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Reactivity to smoking-related cues may be an important factor that precipitates relapse in smokers who are trying to quit. The neurobiology of smoking cue reactivity has been investigated in several fMRI studies. We combined the results of these studies using activation likelihood estimation, a meta-analytic technique for fMRI data. Results of the meta-analysis indicated that smoking cues reliably evoke larger fMRI responses than neutral cues in the extended visual system, precuneus, posterior cingulate gyrus, anterior cingulate gyrus, dorsal and medial prefrontal cortex, insula, and dorsal striatum. Subtraction meta-analyses revealed that parts of the extended visual system and dorsal prefrontal cortex are more reliably responsive to smoking cues in deprived smokers than in non-deprived smokers, and that short-duration cues presented in event-related designs produce larger responses in the extended visual system than long-duration cues presented in blocked designs. The areas that were found to be responsive to smoking cues agree with theories of the neurobiology of cue reactivity, with two exceptions. First, there was a reliable cue reactivity effect in the precuneus, which is not typically considered a brain region important to addiction. Second, we found no significant effect in the nucleus accumbens, an area that plays a critical role in addiction, but this effect may have been due to technical difficulties associated with measuring fMRI data in that region. The results of this meta-analysis suggest that the extended visual system should receive more attention in future studies of smoking cue reactivity. ► Meta-analysis of 11 fMRI studies of cigarette cue reactivity. ► Compared cigarette and neutral cues, deprived and non-deprived smokers. ► Larger responses to cigarette cues in posterior parietal cortex and cingulate gyrus. ► Deprived smokers had larger responses in dorsal prefrontal cortex. ► These areas may be important neuroanatomical substrates of tobacco addiction.

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

Despite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of which were protective ( CYP2B6 (rs1175607105), HTR3B (rs1413172952; rs1204720503), rs80210037 on chr15), and 2 of which were associated with reduced cessation ( PARP15 (rs2173763), SCL18A2 (rs363222)). The others mapped to areas associated with cancer including FOXP1 (rs1288980) and ZEB1 (rs7349). Network analysis identified significant canonical pathways for the serotonin receptor signaling pathway, nicotine and bupropion metabolism, and several related to tumor suppression. Two novel markers (rs6749438; rs6718083) on chr2 are flanked by genes associated with regulation of bodyweight. The identification of novel loci in this study can provide new targets of pharmacotherapy and inform efforts to develop personalized treatments based on genetic profiles.

Background: Smoking negatively affects overall survival after successful breast cancer (BC) treatment. We hypothesized that smoking cessation would improve survival outcomes of BC patients who were smokers at the time of diagnosis. Methods: This was a retrospective analysis of self-identified smokers with BC treated at The University of Texas MD Anderson Cancer Center. Patient demographics, date of diagnosis, tumor stage, tobacco treatment program (TP) participation, and time to death were extracted from our departmental databases and institutional electronic health records. We examined associations between tobacco abstinence status and survival using survival models, with and without interactions, adjusted for personal characteristics and biomarkers of disease. Results: Among all 31,069 BC patients treated at MD Anderson between 2006 and 2017, we identified 2126 smokers (6.8%). From those 2126 self-identified smokers, 665 participated in the TP, reporting a conservative estimate of 31% abstinence (intent-to-treat) 9 months into the program. Patients without reported follow-up abstinence status (including TP and non-TP participants) were handled in the analyses as smokers. Survival analysis controlled for multiple factors, including disease characteristics and participation in the TP, indicated that abstainers were more likely to be alive with no evidence of disease compared to non-abstainers (HR, 0.593; 95% CI, 0.386–0.911; p = 0.017). Conclusion: Our results suggest that quitting smoking is associated with improved survival among BC patients who were smokers at time of diagnosis across all tumor stages. Comprehensive approaches for smoking cessation in patients diagnosed with BC may prolong survival when started as early as the time of diagnosis.

With the increasing availability of smartphones, many tobacco researchers are exploring smartphone-delivered mobile smoking interventions as a disseminable means of treatment. Most effort has been focused on the development of smartphone applications (apps) to conduct mobile smoking research to implement and validate these interventions. However, developing project-specific smartphone apps that work across multiple mobile platforms (e.g., iOS and Android) can be costly and time-consuming. Here, using a hypothetical study, we present an alternate approach to demonstrate how mobile smoking cessation and outcome evaluation can be conducted without the need of a dedicated app. Our approach uses the Qualtrics platform, a popular online survey host that is used under license by many academic institutions. This platform allows researchers to conduct device-agnostic screening, consenting, and administration of questionnaires through Qualtrics's native survey engine. Researchers can also collect ecological momentary assessment data using text messaging prompts with the incorporation of Amazon Web Services' Pinpoint. Besides these assessment capabilities, Qualtrics has the potential for delivering personalized behavioral interventions through the use of JavaScript code. By customizing the question's web elements in Qualtrics (e.g., using texts, images, videos, and buttons), researchers can integrate interactive web-based interventions and complicated behavioral and cognitive tasks into the survey. In conclusion, this Qualtrics-based methodology represents a novel and cost-effective approach for conducting mobile smoking cessation and assessment research.

