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Background: Nicotine use disorder is highly prevalent among methadone maintenance patients with its tobacco-related problems. However, the treatment modalities for nicotine use disorder remain limited., Objective: Our meta-analysis aims to examine the effectiveness of smoking cessation treatment in this group of patients., Methods: A total of 1358 participants were recruited from 9 eligible studies, published from the start of studies in this field till Feb 2016, identified from PubMed, OVID, EMBASE and Google Scholar databases. Two independent reviewers assessed the eligibility of each report based on predefined inclusion criteria. Pooled odd ratios or weighted mean difference was performed using random effects., Results: The treatments for smoking cessation among MMT patients are behavioral and pharmacological therapies. Smoking cessation was better achieved with nicotine replacement therapy (NRT) especially with adjunctive behavioral therapy. The pooled odds ratio of smokers' abstinence of smoking by the end of the treatment between NRT and placebo group was 6.32 (95% CI = 1.18 to 33.75, p = 0.03) and is statistically significant. Any additional behavior therapy among MMT patients who received the smoking cessation pharmacotherapy as the primary treatment was not better than those who only received standard care (Odds ratio was 2.53, 95% CI = 0.75 to 8.56, p = 0.14)., Conclusions: Although NRT is proven to be effective in smoking cessation, more studies are warranted to prove the effects of other pharmacotherapy in smoking cessation.

Nicotine is a stimulatory component in tobacco that activates the central nervous system reward pathway and causes nicotine dependence. We found that the anti-inflammatory agent, curcuminoid, prevents nicotine dependence and relapse, as assessed by the conditioned placed preference test. Curcuminoid (1, 3.2, and 10 mg·kg-1, oral) dose-dependently inhibited nicotine dependence and enhanced nicotine extinction when administrated 30 min prior to nicotine administration (0.5 mg·kg-1, i.p.) for 7 days. In addition, curcuminoid significantly suppressed the priming effects of nicotine and inhibited acetylcholinesterase (AChE) activity. Taken together, curcuminoid ameliorates nicotine dependence and relapse, in part via the inhibition of the AChE activity in the brain., (© 2018 S. Karger AG, Basel.)

Rationale: Individuals with attention deficit hyperactivity disorder (ADHD) start smoking earlier, are more likely to progress to nicotine dependence, and have a more difficult time quitting smoking compared to their non-ADHD peers. Little is known about the underlying behavioral mechanisms associated with this increased risk, particularly at the adolescent stage., Objective: This study aimed to assess the effects of overnight nicotine abstinence and smoking reinstatement on subjective withdrawal states in adolescent smokers with and without ADHD., Methods: Adolescent daily smokers (27 with ADHD and 17 without ADHD) completed three experimental sessions: (1) a placebo patch followed by smoking a nicotine cigarette, (2) placebo patch followed by smoking a nicotine-free cigarette, and (3) nicotine patch followed by smoking a nicotine-free cigarette. Subjects abstained overnight before each session, and patches were administered 45 min before smoking. The primary outcome measure was a smoking withdrawal symptom questionnaire., Results: ADHD smokers experienced greater difficulty concentrating and impatience/restlessness during abstinence than non-ADHD smokers. Smoking a cigarette improved abstinence-induced difficulty concentrating and restlessness, regardless of its nicotine content, and regardless of whether transdermal nicotine was received or not., Conclusions: Thus, sensorimotor aspects of smoking, rather than nicotine itself, appeared to relieve withdrawal. Although ADHD smokers report greater withdrawal symptoms than non-ADHD smokers, they responded strongly to the sensorimotor aspects of smoking during withdrawal. These findings suggest that even lighter, adolescent smokers with ADHD are vulnerable to smoking progression through altered smoking abstinence and withdrawal relief processes.

Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related or food-related video clips prior to randomization to treatment with varenicline (n = 80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN blood-oxygen-level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In correcting for baseline smoking and other clinical variables, which have been shown to be related to treatment outcome in previous work, a less positive Smoke - Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (P = 0.005, β = -0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke - Food difference score for executive control network predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have a direct clinical relevance in NUD., (© 2017 Society for the Study of Addiction.)

Rationale: Policies that establish a standard for reduced nicotine content in cigarettes can decrease the prevalence of smoking in the USA. Cigarettes with nicotine yields as low as 0.05 mg produce substantial occupancy of nicotinic acetylcholine receptors (26%), but women and men respond differently to these cigarettes., Objective: This study aimed to measure responses to smoking cigarettes that varied widely in nicotine yields, investigating whether sex differences in the effects on craving, withdrawal, and affect would be observed at even lower nicotine yields than previously studied, and in young smokers., Methods: Overnight abstinent young smokers (23 men, 23 women, mean age 22.18) provided self-reports of craving, withdrawal, and affect before and after smoking cigarettes with yields of 0.027, 0.110, 0.231, or 0.763 mg nicotine, and evaluated characteristics of each cigarette., Results: Compared to abstinent young men, abstinent young women reported greater negative affect, psychological withdrawal, and sedation, all of which were relieved equally by all cigarettes. Men but not women reported greater craving reduction, perceived nicotine content, and cigarette liking with increasing nicotine dose., Conclusions: Men may experience less smoking-related relief of craving, and enjoy cigarettes less, if nicotine yields are reduced to very low levels. Conversely, women respond equally well to cigarettes with nicotine yields as low as 0.027 mg as to cigarettes with nicotine yields 28-fold higher (0.763 mg). These differences are relevant for policy regarding reduced nicotine in cigarettes and may influence the efficacy and acceptability of reduced-nicotine cigarettes as smoking cessation aids.

