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Cigarette smoking is thought to be at least partially maintained by the attentional bias (AB) toward smoking cues that develops as a consequence of drug dependence. This study evaluated the impact of smartphone-delivered, in-home attentional bias modification (ABM) to reduce AB to smoking cues and to reduce smoking behavior and withdrawal-related symptoms when used as an adjunct to conventional smoking cessation treatment.Participants (We found that ABM training reduced AB to smoking stimuli on both the dot-probe task, ηThirteen days of smartphone-delivered ABM training, as an adjunct to smoking cessation treatment, reduced AB to both modality-specific and cross-modality smoking cues but did not impact smoking-related behavior. While ABM can reduce AB to smoking cues across modalities, it is unclear whether it has therapeutic potential as an adjunct to conventional smoking cessation therapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction There is mixed evidence regarding whether older (vs. younger) smokers are more or less likely to quit smoking. We examined how age is associated with cigarette and all tobacco product abstinence and the potential moderating effects of smoking frequency. Aims and Methods Data from a 4-year cohort of the Population Assessment of Tobacco and Health (PATH) study were used, including 7512 smokers at Wave 1 who had smoking status data at Wave 4. Logistic regression models were used to examine the effects of age (18–24, 25–34, 35–44, 45–54, and ≥55 years) on Wave 4, 30-day and 12-month cigarette and all tobacco product abstinence, adjusting for covariates and the interaction between age and cigarette use frequency (nondaily, light daily, and heavy daily). Results Older smokers (≥55 years) were more likely to be heavy daily smokers than younger smokers 18–24 and 25–34 years, but were less likely to have a past-year cigarette quit attempt. Younger smokers 45–54 years were less likely to report 12-month cigarette abstinence than older smokers (odds ratio = 0.72 [0.54–0.95]). Younger smokers 18–24 and 45–54 years were less likely to report 12-month tobacco product abstinence than older smokers (odds ratio = 0.65 [0.45–0.93]; odds ratio = 0.73 [0.55–0.96], respectively). Thirty-day cigarette abstinence significantly decreased as age increased for nondaily smokers, significantly increased for heavier daily smokers, but remained similar across age for light daily smokers. Conclusions Older smokers were more likely to report 12-month cigarette and tobacco abstinence than younger smokers 45–54 years old, and the effect of age on abstinence differed by smoking frequency/intensity. Smoking cessation interventions need to be age specific and consider smoking frequency. Implications This study shows that although older smokers are more likely to be heavy smokers and less likely to have a quit attempt at baseline, they are more likely to have 12-month cigarette and tobacco abstinence than younger smokers. Furthermore, 30-day cigarette abstinence significantly decreases as age increases for nondaily smokers and significantly increases for heavy daily smokers, suggesting that the effect of cigarette smoking frequency and intensity changes with age. Smoking cessation interventions need to be age specific as well as consider the smoking frequency/intensity of each age group. Younger smokers may need more targeted cessation interventions to successfully quit.

BACKGROUND: There is preliminary evidence that the anticonvulsant topiramate increases the likelihood of both smoking and alcohol abstinence among smokers with alcohol use disorder (AUD), but its therapeutic mechanism has not been determined. We used event-related potentials (ERPs) to evaluate topiramate’s effect on the salience of drug-related, emotional, and neutral pictorial cues to identify whether one of its potential therapeutic mechanisms involves reduction of the salience of motivationally relevant cues. METHODS: Participants, who were enrolled in a multisite clinical trial treating smokers with AUD, were randomized to receive placebo, low-dose topiramate (up to 125 mg/day), or high-dose topiramate (up to 250 mg/day), along with brief behavioral compliance enhancement treatment. A subsample (n=101) completed ERP assessments at baseline (1 week pre-medication) and week 5 (5 weeks on medication; 1 week pre-quit). We assessed the salience of pleasant, unpleasant, cigarette-related, alcohol-related, and neutral pictorial cues using the late positive potential (LPP) ERP component, and measured self-reported substance use, reinforcement, craving, and withdrawal. RESULTS: Five weeks of high-dose topiramate treatment decreased LPP amplitudes to both emotional (pleasant and unpleasant) and drug-related cues (alcohol and cigarette), but not to neutral cues. However, results showed that the LPPs were not significant mediators of the relationship between topiramate dose and post-quit measures of substance use, reinforcement, craving, or withdrawal. CONCLUSIONS: These findings suggest that high-dose topiramate (up to 250 mg/day) decreases the motivational salience of both drug-related and emotional cues among smokers with AUD. However, the nonsignificant mediation analyses preclude any firm conclusions about whether this effect represents one of topiramate’s therapeutic mechanisms of action.

BACKGROUND Smoking remains a significant public health problem and it is important to provide a variety of efficacious and appealing options to encourage smokers to quit. Scheduled smoking is a method of gradual reduction, preparing smokers to quit, by systematically reducing cigarette consumption according to a pre-determined schedule that increases the time between cigarettes. Gradual reduction may be preferred to abrupt quitting by some smokers, but the efficacy of this cessation approach is unclear. OBJECTIVE The aims of the current study were 1) to evaluate the overall effectiveness of scheduled smoking alone, or in combination with pre-cessation nicotine replacement therapy (NRT), vs. standard NRT starting on the quit date with no prior smoking reduction, and 2) assess and evaluate the impact of schedule compliance on the effectiveness of the intervention. METHODS 916 participants recruited from the Houston metropolitan area were randomly assigned to one of three groups: Scheduled Smoking plus pre-cessation Nicotine Patch (SSNP; N=306), Scheduled Smoking only with no pre-cessation patch (SS; N=309) and Enhanced Usual Care (EUC; N=301). Scheduled smoking was implemented using a handheld device for 3 weeks prior to quitting. The device was used by all groups in the post-quitting phase to provide routines to manage relapse. All groups used NRT post-quit. RESULTS Participants reported an average age of 43 years old, were mostly white, were equally distributed between male and female, smoked slightly more than a pack of cigarette per day (mean = 23), and were moderately dependent on nicotine (mean FTCD score = 5). The results for aim 1 showed no overall differences in abstinence in the 3 groups in both unadjusted and adjusted (for covariates) models. However, the results for aim 2 showed a clear effect on abstinence by schedule compliance, at 2- and 4-weeks and 6-months post-quit, with the differences at 2- and 4-weeks post-quit being the most robust. In addition, we found that scheduled smoking was related to a significant reduction in several symptoms of nicotine withdrawal, negative affect, and craving versus controls. CONCLUSIONS Scheduled smoking, when combined with pre-cessation use of NRT, can result in significantly higher abstinence rates than usual care (abrupt quitting with NRT), particularly in the early post-quit phase (2 and 4-weeks post-cessation) when smokers are compliant with the procedure. There was also evidence for a clinically meaningful effect (OR>1.5) at 6-months post-quit, though statistical differences were reduced with adjustments for multiple comparisons. Scheduled smoking also produced a better overall quitting experience by reducing symptoms of nicotine withdrawal and craving, in comparison to usual care, which could encourage future quit attempts. Future studies in this area should concentrate on use of counseling or other methods to improve adherence. CLINICALTRIAL This trial was not registered because data collection began prior to July 1, 2005.

