Weight gain typically accompanies smoking cessation, and women smokers concerned about postcessation weight gain are prone to substantial gain. Little is known about the ways in which cessation affects dietary composition. Understanding postcessation changes in dietary composition may inform the design of smoking cessation interventions to address postcessation weight gain. Participants were women smokers concerned about postcessation weight gain enrolled in a randomized trial and assigned to either bupropion or placebo, and either standard cessation intervention or standard intervention plus components to address weight concerns. Women completed three, 24-hour food recall interviews at baseline, and at 1 and 6 months following a targeted quit date. At 6 months, 22% of women were abstinent and had gained 3.6 (±2.7) kg, compared to 0.91 (±2.0) kg for women who continued to smoke, p = 0.42. Abstinent women reported significantly higher energy intake and consumed a smaller percentage of fat across assessment points than did those who continued to smoke. Intervention was not associated with differential weight gain, or change in percent of calories from protein, fat or carbohydrates. This study is the first documentation of energy and macronutrient intake during smoking cessation treatment using a validated 24-hour dietary recall methodology. Although cessation was associated with overall increases in energy intake among women, neither bupropion nor weight concerns treatment affected energy or macronutrient intake. Future research to understand the relation between cessation and dietary intake needs to replicate and extend these findings to elucidate how, if at all, smoking cessation affects dietary intake.
Smoking cessation; Dietary intake; Weight concerns; Macronutrients
Negative mood situations often increase smoking behavior and reward, effects that may be greater among women and smokers low in tolerance for distress.
Adult dependent smokers (N = 164; 86 men, 78 women) first completed measures of distress tolerance via self-report and by mirror-tracing and breath-holding tasks. They then participated in 2 virtually identical laboratory sessions, involving induction of negative versus neutral mood (control) via pictorial slides and music. They rated negative affect (NA) before and during mood induction and smoked their preferred brand ad libitum during the last 14 min of mood induction. Our aim was to examine mood effects on NA, smoking reward (“liking”), and smoking intake (puff volume and number) as a function of sex and distress tolerance.
Negative mood induction increased NA, as planned, and smoking reward and intake compared with neutral mood. Increases in NA and puff volume due to negative mood were greater in women compared with men, as hypothesized, but no main effects of the self-report or behavioral distress tolerance measures were seen in responses to mood induction. However, unexpectedly, lower self-reported distress tolerance was associated with greater smoking intake due to negative (but not neutral) mood in men and generally due to neutral (but not negative) mood in women.
Negative mood may increase smoking intake more in women compared with men. Yet, low distress tolerance may enhance smoking intake due to negative versus neutral mood differentially between women and men, suggesting that sex and distress tolerance may interact to influence smoking responses to negative mood.
Functional CYP2A6 genetic variation partially determines nicotine metabolism. In 2005, we examined functional CYP2A6 variants associated with reduced metabolism (CYP2A6*2, CYP2A6*9, CYP2A6*4), smoking history, and change in smoking in 878 adult smokers undergoing lung cancer screening in an urban setting. At one year, 216 quit smoking for more than 30 days while 662 continued smoking. Compared to subjects who smoked 30 cigarettes per day at baseline, the odds of a reduced metabolism genotype was 52% higher in subjects smoking 20–29 cigarettes per day and 86% higher in subjects smoking less than 20 cigarettes per day (p-trend = 0.016). Reduced metabolism genotypes appeared unrelated to quitting. Though related to smoking dose, CYP2A6 may not influence cessation.
smoking cessation; smoking initiation; cigarette smoking; genetics; cytochrome P450; nicotine metabolism
The association between smokers’ cue-induced craving and subsequent ability to initiate abstinence is unclear. Dependent smokers (N=158) completed a single cue-reactivity session prior to participating in a larger within-subjects study, which independently examined predictors of initiating quitting during 5 days each on nicotine versus placebo patch. In the larger study, all smokers used nicotine and placebo patch (double blind) for one week each following a preceding week of ad lib smoking, in a 2x2 cross-over design. Generalized estimating equation (GEE) models determined the predictive ability of cue-induced craving (cue reactivity) on subsequent success at initiating a quit attempt (at least 24hrs quit) for each patch condition. Smokers who exhibited greater craving during exposure to smoking cues had significantly greater odds of successfully initiating abstinence during either quit attempt week (i.e., the nicotine or placebo patch week). This relationship was not statistically significant for self-reported craving in response to neutral cues. However, a greater smoking-neutral cue difference score for cue-induced craving was also a significant predictor successfully initiating abstinence, but only among those not monetarily reinforced. Implications of these seemingly counterintuitive findings are discussed.