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To investigate whether age is associated with access to smoking cessation services., Design: Data from the Smoking Toolkit Study 2006-2015, a repeated multiwave cross-sectional household survey (n=181 157)., Setting: England., Participants: Past-year smokers who participated in any of the 102 waves stratified into age groups., Outcome Measures: Amount smoked and nicotine dependency, self-reported quit attempts and use of smoking cessation interventions. Self-report of whether the general practitioner (GP) raised the topic of smoking and made referrals for pharmacological support (prescription of nicotine replacement therapies (NRTs)) or other support (counselling or support groups)., Results: Older smokers (75+ years) were less likely to report that they were attempting to quit smoking or seek help from a GP, despite being less nicotine-dependent. GPs raised smoking as a topic equally across all age groups, but smokers aged 70+ were more likely not to be referred for NRT or other support (ORs relative to 16-54 years; 70-74 years 1.27, 95% CI 1.03 to 1.55; 75-79 years 1.87, 95% CI 1.43 to 2.44; 80+ years 3.16, 95% CI 2.20 to 4.55; p value for trend <0.001)., Conclusions: Our findings suggest that there are potential missed opportunities in facilitating smoking cessation in older smokers. In this large population-based study, older smokers appeared less interested in quitting and were less likely to be offered support, despite being less addicted to nicotine than younger smokers. It is unclear whether this constitutes inequitable access to services or reflects informed choices by older smokers and their GPs. Future research is needed to understand why older smokers and GPs do not pursue smoking cessation. Service provision should consider how best to reduce these variations, and a stronger effectiveness evidence base is required to support commissioning for this older population so that, where appropriate, older smokers are not missing out on smoking cessation therapies and the health benefits of cessation at older ages., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Many cigarette smokers express a desire to quit smoking, but ~85% of cessation attempts fail. In our attempt to delineate genetic modulators of smoking persistence, we have earlier shown that a locus within an ~250 kb haplotype block spanning the 5' untranslated region region of insulin-degrading enzyme is associated with serum cotinine levels; the study's measure of smoking quantity. Based on our findings, and coupled with recent preclinical studies showing the importance of multiple neuropeptides in reinstatement of drug use, we formulated intranasal insulin to evaluate its efficacy during acute abstinence from smoking. Our original study was a crossover trial including 19 otherwise healthy smokers who abstained from smoking for 36 h. The morning following their second night of abstinence, in random order, study participants received intranasal insulin (60 IU) or placebo (8.7% sodium chloride). The goal of our second study was to replicate the craving findings from the original trial and expand this research by including additional stress-related measures. Thirty-seven study participants abstained from smoking overnight. The next day, they were administered either intranasal insulin (60 IU) or placebo, following which they participated in the Trier Social Stress Test Task. This was a parallel design study focusing on the standard stress subjective, hormonal and cardiovascular measures. We also evaluated any changes in circulating glucose, insulin and c-peptide (a marker of endogenous insulin). In the original study, intranasal insulin significantly reduced morning nicotine craving (b=3.65, P⩽0.05). Similarly, in the second study, intranasal insulin reduced nicotine cravings over time (b=0.065, P⩽0.05) and the effect lasted through the psychosocial stress period. Intranasal insulin also increased circulating cortisol levels (F=12.78, P⩽0.001). No changes in insulin or c-peptide were detected. A significant treatment × time interaction (P⩽0.05) was detected for glucose, but subjects remained well within the euglycemic range. Previous studies have shown that heightened nicotine cravings and blunted response to stress are independent and significant predictors of relapse to smoking. In our study, intranasal insulin normalized the subjective and hormonal response to stress. As such, intranasal insulin should further be studied in a larger clinical trial of smoking cessation. In support of this, we provide evidence that the treatment is safe and effective and, based on absence of peripheral insulin changes, conclude that the pharmacodynamic effect is centrally driven.

Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation. Smoking related behaviors and neurotransmitter concentrations in the dorsal anterior cingulate cortex were assessed before and after treatment. Forty-seven non-smoking males served as baseline controls. Smokers showed higher baseline glutamate but similar gamma-aminobutyric acid concentrations than non-smokers. There were no treatment effects on dorsal anterior cingulate cortex neurotransmitter concentrations, smoking cessation, craving, or withdrawal symptoms. These results confirm glutamate disbalance in smokers, but not efficacy of N-acetylcysteine.

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., (Copyright © 2016 John Wiley & Sons, Ltd.)

Evidence is mixed on whether timing of a target quit date (TQD) has an effect on quit success. The purpose of this secondary analysis of data from a prospective longitudinal study was to determine if time to TQD was a predictor of smoking abstinence at follow-up. Between 2011 and 2013, a total of 5,793 adult smokers participated in a 1-hr psychoeducation workshop and received 5 weeks of nicotine patch treatment. All participants were required to indicate a TQD within 1 month of the workshop. Latency to TQD was categorized into quartiles: 0 to 1 day (first quartile: 28.1%); 2 to 6 days (second quartile: 22.4%); 7 to 19 days (third quartile: 25.4%); 20-31 days (fourth quartile: 24.0%). Compared with participants who chose an immediate TQD within 1 day of the workshop, odds of having quit smoking at end-of-treatment and 6-month follow-up did not significantly differ among those who set a TQD within 2-6 days (5-weeks: adjusted odds ratio [AOR] = 0.89, p = .315; 6-months: AOR = 0.89, p = .417), but were significantly lower for those who chose a TQD either 7-19 days (5-weeks: AOR = 0.76, p = .023; 6-months: AOR = 0.70, p = .013) or 20-31 days (5-weeks: AOR = 0.64, p = .001; 6-months: AOR = 0.69, p = .017) after the workshop. TQD timing was an independent predictor of smoking cessation outcomes after controlling for potential confounding variables including confidence in quitting ability, importance of quitting, nicotine dependence, and number of nicotine patches used. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Nicotine replacement therapy is widely used in critically ill smokers and its effect on delirium, mortality and duration of intensive care unit (ICU) admission is unknown. The aims of this review were to determine whether the management of nicotine withdrawal with nicotine replacement therapy reduces delirium, mortality or length of stay in critically ill smokers in ICU. The primary outcome was incidence of author-defined ICU delirium. Secondary outcomes were ICU or hospital mortality, ICU-free days at day 28, and ICU or hospital length of stay. We conducted a systematic review and meta-analysis of the data sources MEDLINE, EMBASE, CINAHL, and the Cochrane Database of Systematic Reviews for randomised controlled trials and observational studies. Clinical trials, observational studies and systematic reviews comparing nicotine replacement therapy with placebo or no treatment were included. Case reports, case series, non-systematic reviews and studies that involved children were excluded. Eight studies were eligible (n=2,636) for inclusion in the data synthesis. In a meta-analysis of observational studies, nicotine replacement therapy was associated with increased delirium (three studies; n=908; I 2 =0%; finite element method: odds ratio 4.03 [95% confidence interval 2.64, 6.15]; P <0.001). There was no difference in ICU mortality (three studies; n=1,309; P =0.10, I 2 =44%; finite element method: odds ratio 0.58; 95% confidence intervals 0.31-1.10) and hospital mortality or 28-day ICU-free days. In the absence of high-quality data, nicotine replacement therapy cannot currently be recommended for routine use to prevent delirium or to reduce hospital or ICU mortality in critically ill smokers.

