Reactivity to in vivo smoking cues in older adolescent cigarette smokers.

Most smokers initiate smoking in adolescence, and craving for cigarettes may play an important role in maintenance of smoking behavior and relapse to smoking during a quit attempt. Although a significant body of literature explores cue-reactivity in adult smokers, little has been published on cue-reactivity among adolescent smokers. In a previously published work, we found that videotaped smoking cues may not be robust in eliciting craving among adolescent smokers. Hence, in this preliminary study, we examined reactivity to in vivo smoking cues among adolescent smokers (N = 11, average age = 18.1 years, range = 15-19 years, predominantly female). Participants were presented with in vivo smoking and neutral cues (counterbalanced). We recorded subjective craving and real-time heart rate in response to each type of cue. Adolescent smokers had a significantly greater "desire" to smoke (p < .05) in response to smoking cues vs. both baseline and neutral cues. Participants had faster heart rates after the smoking cues during the epochs of 21-30 s and 31-40 s (p values<.05) as compared with baseline, and mean heart rate was higher during the smoking cues relative to neutral cues among participants who received the smoking cues first (p < .05). Results of this preliminary study further demonstrate the feasibility of conducting cue-reactivity studies with adolescent cigarette smokers. Findings from this study suggest that adolescent smokers may show patterns of responding to smoking cues similar to those of adult smokers. Implications for future laboratory studies with adolescent smokers are discussed.     

Carry-over effects of smoking cue exposure on working memory performance.

The present study investigated the effects of drug cue exposure on working memory performance in cigarette smokers. Adult smokers (N = 23) deprived for 12 hr performed a working memory task during which they were exposed to three types of task-irrelevant stimuli: Pictures containing smoking related-content, pictures devoid of smoking content, and a fixation cross. Consistent with prior research, we found that drug cue exposure affected the processing of subsequent items (i.e., carry-over effects). Specifically, we found that working memory performance was worse on trials containing neutral pictures preceded by trials containing smoking cues compared with performance on trials containing neutral pictures preceded by trials not containing smoking-related stimuli. Previously observed effects of smoking cue exposure on cognitive processing were replicated but only after removing trials subject to carry-over effects. These results replicate and extend previous research demonstrating similar effects and highlight the significant methodological and conceptual implications of carry-over effects.     

Instructed smoking expectancy modulates cue-elicited neural activity: a preliminary study.

In recent years, research applying functional neuroimaging to the study of cue-elicited drug craving has emerged. This research has begun to identify a distributed system of brain activity during drug craving. A review of this literature suggested that expectations regarding the opportunity to use a drug affected the pattern of neural responses elicited by drug cues. Using functional magnetic resonance imaging (fMRI), we examined the effects of smoking expectancy on the neural response to neutral (e.g., roll of tape) and smoking-related (a cigarette) stimuli in male cigarette smokers deprived of nicotine for 8 hr. As predicted, several brain regions (e.g., the anterior cingulate cortex) exhibited differential activation during cigarette versus neutral cue exposure. Moreover, we found that subregions of the prefrontal cortex (i.e., ventromedial, ventrolateral, and dorsolateral prefrontal cortices) showed cue-elicited activation that was modulated by smoking expectancy. These results highlight the importance of perceived drug use opportunity in the neurobiological response to drug cues.     

The effects of smoking deprivation and nicotine administration on emotional reactivity.

Although converging lines of evidence suggest that nicotine and mood are related at a fundamental biological level, this link has not been reliably demonstrated in laboratory studies. In this study, startle probe methodology was used to examine the effects of nicotine administration and deprivation on emotional processes associated with motivation. Smokers (N = 115) completed four laboratory sessions crossing deprivation (12-hr deprived vs. nondeprived) with nicotine spray (active vs. placebo). Participants viewed affective pictures (positive, negative, neutral) and pictures involving cigarette cues, while startle probes were administered. Deprivation decreased startle responding to cigarette cues, suggesting an activation of appetitive processes. Nicotine administration suppressed overall startle responding during deprivation. In addition, during deprivation, random exposure to negative stimuli over two blocks of trials resulted in decreased adaptation of the startle response, suggesting that some sensitization to negative emotional cues may take place during nicotine withdrawal. These effects are consistent with formulations of addiction, stressing that withdrawal may both increase the reinforcement salience of smoking stimuli and decrease habituation to negative emotional stimuli.     