Predictors; Relapse; Cue reactivity; Abstinence initiation; Smoking cessation
Social learning theory considers self-efficacy as a causal factor in behavior change. However, in line with behavioral theory, recent clinical research suggests that self-efficacy ratings may reflect, rather than cause, behavior change. To test these two disparate views, self-efficacy was related to actual smoking abstinence on the next day (i.e. self-efficacy causes change), and abstinence status over one day was tested as a predictor of rated self-efficacy for being quit the next day (i.e. reflects change). All data were from two very similar cross-over studies evaluating the short-term effects of both placebo versus medication, nicotine patch (n=209) or varenicline (n=123), on smoking abstinence during week-long practice quit attempts. Placebo versus active medication periods were separated by an ad lib smoking washout, and analyses controlled for prior day's abstinence or self-efficacy values. Results were very consistent between studies in showing essentially bi-directional associations: daily self-efficacy predicted next day's abstinence, and current day's abstinence status predicted self-efficacy for not smoking the next day. However, secondary factors differentially predicted abstinence and, to a lesser extent, self-efficacy between these two medication studies. These data provide some support for both social learning and behavioral theories of smoking behavior change, although self-efficacy may only briefly predict subsequent short periods of abstinence as assessed in these studies. Nonetheless, because self-efficacy has long been assumed to cause behavior change, including smoking cessation, the notion of self-efficacy as a reflection of recent smoking behavior change in these studies warrants greater attention in clinical research on smoking cessation treatment.
smoking cessation; self-efficacy; smoking behavior; abstinence; nicotine dependence; behavior change
Acute smoking behavior (i.e., puff topography) and subjective responses during the ad lib smoking of a single cigarette in the laboratory may provide useful measures of smoking reinforcement and reward, respectively. However, the reliability of such measures is not clear, leaving uncertain the utility of a single assessment of smoking behavior as an individual difference measure.
Dependent smokers (N = 94) smoked normally prior to each of 4 laboratory sessions during which they were instructed to smoke 1 cigarette of their preferred brand in ad libitum and unblinded fashion and then rate it for subjective effects. Puff topography (puff number, total volume, and maximum volume) was assessed via portable Clinical Research Support System device. Subjective reward and perception were assessed by visual analog scales of “liking” and “how strong,” respectively. The reliability of puff topography and subjective measures was determined across days by intra-class correlations (ICCs). Differences due to sex and nicotine dependence (high and low Fagerström Test for Nicotine Dependence score) were also examined.
Reliability was highly significant for each measure. ICCs were .70 for total puff volume, .60 for maximum puff volume, .73 for puff number, .64 for liking, and .78 for how strong. Reliability generally did not differ by sex or dependence, but absolute values for total volume and maximum puff volume were greater in men and in high dependent smokers. Liking was also greater in high dependent smokers.
Puff topography and subjective measures during the ad lib smoking of a single cigarette are highly reliable. Smoking responses during a single ad lib smoking session may be useful in identifying stable individual differences in smoking reinforcement and reward.
Acutely increased urge to smoke, or craving, in response to smoking cues (i.e., “cue reactivity”) is often believed to identify those less able to later quit smoking. Although absolute craving level can predict smoking behavior, smoking cue reactivity per se may not predict cessation outcome.
All clinical trials of cue reactivity and cessation outcome published before 2007 were identified and supplemented with a web-based search of clinical studies published after 2006, producing one additional trial. Examined were a total of 6 studies that directly related self-reported craving in response to laboratory-presented smoking cues with subsequent ability to quit smoking.
Of the 6 studies, only one found that lower cue reactivity predicted greater quitting success (with nicotine but not placebo patch). Another study found the opposite, that higher cue reactivity was related to greater, rather than less, quitting success (in an unaided attempt). The other studies showed no association between cue reactivity and cessation outcome.
This limited research does not clearly support self-reported craving in response to smoking cues per se as a predictor of later quitting success. Lack of consistent results may partly be due to variability in methods of smoking cue assessment, type of cessation treatment, and duration of follow-up assessment. If it is to improve our understanding of an individual’s ability to quit smoking, research on cue reactivity needs to show significant and reliable associations with subsequent long-term smoking behavior.