The United States Food and Drug Administration has the authority to reduce the nicotine content in cigarettes to minimal or non-addictive levels and could do so immediately or gradually over time. A large clinical trial compared the two approaches. This secondary analysis assesses abstinence and cessation-related outcomes one month after the trial concluded, when participants no longer had access to very low nicotine content (VLNC) research cigarettes. Smokers not interested in quitting (N = 1250) were recruited for the parent trial from 2014 to 2016 across 10 sites throughout the US and randomized to a 20-week study period during which they immediately switched to VLNC cigarettes, gradually transitioned to VLNC cigarettes with five monthly dose reductions, or smoked normal nicotine research cigarettes (control). At the one-month follow-up, both immediate and gradual reduction resulted in greater mean cigarette-free days (4.7 and 4.6 respectively) than the control group (3.2, both p .05). Immediate reduction resulted in fewer mean cigarettes per day (CPD = 10.3) and lower Fagerström Test for Cigarette Dependence (FTCD = 3.7) than the gradual (CPD = 11.7, p = .001; FTCD = 3.8, p = .039) and control (CPD = 13.5, p .001; FTCD = 4.0, p .001) groups. Compared to controls, gradual reduction resulted in reduced CPD (p = .012) but not FTCD (p = .13). Differences in CO-verified 7-day point-prevalence abstinence were not significant. Findings demonstrate that switching to VLNC cigarettes resulted in reduced smoking and nicotine dependence severity that was sustained for at least a month after the VLNC trial period in smokers who were not interested in cessation. The greatest harm reduction endpoints were observed in those who immediately transitioned to VLNC cigarettes.

BACKGROUND AND OBJECTIVES: Bupropion extended release (XL; once-daily dosing) has equal efficacy with the sustained release (SR) formulation (twice-daily dosing) for treating depression, but no studies have compared the two formulations for the treatment of smoking. In a naturalistic open label study, we compared the effectiveness and the adverse event profiles of XL and SR in treating cancer patients for smoking. METHODS: Cancer patients (N=648) were prescribed bupropion XL (n=454) or SR (n=194) alone or in combination with nicotine replacement therapy (NRT) for treating smoking from September 2006 to December 2017. We analyzed 7-day point prevalence abstinence at end-of-treatment (EOT; 3 months post-medication initiation) and evaluated for noninferiority. We also analyzed the adverse event profile differences between the medications. RESULTS: There were no significant differences in abstinent rates at EOT between bupropion XL and SR when using intent-to-treat models, regardless of concomitant NRT. XL demonstrated noninferiority in treatment efficacy compared to SR when excluding those on combined treatment with NRT. Further, there were no significant differences in spontaneously reported adverse events between XL and SR. CONCLUSIONS: Our data did not reveal a difference between bupropion XL and SR formulations in terms of effectiveness or adverse event profiles among cancer patients prescribed bupropion alone or in combination with NRTs to quit smoking. SCIENTIFIC SIGNIFICANCE: In this first published direct comparison of their effectiveness and adverse event profiles, we found that bupropion XL is likely therapeutically equivalent to bupropion SR when treating smoking among cancer patients, and produces similar side effects.

Smoking is highly prevalent in individuals with psychiatric disorders. The relationship between smoking and anxiety disorders has received less attention than that of depression and substance use disorders, despite the fact that anxiety disorders are the most common of mental illnesses across the globe. In this study, we investigated the relationship between psychiatric disorders, including anxiety, depression, alcohol abuse, and comorbid combinations of these primary Axis I disorders and smoking cessation, in a cohort of 1,425 cancer patients who were participating in a smoking cessation clinical program. Patients were followed prospectively and assessed for abstinence status at the end of treatment and at 6-month posttreatment. Treatment involved six to eight behavioral smoking cessation counseling sessions over a 12- to 16-week period, and up to 12 weeks of smoking cessation pharmacotherapy. We hypothesized that patients with current anxiety disorders as well as other psychiatric disorders would have lower smoking cessation rates than those with no psychiatric disorders. There were no differences in abstinence rates between patients with anxiety disorders and those with no psychiatric disorders at end of treatment or 6 months. Patients with major depression or alcohol abuse had lower cessation rates than patients with no psychiatric disorders at 6 months. Findings suggest that both major depression and alcohol abuse may adversely affect treatment outcome in cancer patients. However, these findings should be considered within the limitations of observational studies that involve comparisons between nonrandomly assigned groups. Keywords: smoking cessation; anxiety; depression; alcohol Smoking is highly prevalent in individuals with psychiatric disorders. Recent epidemiologic data show that smoking prevalence was 40.1% among adults who had mental illness within the previous 12 months, compared to 21.3% in adults who reported no mental illness in the previous 12 months (Lawrence, Mitrou, & Zubrick, 2009), a level that is similar to that of the general U.S. population (Centers for Disease Control and Prevention, 2005). Among individuals with current major depression and alcohol abuse or dependence, the smoking rate is estimated to be 45% and 56%, respectively (Lasser et al., 2000). Rates of nicotine dependence are higher in smokers with depression and alcohol use disorders than those with no psychiatric disorder (Grant, Hasin, Chou, Stinson, & Dawson, 2004; Pratt & Brody, 2010), and smokers with these disorders are less likely to quit (Breslau, Peterson, Schultz, Andreski, & Chilcoat, 1996; Pratt & Brody). The relationship between smoking and anxiety disorders has received less attention than that of depression and substance use disorders, despite the fact that anxiety disorders are the most common of mental illnesses across the globe (World Health Organization World Mental Health Survey Consortium, 2004). It has been estimated that approximately 38% of individuals with an anxiety disorder are current smokers, and that among all current adult smokers, 23% meet criteria for an anxiety disorder within the past 12 months (Lawrence et al., 2009). Smoking rates for each of the anxiety disorders are approximately double the rates of nonpsychiatrically disordered smokers (21.3%) and range from 45.2% for panic, 45.2% for generalized anxiety, 42.0% for agoraphobia, 40.0% for posttraumatic stress disorder, and 35% for social phobia (Lawrence et al.). The presence of anxiety disorders is related to nicotine dependence, withdrawal, and history of unsuccessful quit attempts (Breslau, Kilbey, & Andreski, 1991; Cougle, Zvolensky, Fitch, & Sachs-Ericsson, 2010). Current anxiety disorders have been shown to increase the risk of transition to nicotine dependence among daily smokers (Breslau, Novak, & Kessler, 2004). The presence of anxiety disorders has also been found to increase symptoms of nicotine withdrawal in a doseresponse fashion (John, Meyer, Rumpf, & Hapke, 2004). …

