Psychological and pharmacological influences in cigarette smoking withdrawal: Effects of nicotine gum and expectancy on smoking withdrawal symptoms and relapse.

To determine the relative effects of expectancy and nicotine depletion on aversive withdrawal symptoms, we gave 109 smokers attempting to quit either nicotine gum or placebo within a balanced placebo design and monitored their withdrawal symptoms and smoking for 2 weeks. Subjects who believed they were getting nicotine gum reported less physical symptoms of withdrawal, showed less arousal, and smoked fewer cigarettes during the first week of quitting when compared with those who thought they were receiving placebo gum. The actual nicotine content of gum had no effect on withdrawal or relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High-dose transdermal nicotine and naltrexone: Effects on nicotine withdrawal, urges, smoking, and effects of smoking.

Although treatment with transdermal nicotine replacement (TNR) has improved smoking abstinence rates, higher doses of TNR could improve effects on urge to smoke, nicotine withdrawal, and reinforcement from smoking, and naltrexone might further reduce reinforcement and urges. A laboratory investigation with 134 smokers using a 3 × 2 parallel-group design evaluated the effects of TNR (42-mg, 21-mg, or 0-mg patch) as crossed with a single dose of naltrexone (50 mg) versus placebo on urge to smoke, withdrawal, and responses to an opportunity to smoke (intake, subjective effects) after 10 hr of deprivation. Urge and withdrawal were assessed both prior to and after cigarette cue exposure. Only 42 mg TNR, not 21 mg, prevented urge to smoke, heart rate change, and cue-elicited increase in withdrawal. Both 21 and 42 mg TNR blocked cue-elicited drop in heart rate and arterial pressure. Naltrexone reduced cue-elicited withdrawal symptoms but not urges to smoke or deprivation-induced withdrawal prior to cue exposure. Neither medication significantly affected carbon monoxide intake or subjective effects of smoking except that 42 mg TNR resulted in lower subjective physiological activation. No interaction effects were found, and no results differed by gender. Results suggest that starting smokers with 42 mg TNR may increase comfort during initial abstinence, but limited support is seen for naltrexone during smoking abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of nicotine dose and nicotine dose expectancy on the cognitive and subjective effects of cigarette smoking.

This study investigated the independent and interactive effects of nicotine dose and nicotine dose expectancy on smoking outcomes using a 2 (given nicotine vs. placebo) × 2 (told nicotine vs. placebo) Balanced Placebo Design (BPD). Smokers (N = 148) completed the Rapid Visual Information Processing Task (RVIP) and measures of smoking urge, mood, and cigarette ratings (e.g., satisfying) after smoking a nicotine or placebo cigarette crossed with instructions that the cigarette contained either nicotine or no nicotine. Nicotine cigarettes (0.6 mg nicotine) produced better sustained attention performance than placebos as indicated by RVIP reaction time, hits, and sensitivity (A′). Nicotine cigarettes also produced better mood and greater rewarding subjective effects of the cigarettes on 11 of 11 dimensions compared to placebos. Nicotine instructions resulted in fewer RVIP false alarms, better mood, and greater rewarding subjective effects of the cigarettes on 9 of 11 dimensions compared to placebo instructions. Nicotine dose by nicotine dose expectancy interactions were also observed for urge and tension-anxiety, such that the dose expectancy manipulation produced differential effects only among those who smoked placebo cigarettes. In contrast a significant interaction for self-reported vigor-activity demonstrated that the dose expectancy manipulation produced effects only among those who smoked nicotine cigarettes. This study provides additional evidence that nicotine improves cognitive performance, and provides initial evidence that denicotinized cigarettes smoked under the guise that they contain nicotine influence cognitive performance, albeit with less robust effects than nicotine. These data may inform the development of expectancy-based interventions for tobacco dependence. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Gender and the effects of different doses of nicotine gum on tobacco withdrawal symptoms.

Women and men were compared on the extent to which 2-mg (n?=?40), 4-mg (n?=?41), and 4-mg then 2-mg (n?=?47) nicotine gum prescribed over an 8-week period relieved cigarette withdrawal symptoms. Gender differences for nicotine gum withdrawal symptoms across doses were also examined. Results showed that women assigned to 2-mg nicotine gum experienced more severe cigarette withdrawal symptoms than those assigned to the other gum conditions. In general, no differences for nicotine gum dose in relieving cigarette withdrawal symptoms were observed in men. Women experienced more severe cigarette withdrawal symptoms than men, predominantly in the 2-mg nicotine gum condition. Women also experienced greater withdrawal symptoms from nicotine gum compared with men. For both genders, those assigned to the 4-mg nicotine gum group throughout treatment experienced more severe nicotine gum withdrawal than those assigned to the other nicotine gum conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context modulated effects of nicotine abstinence on human cooperative responding.

