In Vivo Versus Imaginal Smoking Cue Exposures: Is Seeing Believing?

Smokers experience cigarette cravings in response to both imaginal and in vivo cigarette cues, and some studies suggest that the magnitude of this reactivity relates to difficulty quitting. Few studies, however, have systematically examined these two paradigms head-to-head. To this end, the authors exposed 225 smokers to imaginal and in vivo smoking cues and measured craving reactions. Results indicated that both imaginal and in vivo smoking cues increased craving. The magnitude of imaginal and in vivo reactions were statistically comparable and were moderately correlated. In vivo, but not imaginal, reactivity was related to duration of previous quits, particularly in men. Findings suggest that although both paradigms induce craving, the in vivo reactivity paradigm may be, at least in men, more effective for predicting smoking cessation failure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The DRD4 VNTR polymorphism influences reactivity to smoking cues.

Recent research has indicated that craving for tobacco can be reliably elicited by exposure to smoking cues, suggesting that cue-elicited craving for tobacco may be a useful phenotype for research on genetic factors related to nicotine dependence. Given the potential role of dopamine in cue-elicited craving, the authors examined whether the DRD4 VNTR polymorphism is associated with cue-elicited craving for tobacco. Participants who were homozygous or heterozygous for the 7 repeat (or longer) allele were classified as DRD4 L and all other participants were classified as DRD4 S. Participants were exposed to smoking cues before smoking either high-nicotine cigarettes or control cigarettes. Analyses suggested that participants in the L group demonstrated significantly greater craving, more arousal, less positive affect, and more attention to the smoking cues than did the participants in the S group. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cue-Provoked Craving and Nicotine Replacement Therapy in Smoking Cessation.

Cue exposure paradigms have been used to examine reactivity to smoking cues. However, it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy (NRT) in clinical samples. Cue-provoked craving ratings and reaction time responses were measured on the 1st day of abstinence among 158 smokers who had been randomized to high-dose nicotine (35 mg) or placebo patch. The nicotine patch reduced overall levels of craving but did not attenuate cue-provoked craving increases or reaction time responses. Cue-provoked craving predicted relapse among participants on the nicotine patch but not among those on placebo. In summary, NRT users could benefit from treatment that attenuates cue-provoked craving. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induction of smoking urge through imaginal and in vivo procedures: Physiological and self-report manifestations.

This experiment assessed reactivity to imaginal and in vivo smoking and control cues. One hundred current smokers were assessed during 2 sessions separated by a 6-hr interval, and half of the participants were abstinent from smoking over this interval. Verbal and physiological reactivity measures were selected based on their relevance for several models of urge. Results indicated that imaginal and in vivo smoking cues were equally effective at eliciting high levels of self-reported urges. Smoking deprivation led to a general enhancement in urge report, rather than a specific increase to smoking cues. Physiological responding differed somewhat as a function of urge induction method, although autonomic responses to smoking cues were uniformly consistent with the direct effects of nicotine. There was no relationship between verbal and physiological urge indices. Implications of the findings for several contemporary models of drug urges are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments

OBJECTIVE: To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments. DESIGN: Two independent randomized placebo-controlled double-blind trials. SETTING: Smoking cessation clinic. SUBJECTS: Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking. INTERVENTIONS: Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2). MAIN OUTCOME MEASURES: Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving). RESULTS: Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking. CONCLUSION: Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms.     

Prolonged duration of craving, mood, and autonomic responses elicited by cues and imagery in smokers: Effects of tobacco deprivation and sex.

Increases in self-reported craving and changes in autonomic functioning are reliably elicited when smokers are exposed to tobacco-related stimuli compared with neutral stimuli. However, few studies have reported the time course of cue-elicited craving or have directly compared the effectiveness of smoking cues versus imagery to evoke a craving response. In addition to these two issues, we investigated the influence of tobacco deprivation and sex on craving, mood, and autonomic responses. Sixty cigarette smokers (30 men, 30 women) were tested in two counterbalanced sessions, one after overnight tobacco deprivation and one during ad libitum smoking. At each session, participants were exposed to four randomized experimental trials: smoking imagery, neutral imagery, smoking cues, and neutral cues. Tobacco craving and mood were assessed repeatedly and physiological measures were recorded continuously for 30 min after imagery or cue exposure. Compared with neutral trials, smoking cues and smoking imagery reliably increased tobacco craving, negative mood, heart rate, and blood pressure and decreased positive mood ratings. Changes were observed immediately after cue and imagery presentation and remained unchanged for 30 min. Responding was greater in the nondeprived condition, and cues elicited more robust responding than imagery for most measures. Women responded more robustly to smoking cues only in the nondeprived condition, whereas imagery evoked greater responses in men during both conditions. These findings provide new data on the time course, magnitude, and tobacco deprivation effects on elicited craving. Sex differences were dependent on stimulus type and deprivation condition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do heavy smokers benefit from higher dose nicotine patch therapy?