Background: Prevalence of smoking among individuals with posttraumatic stress disorder (PTSD) is disproportionately high, and PTSD is associated with especially poor response to smoking cessation treatment., Objective: The current study examined whether integrating treatments for smoking cessation (varenicline plus smoking cessation counseling; VARCC) and PTSD (prolonged exposure therapy; PE) enhances smoking outcomes among smokers diagnosed with PTSD., Method: 142 adults with nicotine dependence (ND) and PTSD were randomized to a treatment program consisting of varenicline, smoking cessation counseling, and PE (VARCC + PE) or to VARCC only. Seven-day point prevalence abstinence (PPA) at posttreatment (3-months postquit day) and follow-up (6-months postquit day), verified by serum cotinine levels and exhaled carbon monoxide, was the primary smoking outcome. Psychological outcomes were PTSD and depression severity. Mixed effects models included baseline PTSD severity as a moderator of treatment condition effects., Results: Overall, VARCC + PE participants did not show greater PPA than VARCC participants. However, treatment effects were moderated by baseline PTSD severity. For participants with moderate and high PTSD severity, VARCC + PE led to significantly higher PPA than VARCC alone (ps<.05). No differences between treatment conditions emerged for participants with low baseline PTSD severity. Participants who received PE showed significantly greater reduction of PTSD and depression symptoms than those who did not receive PE., Conclusions: Integrating psychological treatment for PTSD and smoking cessation treatment enhances smoking cessation for participants with moderate or severe PTSD symptom severity, but does not enhance smoking cessation for participants with low baseline PTSD severity. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

The strong reinforcing effects of nicotine and the negative symptoms such as anxiety experienced during a quit attempt often lead to relapse and low success rates for smoking cessation. Treatments that not only block the reinforcing effects of nicotine but also attenuate the motivation to relapse are needed to improve cessation rates. Recent genetic and preclinical studies have highlighted the involvement of the α3, β4, and α5 nicotinic acetylcholine receptor (nAChR) subunits and the α3β4 nAChR subtype in nicotine dependence and withdrawal. However, the involvement of these nAChR in relapse is not fully understood. We previously reported that the α3β4 nAChR partial agonist AT-1001 selectively decreases nicotine self-administration in rats without affecting food responding. In the present experiments, we examined the efficacy of AT-1001 in attenuating reinstatement of nicotine-seeking behavior in a model of stress-induced relapse. Rats extinguished from nicotine self-administration were treated with the pharmacological stressor yohimbine prior to AT-1001 treatment and reinstatement testing. We also examined whether AT-1001 produced any withdrawal-related effects when administered to nicotine-dependent rats. We found that AT-1001 dose-dependently reduced yohimbine stress-induced reinstatement of nicotine seeking. When administered to nicotine-dependent rats at the dose that significantly blocked nicotine reinstatement, AT-1001 elicited minimal somatic withdrawal signs in comparison to the nicotinic antagonist mecamylamine, which is known to produce robust withdrawal. Our data suggest that α3β4 nAChR-targeted compounds may be a promising approach for nicotine addiction treatment because they can not only block nicotine's reinforcing effects, but also decrease motivation to relapse without producing significant withdrawal effects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Post-cessation weight gain (PCWG) is a major barrier to maintaining abstinence, especially in weight-concerned smokers. Varenicline is the most effective medication for smoking cessation but has minimal impact on PCWG. Lorcaserin is an FDA-approved medication for weight management in overweight or obese patients which also provides a noticeable benefit in treating drug dependence. We hypothesized that combining varenicline with lorcaserin may help prevent PCWG. We conducted an open-label, single arm, Phase II clinical pilot study to obtain preliminary data on the safety and effectiveness of combination varenicline and lorcaserin in preventing PCWG in overweight and obese smokers., Methods: Twenty overweight or obese (body mass index 27-40 kg/m2) cigarette smokers were enrolled. The primary outcomes were weight and waist circumference (WC) changes at 12 and 26 weeks in smokers meeting criteria for prolonged smoking abstinence. All participants received open-label varenicline (1 mg twice a day) and lorcaserin (10 mg twice a day) for 12 weeks with follow-up at 26 weeks., Results: Ten subjects met criteria for prolonged smoking abstinence at 12 weeks (50%) and 6 at 26 weeks (30%). Among those achieving prolonged smoking abstinence at 12 weeks, WC was +0.2 ± 6.0 cm (90% CI; -2.9, +3.4) and weight gain was +1.1 ± 3.9 kg (90% CI; -0.9, +3.1)., Conclusions: Weight gain and WC increases following prolonged smoking abstinence may be reduced among overweight and obese smokers using combination varenicline and lorcaserin. This combinatory treatment warrants further research in the obese and weight-concerned smoking population., Implications: This is the first published prospective pilot study to evaluate lorcaserin for use in reducing PCWG in overweight and obese smokers. When combined with varenicline, lorcaserin minimized PCWG and increases in WC. In addition to the benefit on PCWG reduction, lorcaserin may be a potential new pharmacological treatment for smoking cessation and warrants further larger studies., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: This study assessed the impact of expectancy and administration components of acute nicotine inhaler use on craving, heart rate, and smoking behavior in smokers with varying intentions to quit., Methods: 47 dependent smokers that differed in self-reported intention to quit (no intention to quit during the next month N = 26 vs. intention to initiate a quit attempt within 2 weeks N = 21) were randomly administered a 4 mg nicotine or nicotine-free inhaler across two sessions. Instructions regarding the inhaler's nicotine content (expect nicotine vs. expect nicotine-free; nicotine expectancy) and flavor (mint vs. citrus) varied across sessions. Craving and heart rate were assessed before and after inhaler administration (two-second inhalations every 10 seconds over 20 minutes). Next, participants were offered an opportunity to self-administer puffs of their preferred tobacco brand during an hour-long progressive ratio task., Results: Across participants, nicotine expectancy independently reduced withdrawal related craving (p = .018), but no comparable effects of nicotine administration were evident. In quitting motivated smokers, nicotine expectancy and administration interacted to reduce intention to smoke (p = .040), while nicotine expectancy (p = .047) and administration (p = .025) independently reduced intention to smoke in quitting unmotivated smokers. Blunted heart rate reactivity to nicotine administration was observed in quitting motivated relative to unmotivated smokers (p = .042); however, neither expectancy nor administration impacted smoking behavior in either group (p values > .25)., Conclusions: Findings indicate that participant quitting intentions moderate acute nicotine replacement therapy responses. In quitting motivated smokers, a combination of pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving., Implications: Findings from this study demonstrate that motivations to quit smoking moderate subjective and physiological responses to acute nicotine administration and expectancy in dependent cigarette smokers. Quitting motivated smokers showed blunted heart rate reactivity to nicotine administration, suggesting that they may be less sensitive to the rewarding aspects of nicotine consumption. Nicotine administration and expectancy were found to interact to reduce craving in quitting motivated but not in unmotivated smokers, suggesting that pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving in smokers who plan to quit., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Altered resting state functional connectivity (rsFC) and functional network connectivity (FNC), which is a measure of coherence between brain networks, may be associated with nicotine use disorder (NUD). We hypothesized that higher connectivity between insula and 1) dorsal anterior cingulate cortex (dACC) and 2) dorsolateral prefrontal cortex (dlPFC) would predict better treatment outcomes. We also performed an exploratory analysis of the associations between FNC values between additional key frontal and striatal regions and treatment outcomes. One hundred and forty four individuals with NUD underwent a resting state session during functional MRI prior to randomization to treatment with varenicline (n=82) or placebo. Group independent component analysis (ICA) was utilized to extract individual subject components and time series from intrinsic connectivity networks in aforementioned regions, and FNC between all possible pairs were calculated. Higher FNC between insula and dACC (rho=0.21) was significantly correlated with lower levels of baseline smoking quantity but did not predict treatment outcome upon controlling for baseline smoking. Higher FNC between putamen and dACC, caudate and dACC, and caudate and dlPFC significantly predicted worse treatment outcome in participants reporting high subjective withdrawal before the scan. FNC between key regions hold promise as biomarkers to predict outcome in NUD., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Large-scale distribution efforts of free nicotine replacement therapy (NRT) have been documented to be cost-effective interventions for increasing smoking quit rates. However, despite nearly a dozen studies evaluating their effectiveness, none have examined whether free NRT provision promotes further primary care help-seeking and the impact that it may have on cessation efforts., Methods: In the context of a randomized controlled trial, a secondary analysis was conducted on 1000 adult regular smokers randomized to be mailed a 5-week supply of nicotine patches or to a no intervention control group. Recipients and users of free nicotine patches at an 8 week follow-up were successfully case matched to controls based on age, gender, baseline level of nicotine dependence and intent to quit (n = 201 per group). Differences in physician interaction between the two groups were evaluated at both 8 week and 6 month follow-ups. The impact of physician interaction on self-reported smoking abstinence at each follow-up was also examined., Results: Although no differences in physician interaction were noted between groups at the 8 week follow-up, at the 6 month follow-up, nicotine patch users reported greater frequency of discussing smoking with their physician (43.9%), as compared to the control group (30.3%) (p = 0.011). Across both groups, over 90% of those that discussed smoking with a physician were encouraged to quit and approximately 70% were provided with additional support. Separate ANOVAs revealed no significant impact of physician interaction on cessation (p > 0.05), regardless of group or follow-up period, however, at the 6 month follow-up, nicotine patch users who discussed cessation with a physician had made serious quit attempts at significantly greater rates (72.6%), compared to controls (49.1%) (p = 0.007)., Conclusions: Irrespective of group, the majority of smokers in the present study did not discuss cessation with their physician. Recipients and users of nicotine patches however, were more likely to discuss smoking with their physician, suggesting that the provision of free NRT particularly to those who are likely to use it may facilitate opportunities for benefits beyond the direct pharmacological effects of the medication., Trial Registration: clinicaltrials.gov , NCT01429129 . Registered: 2 September 2011.