Sleep disturbance may affect smoking cessation efforts. We describe sleep changes across three months among women in a smoking cessation program and tested whether sleep disturbances at baseline and 1 month post-quit attempt predicted smoking status at three months.
Participants (N = 322) were women in a randomized, clinical trial for smoking cessation. Sleep disturbances, as well as, insomnia, drowsiness, and sleep quality were evaluated prior to and during three months of cessation treatment. Repeated measures mixed models evaluated change in sleep over time by smoking outcome status. Logistic regression analyses determined whether sleep disturbances at baseline and 1 month post-quit were associated with smoking status at 3 months.
Sleep disturbances were reported by more than 25% of women. Drowsiness, insomnia, and sleep quality changed over time. However, contrary to our hypotheses, none of the sleep variables at either baseline or 1 month post-quit attempt was associated with relapse (p′s > .05).
Although mild to severe drowsiness was reported by more women who relapsed than those who remained abstinent, none of the sleep disturbance symptoms predicted smoking relapse. Given high rates of sleep disturbances among women smokers, better prospective evaluations of the relationship of sleep disturbances to smoking cessation treatment outcome are needed.
sleep quality; insomnia; smoking; drowsiness; women; cessation; withdrawal
Previous studies have indicated that high sensation seekers are more sensitive to the reinforcing effects of nicotine, initiate smoking at an earlier age, and smoke greater amounts of cigarettes. This study examined the influence of sensation-seeking status on tobacco smoking following deprivation in regular tobacco users.
Twenty healthy tobacco-smoking volunteers with low or high impulsive sensation-seeking subscale scores completed 2 consecutive test days per week for 3 consecutive weeks. Each week, a range of self-report, performance, and cardiovascular assessments were completed during ad libitum smoking on Day 1 and before and after the paced smoking of a tobacco cigarette containing 0.05, 0.6, or 0.9 mg of nicotine following 24 hr of tobacco deprivation on Day 2. In addition, self-administration behavior was analyzed during a 2-hr free access period after the initial tobacco administration.
In high sensation seekers, tobacco smoking independent of nicotine yield ameliorated deprivation effects, whereas amelioration of deprivation effects was dependent on nicotine yield among low sensation seekers. However, this effect was limited to a small subset of measures. Subsequent cigarette self-administration increased in a nicotine-dependent manner for high sensation seekers only.
Compared with low sensation seekers, high sensation seekers were more sensitive to the withdrawal relieving effects of nonnicotine components of smoking following 24 hr of deprivation on selective measures and more sensitive to nicotine yield during subsequent tobacco self-administration. These results are consistent with studies suggesting that factors driving tobacco dependence may vary as a function of sensation-seeking status.
Pictorial representations of specific environments related to smoking can evoke robust craving to smoke, even in the absence of any proximal cues to smoke (e.g., cigarettes, lighters.) To evaluate the salience of smoking environment cues, we developed a novel procedure for bringing smokers’ real world smoking and nonsmoking environments into the laboratory to compare them with standard (i.e. not personalized) environments within a cue-reactivity paradigm. Seventy-two smokers used digital cameras to take pictures of the environments in which they do and do not smoke. They then completed a cue-reactivity session during which they viewed and rated pictures of smoking and nonsmoking environments, half personal and half standard, all devoid of proximal smoking cues. As hypothesized, personal environments led to a significantly larger smoking-nonsmoking difference in craving, compared with the standard environments. Personalization also enhanced stimuli vividness, relevance, positive affect, and excitement, as well as heart rate changes from baseline. Implications of these findings for exposure-based research and treatment for addiction, as well as other psychological disorders, are discussed.
tobacco; cue reactivity; context; conditioning
We previously documented that cognitive behavioral therapy for smoking-related weight concerns (CONCERNS) improves cessation rates. However, the efficacy of combining CONCERNS with cessation medication is unknown. We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers.