Introduction In smoking cessation clinical trials, timeline followback (TLFB) interviews are widely used to track daily cigarette consumption. However, there are no standard tools for calculating abstinence based on TLFB data. Individual research groups have to develop their own calculation tools, which is not only time- and resource-consuming but might also lead to variability in the data processing and calculation procedures. Aims and Methods To address these issues, we developed a novel open-source Python package named abstcal to calculate abstinence using TLFB data. This package provides data verification, duplicate and outlier detection, missing-data imputation, integration of biochemical verification data, and calculation of a variety of definitions of abstinence, including continuous, point-prevalence, and prolonged abstinence. Results We verified the accuracy of the calculator using data derived from a clinical smoking cessation study. To improve the package’s accessibility, we have made it available as a free web app. Conclusions The abstcal package is a reliable abstinence calculator with open-source access, providing a shared validated online tool to the addiction research field. We expect that this open-source abstinence calculation tool will improve the rigor and reproducibility of smoking and addiction research by standardizing TLFB-based abstinence calculation. Implications Abstinence calculation is an essential task in any smoking intervention study. However, there have not been standard open-source tools available to the researchers. This commentary describes a Python-based package called abstcal that can calculate abstinence from TLFB data, a common methodology to collect smoking consumption data in research settings. The package supports the calculation of point-prevalence, prolonged, and continuous abstinence. Importantly, the package has a web app interface that allows researchers to use the tool without any coding experience. This tool will facilitate smoking research by providing a standardized and easy-to-use abstinence calculation tool.

Background and Objectives: Behavioral economic purchase tasks are widely used to assess drug demand in substance use disorder research. Comorbid alcohol use is common among cigarette smokers and associated with greater difficulty in quitting smoking. However, demand for alcohol and cigarettes in this population has not been fully characterized. The present study addressed this gap by examining alcohol and cigarette demand among treatment-seeking smokers with alcohol use disorder (AUD).Methods: Alcohol and cigarette demand was assessed among 99 smokers with AUD. We conducted Principal Component Analysis (PCA) and correlational analyses on the demand indices.Results: Participants showed higher demand for alcohol than for cigarettes, as evidenced lower elasticity (resistance to increasing price) and higher Omax (maximum response output for drug). PCA revealed a two-factor structure (Persistence and Amplitude) for both alcohol and cigarette demand indices. Cigarette-related demand indices were positively correlated with nicotine dependence, but alcohol-related demand indices were not associated with alcohol dependence, suggesting dissociation between alcohol demand and use behaviors.Discussion and Conclusions: Our results suggest that smokers with AUD were more resistant to price elevations in relation to reducing alcohol consumption as compared to cigarette consumption, suggesting preferential demand for alcohol over cigarettes. However, it is unclear how acute substance exposure/withdrawal impacts the demand indices.Scientific Significance: Potentially differential alcohol and cigarette demands among smokers with AUD should be considered in the concurrent treatment of smoking and alcohol.

Author(s): Hatsukami, Dorothy K; Luo, Xianghua; Heskin, Alisa K; Tang, Mei Kuen; Carmella, Steven G; Jensen, Joni; Robinson, Jason D; Vandrey, Ryan; Drobes, David J; Strasser, Andrew A; al'Absi, Mustafa; Leischow, Scott; Cinciripini, Paul M; Koopmeiners, Joseph; Ikuemonisan, Joshua; Benowitz, Neal L; Donny, Eric C; Hecht, Stephen S | Abstract: AimA previous study showed significantly greater reductions in number of cigarettes smoked and biomarkers of toxicant and carcinogen exposure in smokers assigned to immediate reduction of nicotine in cigarettes to very low levels versus gradually over time or continued smoking of normal nicotine content cigarettes. This study examines the effects of these approaches on selected biomarkers associated with harmful biological effects.DesignThree-arm, randomized controlled trial.SettingTen United States academic institutional sites.ParticipantsDaily smokers uninterested in quitting smoking with a mean age of 45.1 [standard deviation (SD)n=n13.4)] years and smoking 17.1 (SDn=n8.5) cigarettes/day; 43.9% (549 of 1250) female; 60.6% (758 of 1250) white ethnicity.Interventions(1) Smoking cigarettes where nicotine content was immediately reduced to very low levels (nn=n503); (2) smoking cigarettes where nicotine content was gradually reduced, with dose changes occurring monthly (nn=n498); and (3) continued smoking with normal nicotine content cigarettes (nn=n249).MeasurementsSmokers were assessed at baseline while smoking their usual brand cigarettes, and again at 4, 8, 12, 16 and 20nweeks. Outcomes were areas under the concentration time curve (AUC) for the period of study of biomarkers of inflammation, oxidative stress and hematological parameters.FindingsNo consistent significant differences were observed across groups (Bayes factors showing data to be insensitive), with the only exception being red blood cell size variability, which was observed to be lower in the immediate versus gradual nicotine reduction [mean differencen=nn-0.11; 95% confidence interval (CI)n=n-0.18, -0.04, Pn=n0.004] and normal nicotine control groups (mean differencen=n-n0.15, 95% CIn=n-0.23, -0.06, Pn=n0.001).ConclusionIt remains unclear whether switching to very low nicotine cigarettes leads to a short-term reduction in biomarkers of tobacco-related harm.