Background/aim: Because of the major health problems and annual economic burden caused by cigarette smoking, effective new tools for smoking intervention are urgently needed. Our previous randomized controlled trial (RCT) provided promising results on the efficacy of slow-release L-cysteine lozenge in smoking intervention, but the study was not adequately powered. To confirm in an adequately-powered study the results of the previous RCT implicating that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium® lozenge, Biohit Oyj, Helsinki), would assist in smoking cessation by reducing acetaldehyde-enhanced nicotine addiction. On this matter, we undertook a double-blind, randomized, placebo-controlled trial comparing Acetium® lozenge and placebo in smoking intervention., Materials and Methods: A cohort of 1,998 cigarette smokers were randomly allocated to intervention (n=996) and placebo arms (n=1,002). At baseline, smoking history was recorded by a questionnaire, with nicotine dependence testing according to the Fagerström scale (FTND). The subjects used smoking diary recording the daily numbers of cigarettes, lozenges and subjective sensations of smoking. The data were analysed separately for point prevalence of abstinence (PPA) and prolonged abstinence (PA) endpoints., Results: Altogether, 753 study subjects completed the trial per protocol (PP), 944 with violations (mITT), and the rest (n=301) were lost to follow-up (LTF). During the 6-month intervention, 331 subjects stopped smoking; 181 (18.2%) in the intervention arm and 150 (15.0%) in the placebo arm (OR=1.43; 95%CI=1.09-1.88); p=0.010). In the PP group, 170 (45.3%) quitted smoking in the intervention arm compared to 134 (35.4%) in the placebo arm (OR=1.51, 95%CI=1.12-2.02; p=0.006). In multivariate (Poisson regression) model, decreased level of smoking pleasure (p=0.010) and "smoking sensations changed" were powerful independent predictors of quit events (IRR=12.01; 95%CI=1.5-95.6)., Conclusion: Acetium® lozenge, herein confirmed in an adequately powered study to be an effective means to aid smoking quit, represents a major breakthrough in the development of smoking intervention methods, because slow-release L-cysteine is non-toxic, with no side-effects or limitations of use., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Aims: The effects of medically-aided smoking cessation on vascular function and oxidative stress are not fully clarified., Methods: One hundred eighty-eight current smokers were randomized to varenicline or nicotine replacement treatment (NRT) for a 3-month period. We assessed: (a) augmentation index (Aix) and pulse wave velocity (PWV); (b) perfusion boundary region (PBR) of sublingual microvasculature (range:5-25 μm), an index of the endothelial glycocalyx thickness, using Sideview, Darkfield imaging; (c) the exhaled CO; and (d) the malondialdehyde (MDA) and protein carbonyls (PC) plasma levels, as markers of oxidative stress, at baseline and after 3 and 12 months., Results: After 3 months of treatment, CO, MDA, PC and Aix were decreased in all subjects (median CO: 25 vs. 6 ppm, MDA: 0.81 vs. 0.63 nmol/L, PC: 0.102, vs. 0.093 nmol/mg protein, Aix: 13% vs. 9%, p < 0.05) while PWV remained unchanged. Endothelial glycocalyx integrity showed a greater improvement in the varenicline than the NRT treatment (PBR range 5-9 μm: 1.07 ± 0.02 vs. 1.17 ± 0.02 μm, p = 0.03) in parallel with the greater CO reduction (5 vs. 7 ppm, p = 0.02). At 1-year follow-up, MDA, PC, Aix and PBR at 5-25 μm range were further improved in subjects who abstained from smoking (n = 84 out of 188), while the above markers and PWV deteriorated in relapsed smokers (p < 0.05)., Conclusions: A smoking cessation program using varenicline or NRT for 3 months resulted in a decrease of CO, oxidative stress, arterial stiffness and restored endothelial glycocalyx. These effects were more evident after varenicline treatment, likely because of a greater CO reduction, and were maintained after 1 year only in subjects who abstained from smoking., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Research shows that abstinence from tobacco leads to a withdrawal-related decrement in responsivity to nondrug rewards (ie, anhedonia). However, it remains unclear how anhedonia relates to other key withdrawal symptoms and withdrawal-related constructs over time. We analyzed ecological momentary assessment data to examine whether a decrement in response to rewards during a 10-day period following quitting shows a pattern of associations with other variables (ie, treatment, tobacco dependence, negative affect, and craving) that is consistent with anhedonia being a tobacco withdrawal symptom., Methods: As part of a randomized controlled trial of smoking cessation therapies, 1122 adults (58% female) were assigned to: placebo (n = 131), bupropion (alone or with nicotine lozenge; n = 401), or nicotine replacement therapy (NRT; lozenge, patch, both; n = 590). Participants completed 4 ecological momentary assessments per day for 10 days postquit, resulting in 22 575 assessments., Results: Time-varying effect modeling showed that anhedonia was significantly greater among those high in dependence relative to lower dependent smokers out to day 9 postquit. The placebo group showed elevated anhedonia immediately postquit, which fell to levels similar to the treatment groups by day 7. NRT effectively reduced anhedonia and its time-varying association with craving early in the quit attempt. The positive association between negative affect and anhedonia was moderate and stable over time for both active treatment groups., Conclusions: These results provide additional support that anhedonia following quitting smoking is a manifestation of the tobacco withdrawal syndrome., Implications: This study supported the hypothesis that diminished responsivity to nondrug rewards (ie, anhedonia) is a symptom of the tobacco withdrawal syndrome. Results showed that anhedonia: (1) was significantly associated with dependence, especially during the early postquit period when withdrawal was at its peak intensity; (2) showed significant time-varying associations with other withdrawal symptoms, especially craving; and (3) was significantly suppressed by agonist administration as was its association with craving over time., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Rationale: The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction., Objectives: The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking., Results: The reviewed studies indicate that several drugs that target neuropeptide systems diminish the rewarding effects of nicotine by preventing the activation of dopaminergic systems. Other peptide-based drugs diminish the hyperactivity of brain stress systems and diminish withdrawal-associated symptom severity. Blockade of hypocretin-1 and nociceptin receptors and stimulation of galanin and neurotensin receptors diminishes the rewarding effects of nicotine. Both corticotropin-releasing factor type 1 and kappa-opioid receptor antagonists diminish dysphoria and anxiety-like behavior associated with nicotine withdrawal and inhibit stress-induced reinstatement of nicotine seeking. Furthermore, blockade of vasopressin 1b receptors diminishes dysphoria during nicotine withdrawal, and melanocortin 4 receptor blockade prevents stress-induced reinstatement of nicotine seeking. The role of neuropeptide systems in nicotine-primed and cue-induced reinstatement is largely unexplored, but there is evidence for a role of hypocretin-1 receptors in cue-induced reinstatement of nicotine seeking., Conclusion: Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience.