In a randomized, double-blind, placebo-controlled trial, weight-concerned women (n = 349; 86% white) received smoking cessation counseling and were randomized to 1 of 2 adjunctive counseling components: CONCERNS or STANDARD (standard cessation treatment with added discussion of smoking topics but no specific weight focus), and 1 of 2 medication conditions: bupropion hydrochloride sustained release (B) or placebo (P) for 6 months. Rates and duration of biochemically verified prolonged abstinence were the primary outcomes. Point-prevalent abstinence, postcessation weight gain, and changes in nicotine withdrawal, depressive symptoms, and weight concerns were evaluated.
Women in the CONCERNS + B group had higher rates of abstinence (34.0%) and longer time to relapse than did those in the STANDARD + B (21%; P = .05) or CONCERNS + P (11.5%; P = .005) groups at 6 months, although rates of prolonged abstinence in the CONCERNS + B and STANDARD + B groups did not differ significantly at 12 months. Abstinence rates and duration did not differ in the STANDARD + B group (21% and 19%) compared with the STANDARD + P group (10% and 7%) at 6 and 12 months, respectively. There were no differences among abstinent women in postcessation weight gain or weight concerns, although STANDARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did STANDARD + P.
Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence. This effect was not related to differences in postcessation weight gain or changes in weight concerns.
Varenicline may aid smoking cessation by attenuating smoking behavior and reward. We compared the effects of varenicline versus placebo on smoking behavior and reward, assessed both prospectively and retrospectively, and related these effects to subsequent success in a brief simulated quit attempt with medication.
Materials and methods
Smokers (n=124) with high or low interest in quitting smoking participated in a double-blind crossover study of varenicline versus placebo effects on smoking behavior and reward. In each of two phases, subjects received a week of medication run-up with varenicline (0.5 mg, b.i.d.) or placebo while continuing to smoke, followed the next week by an attempt to quit while on medication. At the end of each run-up week, subjects completed retrospective measures of smoking reward (liking) and number of cigarettes over the prior 24 hrs, and they provided an expired air carbon monoxide (CO) measure. They then completed a prospective session in which they ad lib smoked and rated the rewarding effects of one of their preferred cigarettes while blind to brand.
Varenicline decreased smoking reward significantly in the prospective assessment, but only marginally in the retrospective assessment. Varenicline did not alter smoking behavior prospectively, but did reduce CO and retrospective report of smoking amount. None of these effects of varenicline predicted subsequent days of abstinence due to varenicline.
During medication run-up, varenicline decreases acute smoking reward and may attenuate smoking behavior, but these effects do not appear to directly predict varenicline’s influence on smoking abstinence in a short-term test.
Smoking; Varenicline; Reward; Smoking cessation; Nicotine dependence
Negative mood increases smoking reinforcement and may do so to a greater degree in smokers vulnerable to negative mood dysregulation.
Adult smokers (N = 71) without current depression were randomly assigned to one of two smoking conditions (nicotine or denic cigarettes, presented blind) maintained across all sessions. Subjects completed one neutral mood session and four negative mood induction sessions. Negative mood inductions included one each of the following: 1) overnight smoking abstinence, 2) challenging computer task, 3) public speech preparation, 4) watching negative mood slides. In each session, subjects took 4 puffs on their assigned cigarette, rated it for “liking” (reward), and then smoked those cigarettes ad libitum (reinforcement) during continued mood induction. Affect was assessed intermittently before and after smoking. Differences in responses were examined as functions of self-reported history of major depression and levels of distress tolerance and anxiety sensitivity.
Smoking reinforcement, but not reward or negative affect relief, was greater in all sessions in those with a history of depression and greater after overnight abstinence in those with lower distress tolerance. Reward and affect relief, but not reinforcement, were greater during speech preparation among those high in anxiety sensitivity.
Low distress tolerance may enhance acute smoking reinforcement due to abstinence, while depression history may broadly increase acute smoking reinforcement regardless of mood. Neither smoking reward nor affect help explain these individual differences in smoking reinforcement.