Smoking remains a major public health problem, and it is important to provide a variety of efficacious and appealing options to encourage smokers to quit smoking. Scheduled smoking is a method of gradual reduction, preparing smokers to quit by systematically reducing cigarette consumption according to a predetermined schedule that increases the time between cigarette consumption. Gradual reduction may be preferred to abrupt quitting, but the efficacy of this cessation approach is unclear. This study aims, first, to evaluate the overall effectiveness of scheduled smoking alone, or in combination with precessation nicotine replacement therapy (NRT), versus standard NRT starting on the quit date with no prior smoking reduction and, second, to evaluate the impact of schedule compliance on the effectiveness of the intervention. A total of 916 participants recruited from the Houston metropolitan area were randomly assigned to 1 of the following 3 groups: scheduled smoking plus a precessation nicotine patch (n=306, 33.4%), scheduled smoking only with no precessation patch (n=309, 33.7%), and enhanced usual care (n=301, 32.9%) control. The primary abstinence outcomes were carbon monoxide-verified, self-reported, 7-day point prevalence abstinence at 2 and 4 weeks after the quit date. Unadjusted and adjusted logistic regression analyses were performed to evaluate the intervention effect. Scheduled smoking was implemented using a handheld device for 3 weeks before quitting. This trial was not registered because data collection began before July 1, 2005. Results for the first aim showed no overall differences in abstinence among the 3 groups in both the unadjusted and adjusted models. However, the results for the second aim showed a clear effect on abstinence by schedule compliance at 2 and 4 weeks and 6 months after quitting (odds ratio [OR] 2.01, 95% CI 1.31-3.07), 4 weeks (OR 1.58, 95% CI 1.05-2.38), and 6 months (OR 1.68, 95% CI 1.04-2.64), with the differences at 2 and 4 weeks after quitting being the most robust. We also found that scheduled smoking was related to a reduction in nicotine withdrawal, negative affect, and craving when compared with the controls. Scheduled smoking, when combined with precessation use of NRT, can result in significantly higher abstinence rates than usual care (abrupt quitting with NRT), particularly in the early postquit phase (2 and 4 weeks after cessation) when smokers are compliant with the procedure. Scheduled smoking also produced a better overall quitting experience by reducing symptoms of nicotine withdrawal and craving, in comparison with usual care, which could encourage future quit attempts. Studies in this area should focus on the use of counseling or other methods to improve adherence.

The Food and Drug Administration has the authority to reduce the nicotine content of cigarettes. In this randomized trial, participants assigned to reduced-nicotine cigarettes smoked fewer cigarettes than those assigned to standard-nicotine cigarettes. Twenty years ago, Benowitz and Henningfield published a landmark commentary that coincided with initial attempts by the Food and Drug Administration (FDA) to regulate tobacco products. 1 They reasoned that if the nicotine content of cigarettes were limited to approximately 0.5 mg per cigarette (approximately 0.7 mg per gram of tobacco), cigarettes would be rendered nonaddictive. Although a reduction in nicotine content was endorsed by representatives of the medical community, 2 in 2000, the FDA lost its initial argument to regulate cigarettes in a hearing before the Supreme Court, and the proposal ultimately languished. 3 In the past 8 years, the prospect of . . .

Abstract Introduction As the tobacco industry and market evolves, there is a growing need to understand the patterns of use of tobacco products and how they relate to demographics, dependency, withdrawal, and quit behavior. Methods We analyzed data from wave 1 of the PATH Study consisting of 14856 individuals. Current users were defined as consuming at least 1 of 10 tobacco products. We performed a latent class analysis (LCA) to identify patterns of tobacco use. We used multinomial regression analysis to explore the association between these patterns with covariates representing socioeconomic status dependence/addiction, past quit attempts, and withdrawal severity. Results We identified four groups of current tobacco users with distinct profiles: (1) 61% of the sample were identified as cigarette-only users; (2) 9% were smokeless tobacco users; (3) 17% of the sample were characterized by being current users of all types of combustible tobacco including cigars, cigarillos, filtered cigars, and smoking a pipe (4) finally, 13% were e-cig and hookah users. All classes also shared a varying frequency of cigarette use. Exclusive cigarette users were more likely to be older and female, and experienced higher dependency and withdrawal. Users of e-cigs and hookah were the younger, most educated of all four subgroups, and presented the lowest dependency and withdrawal among the four groups. Conclusions FDA policy makers may want to discourage the use of tobacco products associated with higher tobacco dependency, and products that may contribute to experiencing higher levels of withdrawal symptoms by the user when trying to quit. Implications We identified four patterns of tobacco product use that are significantly related to demographic characteristics, dependency, and withdrawal. Policies should target users more likely to use tobacco products that increase dependency and withdrawal, making quitting more difficult.

