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Psychopharmacology  2013;231(1):1-11.
Initial screening of new medications for potential efficacy (i.e. FDA early Phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing.
This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested, as model drugs, in 3 separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil.
This crossover procedure showed sensitivity (increased days of abstinence) during week-long “practice” quit attempts with each of the active cessation medications (positive controls) vs. placebo, but not with modafinil (negative control) vs. placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e. already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation).
A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent Phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.
PMCID: PMC3910509  PMID: 24297304
Medication screening; Pharmacotherapy; Nicotine dependence; Addiction
3.  Do People Serve as Cues to Smoke? 
Nicotine & Tobacco Research  2013;15(12):2081-2087.
Recent research has identified that the environments in which smoking has previously occurred can alone, in the absence of any explicit smoking stimuli (e.g., cigarettes, lighters), serve as cues that induce robust craving to smoke. The goal of the present study was to determine if people can similarly function as smoking and nonsmoking cues capable of directly affecting smokers’ cue-induced craving.
Smokers (N = 72) borrowed cameras to take photos of the people in their lives around whom they do and do not smoke (“personal” smoking and nonsmoking people, PS and PN, respectively). Self-report and physiological cue reactivity to those photos were compared with smokers’ reactivity to photos of people unknown to them (“standard” smoking and nonsmoking people, SS and SN, respectively).
Results suggest that the people around whom smokers regularly smoke (PS) can alone function as cues capable of eliciting patterns of reactivity similar to that evoked by proximal and environment smoking cues, namely, increased craving to smoke, negative affect, and excitement. In contrast, the people around whom smokers do not smoke become associated with not smoking (PN) and serve a potential protective function by reducing craving and increasing calm.
This novel investigation and its results have implications for promoting smoking cessation by developing strategies to manage a smoker’s social environment.
PMCID: PMC3819981  PMID: 23873978
Drug and alcohol dependence  2013;133(1):283-286.
Bupropion may aid tobacco abstinence by quickly relieving symptoms of nicotine withdrawal, perhaps including impaired cognitive performance. We examined whether bupropion would attenuate abstinence-induced cognitive deficits on the first day of a brief quit attempt, when smokers are most likely to relapse.
Smokers (N=24) with high quit interest were recruited for a within-subjects cross-over test of bupropion vs placebo on ability to abstain during separate short-term practice quit smoking attempts. After introduction to working memory (N-back) and sustained attention (continuous performance task; CPT) tasks during the pre-quit smoking baseline, performance on these tasks was assessed after abstaining overnight (CO<10 ppm) on the first day of each quit attempt, while on bupropion and on placebo.
Compared to placebo, bupropion after abstinence improved correct response times for working memory (p=.01 for medication by memory load interaction) and for one measure of sustained attention (numbers, but not letters; p<.05).
Bupropion may attenuate some features of impaired cognitive performance due to withdrawal on the first day of a quit attempt. Future studies could examine whether this effect of bupropion contributes to its efficacy for longer-term smoking cessation.
PMCID: PMC3786016  PMID: 23726977
cognition; working memory; attention; tobacco dependence; smoking cessation; bupropion
Drug and alcohol dependence  2013;133(1):167-171.
Nicotine’s acute effects on enhancing reinforcement from sensory rewards, shown in animal models, appear to occur with smoking in humans. These effects may vary due to reinforcer magnitude and amount of acute smoke intake (dose).
In a fully within-subjects design, dependent smokers (n=23) participated in 3 sessions. Each session followed overnight abstinence and involved 4 trials to assess responding via progressive ratio (PR50%) for sensory reinforcement from high, moderate, or low preference music, or no reward (counter-balanced, 30-sec/reinforcer). Sessions differed in smoking prior to each trial: 8 puffs on arrival and 2 puffs/trial (“8+2”), 2 puffs/trial only (“0+2”), or no smoking. Puffs were consumed via CReSS (Clinical Research Support System) to control topography, and smoking involved own brand to ensure palatability and increase generalizability of results.
Reinforced responding was influenced by main effects of smoking condition (p<.05) and music reward type (p<.001). Compared to no smoking, responding for music was increased after smoking 8+2/trial puffs (p<.005), but not after 0+2/trial puffs. Smoking condition significantly increased reinforced responding only for the high preference music (p=.01), and not for moderate or low preference music, or for no reward. Withdrawal did not differ between the two smoking sessions, ruling out withdrawal relief as an explanation for differential reinforcement enhancement.
Our findings confirm that just one cigarette after abstinence is sufficient for reinforcement enhancing effects and suggest that such enhancement is greater as magnitude of a reward’s reinforcing efficacy increases.