When trying to quit, women are less likely than men to achieve long-term smoking abstinence. Identifying the neuropsychological mechanisms underlying women’s higher relapse vulnerability will help clinicians to develop effective tailored smoking cessation interventions. Here we used event-related potentials (ERPs), a direct measure of brain activity, to evaluate the extent to which neurophysiological responses to cigarette-related and other emotional stimuli differ between female and male smokers. Both women and men showed similar patterns of brain reactivity across all picture categories; pleasant and unpleasant images prompted larger Late Positive Potentials (LPPs, a robust measure of motivational relevance) than neutral images in both groups, and cigarette-related images prompted lower LPPs than high arousing emotional images in both groups. Unlike previous studies, there were no differences between male and female smokers with regard to LPP responses to cigarette-related images. This suggests that the LPP may not be ideally suited to discriminate neurophysiological gender differences or that there are simply no gender differences in the neurophysiological responses to cigarette-related stimuli. We collected ERPs from 222 non-nicotine-deprived smokers (101 women) while they watched a slideshow that included high and low emotionally arousing pleasant and unpleasant pictures, cigarette-related, and neutral pictures. We used the mean amplitude of the LPP to assess the affective significance that participants attributed to these pictures.

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.

Introduction By improving our understanding of the neurobiological mechanisms underlying addiction, neuroimaging research is helping to identify new targets for personalized treatment interventions. When trying to quit, smokers with larger electrophysiological responses to cigarette-related, compared with pleasant, stimuli (“C > P”) are more likely to relapse than smokers with the opposite brain reactivity profile (“P > C”). Aim and Method The goal was to (1) build a classification algorithm to identify smokers characterized by P > C or C > P neuroaffective profiles and (2) validate the algorithm’s classification outcomes in an independent data set where we assessed both smokers’ electrophysiological responses at baseline and smoking abstinence during a quit attempt. We built the classification algorithm applying discriminant function analysis on the event-related potentials evoked by emotional images in 180 smokers. Results The predictive validity of the classifier showed promise in an independent data set that included new data from 177 smokers interested in quitting; the algorithm classified 111 smokers as P > C and 66 as C > P. The overall abstinence rate was low; 15 individuals (8.5% of the sample) achieved CO-verified 12-month abstinence. Although individuals classified as P > C were nearly 2.5 times more likely to be abstinent than smokers classified as C > P (12 vs. 3, or 11% vs. 4.5%), this result was nonsignificant, preliminary, and in need of confirmation in larger trials. Conclusion These results suggest that psychophysiological techniques have the potential to advance our knowledge of the neurobiological underpinnings of nicotine addiction and improve clinical applications. However, larger sample sizes are necessary to reliably assess the predictive ability of our algorithm. Implications We assessed the clinical relevance of a neuroimaging-based classification algorithm on an independent sample of smokers enrolled in a smoking cessation trial and found those with the tendency to attribute more relevance to rewards than cues were nearly 2.5 times more likely to be abstinent than smokers with the opposite brain reactivity profile (11% vs. 4.5%). Although this result was not statistically significant, it suggests our neuroimaging-based classification algorithm can potentially contribute to the development of new precision medicine interventions aimed at treating substance use disorders. Regardless, these findings are still preliminary and in need of confirmation in larger trials.

Background and aims Despite the availability of several efficacious smoking cessation treatments, fewer than 25% of smokers who quit remain abstinent 1 year post-treatment. This study aimed to determine if varenicline and bupropion combination treatment would result in higher abstinence rates than varenicline alone. Design A double-blind, randomized, parallel-group smoking cessation clinical trial in which participants were exposed to 12 weeks of treatment and followed for 12 months. Setting Hospital-based out-patient clinic in Texas, USA specializing in cancer prevention. Participants A total of 385 community smokers (58.44% male) who smoked 1 pack of cigarettes/day [mean = 19.66 cigarettes/day, standard deviation (SD) = 9.45]; had average carbon monoxide (CO) of 26.43 parts per million (SD = 13.74); and were moderately dependent (Fagerstrom Test for Cigarette Dependence = 4.79; SD = 2.07). Interventions and comparator Smokers were randomized in a 3 : 1 (active: Placebo) ratio to 12 weeks of treatment as follows: placebo (n = 56), varenicline (Var; n = 166), and varenicline + bupropion (Combo; n = 163). Measurements A priori primary outcome: prolonged abstinence at 12 months. Secondary outcomes 7-day point prevalence abstinence and continuous abstinence; all abstinence measures at end of treatment and 6-month follow-ups. Findings Intention-to-treat analysis: the Combo group (n = 163) failed to demonstrate superiority to the Var group (n = 166) for prolonged abstinence at 12 months [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.50-1.64], supported by Bayes factor = 0.06. Both the Var (OR = 6.66, 95% CI = 1.61-59.27) and Combo groups (OR = 6.06, 95% CI = 1.45-54.09) demonstrated superiority to the Placebo group (n = 56; score = 8.38, P Conclusions The addition of bupropion to varenicline treatment does not appear to increase smoking abstinence rates above that of varenicline alone. The findings support previous research showing a consistently favorable effect of both varenicline and the combination of varenicline and bupropion on smoking cessation compared with placebo.

