or hedonic (scores ≤ 2). Bioverified 7-day point prevalence abstinence was measured at week 8. Using logistic regression analysis, we tested the interaction of anhedonia by gender predicting abstinence, adjusting for age, race, nicotine dependence, and baseline depressive symptomatology.Results: Seventy participants (13%) were classified as anhedonic. Men were more likely to be anhedonic than women (16.6% vs. 10.2%, p = .03). Contrary to our hypothesis, the interaction of anhedonic status (hedonic vs. anhedonic) by gender was nonsignificant (p = .18). There was a main effect of hedonic capacity, such that anhedonia predicted abstinence, odds ratio = 3.24, 95% confidence interval = 1.39-7.51, p = .006.Conclusion: Both male and female anhedonic smokers were more likely to be abstinent, which contrasts with prior research indicating that anhedonia is a risk factor for difficulty quitting. This unexpected finding may be explained by a possible selective benefit of nicotine patch therapy, which has been observed in some studies to have antidepressant effects.Implications: This is the first study to examine whether the association between pretreatment anhedonia and smoking cessation differs by gender. For both women and men, anhedonia was associated with a greater likelihood of abstinence after 8 weeks of treatment with 21mg/day nicotine patch and behavior counseling. Our findings indicate that the association between anhedonia and smoking cessation is not as clear as has been assumed and may depend in part on the type of treatment delivered. [ABSTRACT FROM AUTHOR]

Accumulating data support the role of genetic factors in smoking initiation, progression to tobacco dependence, and smoking persistence. This review summarizes current research on the heritability of tobacco use phenotypes and genetic association studies of smoking-related behaviors. Although progress has been made in genetics research on smoking behavior, many studies have methodological limitations, including insufficient samples for detecting gene-gene and gene-environment interactions and use of less refined phenotypes. Pharmacogenetic investigations also are identifying variants in drug-metabolizing enzymes, receptors, and transporters that modify therapeutic response to smoking cessation medications; however, the field is relatively new, and most findings in this area have yet to be replicated. As this research advances, it will be important to study and address practical, economic, ethical, and social barriers to the translation of genetics research on tobacco use to clinical practice. [ABSTRACT FROM AUTHOR]

Background and Objective: 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.Methods: 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.Results: 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.Conclusions and Scientific Significance: 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). [ABSTRACT FROM AUTHOR]

Introduction: 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.Methods: 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.Results: 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.Conclusions: NMR was associated with 1-week smoking abstinence; NMR may be a useful addition to medication screening approaches evaluating treatments for nicotine dependence. [ABSTRACT FROM AUTHOR]

This study examined changes in tobacco craving, withdrawal, and affect as correlates of efficacy in a phase-2 clinical trial of varenicline for smokeless tobacco dependence in India. Smokeless tobacco users (N = 237) at the All India Institute of Medical Sciences were randomized to placebo or varenicline. Abstinence was defined as cotinine-verified seven-day point prevalence cessation at end of treatment (EOT). General Linear Model repeated measures assessed the effects of treatment condition, time, abstinence state, and interaction effects on changes in craving, withdrawal, positive (PA) and negative affect (NA) from baseline to EOT. All participants showed a significant reduction in withdrawal (p < .001), total craving (p < .001), positive reinforcement (PR) craving (p < .001), and NA (p = .02), and an increase in PA (p = .04) from baseline to EOT. However, there were no differences between placebo and varenicline participants in measures of withdrawal, craving, or affect from baseline to week 3 or at EOT. Significant interactions between time and abstinence state were found for total craving (p = .008), PR craving (p < .001), and withdrawal (p = .001), indicating reductions in these processes among those abstinent vs. those still chewing smokeless tobacco. Additional research is needed concerning the effects of varenicline on craving, withdrawal, and affect among smokeless tobacco users. [ABSTRACT FROM PUBLISHER]