Heavy smokers (N?=?408, smoking more than 25 cigarettes/day) were randomized to receive high-dose (25 mg) or standard-dose (15 mg) nicotine patch therapy delivered during the daytime only (16 hr) for a period of 6 weeks. Treatment effects of each dose were similar. The percentages of participants not smoking at 2-, 6-, and 12-month follow-ups were 26 versus 20, 14 versus 16, and 14 versus 14 for the 15-mg and 25-mg doses, respectively. The higher dose was well tolerated, and adverse event profiles for both treatment doses were very similar. Stepwise Cox proportional hazards analyses indicated that initial postrandomization craving and baseline scores on the Center for Epidemiological Studies Depression Instrument predicted time-to-relapse during treatment; only initial craving predicted relapse over the entire study interval (12 months). The results of this trial do not support the routine use of higher dose nicotine patch therapy in the treatment of nicotine dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Trauma-focused imaginal exposure for individuals with comorbid posttraumatic stress disorder and alcohol dependence: Revealing mechanisms of alcohol craving in a cue reactivity paradigm.

With a sample (N = 43) of participants meeting current diagnostic criteria for both alcohol dependence and posttraumatic stress disorder (PTSD), the authors tested the hypothesis that alcohol craving elicited by a trauma cue might be attenuated if trauma-elicited negative emotion were reduced following trauma-focused imaginal exposure. In a laboratory-based experiment, participants were randomly assigned to either trauma-focused imaginal exposure or imagery-based relaxation. A cue reactivity paradigm was used to assess alcohol craving prior to, and after completion of, the 6 clinical sessions. Attrition was high but did not differ between experimental conditions. For study completers, PTSD symptoms decreased in the exposure condition but not in the relaxation condition. Alcohol craving and distress elicited by trauma images decreased in the exposure condition but did not change in the relaxation condition. Results support the hypothesis that negative emotion is a mechanism of alcohol craving. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reducing craving for cigarettes while decreasing smoke intake using capsaicin-enhanced low tar cigarettes.

The effects on smoking behavior and subjective evaluation of adding capsaicin (a pungent principle of chili pepper) to a low tar and nicotine cigarette were studied in 12 cigarette smokers. In a 4-hr session, Ss inhaled smoke from 3 types of cigarettes: low tar and nicotine with capsaicin added; low tar and nicotine without capsaicin (control); and commercial high tar and nicotine. Ss puffed significantly less on the capsaicin cigarettes than on the other 2 types of cigarettes and reported greater reduction in cigarette craving after smoking capsaicin cigarettes than after smoking control low nicotine cigarettes. Estimated nicotine intake and respiratory tract sensations for the capsaicin cigarettes were also significantly higher than for the control cigarettes. Results support the view that respiratory tract sensations are important in reducing smokers' craving for cigarettes and in modulating smoking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identifying individuals with high fat levels and low P:S ratios, in their diets, for intensive dietary intervention