Objective: To compare the effect of maintenance pharmacotherapy on sustained abstinence rates between recently abstinent smokers with schizophrenia and bipolar disorder (SBD) and general population smokers without psychiatric illness., Method: We performed a person-level, pooled analysis of two randomized controlled trials of maintenance varenicline, conducted in adult smokers with SBD and general population smokers, controlling for severity of dependence. Smokers abstinent after 12-weeks of open varenicline treatment were randomly assigned to ≥12-weeks maintenance varenicline or identical placebo., Results: In those assigned to maintenance placebo, the abstinence rate at week-24 was lower in those with SBD than for those without psychiatric illness (29.4±1.1% vs. 61.8±0.4%, OR:0.26, 95% CI: 0.13, 0.52, p<0.001). In smokers assigned to maintenance pharmacotherapy, however, there was no effect of diagnosis on abstinence rates at week-24 (87.2±0.8% vs. 81.9±0.2%, OR: 1.68, 95% CI: 0.53, 5.32, p=0.38). Time to first lapse was shortest in those with SBD assigned to maintenance placebo (Q1=12days, 95%CI: 4, 16), longer in those without psychiatric illness assigned to maintenance placebo (Q1=17days, 95%CI: 17, 29), still longer in general-population smokers assigned to maintenance varenicline (Q1=88, 95% CI:58,91, and longest in those with SBD who received maintenance varenicline (Q1>95days, 95%CI:non-est), (Χ 2 3df =96.99, p<0.0001; all pairwise comparisons p<0.001)., Conclusions: Following a standard 12-week course of pharmacotherapy, people with schizophrenia and bipolar disorder were more likely to relapse to smoking without maintenance varenicline treatment. Maintenance pharmacotherapy could improve longer-term tobacco abstinence rates and reduce known smoking-related health disparities in those with SMI., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Nicotine addiction continues to be a health challenge across the world. Despite several approved medications, smokers continue to relapse. Several human and animal studies have evaluated the role of the endogenous opioid system as a potential target for smoking cessation medications., Methods: In this review, studies that have elucidated the role of the mu (MORs), delta (DORs), and kappa (KORs) opioid receptors in nicotine reward, nicotine withdrawal, and reinstatement of nicotine seeking will be discussed. Additionally, the review will discuss discrepancies in the literature and therapeutic potential of the endogenous opioid system, and suggest studies to address gaps in knowledge with respect to the role of the opioid receptors in nicotine dependence., Results: Data available till date suggest that blockade of the MORs and DORs decreased the rewarding effects of nicotine, while activation of the MORs and DORs decreased nicotine withdrawal-induced aversive effects. In contrast, activation of the KORs decreased the rewarding effects of nicotine, while blockade of the KORs decreased nicotine withdrawal-induced aversive effects. Interestingly, blockade of the MORs and KORs attenuated reinstatement of nicotine seeking. In humans, MOR antagonists have shown benefits in select subpopulations of smokers and further investigation is required to realize their full therapeutic potential., Conclusion: Future work must assess the influence of polymorphisms in opioid receptor-linked genes in nicotine dependence, which will help in both identifying individuals vulnerable to nicotine addiction and the development of opioid-based smoking cessation medications. Overall, the endogenous opioid system continues to be a promising target for future smoking cessation medications.

Rationale: Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high, and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments., Objective: The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence., Results: Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction., Conclusions: Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence, they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many "off-target" effects to be used clinically. However, newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence.

Firsthand and secondhand tobacco use is linked to a multitude of harmful illnesses, adverse perinatal outcomes, and death. Cessation attempts among women may be hampered by their unique biologic response to nicotine. Current research has revealed epigenetic changes from intrauterine nicotine exposure that have intergenerational consequences. Multiple studies have demonstrated the efficacy of various pharmacologic tobacco cessation interventions in conjunction with behavioral counseling. Based on this evidence, the US Preventative Services Task Force (USPSTF) 2015 guideline recommends pharmacologic therapy for all nonpregnant persons who smoke in addition to behavioral counseling. The effectiveness of pharmacologic treatments among pregnant women is less clear, with far fewer studies evaluating potential benefits and harms. While exposure to pharmacologic therapies raises concerns for fetal safety, these potential risks must be weighed against those of continued tobacco use, which guarantees fetal exposure to nicotine. First-line tobacco cessation medications include nicotine replacement therapy (NRT), bupropion, and varenicline. Second-line medications include nortriptyline and clonidine. Pharmacokinetics, effectiveness, regimens, and safety profiles for nonpregnant, pregnant, and lactating women are reviewed. Alternative tobacco cessation options and potential new pharmacologic tobacco cessation agents are discussed. Initiating brief interventions, using the 5A's and 5R's model is described., (© 2017 by the American College of Nurse-Midwives.)