Subjective and physiological responses to smoking cues in smokers with schizophrenia.

The prevalence of smoking is high among people with schizophrenia. Although several research groups are developing smoking treatments for these smokers, abstinence rates to date have been modest. Methodological tools such as cue exposure are useful in clinical research with smokers in general, but the value of these paradigms with smokers with schizophrenia has yet to be established. The aim of the present study was to determine the subjective and physiological effects of exposure to in vivo smoking cues in smokers with schizophrenia. A total of 25 heavy smokers with schizophrenia or schizoaffective disorder were assessed while nonabstinent and after 2-hr smoking abstinence. Urge to smoke, mood, nicotine withdrawal symptoms, heart rate, and blood pressure were measured during a precue relaxation period, after exposure to neutral cues, and after exposure to smoking cues. Results indicate that both exposure to smoking cues and brief abstinence increased urge levels, nicotine withdrawal symptom levels, and negative affect. Abstinence did not amplify the effects of cues on urges or other cue reactivity measures. These results indicate that smoking cue reactivity laboratory models may be useful for investigating potential smoking treatments for, or neurobiological contributions to, smoking behavior in smokers with schizophrenia.     

Real-time craving and mood assessments before and after smoking.

This study explored some quandaries concerning craving and mood as motivators to smoke. Craving and negative mood have long been associated with day-to-day smoking as two of the primary motivational forces behind the maintenance of the behavior, as well as significant barriers in smokers' attempts to quit. Craving remains a clinically relevant phenomenon, with most smokers describing craving as a troublesome problem when quitting. Smokers' self-reports of negative mood, as an antecedent for smoking, are so robustly reported that many models of nicotine dependence have incorporated a critical role for negative mood in maintaining smoking behavior. However, several naturalistic studies that collected mood ratings with hand held computers from smokers in real time, just before smoking a cigarette, have provided scant evidence that negative mood plays a major role in motivation to smoke. No study to date has examined craving and mood data as a consequence of smoking, that is, collecting the same data immediately after smoking. This study used personal digital assistants (PDAs) to collect craving and mood data immediately before smoking, immediately after smoking, and at random times of day. Nontreatment seeking smokers (N = 72) carried a PDA for an average of 10 days while they recorded their smoking behavior. Results showed that craving and negative mood ratings were lowest immediately after smoking compared with immediately before smoking and at random times of day. These findings suggest that smokers may be at least partially motivated to smoke to lower their craving and improve their mood states.     

Smokers' expectancies for nicotine replacement therapy vs. cigarettes.

Smokers (N=188) recruited from the local community completed a questionnaire that measured expected outcomes of using cigarettes, nicotine gum, nicotine patch, and nicotine nasal spray. Expectancy questions relating to negative affect, craving, weight, and health risks were derived from the Smoking Consequences Questionnaire-Adult. As predicted, smokers held much greater expectancies that cigarettes help control negative affect, craving, and weight relative to nicotine replacement therapy (NRT). All NRT products were expected to cause fewer health risks than cigarette smoking. As predicted, smokers held strong negative affect reduction expectancies for cigarette smoking. For NRT, although still relatively low, craving reduction was the strongest expectancy. Individuals who had experience using the nicotine patch had greater positive expectancies for NRT. Greater positive expectancies for NRT were correlated with more immediate plans to quit smoking. In summary, cigarette smokers' positive expectancies about cigarettes do not appear to generalize to NRT products, which may limit their use and effectiveness.     

Extinguishing the rewarding value of smoke cues: pharmacological and behavioral treatments.