Smoking; Reinforcement; Nicotine; Depression history; Distress tolerance; Anxiety sensitivity; Negative affect; Mood; Withdrawal
As many as one-half of smokers relapse in the first week following a quit attempt, and subjective reports of cognitive deficits in early abstinence are associated with increased relapse risk. This study examined whether objective cognitive performance after three days of abstinence predicts smoking resumption in a 7-day simulated quit attempt. Sixty-seven treatment-seeking smokers received either varenicline or placebo (randomized double-blind) for 21 days. Following medication run-up (days 1-10), there was a 3-day mandatory (biochemically confirmed) abstinence period (days 11-13) during which working memory (Letter-N-Back Task) and sustained attention (Continuous Performance Task) were assessed (day 13). Participants were then exposed to a scheduled smoking lapse and instructed to try to remain abstinent for the next 7 days (days 15-21). Poorer cognitive performance (slower correct reaction time on Letter-N-Back task) during abstinence predicted more rapid smoking resumption among those receiving placebo (p=.038) but not among those receiving varenicline. These data lend further support for the growing recognition that cognitive deficits involving working memory are a core symptom of nicotine withdrawal and a potential target for the development of pharmacological and behavioral treatments.
nicotine; addiction; withdrawal; smoking relapse; cognition
Computed tomography (CT) lung cancer screening offers a unique clinical setting in which to promote smoking cessation. Focusing on outcomes related to the reporting of CT abnormality, we examined the natural history of smoking in the Pittsburgh Lung Screening Study (PLuSS).
PLuSS recruited 50 to 79 year-old current and former cigarette smokers living in the Pittsburgh area. We examined self-reported smoking outcomes one year after study entry in a subgroup that contained n=2094 active cigarette smokers without interval lung cancer diagnosis (50.7% women, median age 57 years, 40 year median duration of cigarette smoking, and 65.2% ≥ 20 cigarettes per day). Analyses compared efforts to quit in relation to physician referral for abnormal CT.
Since study entry, 58.5% (95% confidence interval (CI) 56.3%, 60.6%) reported any quit attempt and 27.2% (95% CI 25.3%, 29.1%) any quit interval longer than 30 days. One year after study entry, 15.5% (95% CI 14.0%, 17.1%) reported not smoking for more than 30 days. Comparing persons referred because of CT abnormalities creating moderate or high lung cancer suspicion (n=156; 7.4%) to persons not referred for any reason (n=1145; 54.7%), propensity score-adjusted fractions with any quit attempt and with any quit interval longer than 30 days increased 18.8% (95% CI 11.1%, 26.5%) and 17.7% (95% CI 9.4%, 26.0%), respectively. The fraction quit more than 30 days at one year increased 12.2% (95% CI 4.9%, 19.5%).
Persons who experienced referral because of abnormal CT reported more smoking cessation.
craving; cue reactivity; smoking behaviour; drug-seeking behaviour; relapse; dependence; drug reinforcement; environmental cues
Smokers are highly reactive to smoking-related cues that are directly linked, or most proximal, to actual smoking behavior (e.g., lit cigarettes). However, over the course of smoking, proximal cues may not be the only stimuli to become strongly associated with smoking. Distal cues, such as the environments in which smoking occurs (e.g., bar) might also gain associative properties and come to evoke robust reactivity from smokers. To test this, a pilot study was first conducted to develop standard pictorial stimuli of smoking and nonsmoking environments, all of which were completely devoid of proximal smoking cues. A comparison set of smoking and nonsmoking proximal cues was then created. Using the 12 total pictorial cues developed, 62 adult smokers participated in a cue-reactivity study during which they viewed and rated pictorial smoking and nonsmoking environment and proximal cues. Results demonstrate that, similar to proximal cues, environments associated with smoking can alone function as stimuli capable of evoking strong subjective reactivity from smokers. This work supports a broader conceptualization of drug-related cues in cue-based research and treatment development that includes proximal and distal cues as distinct categories.
craving; cue reactivity; proximal and distal stimuli; environments; smoking
Genes coding for nicotinic acetylcholine receptors (nAChRs) may influence response to nicotine replacement therapy (NRT) for smoking cessation. We examined the association of a 3’ UTR polymorphism (rs2072661) in the nAChR β2 subunit (CHRNB2) gene with quitting success in response to nicotine vs. placebo patch during a short-term test of patch effects. In a within-subjects cross-over design, smokers of European descent (n = 156) received 21 mg nicotine and placebo patch, in counter-balanced order, during two separate 5-day simulated quit attempts, each preceded by a week of ad lib smoking. Abstinence was assessed daily by carbon monoxide (CO) < 5 ppm. Smokers with the CHRNB2 GG genotype had more days of abstinence during the nicotine versus placebo patch week, compared to those with the AG or AA genotypes (p<.01). Moreover, nicotine patch increased the probability of quitting on the target quit day, quitting anytime during the patch week, and avoiding relapse among those with the GG genotype but not the AA/AG genotypes, although the nicotine x genotype interaction was significant only for quitting on the target quit day (p<.05). Regardless of patch condition, quitting on the target quit day was more likely in those with the GG genotype vs. AA/AG genotypes (p<.05). Genetic associations were not observed for craving or withdrawal responses to nicotine versus placebo patch. These findings are consistent with prior evidence of association of this variant with smoking cessation and suggest that polymorphisms in the nAChR β2 subunit gene may influence therapeutic responsiveness to cessation medications.