The effects of ad libitum smoking, abstinence, and 0-, 2-, and 4-mg nicotine gum on human cooperative responding were examined in 10 male and female tobacco smokers (aged 21–39 yrs). Participants were provided the opportunity to respond cooperatively or independently to episodes initiated by a computer-simulated other person. Participants could also initiate episodes that ostensibly provided the other person the opportunity to respond cooperatively or independently of the participant. Working cooperatively added points to both the participant's and other person's counters. Working independently added points only to the participant's counter. Results showed that abstinence decreased cooperative responses during episodes initiated by the computer-stimulated other person. Relative to abstinence and placebo gum conditions, ad libitum smoking and administration of 2- and 4-mg nicotine gum increased these cooperative responses. Nicotine increased reports of vigor and decreased abstinence-engendered reports of depression, anger, confusion, and tension. The difference in the effects of nicotine abstinence on the 2 classes of cooperative responding demonstrates that the social contingency mediates the behavioral effects of abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low-dose nicotine nasal spray use and effects during initial smoking cessation.

The purposes of this study were to determine if smokers wanting to quit smoking would use a low-dose nicotine nasal spray (i.e., acceptability) and what effect this spray use would have on withdrawal during the 1st week of cessation. Smokers (n?=? 52) were assigned double-blind to either placebo or nicotine spray (1.5 μg/kg. or approx. 0.1 mg, per spray) for ad lib use during the first week of cessation. All received group behavioral counseling. There was no difference in continuous 1-week abstinence (daily COa?     

The effects of smoking and smoking abstinence on verbal and visuospatial working memory capacity.

Several studies have examined the effects of smoking and abstaining from smoking on working memory (WM) but have yielded inconclusive findings. Thus, the authors used a repeated measures design to assess the effects of smoking and abstaining from smoking on both visuospatial and verbal WM capacity (WMC) using highly reliable, well-validated, and theoretically driven WM span tasks. Verbal n-back was also administered to examine its relationship to these complex WM span tasks and to compare this study's results with previous findings. Smokers (n = 23) and nonsmokers (n = 21) participated in 2 sessions separated by 1 week. During 1 session, smokers completed the WM tasks after abstaining from smoking for at least 12 hr, whereas in the other session smokers did not abstain from smoking and were tested immediately after smoking (all WM tasks were completed 45 min or less since last cigarette). Results indicated that smokers' verbal WM span was lower than nonsmokers' and was lower during the nonabstinent session compared with the abstinent session. Smokers' verbal n-back performance was also lower than nonsmokers', although there was no difference in verbal n-back performance between the smoking sessions. In contrast, there was no difference in visuospatial WM span between the smoking sessions or between smokers and nonsmokers. Taken together, these findings demonstrate that (a) smokers' verbal WM is lower than nonsmokers, (b) smokers' verbal WMC is lower during nonabstinence compared with abstinence, and (c) smoking exhibits differential effects on the different WM domains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactive effects of depression symptoms, nicotine dependence, and weight change on late smoking relapse.

Signal detection methods were used to develop an algorithm useful in distinguishing those at risk for late relapse from those likely to maintain abstinence. Four subgroups with 24-month survival (nonrelapse) rates ranging from 79% to 33% were identified. Among participants whose depression symptoms decreased from baseline to the end of treatment, lower levels of nicotine dependence were associated with less relapse at the 24-month follow-up (odds ratio?=?2.77; 95% confidence interval: 1.36–5.62). Among participants whose depression symptoms increased from baseline to the end of treatment, greater weight gain was associated with less relapse at follow-up (odds ratio?=?2.90; 95% confidence interval: 1.41–5.96) . This study suggests that it may become possible to use both baseline and treatment information to "titrate" interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cigarette abstinence impairs memory and metacognition despite administration of 2 mg nicotine gum.

The authors assessed the effects of cigarette abstinence (nonabstinent vs. minimum 8 hours abstinent) and nicotine gum (0 mg vs. 2 mg nicotine) on sustained attention, free recall, and metacognition using a within-subjects design. Moderate smokers (10 women and 22 men) received one training session followed by four test sessions on consecutive days. Nicotine gum improved sustained attention in both abstinent and nonabstinent states, but had no significant effect on predicted or actual recall levels. Cigarette abstinence significantly impaired free recall and reduced the magnitude of participants' predictions of their own performance. In addition, participants were significantly more overconfident about their future memory when abstinent. Thus, nicotine gum can improve smokers' performance in basic aspects of cognition (e.g., sustained attention) but may not alleviate the detrimental effects of cigarette abstinence on higher-level processes such memory and metacognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of abstinence on cigarette smoking among outpatients with schizophrenia.