The present study examined several pharmacological and behavioral treatments designed to promote extinction of the responses to rewarding cigarette smoke cues. Pharmacological treatments comprised nicotine skin patches (21 mg/24 hr) and the nicotinic acetylcholine receptor antagonist mecamylamine (10 mg/day), administered separately or in combination. Behavioral manipulations included switching to denicotinized cigarettes, to cigarettes having different menthol flavor, or to ventilated-filter (low tar and nicotine) cigarettes. Smokers were assigned to the various treatments for 2 weeks before they quit smoking. During weekly test sessions, subjects rated the rewarding effects of their usual brands of cigarettes or cigarettes with different menthol content (mentholated vs. nonmentholated). Over the 2-week treatment period, all pharmacological treatments reduced ratings of reward for the usual-brand test cigarettes. Switching to smoking denicotinized cigarettes for 2 weeks similarly decreased rewarding effects of the usual-brand test cigarettes. Subjects also strongly preferred cigarettes with the same menthol content to which they were accustomed. However, manipulating the menthol content of the cigarettes smoked during the 2 weeks of treatment had different effects, depending on whether smokers habitually smoked mentholated or nonmentholated cigarettes. For menthol smokers, removal of the menthol cue hampered extinction of reward ratings for the usual-brand (mentholated) test cigarette. For nonmenthol smokers, addition of the menthol cue did not affect the progress of extinction of nonmenthol smoke cues. These findings demonstrate the importance of sensory cues in determining subjective reward and show that the reward value of these cues can be altered by removal of nicotine from tobacco or by pharmacological manipulations that interfere with the reinforcing effects of nicotine.     

The role of impulsivity on smoking maintenance.

In order to better understand why those higher in impulsivity experience more difficulties during smoking abstinence, the current study examined the possible mechanisms contributing to cigarette smoking relapse. Fifty dependent cigarette smokers completed measures designed to assess craving, tobacco withdrawal severity, and negative affect during 48 hours of nicotine abstinence. Using a series of multilevel models (SAS Proc Mixed Procedure), significant impulsivity x time analyses revealed differences in craving, F(2, 96) = 3.74, p<.05, and anxiety, F(2, 96) = 3.23, p<.05. Simple slopes analyses indicated that heightened trait-impulsivity predicted greater increases in craving and anxiety during a 48-hour abstinence period. These findings suggest that smokers with higher levels of impulsivity may lack the ability to find an accessible and comparable substitute for cigarette smoking during a cessation attempt. This study also highlights the importance of considering individual differences when treating those who wish to quit smoking.     

Effects of nicotine on brain responses to emotional pictures.

Given that nicotine reduces negative affect, one would expect nicotine to have different effects on brain responses to emotionally negative stimuli than it does on responses to emotionally neutral or positive stimuli. However, no studies have assessed this possibility. The present study assessed the effects of nicotine patch versus placebo patch on brain event-related potential (ERP) responses to emotion-inducing negative, positive, and neutral color pictures in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included four experimental sessions. After overnight smoking deprivation (12 hr or more), active nicotine patches were applied to participants during one of the first two sessions and during one of the last two sessions. Placebo patches were applied during the other two sessions. Nicotine reduced frontal ERP processing voltage negativity (from 144-488 ms poststimulus onset) evoked by viewing emotionally negative pictures to a greater extent than it did when emotionally neutral pictures were viewed, whereas it had no effect on processing negativity evoked by positive pictures. Nicotine also enhanced P390 amplitudes evoked by emotionally negative pictures more than it did when emotionally neutral and positive pictures were viewed. Across picture types, nicotine (relative to placebo) reduced N300 amplitude (more at anterior and dorsal sites) and increased P390 amplitude. Overall, nicotine influenced ERPs to emotionally neutral and positive pictures less than it did to negative pictures.     