Identifying smokers at high risk of relapse could improve the effectiveness of cessation therapies. Although altered regional brain function in smokers has been reported, whether the whole-brain functional organization differs smokers with relapse vulnerability from others remains unclear. Thus, the goal of this study is to investigate the baseline functional connectivity differences between relapsers and quitters. Using resting-state fMRI, we acquired images from 57 smokers prior to quitting attempts. After 12-week treatment with varenicline, smokers were divided into relapsers (n=36) and quitters (n=21) (quitter: continuously abstinent for weeks 9-12). The smoking cessation outcomes were cross-validated by self-reports and expired carbon monoxide. We then used eigenvector centrality (EC) mapping to identify the functional connectivity differences between relapsers and quitters. When compared to quitters, increased EC in the right dorsolateral prefrontal cortex (DLPFC), left middle temporal gyrus (MTG) and cerebellum anterior lobe was observed in relapsers. In addition, a logistic regression analysis of EC data (with DLPFC, MTG and cerebellum included) predicted relapse with 80.7% accuracy. These findings suggest that the DLPFC, MTG and cerebellum may be important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified before quit attempts, which could enable personalized treatment and improve smoking cessation outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: This prospective analysis of the Japanese subpopulation of the varenicline reduce to quit study was conducted to evaluate whether results for Japanese participants were consistent with the full study population., Methods: Patients received varenicline or placebo for a 24-week treatment period (12-week smoking reduction phase then a 12-week smoking abstinence phase) followed by a 28-week nontreatment, follow-up phase. Participants were to reduce the daily number of cigarettes smoked by at least 50% by week 4 and by a further 50% by week 8, with the goal of achieving complete abstinence by week 12. The primary efficacy end point was the carbon monoxide-confirmed continuous abstinence during weeks 15 to 24., Findings: Overall, 210 Japanese patients were randomly assigned to 1 of the 2 study groups (varenicline, 107; placebo, 103). Continuous abstinence rates for weeks 15 to 24 were higher for participants in the varenicline group versus the placebo group (46.7% vs 12.6%; odds ratio = 14.68; 95% CI, 5.38-40.05), and the 7-day point prevalence of abstinence rates were higher for varenicline versus placebo at week 12 (odds ratio = 13.76; 95% CI, 5.28-35.86). The number of participants with a ≥50% reduction in the number of daily cigarettes smoked from baseline to week 4 and a ≥75% reduction by week 8 was greater in the varenicline group versus the placebo group (week 4: 59.8% vs 30.1%; week 8: 38.3% vs 12.6%). Serious adverse events were reported in 3.7% of varenicline participants and 1.0% of placebo participants., Implications: The efficacy and tolerability results of this analysis are consistent with those of the full varenicline reduce to quit study. Varenicline treatment and cigarette reduction before quitting may provide an alternative approach to smoking cessation in Japanese smokers who are not ready to quit immediately. ClinicalTrials.gov identifier: NCT01370356., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Co-occurring addictive disorders are common, however treatment strategies for this population have not been extensively studied. This is especially the case for behavioral addictions., Methods: We present a patient (N = 1) with tobacco use disorder and problematic pornography use treated with naltrexone., Results: Naltrexone treatment resulted in a decrease in pornography viewing and cigarette smoking, however had the adverse effect of anhedonia. A lower dose modestly impacted pornography viewing but not smoking., Discussions and Conclusions: Relevant literature regarding co-occurring addictions as well as use of naltrexone is reviewed., Scientific Significance: This report represents the first case of tobacco and pornography co-addiction in the literature and supports the assertion that treatment of one addictive disorder can benefit another in the dually addicted patient. The efficacy of naltrexone for smoking is notable as previous studies of naltrexone in smoking have been disappointing. This case suggests future treatment strategies for comorbid addictions. (Am J Addict 2017;26:115-117)., (© 2017 American Academy of Addiction Psychiatry.)

Objective: To assess state coverage and utilization of Medicaid smoking cessation medication benefits among fee-for-service enrollees who smoked cigarettes., Methods: We used the linked National Health Interview Survey (survey years 1995, 1997-2005) and the Medicaid Analytic eXtract files (1999-2008) to assess utilization of smoking cessation medication benefits among 5,982 cigarette smokers aged 18-64 years enrolled in Medicaid fee-for-service whose state Medicaid insurance covered at least one cessation medication. We excluded visits during pregnancy, and those covered by managed care or under dual enrollment (Medicaid and Medicare). Multivariate logistic regression was used to determine correlates of cessation medication benefit utilization among Medicaid fee-for-service enrollees, including measures of drug coverage (comprehensive cessation medication coverage, number of medications in state benefit, varenicline coverage), individual-level demographics at NHIS interview, age at Medicaid enrollment, and state-level cigarette excise taxes, statewide smoke-free laws, and per-capita tobacco control funding., Results: In 1999, the percent of smokers with ≥1 medication claims was 5.7% in the 30 states that covered at least one Food and Drug Administration (FDA)-approved cessation medication; this increased to 9.9% in 2008 in the 44 states that covered at least one FDA-approved medication (p<0.01). Cessation medication utilization was greater among older individuals (≥ 25 years), females, non-Hispanic whites, and those with higher educational attainment. Comprehensive coverage, the number of smoking cessation medications covered and varenicline coverage were all positively associated with utilization; cigarette excise tax and per-capita tobacco control funding were also positively associated with utilization., Conclusions: Utilization of medication benefits among fee-for-service Medicaid enrollees increased from 1999-2008 and varied by individual and state-level characteristics. Given that the Affordable Care Act bars state Medicaid programs from excluding any FDA-approved cessation medications from coverage as of January 2014, monitoring Medicaid cessation medication claims may be beneficial for informing efforts to increase utilization and maximize smoking cessation.