PMCID: PMC3786025  PMID: 23768842
nicotine; reinforcement enhancement; smoking; reinforcing efficacy; music; CReSS
Addiction (Abingdon, England)  2013;108(11):1962-1968.
Background and aim
It is important to find economical methods in early Phase 2 studies to screen drugs potentially useful to aid smoking cessation. A method has been developed that detects efficacy of varenicline and nicotine patch. This study aimed to evaluate whether the method would detect efficacy of bupropion and correctly identify lack of efficacy of modafinil.
Using a within-subject double crossover design, smokers attempted to quit during each treatment, with bupropion (150 mg b.i.d.), modafinil (100 mg b.i.d.), or placebo (double-blind, counter-balanced order). In each of three medication periods, all smoked with no drug on week 1 (baseline or washout), began dose run-up on week 2, and tried to quit every day during week 3.
A university research center in the United States.
Forty-five adult smokers high in quit interest.
Abstinence was verified daily each quit week by self-report of no smoking over the prior 24 hr and CO<5 ppm.
Compared with placebo, bupropion did (F(1,44)=6.98, p=.01), but modafinil did not (F(1,44)=.29, p=.60), increase the number of abstinent days. Also, bupropion (versus placebo) significantly increased the number of those able to maintain continuous abstinence on all 5 days throughout the quit week (11 vs 4), Z= 2.11, p <.05, while modafinil did not (6).
Assessing days abstinent during 1 week of use of medication versus placebo in a cross-over design could be a useful early Phase 2 study design for discriminating between medications useful vs not useful in aiding smoking cessation.
PMCID: PMC3797155  PMID: 23773319
Self-reported cigarettes per day (CPD) is a very common screening, as well as dependent or independent, measure in clinical and non-clinical research on smoking, but consistency of CPD across days in dependent smokers is uncertain. Adult dependent smokers (N=357; 170 men, 187 women) retrospectively reported “usual” CPD at screening and then prospectively self-monitored CPD on 3 consecutive days of one week during an ad libitum baseline period. Participants were those recruited for later tests of brief medication effects in those with high (n=170) versus low (n=187) interest in quitting smoking soon (within 3 months). Consistency was determined by intraclass correlation (ICC). Prospective daily CPD was generally consistent (ICC = 0.78, 95% CI of 0.74–0.81), but CPD changed (increase or decrease) by 5 cigarettes/day or more in 40% of participants and by at least 10/day in 10%. Consistency in CPD was greater in higher dependent smokers and in women with low (vs. high) quit interest, but consistency tended to be greater in men with high (vs. low) quit interest. Although retrospectively reported CPD at screening was consistent with the overall mean for prospectively monitored daily CPD, 15% of participants differed by at least 5/day between methods, and digit bias was twice as likely with retrospective versus prospective CPD, which was at chance levels. Understanding variability in CPD may improve knowledge of dependence and factors that foster or discourage daily smoking amount, but precise assessment of daily CPD likely requires prospective monitoring.
PMCID: PMC3822912  PMID: 23088404
smoking behavior; cigarettes per day; dependence; sex differences
Psychopharmacology  2013;228(3):479-486.
In animals, nicotine enhances reinforcement from stimuli unrelated to nicotine intake. Human research is suggestive but has not clearly shown a similar influence of nicotine.
We assessed acute effects of nicotine via smoking on enhancement of positive (money, music) or negative (termination of noise) reinforcers, or no “reward” (control). These different rewards determined the generalizability of nicotine effects.
Materials and Methods
Dependent (n=25) and nondependent (n=27) smokers participated in three sessions, each after overnight abstinence. Using a within-subjects design, sessions involved no smoking or smoking denicotinized (0.05 mg) or nicotine (0.6 mg) QuestR brand cigarettes. For comparison, a fourth session involved no abstinence prior to smoking one’s own brand to gauge responses under typical nicotine satiation. Reinforcement was assessed by responses on a simple operant computer task for the rewards, each available singly on a progressive ratio schedule during separate trials.
The reinforcing effect of music, but not other rewards, was greater due to the nicotine cigarette, compared to the denicotinized cigarette or no smoking. Reinforcement enhancing effects of nicotine did not differ between dependent and nondependent groups, indicating no influence of withdrawal relief. Responding due to acute nicotine after abstinence was very similar to responding one’s own brand after no abstinence.