Ad lib smoking in post-traumatic stress disorder: an electronic diary study

Using ambulatory methods for 1 week of monitoring, this study investigated the association between smoking and situational cues in 22 smokers with post-traumatic stress disorder (PTSD) and 23 smokers without PTSD. Generalized estimating equations contrasted 1,759 smoking and 1,088 nonsmoking situations by group status controlling for multiple covariates. PTSD smokers reported higher stress and PTSD symptoms across daily activities. For all smokers, higher nicotine dependence, craving, food and caffeine consumption, and being outside were related to smoking. PTSD smokers were more likely to smoke when experiencing PTSD symptoms, anxiety, and stress. Following smoking, smokers with PTSD reported a significant reduction in negative affect. These results are consistent with previous ambulatory findings regarding mood in smokers, and underscore that in smokers with PTSD, PTSD symptom variables as well as stress and anxiety are significantly associated with ad lib smoking.     

A self-administered questionnaire to measure cigarette withdrawal symptoms: the Cigarette Withdrawal Scale.

Because few tobacco withdrawal scales have been submitted to appropriate validity analyses, we sought to develop and assess the validity of a new, self-administered scale measuring cigarette withdrawal symptoms. We generated the instrument content by conducting a qualitative survey of 404 smokers and ex-smokers. Then we tested 61 items on the Internet in 3,050 smokers and ex-smokers. Subsamples provided comprehensive retest data after 17 days (n = 1218) and smoking status after 41 days (n = 673). The study resulted in a 21-item, six-dimension scale labeled the Cigarette Withdrawal Scale (CWS-21). The six subscales cover the main components of nicotine or tobacco withdrawal in the Diagnostic and Statistical Manual of Mental Disorders and International Statistical Classification of Diseases and Related Health Problems and in qualitative data: Depression-anxiety, craving, irritability-impatience, appetite-weight gain, insomnia, and difficulty concentrating. The six scores had a satisfactory test-retest reliability (r = .60-.71) and a high internal consistency (Cronbach's alpha = .83-.96). The factor structure of the scale was robust in a bootstrap resampling procedure. In ex-smokers, all scores except appetite-weight gain and insomnia predicted relapse at 41-day follow-up. In recent ex-smokers who had quit smoking less than 14 days before baseline, all scores except appetite-weight gain decreased between baseline and the 17-day retest. In baseline ex-smokers who relapsed to smoking at the 17-day retest, appetite-weight gain decreased and craving increased between baseline and retest. CWS-21 is a reliable, valid, multidimensional measure of cigarette withdrawal symptoms that is sensitive to change over time and predicts relapse to smoking.     

Severity of nicotine dependence moderates performance on perceptual-motor tests of attention.

Acute abstinence from cigarette smoking by nicotine-dependent smokers has been linked with cognitive deficits, but the role of nicotine dependence per se in these effects is not known. We therefore tested the relationships of nicotine dependence and smoking history with performance in perceptual-motor, timed tests of attention. Nicotine-dependent smokers (n = 37) and nonsmokers (n = 48), 18-55 years old, took both the d2 Test of Attention and the Digit Symbol Test on each of 2 test days. For smokers, testing on one day began after ad libitum smoking (<45 min since last cigarette); and on the other day, it began after overnight abstinence (>13 hr since last cigarette). On each test day, there were two test blocks with an intervening break, when only the smokers each smoked one cigarette. There were no significant effects of abstinence or of smoking one cigarette on the performance of smokers; however, across conditions, the smokers' performance on both tests correlated negatively with severity of nicotine dependence but not lifetime cigarette consumption or cigarette craving. Smokers with high nicotine dependence performed more slowly on both tests than less dependent smokers or nonsmokers. The findings suggest that severity of nicotine dependence and slowness in perceptual-motor tasks of attention share an underlying basis.     

Butt lengths differ by area deprivation level: a field study to explore intensive smoking.