While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal. Insights into how this circuit interconnects with regions more classically associated with anxiety, and how chronic nicotine exposure induces neuroadaptations resulting in an anxiogenic state, may thereby provide novel strategies and molecular targets for therapies that facilitate smoking cessation, as well as for anxiety relief., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Individuals in the U.S. criminal justice system now represent over 12% of all current U.S. smokers. With smoking banned in most U.S. jails and prisons, the cessation focus for this population has shifted to individuals who are under community correction supervision (e.g., probation, parole). The aim of this study was to examine predictors of successful smoking cessation among criminal justice individuals supervised in the community., Methods: Five hundred participants under community corrections supervision were randomized to receive either four sessions of smoking cessation counseling or no counseling in conjunction with 12weeks of bupropion treatment plus brief physician advice to quit. Logistic regression analyses examined associations of smoking variables with medication adherence and successful abstinence. Mediation analysis evaluated the indirect effects of medication adherence on smoking abstinence., Results: The strongest associate of medication adherence was previous use of bupropion, while the strongest associate of smoking abstinence was medication adherence. Mediation analysis indicated that previous use of bupropion indirectly increased cessation rates through the pathway of increased medication adherence., Conclusions: These results highlight the importance of medication adherence for smoking cessation among community corrections smokers. Providing exposure to medication may be a promising intervention to increase medication adherence and subsequent cessation rates in this population., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Rationale: Behavioral economic measures of demand provide estimates of tobacco product abuse liability and may predict effects of policy-related price regulation on consumption of existing and emerging tobacco products., Objective: In the present study, we examined demand for snus, a smokeless tobacco product, in comparison to both cigarettes and medicinal nicotine. We used both a naturalistic method in which participants purchased these products for use outside the laboratory, as well as laboratory-based self-administration procedures., Methods: Cigarette smokers (N = 42) used an experimental income to purchase their usual brand of cigarettes and either snus or gum (only one product available per session) across a range of prices, while receiving all products they purchased from one randomly selected price. In a separate portion of the study, participants self-administered these products during laboratory-based, progressive ratio sessions., Result: Demand elasticity (sensitivity of purchasing to price) was significantly greater for snus than cigarettes. Elasticity for gum was intermediate between snus and cigarettes but was not significantly different than either. Demand intensity (purchasing unconstrained by price) was significantly lower for gum compared to cigarettes, with no significant difference observed between snus and cigarettes. Results of the laboratory-based, progressive ratio sessions were generally discordant with measures of demand elasticity, with significantly higher "breakpoints" for cigarettes compared to gum and no significant differences between other study products. Moreover, breakpoints and product purchasing were generally uncorrelated across tasks., Conclusions: Under naturalistic conditions, snus appears more sensitive to price manipulation than either cigarettes or nicotine gum in existing smokers.

Aims/introduction: Stopping smoking deserves high priority in preventing complications of diabetes; however, only sparse data are available regarding the efficacy of pharmacotherapy in smokers with diabetes. We assessed the efficacy and safety of varenicline in smokers with diabetes who participated in 15 double-blind, randomized, placebo-controlled studies., Materials and Methods: This retrospective pooled analysis included data from smokers of ≥10 cigarettes per day with diabetes. Participants received varenicline 1 mg b.i.d. or placebo for 12 weeks. We examined carbon monoxide-confirmed continuous abstinence rates (CARs) for weeks 9-12, 9-24 and 9-52, and compared safety in participants with and without diabetes., Results: Of 6,771 participants, 323 had diabetes (varenicline n = 162; placebo n = 161). Week 9-12 CAR was higher with varenicline than placebo (43.8% vs 24.8%; odds ratio 2.36, 95% CI 1.47-3.79), as was week 9-24 CAR (27.5% vs 14.4%; odds ratio 2.25, 95% CI 1.27-4.00). Week 9-52 CAR was 18.4% for varenicline and 10.1% for placebo (odds ratio 2.00, 95% CI 0.90-4.49). The most commonly-reported adverse events in participants with diabetes for varenicline vs placebo were: nausea (27.2% vs 8.1%); headache (9.3% vs 9.9%); and insomnia (8.6% vs 5.6%), incidences that were similar in participants without diabetes (29.6% vs 9.7%; 13.4% vs 10.9%; and 11.4% vs 7.1%, respectively). Weight gain in quitters with diabetes (1.7 kg) was similar to that of those without diabetes (2.1 kg)., Conclusions: Varenicline was an effective and well-tolerated aid for smoking cessation in individuals with diabetes. Safety was comparable with participants without diabetes., (© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Cigarette smoking can affect drug metabolism via pharmacokinetic and pharmacodynamic mechanisms, and a sudden change in smoking status can render patients at risk of serious adverse reactions, eg. after clozapine. Patients should be regularly monitored with regard to their smoking status and extent of cigarette consumption and doses of relevant medications adjusted accordingly.

Objective: Individuals with mental illnesses (MIs) are disproportionately affected by tobacco-related disease burden because of higher tobacco use prevalence and poor tobacco treatment outcomes. This pilot study examines the outcomes of delivering an evidence-based tobacco treatment program (the Cooper-Clayton program) in a community mental health setting., Design: A prospective nonequivalent group design was used to assess outcomes., Sample: This study included 47 participants, of which 19 were in a community mental health setting and 28 were from two non-mental-health settings., Measurements: Information on sociodemographic (gender, age, educational level, and current life stressors) and medical, MI, substance use, and tobacco use and cessation histories were obtained. Program completion and smoking cessation at the end of treatment (verified with expired carbon monoxide monitoring) were assessed., Intervention: The program consists of combining behavioral counseling with nicotine replacement therapy for 12 weeks., Results: Participants from the mental health setting were significantly less educated, had greater medical comorbidities, had greater psychiatric and mental health histories, and had greater perceived secondhand tobacco smoke exposure as compared with those from the non-mental-health settings. Thirty-two percent of the participants (6/19) completed the program in the mental health site as compared with 68% (19/28) from the non-mental-health site. None of those from the mental health site achieved cessation as compared with 68% of those from non-mental-health sites., Conclusions: The differential outcomes of evidence-based tobacco treatment programs in non-mental-health versus mental health settings may suggest the need to modify existing tobacco treatment approaches for those with MIs in community settings.