The authors of this study examined the effects of brief smoking abstinence on smoking among 6 individuals with schizophrenia or schizoaffective disorder. Before 6 of 12 experimental sessions, participants were required to provide breath carbon monoxide (CO) samples indicative of smoking abstinence; before the remaining sessions, participants provided CO samples indicating no abstinence. During sessions, participants obtained smoking opportunities (2 puffs/opportunity) under either fixed ratio-1 or progressive ratio (PR) schedules of reinforcement. Abstinence increased smoking under both schedules and increased breakpoint for smoking under the PR schedule. These data offer further evidence that smoking by individuals with schizophrenia is orderly, operant behavior that is modulated, at least in part, by variables that also affect smoking in people without major mental illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context modulates effects of nicotine abstinence on human cooperative responding

The effects of ad libitum smoking, abstinence, and 0-, 2-, and 4-mg nicotine gum on human cooperative responding were examined. Participants were provided the opportunity to respond cooperatively or independently to episodes initiated by a computer-simulated other person. Participants could also initiate episodes that ostensibly provided the other person the opportunity to respond cooperatively or independently of the participant. Working cooperatively added points to both the participant's and other person's counters. Working independently added points only to the participant's counter. Results demonstrated that abstinence decreased cooperative responses during episodes initiated by the computer-stimulated other person. Relative to abstinence and placebo gum conditions, ad libitum smoking and administration of 2- and 4-mg nicotine gum increased these cooperative responses. No gender differences were observed. The number of cooperative episodes initiated by the participants was not affected significantly by the smoking or gum conditions. Nicotine increased reports of vigor and decreased abstinence-engendered reports of depression, anger, confusion, and tension. The difference in the effects of nicotine abstinence on the 2 classes of cooperative responding demonstrates that the social contingency mediates the behavioral effects of abstinence.     

Effects of nicotine dose, instructional set, and outcome expectancies on the subjective effects of smoking in the presence of a stressor.

The balanced placebo design (BPD) was used to evaluate the independent effects of nicotine dose and smoking-related expectancies on self-reported anxiety, urge to smoke, and withdrawal symptoms. After anxious mood was induced, participants smoked either a de-nicotinized cigarette or one with standard nicotine content. Nicotine dose was crossed with instructions that the cigarette was either de-nicotinized or standard. Nicotine cigarettes produced greater anxiety reduction than de-nicotinized cigarettes. Nicotine instructions attenuated anxiety only among those who held relevant expectancies. Nicotine dose and instructional set interacted such that either nicotine cigarettes or instructions that the cigarettes contained nicotine were sufficient to reduce urge to smoke. Implications of these findings and methodological issues regarding use of the BPD with cigarettes are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of nicotine fading and relapse prevention on smoking cessation.

In a pilot study, a combined nicotine-fading/relapse-prevention program for 24 smokers (mean age 38.6 yrs) achieved a 46% abstinence rate at 6-mo follow-up. The combined program was then compared to conditions in which 46 smokers (mean age 34.8 yrs) received nicotine fading or relapse prevention only or combination treatment. There was no difference among groups in abstinence or rate at any follow-up point, and overall abstinence levels were only 15% and 9% at 6-mo and 1-yr follow-ups, respectively. Groups receiving nicotine fading tended to retain lower estimated nicotine intake levels. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olanzapine reduces urge to smoke and nicotine withdrawal symptoms in community smokers.

Olanzapine (OLAN), an atypical antipsychotic medication with mixed 5-HT2/DA antagonist properties, was predicted to dose-dependently decrease urge to smoke, withdrawal, and cigarette reinforcement in smokers without psychosis. A double-blind placebo-controlled within-subjects cross-over trial investigated the acute effects of OLAN (0, 2.5, and 5.0 mg; counterbalanced order) in 24 community smokers who underwent 10-hr smoking deprivation. Urge to smoke, tobacco withdrawal, and cigarette reinforcement were assessed with cue reactivity and behavioral choice procedures. OLAN (2.5 mg) reduced withdrawal symptoms before and during cue exposure and decreased urge associated with anticipated positive affect from smoking before and during cue exposure; 5.0 mg OLAN decreased withdrawal only when cues were included. OLAN did not affect preference for cigarette puffs versus money, smoke intake, or urge to smoke associated with negative affect relief. The results indicate a potentially beneficial effect of 2.5 mg OLAN on tobacco withdrawal and urge to smoke. Combined 5HT/DA antagonists should be considered for future development of pharmacotherapies for smoking cessation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Progression from a smoking lapse to relapse: Prediction from abstinence violation effects, nicotine dependence, and lapse characteristics.