OBJECTIVE: Interindividual variability in plasma concentrations of nicotine and its proximate metabolite, cotinine, is considerable during smoking and transdermal nicotine treatment, even among individuals taking in nominally similar doses of nicotine. This report explores the determinants of this variability and the utility of baseline (smoking) plasma concentrations to predict concentrations during transdermal nicotine treatment. METHODS: Data were analysed from a smoking cessation study (n = 466), and from a pharmacokinetic study (n = 12). Multiple regression models examined the relationships of plasma concentrations to individual characteristics such as smoking pattern, absorbed dose of nicotine, and pharmacokinetic parameters. RESULTS: Plasma concentrations of nicotine and cotinine were highly variable in both studies. Indirect estimates of plasma clearance (baseline plasma concentration divided by cigarettes per day) together with other factors could account for 18 to 33% of the variability during transdermal nicotine treatment in the smoking cessation study. In contrast, 75 to 99% was accounted for by direct measurements of plasma clearances and systemic dose of nicotine in the pharmacokinetic study. CONCLUSION: Plasma concentrations of nicotine and cotinine during transdermal nicotine treatment are poorly predicted by clinical history or baseline plasma concentrations. This is a result of inadequate characterisation of highly variable individual pharmacokinetic parameters and absorbed dose of nicotine. Considering the interindividual variability of plasma nicotine and cotinine concentrations together with the lack of clinical end-points for transdermal nicotine dosing, it seems logical to investigate the utility of a therapeutic drug monitoring approach for transdermal nicotine treatment-particularly for high dose regimens (> 22 mg per 24 hours).     

Effects of Transdermal Nicotine During Imaginal Exposure to Anxiety and Smoking Cues in College Smokers.

In a 2 (patch) × 2 (smoking) × 2 (anxiety) mixed design, 52 undergraduate smokers randomly received a nicotine (21 mg) or placebo patch. After a 4-hr nicotine absorption/deprivation period, participants imagined several scenarios varying in cue content: (a) anxiety plus smoking, (b) anxiety, (c) smoking, and (d) neutral. Although smoking urge increased in both the nicotine and placebo conditions after the absorption/deprivation period, those who received the placebo reported significantly greater urge. During the cue reactivity trials, a significant Patch × Smoking × Anxiety interaction effect was observed for urge. However, participants who received nicotine still experienced moderate urges, indicating that nicotine did not attenuate cue-elicited urge. Transdermal nicotine did not diminish anxiety during the absorption/deprivation period or in response to the cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Smoking cues decrease prepulse inhibition of the startle response and increase subjective craving in humans.

The present study investigated whether exposure to smoking cues would attenuate prepulse inhibition (PPI) of the startle reflex and increase craving among smokers across 2 experimental sessions. It was hypothesized that exposure to smoking cues would result in a decrease in PPI. Twenty-six smokers were exposed to smoking cues and control cues in 2 experimental sessions 1 week apart. Results indicate that smoking cues reliably attenuated PPI in both the 1st and 2nd sessions as compared with control cues. Findings also suggest that smoking cues reliably increased craving, increased negative affect, and reduced positive affect relative to baseline measures in both sessions. Results are consistent with the premise that exposure to smoking cues precipitates increases in dopamine activation or changes in information processing that cause a disruption of PPI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Placebo cigarettes in smoking research.

This review outlines the development and use of placebo cigarettes in smoking research. Research on effects of smoking has been disadvantaged by the lack of an adequate placebo condition. Recently, tobacco-based denicotinized cigarettes have been used in smoking research to distinguish effects of smoking due to the delivery of nicotine, other components of tobacco smoke, and the sensory process of smoking. Placebo cigarettes do not increase heart rate and blood pressure or produce electroencephalogram changes ordinarily associated with nicotine. However, placebo cigarettes reduce subjective measures of tobacco craving, desire to smoke, and tobacco withdrawal. These findings indicate that the effects of cigarette smoking are dependent on the delivery of nicotine, tar, other compounds of tobacco smoke, and the sensory stimuli. The next generation of research may begin to investigate the mechanisms that modulate these placebo effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Craving and physiological reactivity to trauma and alcohol cues in posttraumatic stress disorder and alcohol dependence.

The high comorbidity of posttraumatic stress disorder (PTSD) and alcohol dependence (AD) has been firmly established. Although laboratory studies have examined self-reported craving in response to trauma and alcohol cues, no studies have reported on alcohol-related physiological responding in response to trauma cues in PTSD-AD individuals. Using a cue reactivity paradigm, this study examined the impact of personalized trauma-image cues and in vivo alcohol cues on alcohol-related responding (e.g., salivation, craving) in individuals with PTSD and AD (n = 40). Participants displayed reactivity to both trauma and alcohol cues when compared to neutral cues, including increased self-reported craving and distress, as well as greater salivation. These findings suggest that through repeated pairings of trauma memories and alcohol consumption, salivation may become classically conditioned to trauma cues. Moreover, the fact that the trauma-alcohol cue combination elicited greater alcohol craving, salivary responding, distress, and arousal than either the trauma-neutral or neutral-alcohol cue combinations suggests that effects of the trauma and alcohol cues were additive in nature. Evidence that AD individuals with PTSD report increased alcohol craving and display greater salivation in response to trauma memories, supplements prior research indicating that PTSD-related negative emotion and trauma-related alcohol craving may play an important role in the maintenance of AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Three year continuous abstinence in a smoking cessation study using the nicotine transdermal patch