Background While the notion that smokers reliably show higher reactivity to cigarette-related versus neutral cues is both theoretically and empirically supported, it is unclear why never-smokers also show enhanced brain responses to cigarette-related cues. Methods Using a repetitive picture viewing paradigm, in which responses evoked by affective cues are more resistant to habituation, we assessed the effects of stimulus repetition on event-related potentials (ERPs) evoked by pleasant, unpleasant, cigarette-related, and neutral images in 34 smokers (SMO) and 34 never-smokers (NEV). We examined the early posterior negativity (EPN) and the late positive potential (LPP), two ERP components which are sensitive to a picture's motivational qualities. Results Before stimulus repetition, pleasant, unpleasant, and cigarette-related cues produced greater EPN and LPP amplitudes than neutral cues in all subjects. During stimulus repetition, both components were similarly modulated by emotional arousal, such that pleasant, unpleasant, and cigarette-related cues evoked greater EPN and LPP amplitude, relative to neutral. Smoking status did not modulate these effects. While there were no group differences in self-reported stimulus ratings of valence for pleasant, unpleasant, or neutral stimuli, NEV rated cigarette-related cues as unpleasant. We observed a moderate, negative correlation between LPP amplitude and self-reported valence ratings of cigarette-related cues among NEV. Conclusions These data suggest that cigarette-related cues capture attentional resources of both SMO and NEV, but for different reasons. For SMO, cigarette-related cues have acquired motivational significance through repeated associations with nicotine delivery, whereas for NEV, cigarette-related cues are perceived as unpleasant.

Introduction Varenicline and bupropion are two effective smoking cessation pharmacotherapies. Researchers have hypothesized that they might be effective, in part, because they reduce cue reactivity and cue-induced cravings. Here, we used event-related potentials (ERPs) to directly measure brain responses to cigarette-related and other motivationally relevant images during a pharmacologically aided quit attempt. Methods Smokers involved in a 12-week placebo-controlled double-blind clinical trial of smoking cessation medications (varenicline, bupropion, placebo) took part in the study. We assessed participants at two time points: 24 h (n = 140) and 4 weeks (n = 176) after the quit date. At both sessions, we measured the amplitude of the late positive potential (LPP), an ERP component reliably associated with motivational relevance, and self-reported tonic craving using the brief version of the Questionnaire of Smoking Urges (QSU-Brief). Results At both sessions, emotional and cigarette-related images evoked significantly larger LPPs than neutral images. Neither drug type nor smoking abstinence altered this effect at either session. At both sessions, varenicline and bupropion significantly reduced self-reported tonic craving relative to the placebo condition. Conclusions While both varenicline and bupropion reduced self-reported tonic craving, neither medication altered the amplitude of the LPP to cigarette-related or emotional pictures in smokers attempting to quit. These medications may influence abstinence by means other than by reducing neuroaffective responses to cigarette-related cues. Smokers should be prepared for the likelihood that even after several weeks of successful abstinence, once treatment ends, cigarette-related cues may remain motivationally relevant and trigger cravings that might lead to relapse. Implications Bupropion and varenicline do not alter electrophysiological responses, as measured by the LPP, to cigarette-related and emotional images. These findings help explain why cigarette-related cues can trigger relapse when smoking cessation medication treatments end.

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. Implications The cue reactivity paradigm (ie, comparing responses evoked by drug-related cues to those evoked by neutral cues) cannot provide conclusive information about the motivational relevance of drug-related cues. Responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the level of motivational relevance that substance-dependent individuals attribute to drug-related cues.

Despite the withdrawal of CB1 antagonists, such as rimonabant, from the market and from active clinical development because of concerns about their side effect profiles, research suggests that the endocannabinoid system may play an important role in modulating nicotine's effects. We report the combined results, using a pooled analysis, of three previously unpublished trials assessing rimonabant as a smoking cessation pharmacotherapy conducted between 2002 and 2004. Smokers (n = 2097) motivated to quit were enrolled in three randomized, double-blind, placebo-controlled trials, STRATUS EU, US, and META, which consisted of a 10-week treatment period with either rimonabant 20 mg (n = 789), 5 mg (n = 518; used in only two of the three studies), or placebo (n = 790), in conjunction with brief counseling. The impact of drug on prolonged abstinence and adverse events was examined at 8 weeks (end-of-treatment) and at 48 weeks (available for STRATUS EU and US) after the targeted quit date. Rimonabant 20 mg resulted in significantly higher abstinence at end-of-treatment and at 48 weeks post-targeted quit date compared with placebo, while rimonabant 5 mg and placebo did not differ. Serious AEs did not differ by drug group. The 20 mg rimonabant dose, compared with placebo, produced increased nausea, diarrhea, anxiety symptoms, hyporexia, and vomiting, and decreased headache, constipation, and cough. These results support rimonabant 20 mg as a modestly effective aid for smoking cessation. Although work on CB1 antagonists such as rimonabant has mostly been stopped because of unacceptable adverse events, these results may inform and spur the development of other endocannabinoids for smoking cessation.

We have shown that differences in the level of neural activation to stimuli associated with smoking vs. natural rewards, a biomarker related to reward sensitivity, predict treatment outcome. This paper examined whether this biomarker moderates the impact of bupropion or varenicline on smoking cessation. Prior to treatment randomization, smokers (N = 180) in a placebo-controlled trial using bupropion and varenicline completed event-related potential recording (late positive potential, LPP) while viewing pleasant (P), cigarette (C)-related, and other pictures. We used Bayesian models to estimate the probability of interaction between treatment and the LPP for both efficacy and comparative effectiveness analyses. Efficacy analysis showed that smokers with more neural activation to pleasant vs. cigarette-related stimuli (P > C) had a 98–99% chance of achieving greater abstinence than placebo (OR >1.00), using either medication from the end of treatment (EOT, primary outcome) through the 3-month follow-up. Relative to placebo, smokers with higher activation to cigarette-related vs. pleasant stimuli (C > P) had a 99% chance of increased benefit from varenicline at both time points (OR >1), but only 67 and 43% with bupropion at the EOT and 3-month follow-up, respectively. Comparative effectiveness analysis found that smokers with the C > P activation pattern had a 95–98% chance of benefit from varenicline vs. bupropion, while P > C smokers had a 50–58% chance of similar improvement with varenicline at the EOT and 3 months. Varenicline appears to be the treatment of choice for smokers with the C > P pattern of neural activation, while for those showing P > C, varenicline and bupropion have similar efficacy.