We collected cigarette butts in a range of residential areas, to assess differences in the length of unburnt tobacco in the butts, and in proportions of roll-your-own (RYO) cigarettes. Two high, two medium, and two low deprivation areas, as classified by deciles of the New Zealand Deprivation Index, were selected for the Wellington region. Collected butts were systematically classified and measured. A mixed model of analysis, treating location clusters nested within deprivation level areas as a random effect, was used to assess differences in mean length of unburnt tobacco in the butts. A total of 6,262 cigarette butts and separate filters were collected, of which 3,509 (56.0%) were measurable manufactured cigarette butts, 1,069 were unmeasurable manufactured butts, 1,450 were RYO butts, and 236 were RYO filters. The RYO butts were not measured because of the extent of their degradation. The unburnt tobacco lengths in manufactured cigarette butts were significantly shorter in the most deprived areas, relative to the least deprived areas (p = .035). Deformed manufactured cigarette butts (i.e., that potentially were stubbed out) showed the same pattern (p = .011 between the most and least deprived areas). We found no significant difference between deprivation areas in the proportion of RYO material found. The shorter mean unburnt tobacco length in the most deprived areas is consistent with more intensive smoking among smokers in those areas. This finding is consistent with other evidence of increased price sensitivity among poorer smokers, and with basic economic theory. Further evidence on observed smoking behavior in the field is necessary to better interpret these preliminary findings.     

The impact and acceptability of Canadian-style cigarette warning labels among U.S. smokers and nonsmokers.

Cigarette smoking is a major source of mortality and medical costs in the United States. More graphic and salient warning labels on cigarette packs as used in Canada may help to reduce smoking initiation and increase quit attempts. However, the labels also may lead to defensive reactions among smokers. In an experimental setting, smokers and nonsmokers were exposed to Canadian or U.S. warning labels. Compared with current U.S. labels, Canadian labels produced more negative affective reactions to smoking cues and to the smoker image among both smokers and nonsmokers without signs of defensive reactions from smokers. A majority of both smokers and nonsmokers endorsed the use of Canadian labels in the United States. Canadian-style warnings should be adopted in the United States as part of the country's overall tobacco control strategy.     

Ecological momentary assessment of adolescent smoking cessation: a feasibility study.

Attempts to quit smoking by adolescents typically fail, even when aided by psychosocial and pharmacological treatments. Gaining a better understanding of the process of smoking cessation and relapse in this population could lead to improved treatments and increases in cessation rates. Ecological momentary assessment (EMA) has been used to describe the relapse process among adults, but not among adolescents. This study examined the feasibility of using EMA to examine relapse among adolescent smokers. Participants (N = 13) used a hand-held computer for 3 weeks to report on their smoking behavior, affect state, and exposure to smoking cues during a quit attempt (7 days prequit, 14 days postquit). All of the participants recorded a quit attempt and at least one lapse during the monitoring interval. Compliance with the protocol was generally high but decreased slightly over time. As with adults, evidence indicated that lapses were associated with craving, negative affect, and smoking cues. These data support the feasibility and potential value of using EMA with adolescent smokers.     

The relationship between cigarette use, nicotine dependence, and craving in laboratory volunteers.

Data from epidemiological studies suggest that individual differences in cigarettes per day (CPD) and duration of smoking account for only a small portion of the variance in Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) nicotine dependence. However, DSM-IV may be an insensitive measure of nicotine dependence; other measures might better reflect the true nature of the relationship between use and dependence. This paper describes the relationship between cigarettes per day (CPD) and years smoking and the severity of nicotine dependence as measured by the Nicotine Dependence Syndrome Scale (NDSS). Furthermore, we assessed the validity of individual differences in nicotine dependence by determining whether they related to cue-evoked craving during abstinence. Data were pooled from five laboratory studies of 489 regular (i.e., 15+ CPD) smokers. In contrast to previously reported data demonstrating a relatively strong relationship between CPD and dependence in chippers (Shiffman & Sayette, 2005), CPD and years smoking accounted for a statistically significant, but small (<6%), portion of the variance in nicotine dependence in daily smokers. Individual differences in both CPD and years smoking had little or no relationship with craving. However, the magnitude of craving was significantly related to the degree of nicotine dependence even after controlling for use variables and excluding craving-related items on the NDSS. These data suggest that among moderate to heavy daily smokers, meaningful individual differences in nicotine dependence are observed independent of differences in current daily cigarette consumption and duration of smoking. Further research into the sources of this variance is critical to understanding the process of and risk for nicotine dependence.     