Despite great advances in the understanding and treatment of nicotine dependence, close to 21% of adults in the United States continue to smoke. Tobacco use is the single greatest cause of premature and preventable death in the United States. This article reviews the epidemiology, assessment, neurobiology, genetic etiology, and treatment of nicotine dependence. Enhanced understanding of these dimensions of nicotine dependence may help to advance progress toward lowering the prevalence rate of tobacco use in the U.S. and lowering the rate of tobacco-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Abstract: Background: Nicotine deprivation symptoms, including fatigue and attentional deficits, predict relapse following smoking cessation. Modafinil (Provigil), a wakefulness medication shown to have efficacy for the treatment of cocaine addiction, was tested as a novel therapy for nicotine dependence in a double-blind placebo-controlled trial. Methods: One hundred and fifty-seven treatment-seeking smokers received brief smoking cessation counseling and were randomized to: (1) 8 weeks of modafinil (200mg/day), or (2) 8 weeks of placebo. The primary outcome was biochemically verified 7-day point prevalence abstinence at the end of treatment (EOT). Secondary outcomes included cigarette smoking rate and post-quit nicotine deprivation symptoms (e.g., negative affect, withdrawal). Results: In this interim study analysis, EOT quit rates did not differ between treatment arms (42% for placebo vs. 34% for modafinil; OR=0.67 [0.34–1.31], p =0.24). Further, from the target quit date to EOT, the daily smoking rate was 44% higher among non-abstainers in the modafinil arm, compared to non-abstainers in the placebo arm (IRR=1.44, CI95 =1.09–1.89, p <0.01). Modafinil-treated participants also reported greater increases in negative affect and withdrawal symptoms, vs. participants randomized to placebo (ps<0.05). Conclusions: These data do not support the use of modafinil for the treatment of nicotine dependence and, as a consequence, this trial was discontinued. Cigarette smoking should be considered when modafinil is prescribed, particularly among those with psychiatric conditions that have high comorbidity with nicotine dependence. [Copyright &y& Elsevier]

Nicotine replacement therapies (NRTs), including transdermal patch, gum, lozenge, nasal spray and inhaler, are widely used for the treatment of tobacco dependence; however, only one-quarter to one-third of smokers who utilise NRTs to quit smoking are able to maintain long-term abstinence from tobacco use. Pharmacogenetic studies of NRT may be useful to identify subgroups of smokers who respond more favourably to specific NRTs, and to determine the optimal dose and duration of NRT.To date, pharmacogenetic studies have examined genes coding for nicotine metabolising enzymes, as well as proteins in neurotransmitter pathways that mediate the effects of nicotine. Initial findings suggest that polymorphisms in nicotine metabolising enzymes, and selected genes in the dopaminergic and opioidergic pathways, may have predictive validity for NRT response; however, independent replication is necessary before translation to clinical practice. Larger-scale investigations that incorporate pathway-based or genome-wide analysis, as well as intermediate measures of nicotine dependence (i.e. ‘endophenotypes’), may be necessary to capture the complexity of pharmacogenetic effects. [ABSTRACT FROM AUTHOR]

A recently developed network perspective on tobacco withdrawal posits that withdrawal symptoms causally influence one another across time, rather than simply being indicators of a latent syndrome. Evidence supporting a network perspective would shift the focus of tobacco withdrawal research and intervention toward studying and treating individual withdrawal symptoms and intersymptom associations. Here we construct and examine temporal tobacco withdrawal networks that describe the interplay among withdrawal symptoms across time using experience-sampling data from 1,210 participants (58.35% female, 86.24% White) undergoing smoking cessation treatment. We also construct person-specific withdrawal networks and capture individual differences in the extent to which withdrawal symptom networks promote the spread of symptom activity through the network across time using impulse response analysis. Results indicate substantial moment-to-moment associations among withdrawal symptoms, substantial between-person differences in withdrawal network structure, and reductions in the interplay among withdrawal symptoms during combination smoking cessation treatment. Overall, findings suggest the utility of a network perspective and also highlight challenges associated with the network approach stemming from vast between-person differences in symptom networks. (PsycInfo Database Record (c) 2021 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

Introduction: While 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.Methods: In 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.Results: Using 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.Conclusions: These 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. [ABSTRACT FROM AUTHOR]