It is unclear whether nicotine and perceived nicotine exposure can influence automatic evaluations of cigarette stimuli. In the present study, we investigated the effects of nicotine dose and instructed dose on motivational responses to smoking cues. Forty overnight nicotine-deprived smokers completed an Implicit Association Test (IAT) at each of the four laboratory sessions in a balanced-placebo design that crossed nicotine dose (Given-NIC [given nicotine] vs. Given-DENIC [given denicotinized]) with instructed dose expectancy (Told-NIC [told-nicotine] vs. Told-DENIC. [told-denicotinized]). We measured participants' behavioral performance, including reaction time (RT) and accuracy rate, and the early posterior negativity (EPN) component using the event-related potential (ERP) technique to the target pictures. During congruent trials when the categorization condition was smoking or unpleasant, smokers had greater classification accuracy, shorter RT latency, and greater EPN amplitudes compared to the incongruent trials when the categorization condition was smoking or pleasant. The Given-NIC condition was associated with increased classification accuracy, longer RT latency, and decreased EPN amplitudes compared to the Given-DENIC condition. Similarly, the Told-NIC condition was associated with increased accuracy and decreased EPN amplitudes compared to the Told-DENIC condition, but with shorter RT latency. Cigarette-related pictures produced greater EPN amplitudes than neutral pictures. Both behavioral and ERP results suggest that smokers have negative implicit attitudes toward smoking. While both nicotine dose and expected dose facilitated stimulus categorization, there was no evidence that either factor altered smokers' negative attitudes toward smoking cues. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The late positive potential (LPP) is a common measurement used to study emotional processes of subjects in event-related potential (ERP) paradigms. Despite its extensive use in affective neuroscience, there is presently no gold standard for how to appropriately power ERP studies using the LPP in within-subject and between-subjects experimental designs. The present study investigates how the number of trials, number of subjects, and magnitude of the effect size affect statistical power in analyses of the LPP. Using Monte Carlo simulations of ERP experiments with varying numbers of trials, subjects, and effect sizes, we measured the probability of obtaining a statistically significant effect in 1,489 different experiments repeated 1,000 times each. Predictably, our results showed that statistical power increases with increasing numbers of trials and subjects and at larger effect sizes. In addition, we found that higher levels of statistical power can be achieved with lower numbers of subjects and trials and at lower effect sizes in within-subject than in between-subjects designs. Furthermore, we found that, as subjects are added to an experiment, the slope of the relationship between effect size and statistical power increases and shifts to the left until the power asymptotes to nearly 100% at higher effect sizes. This suggests that adding more subjects greatly increases statistical power at lower effect sizes (1.5 µV) effect sizes.

The late positive potential (LPP) is a common measurement used to study emotional processes of subjects in event-related potential (ERP) paradigms. Despite its extensive use in affective neuroscience, there is presently no gold standard for how to appropriately power ERP studies using the LPP. The present study investigates how the number of trials, number of subjects, and magnitude of the effect size affect statistical power in analyses of the LPP. Using Monte Carlo simulations of ERP experiments with varying numbers of trials, subjects, and synthetic effects of known magnitude, we measured the probability of obtaining a statistically significant effect in 1,489 experiments repeated 1,000 times each. Predictably, our results showed that statistical power increases with increasing numbers of trials and subjects and at larger effect sizes. We also found that higher levels of statistical power can be achieved with lower numbers of subjects and trials and at lower effect sizes in within-subject than in between-subjects designs. Furthermore, we found that as subjects are added to an experiment, the slope of the relationship between effect size and statistical power increased and shifted to the left until the power asymptoted to nearly 100% at higher effect sizes. This suggests that adding more subjects greatly increases statistical power at lower effect sizes (1.5 μV) effect sizes. We confirmed the results from the simulations based on the synthetic effects by running a new series of simulated experiments based on real data collected while participants looked at emotional images.

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).

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.

Greater sage-grouse (Centrocercus urophasianus; sage-grouse) is considered an umbrella species for sagebrush (Artemisia spp.) landscapes in western North America. In 2015, the U.S. Fish and Wildlife Service determined sage-grouse unwarranted for protection under the Endangered Species Act (1973) because of conservation actions in priority areas. Understanding seasonal movements is key to delineation and assessment of priority conservationareas.Wemonitored radiomarked sage-grouse from1998 to2013 throughoutUtah,USA,to determine seasonal movements. Maximum distances from nearest lek to nesting, summer, and winter locations across all radiomarkedgrouse averaged2.20 km(90thpercentile1⁄4 5.06 km), 3.93 km(90thpercentile1⁄4 8.45 km), and3.76 km(90thpercentile1⁄4 7.15 km), respectively.Maximummovements fromnest to summer,nest towinter, and between summer and winter locations across all radiomarked grouse averaged 5.77 km (90th percentile1⁄4 13.60 km), 11.77 km (90th percentile1⁄4 26.36 km), and 14.75 km (90th percentile1⁄4 30.77 km), respectively. Maximum distance from lek of capture to summer locations was greater for males than females, whereas femalesmoved farther thanmales fromlek towinter andsummer towinter locations.Adult femalesmoved farther than yearlings from lek to nest and summer towinter areas. The state ofUtah’s Sage-GrouseManagement Areas included approximately 85% of the radiotelemetry seasonal locations and >95% when weighted by lek counts.Our results suggest that seasonalmovements could be facilitatedby increasingusable habitat space through management actions, as emphasized in Utah’s sage-grouse plan. 2016 The Wildlife Society.