Acute nicotine intake per se from smoking after abstinence enhances the reinforcing value of rewards unassociated with smoking, perhaps in a manner comparable to ad lib smoking after no abstinence. Nicotine’s reinforcement enhancing effects may be specific to certain rewards, perhaps those sensory in nature.
PMCID: PMC3707934  PMID: 23494236
nicotine; reinforcement enhancement; reward; smoking; dependence
9.  The First Seven Days of a Quit Attempt Predicts Relapse: Validation of a Measure for Screening Medications for Nicotine Dependence 
Journal of addiction medicine  2013;7(4):249-254.
There is a critical need for the development of novel treatments for nicotine dependence. Since the majority of smokers who make a quit attempt fail within seven days, medication screening procedures which focus on this early cessation period may provide an indicator of treatment efficacy. To establish the clinical validity of this paradigm, it is critical to demonstrate the association of early abstinence with longer-term abstinence. We tested the number of days abstinent during the first week following the target quit date (TQD) as a predictor of point-prevalence abstinence in three independent pharmacotherapy trials for nicotine dependence.
This was a secondary data analysis of three randomized clinical trials: a placebo-controlled trial of transdermal nicotine (n=545); an open-label nicotine replacement therapy (patch vs. spray) trial (n=566); and a bupropion placebo-controlled trial (n=538). In separate logistic regression models, the maximum number of consecutive days of abstinence during the first week following the TQD was used to predict biochemically-verified 7-day point prevalence abstinence at end-of-treatment and six months post-TQD.
Across the three trials, number of days abstinent significantly predicted abstinence at end-of-treatment and six months (ORs>1.4, ps<0.0001). Likewise, not having any lapse during the first week predicted abstinence at end-of-treatment and six months (ORs>4.7, ps<0.0001).
The first week of abstinence was highly predictive of end-of-treatment and long-term abstinence. Medication screening procedures which focus on this early abstinence period (i.e., six or seven days of consecutive abstinence) represent a valid tool for assessing the presence of a signal for medication efficacy.
PMCID: PMC3737394  PMID: 23669629
Smoking cessation; nicotine dependence; medication screening; relapse
10.  Possible Reinforcement Enhancing Effects of Bupropion During Initial Smoking Abstinence 
Nicotine & Tobacco Research  2012;15(6):1141-1145.
Due to a drop in nicotine, smoking cessation may attenuate reinforcement from sensory stimuli unrelated to nicotine intake. Recent rodent research suggests that bupropion may reverse this attenuation, perhaps helping explain its efficacy in aiding cessation.
In a within-subjects, crossover study, smokers responded on a simple computer task for brief music reward available on a progressive ratio 50% schedule. Testing was done on three separate occasions: after ad lib smoking during prequit baseline and on the first day of two brief quit attempts while taking bupropion or placebo, in counter-balanced order. Number of operant responses was the measure of reinforcement. To more clearly assess abstinence and medication effects, those meeting 24-hr abstinence criteria (CO < 5 ppm; n = 5) or clearly failing to abstain (CO > 10 ppm; n = 5) during both medication conditions were compared.
Among abstainers, repeated measures ANOVA showed that reinforced responding decreased by nearly 50% from baseline after quitting on placebo (p = .03), while responding after quitting on bupropion was similar to that during baseline (–17%; p = .20). In contrast, those unable to abstain showed virtually identical reinforced responding due to either medication or baseline.
These exploratory findings confirm that responding for a reward unrelated to smoking decreases after abstinence and are consistent with animal research showing bupropion effects on enhancing reinforced responding.
PMCID: PMC3646646  PMID: 23100457
11.  Optimal Carbon Monoxide Criteria to Confirm 24-hr Smoking Abstinence 
Nicotine & Tobacco Research  2012;15(5):978-982.
Smoking cessation is typically verified biochemically by expired-air carbon monoxide (CO) levels below 9 ppm (i.e., ≤8 ppm), but this CO criterion may lead many who have smoked within 24hr to be misclassified as abstinent.
Adult dependent smokers (N = 261; 124 men, 137 women) prospectively recorded each cigarette smoked and provided CO on five consecutive days during each of two short-term attempts to quit smoking. Participants were those recruited for crossover tests of the effects of placebo versus medication (nicotine patch or varenicline) on the ability to initiate 24-hr abstinence. All had either a high or low interest in permanently quitting smoking soon (within 3 months) and were randomized to the presence or absence of daily ($12) monetary reinforcement of abstinence.
Total accuracy of sensitivity to detect smoking (83%) plus specificity to verify abstinence (87%) was optimal at a CO criterion for abstinence below 5 ppm (≤4 ppm), compared with below 9 ppm (sensitivity of 60%, specificity of 97%). Overall CO detection of sensitivity and specificity was higher in those with high versus low quit interest, but reinforcement of abstinence made no difference.