A total of 305 subjects from Sydney were randomly allocated to receive either an active (24 hour transdermal nicotine patch over a 10 week course) or placebo nicotine patch. All subjects participated in a multicomponent cognitive-behavioural smoking cessation programme over five weeks in two-hour group sessions. The continuous abstinence rates at three years (validated by expired carbon monoxide) were 13.8% for the active group and 5.2% for placebo group (p = 0.011). The active nicotine patch with behavioural therapy achieved more than double the abstinence rates early in treatment compared with placebo and this difference was maintained throughout the three year follow up.     

Effects of d-amphetamine and smoking abstinence on cue-induced cigarette craving.

In this study, the authors investigated the effects of the indirect dopamine agonist d-amphetamine (AMPH) on cue-induced cigarette craving in smokers. Abstinent or nonabstinent cigarette smokers (N=21) rated their cravings for cigarettes and for food (control) after pretreatment with AMPH (15 mg) or placebo and before and after viewing blocks of smoking-related, food-related, and neutral pictures. Before the cues were presented, AMPH increased cigarette craving and decreased food craving. Smoking and food cues increased craving for cigarettes and for food, respectively. AMPH also further increased cigarette craving (and decreased food craving) after cue presentation, but it did so regardless of cue type (food or smoking). Smoking abstinence markedly increased craving regardless of cue presentation or drug condition. These results suggest that both AMPH and smoking abstinence can increase cigarette craving, but they do not appear to specifically affect responses to conditioned smoking-related cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy.

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2×2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A multimodal approach to assessing the impact of nicotine dependence, nicotine abstinence, and craving on negative affect in smokers.

We used multimodal measurement to evaluate whether (a) nicotine dependence is associated with baseline and postquit negative affect and craving, (b) smoking relapse is associated with greater negative affect and craving than abstinence, and (c) craving is associated with negative affect. Treatment-seeking smokers were randomly assigned to either a brief behaviorally based smoking-cessation treatment condition or to a delayed treatment control condition. Participants in the treatment condition attended four assessment sessions, 4–5 days prequit (baseline), 1–2 days postquit, 3–5 days postquit, and 10–14 days postquit, while controls attended four sessions spaced over the same intervals. Retrospective questionnaires were collected at the beginning of each session, and corrugator EMG and in-session ratings were collected during viewing of affective and cigarette-related slides. The multimodal measures indicated that more dependent smokers experienced greater negative affect and craving at baseline and postquit, regardless of abstinence status. The self-report measures indicated that both relapsed and abstinent smokers reported greater negative affect and craving than control smokers. Craving was associated with negative affect across measurement modalities. These results highlight the benefits of using multimodal measures to study the impact of nicotine dependence and withdrawal on negative affect and craving. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Contingent monetary reinforcement of smoking reductions, with and without transdermal nicotine, in outpatients with schizophrenia.

This study was conducted to examine the effects of contingent monetary reinforcement (CM) for smoking reduction, with and without transdermal nicotine, on cigarette smoking in individuals with schizophrenia. Fourteen outpatients participated in each of 3 conditions: (a) CM combined with 21 mg transdermal nicotine, (b) CM combined with placebo patch, and (c) noncontingent reinforcement combined with placebo patch. Each condition lasted 5 days. Carbon monoxide levels were measured 3 times daily, and nicotine withdrawal symptoms were measured once daily in each condition. Results indicated that CM reduced smoking but that 21 mg transdermal nicotine did not enhance that effect. These results offer further evidence supporting the efficacy of CM for reducing smoking among people with schizophrenia, but higher doses of nicotine replacement therapy, or another pharmacotherapy, may be needed to enhance that effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)