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., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Combination therapy for tobacco dependence is becoming a standard of care. We sought to compare benefits and adverse events for combination therapy versus monotherapy for smokers in The Smokers' Health Project., Methods: This secondary data analysis was derived from adult smokers (n = 198) who initially smoked 15 or more cigarettes per day and participated in The Smokers' Health Project. Participants were grouped as taking 1 medication or 2 concurrent medications for tobacco dependence for 1 year over the 2-year study period. Adverse events were compared between medication groups using chi-square tests. Crude and adjusted odds ratios were calculated for cessation at 6, 12, 18, and 24 months using logistic regression., Results: No differences were seen in the proportion of incident adverse events between the monotherapy (28.3%) and combination therapy (32.3%) groups (P = 0.54). At 6 months, the odds of quitting were less in the combination therapy group relative to those taking monotherapy (adjusted odds ratio = 0.47 [95% CI 0.24-0.93]). At 12, 18, and 24 months, the odds of quitting did not differ between therapy groups (P = 0.07, 0.33, 0.55, respectively)., Conclusion: Monotherapy and combination therapy for smoking cessation are similarly effective up to 24 months, and they exhibit similar adverse event attributes., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Alcohol and nicotine dependence frequently co-occur, and quitting smoking might enhance long-term alcohol abstinence. Topiramate appears to help non-alcohol-dependent individuals quit smoking, and our pilot work suggested efficacy only in men. It also prevents relapse to alcohol in recently detoxified alcoholics. We evaluated topiramate in abstinent alcohol-dependent men to assess whether this medication (i) promotes smoking cessation and (ii) prevents alcohol and other drug relapse in the context of smoking cessation treatment., Methods: One hundred and twenty-nine alcohol-abstinent (mean ~6 months) alcohol-dependent male smokers (80% with other substance use disorders) participated in this 12-week randomized, double blind, parallel group comparison of topiramate (up to 200 mg/d) and placebo with a 24-week nontreatment follow-up period. The study was carried out sequentially at 2 academic centers in the Midwest and Southern California between March 23, 2009 and November 20, 2014. All participants received manual-guided smoking cessation counseling combined with medication-focused compliance enhancement therapy. Randomization was block designed by the research pharmacist in a 1:1 ratio. Participants, investigators, and research personnel were masked to treatment assignment. The primary smoking end point was biochemically confirmed 4-week continuous abstinence from smoking during weeks 9 to 12, while the secondary end point was relapse to any drinking or drug use during the entire 36-week evaluation period. Logistic regression was used to determine the effects of topiramate on quitting smoking and alcohol relapse, controlling for relevant covariates. The trial is registered at ClinicalTrials.gov (number NCT00802412) and is now closed., Results: Only a small proportion (7.9%) of topiramate-treated participants were able to quit smoking, and this cessation rate was similar to placebo (10.6%; odds ratio = 1.60; 95% confidence interval 0.4, 6.5; p = 0.51). Roughly 30% of the sample had a documented relapse to drinking or drug use during the study, and these rates were similar in the topiramate (20/63; 31.8%) and placebo groups (18/66; 27.3%; p = 0.58). Results of a longitudinal logistic regression model examining time to any alcohol relapse revealed no medication effect., Conclusions: Topiramate at a daily dosage of up to 200 mg per day, combined with smoking cessation and medication adherence counseling, had no effects on smoking cessation or the prevention of alcohol or drug relapse in male smokers who were in early or sustained full remission from alcohol and motivated to make a quit attempt. Alternative approaches for treating this high-risk, dually dependent population are needed., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Objectives: It is common practice to individualize smoking cessation pharmacotherapy based on clinical judgment and patient response. However, little has been documented about the use and outcomes of smoking cessation pharmacotherapy in real-world settings. This study examines factors associated with using smoking cessation pharmacotherapy and related outcomes among smokers with psychiatric and/or substance use disorders who completed an intensive tobacco treatment program within mental health and addiction services settings in Vancouver, Canada., Methods: A retrospective analysis was used to examine combined program participation data (N = 889) from two tobacco treatment programs (i.e., the Tobacco Dependence Clinic and the Butt Out group) between September 2007 and July 2013. Changes in smoking cessation pharmacotherapy from the initial to final treatment and seven-day point prevalence of smoking abstinence (verified by expired carbon monoxide) were assessed at the end of treatment., Results: During treatment, 60% of participants remained on the initial pharmacotherapy plan, 30% received adjunctive treatment, and 10% had treatment plans that were switched. Those whose pharmacotherapy was switched had higher cigarette consumption and nicotine dependence at baseline and were less likely to have a psychiatric disorder history. When comparing between pharmacotherapy groups, individuals who switched medications were less likely to achieve abstinence at the end of treatment as compared to those whose medication treatment plans remained the same or who received adjunctive treatment (unchanged = 36.8%, adjunctive = 38.1% vs. switched = 20.9%, χ 2 = 9.59, df = 2, p = .008). In multivariate regression analysis, switching pharmacotherapy was associated with lower smoking cessation (OR = .33, 95% CI [.17, .63]) and significantly mediated the effectiveness of pharmacotherapy. As there were differences in medication switching rates at the clinical level, there were limitations in assessing the impact of mental illness or substance use disorder variables., Conclusions: At least 40% of individuals may have their smoking cessation pharmacotherapy plan changed during treatment. Switching pharmacotherapy may indicate a subgroup of smokers characterized by greater challenges in smoking cessation. Our findings may enhance algorithms for using smoking cessation pharmacotherapy in clinical practice and provide directions for future research in treating tobacco use disorder among individuals with mental health and substance use disorders.

Background: Multiple studies suggest a pivotal role of the endocannabinoid system in regulating the reinforcing effects of various substances of abuse. Rimonabant, a CB 1 inverse agonist found to be effective for smoking cessation, was associated with an increased risk of anxiety and depression. Here we evaluated the effects of the CB 1 neutral antagonist AM4113 on the abuse-related effects of nicotine and its effects on anxiety and depressive-like behavior in rats., Methods: Rats were trained to self-administer nicotine under a fixed-ratio 5 or progressive-ratio schedules of reinforcement. A control group was trained to self-administer food. The acute/chronic effects of AM4113 pretreatment were evaluated on nicotine taking, motivation for nicotine, and cue-, nicotine priming- and yohimbine-induced reinstatement of nicotine-seeking. The effects of AM4113 in the basal firing and bursting activity of midbrain dopamine neurons were evaluated in a separate group of animals treated with nicotine. Anxiety/depression-like effects of AM4113 and rimonabant were evaluated 24h after chronic (21 days) pretreatment (0, 1, 3, and 10mg/kg, 1/d)., Results: AM4113 significantly attenuated nicotine taking, motivation for nicotine, as well as cue-, priming- and stress-induced reinstatement of nicotine-seeking behavior. These effects were accompanied by a decrease of the firing and burst rates in the ventral tegmental area dopamine neurons in response to nicotine. On the other hand, AM4113 pretreatment did not have effects on operant responding for food. Importantly, AM4113 did not have effects on anxiety and showed antidepressant-like effects., Conclusion: Our results indicate that AM4113 could be a promising therapeutic option for the prevention of relapse to nicotine-seeking while lacking anxiety/depression-like side effects., (© The Author 2016. Published by Oxford University Press on behalf of CINP.)

The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution. After 30min the mice were observed in an elevated plus-maze test or a forced swim test, for anxiety- and depression-like behavior. After 5min of testing, the plasma corticosterone concentration reflecting the activity of the hypothalamic-pituitary-adrenal (HPA) axis was also determined by a chemo-fluorescent method. Half of the animals were treated ICV and evaluated on the 8th day, the other half on the 9th day. On the 8th day, nicotine-treated mice presented signs of anxiolysis and depression, but no significant elevation of the plasma corticosterone concentration. On the 9th day, nicotine-treated mice exhibited signs of anxiety and depression and a significant increase of the plasma corticosterone levels. Central administration of UCN 2 or UCN 3 ameliorated the anxiety- and depression-like state including the hyperactivity of the HPA axis, developed during acute withdrawal following chronic nicotine treatment. The present study suggests that selective CRF2 receptor agonists could be used as a therapy in nicotine addiction., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In Australia and New Zealand, population groups who experience social disadvantage smoke at much higher rates than the general population. As there are limited data specific to these groups regarding the success of nicotine replacement therapy for smoking cessation, this commentary will provide an overview of the relevant international literature supplemented with observational data relevant to the policy contexts in Australia and New Zealand. [Paul C, Wolfenden L, Tzelepis F, Yoong S, Bowman J, Wye P, Sherwood E, Rose S, Wiggers J. Nicotine replacement therapy as a smoking cessation aid among disadvantaged smokers: What answers do we need? Drug Alcohol Rev 2016;35:785-789]., (© 2015 Australasian Professional Society on Alcohol and other Drugs.)