Cue reactivity as a predictor of successful abstinence initiation among adult smokers.

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 1 week each following a preceding week of ad lib smoking, in a 2 × 2 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 24 hr 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 of successfully initiating abstinence, but only among those not monetarily reinforced. Implications of these seemingly counterintuitive findings are discussed.

Is self-efficacy for smoking abstinence a cause of, or a reflection on, smoking behavior change?

Social learning theory considers self-efficacy as a causal factor in behavior change. However, in line with behavioral theory, recent clinical research suggests 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 1 day was tested as a predictor of rated self-efficacy for quitting the next day (i.e., reflects change). All data were from two similar crossover 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 and active medication periods were separated by an ad lib smoking washout, and analyses were controlled for prior-day's abstinence or self-efficacy values. Results were very consistent between studies in showing essentially bidirectional associations: daily self-efficacy predicted next-day's abstinence, and current-day's abstinence status predicted self-efficacy for abstinence 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.

Varenicline's effects on acute smoking behavior and reward and their association with subsequent abstinence.

RATIONALE: 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. RESULTS: 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. CONCLUSIONS: 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.

Nicotinic acetylcholine receptor beta2 subunit (CHRNB2) gene and short-term ability to quit smoking in response to nicotine patch.

Genes coding for nicotinic acetylcholine receptors may influence response to nicotine replacement therapy for smoking cessation. We examined the association of a 3' untranslated region polymorphism (rs2072661) in the nicotinic acetylcholine receptor beta2 subunit (CHRNB2) gene with quitting success in response to nicotine versus 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 libitum smoking. Abstinence was assessed daily by CO < 5 ppm. Smokers with the CHRNB2 GG genotype had more days of abstinence during the nicotine versus placebo patch week compared with those with the AG or AA genotypes (P < 0.01). 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 < 0.05). Regardless of patch condition, quitting on the target quit day was more likely in those with the GG genotype versus AA/AG genotypes (P < 0.05). Genetic associations were not observed for craving or withdrawal responses to nicotine versus placebo patch. These findings are consistent with previous evidence of association of this variant with smoking cessation and suggest that polymorphisms in the nicotinic acetylcholine receptor beta2 subunit gene may influence therapeutic responsiveness to cessation medications.

Severity of tobacco abstinence symptoms varies by time of day.

INTRODUCTION: 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. METHODS: 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: 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. DISCUSSION: 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.

The influence of caffeine on nicotine's discriminative stimulus, subjective, and reinforcing effects.

Caffeine may acutely alter the discriminative stimulus and subjective effects of nicotine, perhaps explaining the association of coffee intake with smoking status. In this study, smokers were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0). Then, generalization of nicotine discrimination was tested, using both 2- and 3-choice ("novel" option) procedures, across a range of doses (0-20 microg/kg) following pretreatment with 0, 2.5, and 5.0 mg/kg caffeine p.o. Nicotine reinforcement was assessed after the end of generalization testing using a choice procedure. Caffeine pretreatment did not alter nicotine discrimination and self-administration. Caffeine and nicotine influenced some subjective and cardiovascular responses, but there were no interaction effects except for diastolic blood pressure. These results do not support the notion that caffeine acutely alters nicotine's discriminative stimulus, subjective, or reinforcing effects.

The discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine as a function of light physical activity.

Smokers often experience the acute effects of cigarette smoking while they are engaged in the light physical activity of routine tasks. However, virtually all laboratory-based research on these effects is conducted under conditions of quiet rest and, thus, may not generalize to effects in the natural environment. We examined changes in the discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine in humans as a function of the level of concurrent physical activity. Men and women smokers (N = 17) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0 microg/kg) at rest. Three sessions then followed, in which the generalization of discrimination was tested across a range of doses (0-20 microg/kg) while at rest or engaged in very light or light physical activity (15% and 30% of heart rate reserve, respectively) via bicycle ergometer. Generalization testing involved both two- and three-choice ("novel" option) quantitative procedures. Self-reported mood via the Profile of Mood States and visual analog scales, and cardiovascular measures of heart rate and blood pressure were obtained concurrent with discrimination responding. Nicotine reinforcement was assessed after the end of generalization testing using a choice procedure under the same rest or activity conditions. Results showed that physical activity did not significantly alter nicotine discrimination or reinforcement, as no interactions between activity and nicotine were observed. When activity and nicotine influenced the same subjective and cardiovascular responses, they acted in a generally additive fashion. These findings suggest that research on the acute effects of nicotine conducted under typical resting laboratory conditions generally are not altered by light physical activity and so may generalize to the effects of nicotine under conditions common in the natural environment.