Results indicate a CO criterion half that used in most clinical research may optimally validate 24-hr cessation and reduce misclassification of smokers as “abstinent.”
PMCID: PMC3733388  PMID: 22990219
Addictive behaviors  2012;38(2):1527-1531.
Negative mood situations increase craving to smoke, even in the absence of any tobacco deprivation (e.g. “stressors”). Individual differences in effects of negative mood situations on craving have received relatively little attention but may include variability between men and women. Across two separate within-subjects studies, we examined sex differences in craving (via the QSU-brief) as functions of brief smoking abstinence (versus satiation; Study 1) and acute induction of negative mood (versus neutral mood; Study 2). Subjective ratings of negative affect (via the Mood Form) were also assessed. In study 1, we compared the effects of overnight (>12 hr) abstinence versus non-abstinence on craving and affect in adult male (n=63) and female (n=42) smokers. In study 2, these responses to negative versus neutral mood induction (via pictorial slides and music) were examined in male (n=85) and female (n=78) satiated smokers. Results from each study were similar in showing that craving during the abstinence and negative mood induction conditions was greater in women than men, as hypothesized, although the sex difference in craving due to abstinence was only marginal after controlling for dependence. Craving was strongly associated with negative affect in both studies. These results suggest that very acute negative mood situations (e.g. just a few minutes in Study 2), and perhaps overnight abstinence, may increase craving to smoke to a greater extent in women relative to men.
PMCID: PMC3462895  PMID: 22726579
sex; abstinence; negative mood; craving; affect; smoking
13.  Dietary intake after smoking cessation among weight concerned women smokers 
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.
PMCID: PMC3475794  PMID: 22799893
Smoking cessation; Dietary intake; Weight concerns; Macronutrients
14.  Smoking in Response to Negative Mood in Men Versus Women as a Function of Distress Tolerance 
Nicotine & Tobacco Research  2012;14(12):1418-1425.
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.
PMCID: PMC3509012  PMID: 22416115
15.  CYP2A6 Genotype and Smoking Behavior in Current Smokers Screened for Lung Cancer 
Substance use & misuse  2013;48(7):490-494.
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.
PMCID: PMC3788637  PMID: 23528144
smoking cessation; smoking initiation; cigarette smoking; genetics; cytochrome P450; nicotine metabolism
16.  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 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.
PMCID: PMC3752834  PMID: 22889039
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.
PMCID: PMC3731142  PMID: 21910550
smoking cessation; self-efficacy; smoking behavior; abstinence; nicotine dependence; behavior change
19.  The Reliability of Puff Topography and Subjective Responses During Ad lib Smoking of a Single Cigarette 
Nicotine & Tobacco Research  2011;14(4):490-494.
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.
PMCID: PMC3313780  PMID: 22039077
20.  Subjective Reactivity to Smoking Cues as a Predictor of Quitting Success 
Nicotine & Tobacco Research  2011;14(4):383-387.
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.
PMCID: PMC3313783  PMID: 22140145
21.  Subjective Sleep Disturbance during a Smoking Cessation Program: Associations with Relapse 
Addictive behaviors  2011;36(8):861-864.
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.
PMCID: PMC3588159  PMID: 21482029
sleep quality; insomnia; smoking; drowsiness; women; cessation; withdrawal
22.  Effects of 24 Hours of Tobacco Withdrawal and Subsequent Tobacco Smoking Among Low and High Sensation Seekers 
Nicotine & Tobacco Research  2011;13(10):943-954.
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.
PMCID: PMC3179670  PMID: 21690318
23.  “Bringing the real world into the laboratory: Personal smoking and nonsmoking environments” 
Drug and alcohol dependence  2010;111(1-2):58-63.
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.
PMCID: PMC2930143  PMID: 20510552
tobacco; cue reactivity; context; conditioning
24.  Bupropion and Cognitive Behavioral Therapy for Weight-Concerned Women Smokers 
Archives of internal medicine  2010;170(6):543-550.
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.
PMCID: PMC3113531  PMID: 20308641
25.  Differences in negative mood-induced smoking reinforcement due to distress tolerance, anxiety sensitivity, and depression history 
Psychopharmacology  2010;210(1):25-34.
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.
PMCID: PMC2882096  PMID: 20217051
Smoking; Reinforcement; Nicotine; Depression history; Distress tolerance; Anxiety sensitivity; Negative affect; Mood; Withdrawal

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