Through Pavlovian conditioning, reward-associated neutral stimuli can acquire incentive salience and motivate complex behaviors. In smokers, cigarette-associated cues may induce cravings and trigger smoking. Understanding the brain mechanisms underlying conditioned responses to cigarette-associated relative to other inherently pleasant stimuli might contribute to the development of more effective smoking cessation treatments that emphasize the rehabilitation of reward circuitry. Here we measured brain responses to geometric patterns (the conditioned stimuli, CSs) predicting cigarette-related, intrinsically pleasant and neutral images (the unconditioned stimuli, USs) using event-related potentials (ERPs) in 29 never-smokers, 20 nicotine-deprived smokers, and 19 non-deprived smokers. Results showed that during US presentation, cigarette-related and pleasant images prompted higher cortical positivity than neutral images over centro-parietal sensors between 400 and 800 ms post-US onset (late positive potential, LPP). The LPP evoked by pleasant images was significantly larger than the LPP evoked by cigarette images. During CS presentation, ERPs evoked by geometric patterns predicting pleasant and cigarette-related images had significantly larger amplitude than ERPs evoked by CSs predicting neutral images. These effects were maximal over right parietal sites between 220 and 240 ms post-CS onset and over occipital and frontal sites between 308 and 344 ms post-CS onset. Smoking status did not modulate these effects. Our results show that stimuli with no intrinsic reward value (e.g., geometric patterns) may acquire rewarding properties through repeated pairings with established reward cues (i.e., cigarette-related, intrinsically pleasant).

BACKGROUND The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. RESULTS A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P

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.

BACKGROUND AND AIMS: Despite the availability of several efficacious smoking cessation treatments, less than 25% of smokers who quit remain abstinent 1 year post treatment. This study aimed to determine if varenicline and bupropion combination treatment would result in higher abstinence rates than varenicline alone. DESIGN: A double-blind, randomized, parallel groups smoking cessation clinical trial in which participants were exposed to 12 weeks of treatment and followed for 12 months. SETTING: Hospital-based outpatient clinic in Texas, USA specializing in cancer prevention. PARTICIPANTS: 385 community smokers (56% male) who smoked 1 pack cigarettes/day (Mean = 19.66 cigs/day, S.D. = 9.45); had an average CO of 26.43 ppm (S.D. =13.74); and were moderately dependent (FTCD = 4.79; S.D. = 2.07). INTERVENTIONS AND COMPARATOR: Smokers were randomized in a 3:1 (Active: Placebo) ratio to 12 weeks of treatment as follows: Placebo (n=56), Varenicline (Var; n=166), and Varenicline + Bupropion (Combo; n=163). MEASUREMENTS: A priori primary outcome: Prolonged abstinence at 12 months. Secondary outcomes: Seven-day point prevalence abstinence and continuous abstinence; all abstinence measures at end of treatment and 6 month follow-ups. FINDINGS: Intent to treat analysis: the Combo group (n=163) failed to demonstrate superiority to the Var group (n=166) for prolonged abstinence at 12 months [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.50–1.64], supported by Bayes Factor = 0.06. Both the Var [OR = 6.66, 95% CI = 1.61–59.27] and Combo groups [OR = 6.06, 95% CI = 1.45–54.09] demonstrated superiority to Placebo group (n=56; Score = 8.38, p< 0.016). CONCLUSIONS: The addition of bupropion to varenicline treatment does not appear to increase smoking abstinence rates above that of varenicline alone. The findings support previous research showing a consistently favorable effect of both varenicline and the combination of varenicline and bupropion on smoking cessation compared with placebo.

Importance 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. Objectives 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. Design, Setting, and Participants 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. Exposures 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. Main Outcomes and Measures 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 Fagerstrom Test for Cigarette Dependence was used as a measure of dependence (possible range, 0-10; higher numbers indicate greater dependence). Results 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; Fagerstrom 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). Conclusions and Relevance 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.

Introduction The reasons that some smokers find it harder to quit than others are unclear. Understanding how individual differences predict smoking cessation outcomes may allow the development of more successful personalized treatments for nicotine dependence. Theoretical models suggest that drug users might be characterized by increased sensitivity to drug cues and by reduced sensitivity to nondrug-related natural rewards. We hypothesized that baseline differences in brain sensitivity to natural rewards and cigarette-related cues would predict the outcome of a smoking cessation attempt. Methods Using functional magnetic resonance imaging, we recorded prequit brain responses to neutral, emotional (pleasant and unpleasant), and cigarette-related cues from 55 smokers interested in quitting. We then assessed smoking abstinence, mood, and nicotine withdrawal symptoms during the course of a smoking cessation attempt. Results Using cluster analysis, we identified 2 groups of smokers who differed in their baseline responses to pleasant cues and cigarette-related cues in the posterior visual association areas, the dorsal striatum, and the medial and dorsolateral prefrontal cortex. Smokers who showed lower prequit levels of brain reactivity to pleasant stimuli than to cigarette-related cues were less likely to be abstinent 6 months after their quit attempt, and they had higher levels of negative affect during the course of the quit attempt. Conclusions Smokers with blunted brain responses to pleasant stimuli, relative to cigarette-related stimuli, had more difficulty quitting smoking. For these individuals, the lack of alternative forms of reinforcement when nicotine deprived might be an important factor underlying relapse. Normalizing these pathological neuroadaptations may help them achieve abstinence.

Identifying neural mechanisms associated with addiction has substantially improved the overall understanding of addictive processes. Indeed, research suggests that drug-associated cues may take advantage of neural mechanisms originally intended for emotional processing of stimuli relevant to survival. In this study, we investigated cortical responses to several categories of emotional cues (erotic, romance, pleasant objects, mutilation, sadness, and unpleasant objects) as well as two types of smoking-related cues (people smoking and cigarette-related objects). We recorded ERPs from 180 smokers prior to their participation in a smoking cessation clinical trial and assessed emotional salience by measuring the amplitude of the late positive potential (LPP; 400 to 600 ms after picture onset). As expected, emotional and cigarette-related pictures prompted a significantly larger LPP than neutral pictures. The amplitude of the LPP increased as a function of picture arousal level, with high-arousing erotic and mutilation pictures showing the largest response in contrast to low-arousing pleasant and unpleasant objects, which showed the smallest response (other than neutral). Compared to females, male participants showed larger LPPs for high-arousing erotic and mutilation pictures. However, unlike emotional pictures, no difference was noted for the LPP between cigarette stimuli containing people versus those containing only objects, suggesting that in contrast to emotional objects, cigarette-related objects are highly relevant for smokers. We also compared the smokers to a small (N=40), convenience sample of never-smokers. We found that never-smokers had significantly smaller LPPs in response to erotic and cigarette stimuli containing only objects compared to smokers.