Rate of nicotine onset from nicotine replacement therapy and acute responses in smokers.

The subjective and reinforcing effects of drugs of abuse may depend partly on their rate of onset, with faster acting formulations typically producing stronger effects than slower ones. In this within-subjects study, we examined the acute effects of nicotine replacement therapy via nicotine nasal spray (fast delivery) vs. transdermal nicotine patch (slow delivery) on craving, withdrawal, cardiovascular responses, subjective ratings, and reinforcing effects of smoking. Smokers (N=30) not seeking treatment participated in three sessions, each after overnight smoking abstinence, involving 14-mg nicotine (Nicoderm) or placebo patch, followed 4 hr later by intermittent administration of nicotine (Nicotrol) or placebo nasal spray. Specifically, the three group comparisons were nicotine patch condition (with placebo spray), nicotine spray condition (with placebo patch), and placebo condition (placebo spray and patch). Nicotine patch and nicotine spray were never administered in the same session. Blood nicotine levels were similar between nicotine patch and nicotine spray conditions, by design. Heart rate and systolic blood pressure were higher following nicotine spray vs. the other conditions, as hypothesized. However, other than reductions in craving related to nicotine spray and patch at some points, no differences between conditions were observed in withdrawal, subjective effects of sprays and smoking, or smoking reinforcement assessed by a computer task. Thus, under these acute conditions, the speed of nicotine delivery from nasal spray vs. patch differentially affected cardiovascular responses and perhaps craving but did not influence withdrawal, subjective ratings, and smoking reinforcement.

The consistency of acute responses to nicotine in humans.

Nicotine has many acute subjective, physiological, and behavioral effects in humans, some of which may explain why nicotine produces dependence. Individual differences in the magnitude of these effects (i.e., nicotine sensitivity) are of interest to many researchers, such as those examining vulnerability to dependence and processes related to chronic tolerance. However, such characterization of individual differences depends on the consistency of the observed responses, and the consistency of acute effects of nicotine in humans has not been studied systematically. We examined the consistency of the acute effects of the same dose of nicotine administered by nasal spray across multiple drug administration trials, within as well as between sessions. Subjective (i.e., self-reported effects), cardiovascular, and performance measures were assessed following each of four dosing trials of nicotine (20 microg/kg) on three sessions and of placebo on one session. For those measures in which the main effect of nicotine vs. placebo was significant, intraclass correlations were calculated for different sets of trials across different numbers of sessions. Our objective was to determine whether the consistency of responses declined when those responses were based on smaller numbers of trials or sessions, in an effort to guide future research in this area. Results indicated that the consistency of nicotine effects is generally high, even across trials within just one session. Additional research is needed to determine the generalizability of these findings to other methods of nicotine administration, including smoking, and to clarify the extent to which this consistency reflects characteristic consistency of the pharmacological actions of nicotine per se vs. consistency of nonspecific responses to the drug administration procedure.

Effects of smoking status and smoking cessation on leptin levels.

Cigarette smoking is associated with lower body weight, and quitting smoking typically produces weight gain. An effect of chronic smoking on increasing leptin, a protein product associated with reducing weight, may help explain this influence of smoking on lowering body weight. We examined fasting serum leptin levels in male and female adult smokers (n = 52) and non-smokers (n = 12) as well as long-time ex-smokers (n = 13), with all groups similar in body mass index (BMI). Partial regression analyses controlling for BMI and, where relevant, age were used to relate leptin to indices of smoking exposure and dependence within the smokers, and with typical alcohol and caffeine intake in the entire sample. Furthermore, a subset of the smokers (n = 22) quit for at least 3 weeks, and changes in leptin and weight were prospectively assessed. Results showed no difference in mean leptin levels as a function of smoking status and no significant associations of leptin with smoking exposure variables after controlling for BMI and age. However, leptin was significantly correlated with alcohol intake (inversely) in women. In addition, smoking cessation increased leptin, the opposite change expected if leptin were responsible for weight gain, but again only in women and not in men. This leptin change remained significant after controlling for the increase in weight observed in both men and women. In conclusion, the influence of cigarette smoking on body weight does not appear to be due directly to changes in leptin levels, as there is no difference in leptin due to smoking status and leptin does not decline after cessation.