Determinants of progression from an initial smoking lapse to relapse, using prospective data from 133 participants were examined. Participants used palm-top computers to record their first lapse, and their reaction to it, within minutes of the event, and were followed for 3 months to assess subsequent smoking. Indicators of the Abstinence Violation Effect—self-efficacy, attributions, and affective reactions to the lapse—generally failed to predict progression to relapse, but participants who felt like giving up after the first lapse progressed more rapidly to a second lapse. Participants who attempted restorative coping were less likely to progress to another lapse on the same day. Those whose lapses were triggered by stress progressed more quickly, whereas those triggered by eating and drinking or accompanied by alcohol consumption progressed more slowly. More nicotine-dependent participants progressed more rapidly toward relapse, but neither the amount smoked in the first lapse nor its subjective reinforcement predicted progression. (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)     

Effects of 24-hr nicotine replacement on sleep and daytime activity during smoking cessation

BACKGROUND: This study uses wrist actigrapy to assess the effects of 24-hr transdermal nicotine replacement on the sleep and daytime activity of smokers during smoking cessation. METHODS: Seventy-one subjects grouped as light (n = 23), moderate (n = 24), or heavy (n = 24) smokers were randomly assigned to placebo or 11, 22, or 44 mg/day doses of transdermal nicotine for 1 week of intensive inpatient treatment of nicotine dependence. Outpatient patch therapy continued for 7 weeks following the inpatient stay. Those initially on placebo were randomly assigned to 11 or 22 mg/day, and those initially on 44 mg/day were reduced to 22 mg/day at Week 4. RESULTS: There was a significant decrease in daytime wrist activity during patch therapy and the 1st week off patch therapy. These changes in daytime wrist activity were positively correlated with percentage of nicotine and cotinine replacement. No changes from baseline in sleep (sleep efficiency or wrist activity) were detected, nor were there differences in sleep among the four patch doses. CONCLUSIONS: Using wrist actigraphy, this study failed to show any disturbing effects of 24-hr high-dose nicotine replacement on sleep. Lower levels of nicotine replacement were associated with a decrease from baseline in daytime wrist activity.     

Combined effects of nicotine and mecamylamine in attenuating smoking satisfaction.

Separate and combined effects of nicotine (NIC) and the nicotinic antagonist mecamylamine (MEC) were studied. 12 smokers rated test cigarettes after administration of MEC vs placebo capsules and NIC vs non-NIC preload. Smoking withdrawal symptoms, task performance, and cardiovascular activity were also measured. MEC attenuated smoking satisfaction, liking, and airway sensations. The NIC preload similarly reduced the enjoyable aspects of subsequent test cigarettes, and this action of the preload was not prevented by MEC. In contrast, MEC blocked NIC-related increases in heart rate and systolic blood pressure. Conversely, NIC counteracted MEC's effects on tapping speed and orthostatic blood pressure response. Although each drug offset potential side effects of the other, they acted in unison to attenuate smoking satisfaction and should be evaluated in combination for smoking cessation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain fMRI reactivity to smoking-related images before and during extended smoking abstinence.

[Correction Notice: An erratum for this article was reported in Vol 18(3) of Experimental and Clinical Psychopharmacology (see record 2010-11933-011). In the article the authors find it necessary to redefine the thresholding procedure used for data analyses, due to problems in the Brain Voyager software. This does not affect the main findings of the paper.] Reactivity to smoking-related cues may play a role in the maintenance of smoking behavior and may change depending on smoking status. Whether smoking cue-related functional MRI (fMRI) reactivity differs between active smoking and extended smoking abstinence states currently is unknown. We used fMRI to measure brain reactivity in response to smoking-related versus neutral images in 13 tobacco-dependent subjects before a smoking cessation attempt and again during extended smoking abstinence (52 ± 11 days) aided by nicotine replacement therapy. Prequit smoking cue induced fMRI activity patterns paralleled those reported in prior smoking cue reactivity fMRI studies. Greater fMRI activity was detected during extended smoking abstinence than during the prequit assessment subcortically in the caudate nucleus and cortically in prefrontal (BA 6, 9, 44, 46), primary somatosensory (BA 1, 2, 3), temporal (BA 22, 41, 42), parietal (BA 7, 40) anterior cingulate (BA 24, 32), and posterior cingulate (BA 31) cortex. These data suggest that during extended smoking abstinence, fMRI reactivity to smoking versus neutral stimuli persists in brain areas involved in attention, somatosensory processing, motor planning, and conditioned cue responding. In some brain regions, fMRI smoking cue reactivity is increased during extended smoking abstinence in comparison to the prequit state, which may contribute to persisting relapse vulnerability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)