CHRNB2; pharmacogenetics; nicotine replacement; smoking cessation
An inability to maintain abstinence is a key indicator of tobacco dependence. Unfortunately, little evidence exists regarding the ability of the major tobacco dependence measures to predict smoking cessation outcome. This paper used data from four placebo-controlled smoking cessation trials and one international epidemiologic study to determine relations between the Fagerström Test for Nicotine Dependence (FTND; Heatherton et al., 1991), the Heaviness of Smoking Index (HSI; Kozlowski et al., 1994), the Nicotine Dependence Syndrome Scale (NDSS; Shiffman et al., 2004) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM; Piper et al. 2004) with cessation success. Results showed that much of the predictive validity of the FTND could be attributed to its first item, time to first cigarette in the morning, and this item had greater validity than any other single measure. Thus, the time to first cigarette item appears to tap a pattern of heavy, uninterrupted, and automatic smoking and may be a good single-item measure of nicotine dependence.
We recently showed effects of nicotine dose and nicotine expectancy on some responses to cigarette smoking, with generally no influence of induced mood on these effects. The present study extended this line of research to Nicotrol nasal spray, to determine whether formulation (spray vs. smoking) alters responses.
Smokers abstained overnight before each of two virtually identical sessions, involving negative or positive mood induction. They were randomized to one of five groups, four comprising the 2 × 2 balanced placebo design, varying actual and expected dose of nicotine in the nasal spray, and the fifth group a no-spray control. Dependent measures included self-reported affect, craving, withdrawal, and spray ratings of “liking” and “how much nicotine.” Analyses were limited to those whose nicotine expectancies were manipulated successfully (N = 48).
The following results matched those from our smoking study: expecting nicotine increased liking; expected, but not actual, nicotine dose increased dose perception; neither actual nor expected nicotine dose had much influence on affect or withdrawal; and mood had no influence on these effects. However, both actual and expected nicotine dose decreased craving in response to spray, contrary to our prior study with smoking.
Formulation made little difference in some effects of nicotine and expectancies, but other effects differed by formulation. Some of these findings, particularly for craving reduction, may have implications for enhancing the acute therapeutic effects of nasal spray and, perhaps, other medications in smokers trying to maintain abstinence after quitting.
Smoking cessation strategies continue to have disappointing results. By determining the interindividual genetic differences that influence smoking behaviors, we may be able to develop tailored strategies that increase the likelihood of successful cessation. This study attempts to determine genetic influences on the relationship between the dopamine pathway and smoking cessation by examining associations with a variable number tandem repeat variation in SLC6A3 and the DRD2 variants TaqIA (A2 vs. A1), TaqIB (B2 vs. B1), C957T (C vs. T), and -141C Ins/Del (C vs. Del). Baseline smokers in the Pittsburgh Lung Screening Study who provided information on smoking status one year later were evaluated. We frequency-matched those who were not abstinent at one year to those who were abstinent at one year by gender, decade of age, and time of enrollment (three month intervals) in a three to one ratio (N=881). Logistic regression was used to identify the effect of genotype on abstinence at one year. In a model containing the matching variables and other genotypes, DRD2 TaqIA was significantly associated with being abstinent at one year (p=0.01). Compared to participants who were homozygous TaqIA major allele (A2A2), participants who carried at least one minor allele (A1) were less likely to quit (Odds Ratio: 0.47, 95% CI: 0.24–0.94). The other dopamine receptor genotypes and the SLC6A3 genotype were not associated with smoking status at one-year. The association between DRD2 TaqIA and smoking cessation supports the hypothesis that genetic variation in the dopamine pathway influences smoking cessation.
tobacco use cessation; genotype; case-control study; dopamine
Neuronal nicotinic acetylcholine receptors (nAChRs) are a key target in medication development efforts for a range of neuropsychiatric disorders, including nicotine dependence. Varenicline, a partial agonist at the α4β2 nAChRs, is a new efficacious medication for nicotine dependence. Its effects on the affective and cognitive dimensions of nicotine withdrawal have yet to be well characterized.