With passage of the 2009 Family Smoking Prevention and Tobacco Control Act, the FDA has authority to regulate tobacco advertising. As bans on traditional advertising venues and promotion of tobacco products have grown, a greater emphasis has been placed on brand exposure and price promotion in displays of products at the point-of-sale (POS). POS marketing seeks to influence attitudes and behavior towards tobacco products using a variety of explicit and implicit messaging approaches. Behavioral laboratory methods have the potential to provide the FDA with a strong scientific base for regulatory actions and a model for testing future manipulations of POS advertisements. We review aspects of POS marketing that potentially influence smoking behavior, including branding, price promotions, health claims, the marketing of emerging tobacco products, and tobacco counter-advertising. We conceptualize how POS marketing potentially influence individual attention, memory, implicit attitudes, and smoking behavior. Finally, we describe specific behavioral laboratory methods that can be adapted to measure the impact of POS marketing on these domains.

Objective Little is known about factors associated with smoking cessation in cancer patients. This study examined the impact of panic attacks on smoking abstinence likelihood among cancer patients receiving tobacco cessation treatment. Method The relationship of panic attacks to 7-day point-prevalence abstinence at mid-treatment, end of treatment, and 6-month post-end of treatment were examined among cancer patients ( N = 2255 patients; 50.1% female; M age = 54.9, SD = 11.0) who received counseling and pharmacotherapy for smoking cessation. Panic attack history indexed by two questions from the Patient Health Questionnaire (PHQ). Point-prevalence abstinence was assessed via the Timeline Follow-Back. Results Cancer patients with a history of panic attacks, ( n = 493, 21.9%) relative to those without, were less likely to be abstinent at mid-treatment ( OR = 0.79, CI 95 % = 0.64–0.98) and end of treatment ( OR = 0.72, CI 95 % = 0.58–0.89). After adjusting for significant covariates, panic attack history remained predictive of decreased abstinence likelihood at end of treatment (OR = 0.78, CI 95 % = 0.62–0.99). Conclusions Panic attacks may be related to poorer cessation outcome during smoking treatment among cancer patients, and may be usefully assessed and targeted for intervention.

We investigated the effects of acute nicotine dose and expected dose on attentional bias (AB) to smoking and affective cues in overnight nicotine-deprived smokers ( n=51; 24 women) using a balanced placebo design, which counterbalanced given nicotine dose (Given-NIC vs. Given-DENIC) with instructed nicotine dose expectancy (Told-NIC vs. Told-DENIC). Before and after smoking a study cigarette, smokers completed a vigilance task where they pressed buttons to every third consecutive even or odd digit, while ignoring intermittent smoking, pleasant, unpleasant, and neutral picture distracters. We examined the early posterior negativity (EPN) and late positive potential (LPP) components of the event-related potentials (ERPs) to the distracters, reaction time (RT) to the target digits, and ratings of the study cigarettes. The EPN was sensitive to both given and instructed nicotine dose, while the instructed dose moderated the impact of given dose for the LPP. The RT metrics were sensitive to given but not to instructed dose. The effects of given dose on ratings following cigarette smoking (e.g. enjoyment) were moderated by the instructed dose. The ERP findings suggest that the anticipated effects of nicotine improve attention much like receiving actual nicotine.

In this study, we examined the relationship between the level of daily cigarette consumption and the startle response to affective and cigarette-related cues among treatment-seeking smokers. Before receiving any behavioral or pharmacological treatment, 136 smokers attended a baseline laboratory session, during which we recorded their reflexive eyeblink responses to acoustic startle probes while they were viewing pleasant, unpleasant, neutral, and cigarette-related pictures. We found that 1) cigarette-related and pleasant pictures similarly reduced the startle magnitude compared to neutral pictures; 2) the magnitude of startle modulation rendered by pleasant or unpleasant pictures did not differ among light, moderate, and heavy smokers; and 3) startle attenuation by cigarette-related pictures was greater in heavy smokers than in light smokers. These results suggest that similar to pleasant stimuli, cigarette-related cues are motivationally salient for smokers, and that this salience increases with nicotine dependence.

Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette-related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole-brain blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole-brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli.

Identifying addicts with higher risk of relapse would provide the opportunity to implement individualized interventions and increase cessation success rates. Unfortunately, the ability to predict the long-term success of drug-cessation treatments continues to elude researchers. We tested whether brain responses to emotional and cigarette-related pictures were predictive of the ability to abstain from smoking. Smokers interested in quitting (n=180) participated in a smoking cessation clinical trial. Before the initiation of any treatment we recorded event-related potentials (ERPs) evoked by emotional (both pleasant and unpleasant), neutral, and cigarette-related images. Cluster analysis was used to assign smokers to two groups based on the amplitude of the late positive potential (LPP) to the experimental stimuli. While both groups showed enhanced responses to cigarette-related cues, one group (n=81) also showed blunted brain responses to intrinsically pleasant stimuli. Smokers in the latter group were significantly less likely to be abstinent at 10, 12, and 24 weeks after their quit date. In conclusion, using event-related potentials, a direct measure of brain activity, we found that smokers with blunted brain responses to intrinsically pleasant stimuli had lower rates of long-term smoking abstinence. This response offers a new biomarker for identifying smokers at higher risk of relapse and for testing the efficacy of new interventions aimed at normalizing brain reward systems’ responses to intrinsically pleasant stimuli.

We conducted a double-blind pilot study involving 11 alcohol- and nicotine-dependent patients randomized to receive either bupropion or placebo. Four of six patients on bupropion and one of five patients on placebo were abstinent from smoking at the end of medication phase. Those in the bupropion group reported significantly less craving (p < .02) and less exposure to cigarette smoke over time (expired carbon monoxide; p < .01). There were no serious adverse events and no main effects of medication group on either per subject or total number of adverse events. All those who completed treatment remained abstinent from alcohol.