Patients with cancer who smoke after diagnosis risk experiencing reductions in treatment effectiveness, survival rates, and quality of life, and increases in complications, cancer recurrence, and second primary cancers. Smoking cessation can significantly affect these outcomes, but to date comprehensive treatment is not widely implemented in the oncologic setting. To describe a potential model tobacco treatment program (TTP) implemented in a cancer setting, report on its long-term outcomes, and highlight its importance to quality patient care. A prospective cohort of smokers was treated in the TTP at a comprehensive cancer center from January 1, 2006, to August 31, 2015. Data analysis was performed from November 2017 to December 2018. Participants included 3245 patients (2343 with current cancer; 309 with previous cancer; 593 with no cancer history) drawn from a population of 5061 smokers referred for treatment in the TTP. Reasons for exclusion included follow-up for a noncancerous disease, no medical consultation, smoked less than 1 cigarette per day; or died before the 9-month follow-up. Treatment consisted of an in-person medical consultation, 6 to 8 in-person and telephone follow-up counseling sessions, and 10 to 12 weeks of pharmacotherapy. Primary outcome was 9-month 7-day point-prevalence abstinence evaluated using time-specific (3-, 6-, and 9-month follow-ups) and longitudinal covariate-adjusted and unadjusted regression models with multiple imputation, intention-to-treat, and respondent-only approaches to missing data. The Fagerström Test for Cigarette Dependence was used as a measure of dependence (possible range, 0-10; higher numbers indicate greater dependence). Of the 3245 smokers, 1588 (48.9%) were men, 322 (9.9%) were of black race/ethnicity, 172 (5.3%) were of Hispanic race/ethnicity, and 2498 (76.0%) were of white race/ethnicity. Mean (SD) age was 54 (11.4) years; Fagerström Test for Cigarette Dependence score, 4.41 (2.2), number of cigarettes smoked per day, 17.1 (10.7); years smoked, 33 (13.2); and 1393 patients (42.9%) had at least 1 psychiatric comorbidity. Overall self-reported abstinence was 45.1% at 3 months, 45.8% at 6 months, and 43.7% at 9 months in the multiply imputed sample. Results across all models were consistent, suggesting that, in comparison with smokers with no cancer history, abstinence rates within this TTP program did not differ appreciably whether smokers had current cancer, were a cancer survivor, or had smoking-related cancers, with the exception of patients with head and neck cancer; the rates were higher at 9 months (relative risk, 1.31; 95% CI, 1.11-1.56; P = .001) and in longitudinal models (relative risk, 1.24; 95% CI, 1.08-1.42; P = .002). In this study, mean smoking abstinence rates did not differ significantly between patients with cancer and those without cancer. These findings suggest that providing comprehensive tobacco treatment in the oncologic setting can result in sustained high abstinence rates for all patients with cancer and survivors and should be included as standard of care to ensure the best possible cancer treatment outcomes.

Neurobiological models of addiction posit that drug use can alter reward processes in two ways: (1) by increasing the motivational relevance of drugs and drug-related cues and (2) by reducing the motivational relevance of non-drug-related rewards. Here, we discuss the results from a series of neuroimaging studies in which we assessed the extent to which these hypotheses apply to nicotine dependence. In these studies, we recorded smokers’ and nonsmokers’ brain responses to a wide array of motivationally relevant visual stimuli that included pleasant, unpleasant, cigarette-related, and neutral images. Based on these findings, we highlight the flaws of the traditional cue reactivity paradigm and we conclude that responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the motivational relevance of cigarette-related cues and to identify smokers attributing higher motivational relevance to drug-related cues than to non-drug-related rewards. Identifying these individuals is clinically relevant as they achieve lower rates of long-term smoking abstinence when attempting to quit. Finally, we show how this approach may be extended beyond nicotine dependence to inform theoretical and clinical research in the study of obesity.