Sixty-seven treatment-seeking smokers were administered varenicline (× 21 days) and placebo (× 21 days) in a double-blind within-subject cross-over design. Following the medication run-up phase (days 1–10), there was a 3-day mandatory smoking abstinence phase (days 11–13) during which subjective symptoms and cognitive performance were assessed. Participants were re-exposed to a scheduled smoking lapse (day 14) and followed for days to lapse (days 15–21) in each medication period.
In the varenicline period, compared to placebo, withdrawal symptoms (p=.04), smoking urges (p<.001), and negative affect (p=.01) were significantly reduced, and levels of positive affect (p=.046), sustained attention (p=.018) and working memory (p=.001) were significantly greater during mandatory abstinence. Varenicline also significantly reduced the subjective rewarding effects of the scheduled smoking lapse (e.g., satisfaction, relief, liking) (p=.003). Medication effects on days to lapse following the scheduled smoking lapse were dependent on treatment order (p=.001); among participants who received placebo in the first period, varenicline increased days of abstinence in the follow-up period.
These data identify novel affective and cognitive effects of varenicline, and may have implications for medication development for other neuropsychiatric conditions.
nicotine; tobacco; dependence; varenicline; affect; cognition
The time of day in which craving, withdrawal, and other tobacco abstinence symptoms are assessed may moderate the influences of abstinence or medication on those symptoms.
Participants were 209 smokers participating in a 4-week crossover study assessing symptoms due to smoking versus abstinence and while using nicotine (21 mg) versus placebo patch when abstinent. None was trying to quit permanently during the study. Abstinence was verified daily by a carbon monoxide level of less than 5 ppm. Participants completed craving (two measures), total withdrawal, and positive affect (PA) and negative affect forms three times per day: in the morning, upon arrival at the clinic in the afternoon, and in the evening. All comparisons of the effects of time of day, abstinence, and nicotine patch treatment were within subjects.
Results showed a main effect of time of day on all measures while smoking, wherein PA was higher and the other four measures lower, during afternoon versus morning or evening ratings. Time of day interacted with abstinence on both craving measures, but not the other measures, such that abstinence increased craving less in the morning versus the other times. Time of day also interacted with nicotine (vs. placebo) patch effects in alleviating negative mood to a greater degree during evening versus morning or afternoon ratings.
The data suggest that, compared with traditional single assessments of symptoms at midday, assessments at several times of the day may reveal greater overall levels of symptoms and perhaps greater effects of abstinence and nicotine replacement on select abstinence symptoms.
Initial sensitivity to nicotine’s effects during early exposure to tobacco may relate to dependence vulnerability. We examined the association of initial nicotine sensitivity with individual difference factors of sex, other drug use history (i.e. cross-tolerance or cross-sensitization), and parental smoking status in young adult nonsmokers (N=131). Participants engaged in 4 sessions, the first 3 to assess the dose-response effects of nasal spray nicotine (0, 5, 10 μg/kg) on rewarding, mood, physiological, sensory processing, and performance effects, and the fourth to assess nicotine reinforcement using a choice procedure. Men had greater initial sensitivity than women to some self-reported effects of nicotine related to reward and incentive salience and to impairment in sensory processing, but men and women did not differ on most other effects. Prior marijuana use was associated with greater nicotine reward, nicotine reinforcement was greater in men versus women among those with prior marijuana use, and having parents who smoked was related to increased incentive salience. However, history of other drug use and parental smoking were not otherwise associated with initial nicotine sensitivity. These findings warrant replication with other methods of nicotine administration, especially cigarette smoking, and in more diverse samples of subjects naïve to nicotine. Yet, they suggest that sex differences in initial sensitivity to nicotine reward occur before the onset of dependence. They also suggest that parental smoking may not increase risk of nicotine dependence in offspring by altering initial nicotine sensitivity, and that cross-tolerance between other drugs and nicotine may not be robust in humans.
nicotine; sensitivity; nonsmokers; reward; reinforcement; sex differences; cross-tolerance; parental smoking history