Characteristics of selectors of nicotine replacement therapy

Objective: To assess differences in demographic and smoking characteristics between smokers who have and have not used nicotine replacement therapy (NRT). Design: Mail survey of US smokers from a national research panel. Participants: Smokers 18 years and over who returned a survey on smoking (n = 9630). The sample was weighted to match the US smoker population on age and sex. Main outcome measures: Compared smokers who had/had not used NRT in a quit attempt (ever NRT use or over the counter (OTC) NRT use) on: demographic characteristics, nicotine dependence, history of craving and withdrawal, expected difficulty quitting, and self reported history of smoking related medical illness and psychopathology. Results: NRT users (both ever-users and OTC users) were more likely to be older, male, and better educated. They were also heavier smokers, had experienced more craving and withdrawal upon quitting, and scored higher on measures of dependence. These differences were evident among light smokers, and remained even when smoking rate and time to first cigarette were controlled. Conclusion: Smokers who elect to use NRT differ from non-NRT users in ways that predispose them to failure in cessation. Controlling for smoking rate and time to first cigarette does not eliminate these differences, even among light smokers. These differences must be considered when comparing the effectiveness of NRT among samples of smokers who self select their treatment and are likely to bias such outcome comparisons.     

Effects of nicotine on affect are moderated by stressor proximity and frequency, positive alternatives, and smoker status

The Situation x Trait Adaptive Response (STAR) model hypothesizes that nicotine reduces negative and enhances positive affect to a greater degree in situations involving internally driven attention, as when stressor stimuli are distal (past or future), thereby allowing nicotine-primed biasing of attentional processing away from negative and toward positive stimuli. To test this hypothesis, the effects of nicotine were assessed in 64 smokers and 64 never-smokers, half of whom viewed emotionally negative pictures in a no-choice picture attention task that required them to focus on the picture stressors. The other half viewed the same stimuli in a two-choice picture attention task that presented stressor pictures in one visual field and simultaneously presented positive or neutral pictures in the other visual field. Participants received a nicotine patch during one session and a placebo patch during the other session. Nicotine modulated affect only in smokers. In smokers, compared with placebo, nicotine patch reduced negative affect more during the distal periods (between stressors) than during actual stressor exposure and in women reduced negative affect more when the proportion of negative stimuli was low. Nicotine also enhanced positive affect more during distal than proximal stressors. Nicotine tended to reduce eye-gaze at negative pictures, especially when the alternative picture was positive. The overall findings are consistent with the view that nicotine biases attention away from negative stimuli when equally salient positive or benign stimuli are present.     

Nicotine dependence, depression, and gender: characterizing phenotypes based on withdrawal discomfort, response to smoking, and ability to abstain.

Smoking is often viewed as a comprehensive phenotype rather than a complex set of traits involving intermediate phenotypes. To explore this issue in a laboratory setting, we tested 69 smokers stratified on depression, nicotine dependence, and gender. On the third day of an initial withdrawal period, we tested for differences among participants in uncued and cued craving and withdrawal; on the fourth day, we exposed them to a controlled dose of smoke and assessed them for physiological and hedonic effects and reduction of craving and withdrawal. Following resumption of smoking for at least a week, we then tested participants on their ability to abstain for an 11-day interval. During the withdrawal test, high-depressed smokers and men exhibited elevated craving and withdrawal scores overall, whereas no differences emerged for dependence. Cue exposure produced significant increases in craving but not withdrawal. During the smoke-exposure test, men were significantly more likely than women, and high-depressed smokers more likely than low-depressed smokers, to show evidence of experiencing pleasurable "buzzes." High-dependent smokers showed significant increases in diastolic blood pressure, possibly suggestive of greater sensitivity to nicotine. During the quit test, high-dependent smokers had more difficulty abstaining than low-dependent smokers, and women more than men; no differences emerged based on depression. Independently of group membership, inability to abstain was predicted by increased anxiety, depression, and difficulty concentrating in response to cue exposure. These findings provide support for the existence of phenotypes that can be distinguished by withdrawal symptomatology (primarily driven by depression) and ability to remain abstinent (primarily driven by dependence).