Introduction: We previously reported poor associations between salivary varenicline and pill counts, and a substantial overestimation of adherence by pill counts in "Measures and predictors of varenicline adherence in the treatment of nicotine dependence" (Peng et al., 2017). We have since conducted supplementary analyses characterizing, and then excluding, individuals with established inaccurate pill count recall.Methods: Based on published varenicline pharmacokinetics (including drug levels, and the long half-life) and our detection limits, conservatively we should be able to detect varenicline in anyone who took at least one pill during the 48h prior to saliva collection; thus, those reporting 1 or more pills in this time frame but who had undetectable salivary varenicline were deemed to have inaccurate pill count recall. Correlations between pill counts and salivary varenicline, and Receiver Operating Characteristics curve analyses were conducted following exclusion of participants with inaccurate pill count recall.Results: Nearly 20% of our participants (N=67/376) had inaccurate self-reported pill counts. These participants were younger, non-white, lower income, and unmarried (evaluated using chi-square or Mann-Whitney U test). Following exclusion of these individuals, the correlations between salivary varenicline and pill count improved and the area under the curve (AUC) of pill counts for discriminating adherence improved modestly.Conclusion: When the 20% of individuals with inaccurate pill count recall were excluded, an improved association between self-reported pill count and salivary varenicline was observed, albeit still weak. A substantial overestimation of adherence by pill counts relative to salivary varenicline is still observed even after exclusion of almost 20% of the group having established inaccurate reporting suggesting that these individuals, with identifiable inaccuracies, were only part of the overestimation of adherence. [ABSTRACT FROM AUTHOR]

Abstract: Background: While more than 50% of smokers make a serious quit attempt each year, less than 10% quit permanently. Evidence from studies of adolescent smoking and other substances of abuse suggest that alternative reinforcers, a construct of Behavioral Economic Theory, may contribute to the likelihood of smoking cessation in adults. This study examined the behavioral economics of smoking cessation within a smoking cessation clinical trial and evaluated how depressive symptoms and behavioral economic variables are associated with smoking cessation. Methods: A sample of 469 smokers, enrolled in an effectiveness trial that provided counseling and 8 weeks of 21mg nicotine patches, was analyzed. Alternative reinforcers (substitute and complementary reinforcers) and depressive symptoms were examined in relation to 7-day point prevalence abstinence, verified with breath carbon monoxide, 8 weeks after the quit date. Results: Controlling for covariates associated with cessation (nicotine dependence, age of smoking initiation, patch adherence), participants who were abstinent at week 8 showed significantly higher substitute reinforcers at all time-points, compared to those who were smoking (p's<.05). Participants who were abstinent at week 8 showed lower complementary reinforcers and depressive symptoms at all time-points, compared to those who were smoking, but significant differences were confined to week 8 (p's<.01). There was no significant interaction between alternative reinforcers and depressive symptoms across the 8 weeks on week 8 abstinence. Conclusions: These results support continued examination of Behavioral Economic Theory in understanding adult smoking cessation in order to inform future treatments and guidelines. [Copyright &y& Elsevier]

Tobacco and alcohol use are leading causes of premature mortality in the US and concurrent use is associated with even greater health risks. A cross-sectional study of 20,310 patients admitted to a Mid-Atlantic acute health care system between July 1, 2018 and June 30, 2019 were categorized according to smoking and alcohol use disorder (AUD) status. Of the total admissions, 1464 (7.2%) were current smokers with an AUD. These patients were younger (52.4 vs. 63.9), more likely to be male (64.1% vs. 38.0%) and covered by Medicaid (46.9% vs. 11.6%), and resided in proximity to higher counts of tobacco (10.3 vs. 4.72) and alcohol (2.24 vs. 1.14) retailers than never smokers without an AUD. Clinically, these patients had higher rates of other substance use disorders (60.4% vs. 6.1%), depression (64.6% vs. 34.8%), HIV/AIDS (3.3% vs. 0.6%), and liver disease (40.7% vs. 13.2%) than never smokers without an AUD. Patients who concurrently smoke and have an AUD face unique and serious health risks. A multimorbidity framework can guide clinical and community-based interventions for individuals with concurrent psychiatric and chronic medical conditions, complex social needs, and adverse environmental exposures. [ABSTRACT FROM AUTHOR]