Circulating leptin levels are associated with increased craving to smoke in abstinent smokers

The adipocyte hormone leptin regulates satiety and energy expenditure. Recent evidence suggests that leptin is associated with increased craving for alcohol and with shorter length of abstinence during alcohol treatment. This study examined leptin's associations with craving for cigarettes and smoking relapse among smokers interested in cessation. Participants (32 smokers; 14 women) attended a laboratory session 24 h following their designated quit day where circulating leptin levels and craving for smoking were assessed. Other measures of withdrawal symptoms, affect, physical symptoms, as well as neuroendocrine and cardiovascular measures were collected before and after performing two stress tasks (public speaking and cognitive tasks). High circulating leptin levels were associated with increased craving, withdrawal symptoms, negative affect, physical symptoms, and reduced positive affect. Circulating leptin levels were not related to cardiovascular and neuroendocrine measures, responses to acute stressors, or to smoking relapse. These results indicate that circulating leptin is a promising biological marker of craving for smoking and warrant further investigation of the links between appetite regulation and nicotine dependence.     

Effects of topiramate on cue-induced cigarette craving and the response to a smoked cigarette in briefly abstinent smokers

Rationale Clinical studies have shown that topiramate, an anticonvulsant medication, may be effective as a treatment for smoking cessation. However, less is known about topiramate effects on nicotine withdrawal and craving and its interactions with a smoked cigarette. Objectives The objective of this study was to investigate the effects of topiramate treatment on abstinence-related nicotine withdrawal, cue-induced cigarette craving, and the acute effects of a smoked cigarette. Materials and methods Fifteen female and 25 male cigarette smokers were randomly assigned to 9-day treatment with topiramate (final titration dose, 75 mg/day) or placebo. On the last day of treatment, after a 3-h smoke-free abstinence period, participants were evaluated for symptoms of nicotine withdrawal and then underwent cigarette and neutral cue reactivity testing. Thirty minutes after completing cue exposure testing, participants were then evaluated for the acute effects of a smoked cigarette. Cue reactivity and acute smoking measures included subjective ratings of cigarette craving and withdrawal and physiological measures of skin conductance and temperature, heart rate, and blood pressure. In addition, smoking topography was measured using a puff volume apparatus. Results Topiramate treatment enhanced subjective ratings of withdrawal after the 3-h abstinence period and reduced pre-cue skin conductance levels. Cigarette cue exposure resulted in a moderate increase in craving, which was unaffected by treatment. Topiramate treatment enhanced the rewarding effects of a smoked cigarette, even while participants smoked less per puff and achieved lower plasma nicotine levels. Conclusion Results suggest that topiramate enhances both nicotine withdrawal and reward. These findings question the utility of topiramate treatment for smoking cessation.     

Exercise effects on withdrawal and mood among women attempting smoking cessation.

This study investigated both acute and longer term ("chronic") effects of vigorous exercise training on affect, nicotine withdrawal, and cigarette craving among women enrolled in a smoking cessation research study. All subjects participated in a 12-week cognitive behavioral smoking cessation program and were randomly assigned to attend three sessions per week of either a vigorous exercise program or contact control. Measures of positive and negative affect, cigarette craving, and nicotine withdrawal were administered immediately before, and again immediately after the final exercise or contact session each week of the program. Study I enrolled 24 women who had been assigned to the exercise condition. Significant reductions in negative affect, nicotine withdrawal and cigarette craving were observed following exercise most weeks of the program. No significant changes in positive affect were observed. In Study II this protocol was repeated among 62 women (44 exercise, 18 contact control) in two consecutive cohorts of the larger study. Significant reduction were observed in negative affect, nicotine withdrawal and cigarette craving during most weeks of the program among exercise subjects but not contact condition subjects. No chronic (baseline to posttreatment) changes in positive or negative affect, cigarette craving or withdrawal symptoms were observed in either study. Vigorous exercise appears to produce acute improvements in withdrawal symptoms, cigarette craving, and negative affect among sedentary women attempting to quit smoking.     

Comparative analysis of waterpipe and cigarette suppression of abstinence and craving symptoms

This study's objective is to examine the relative effectiveness of cigarettes and waterpipe (WP) in reducing tobacco abstinence symptoms in dual cigarette/WP smokers. Sixty-one dual cigarette/WP smokers participated (mean age±SD 22.0±2.6 year; mean cigarettes/day 22.4±10.1; mean WPs/week 5.2±5.6). After 12-hour abstinence participants completed two smoking sessions (WP or cigarette), while they responded to subjective measures of withdrawal, craving, and nicotine effects administered before smoking and 5, 15, 30 and 45 min thereafter. For both tobacco use methods, scores on measures of withdrawal and craving were high at the beginning of session (i.e., before smoking) and were reduced significantly and comparably during smoking. Analysis of smoking and recovery (post-smoking) phases showed similarity in the way both tobacco use methods suppressed withdrawal and craving, but the recovery of some of these symptoms can be faster with cigarette use. This study is the first to show the ability of WP to suppress abstinence effects comparably to cigarettes, and its potential to thwart cigarette cessation.     

Nicotine and Non-Nicotine Smoking Factors Differentially Modulate Craving,Withdrawal and Cerebral Blood Flow as Measured with Arterial Spin Labeling

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.     

Tobacco withdrawal components and their relations with cessation success

Rationale

Tobacco withdrawal is a key factor in smoking relapse, but important questions about the withdrawal phenomenon remain.

Objectives

This research was intended to provide information about two core components of withdrawal (negative affect and craving): (1) how various withdrawal symptom profile dimensions (e.g., mean level, volatility, extreme values) differ between negative affect and craving; and (2) how these dimensions relate to cessation outcome.

Methods

Adult smokers (N?=?1,504) in a double-blind randomized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4?weeks (2?weeks pre-quit and 2?weeks post-quit) via palmtop computers. Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence.

Results

Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms, with higher means, greater variability, and a greater incidence of extreme peaks. Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks. In a multivariate model, the increase in mean craving and negative affect scores each uniquely predicted relapse.

Conclusions

Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome, suggesting that negative affect and craving dimensions each has motivational significance. This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions.     

Within-day temporal patterns of smoking, withdrawal symptoms, and craving

We examined the temporal relationships between smoking frequency and craving and withdrawal. 351 heavy smokers (≥15 cigarettes per day) used ecological momentary assessment and electronic diaries to track smoking, craving, negative affect, arousal, restlessness, and attention disturbance in real time over 16 days. The waking day was divided into 8 2-h "bins" during which cigarette counts and mean levels of craving and withdrawal were computed. Cross-sectional analyses showed no association between restlessness and smoking, and arousal and smoking, but craving (b=0.65, p<0.01) was positively associated, and negative affect (b=-0.20, p<0.01), and attention disturbance (b=-0.24, p<0.01) were inversely associated with smoking. In prospective lagged analyses, higher craving predicted more subsequent smoking and higher smoking predicted lower craving (p's<0.01). Higher restlessness also predicted more subsequent smoking and higher smoking predicted lower restlessness (p's<0.01). Higher negative affect did not predict later smoking, but more smoking preceded lower negative affect (p<0.01). Neither attention disturbance nor arousal predicted, or were predicted by variations in smoking. In short, smoking exhibits time-lagged, reciprocal relationships with craving and restlessness, and a one-way predictive relationship with negative affect. Temporal patterns of craving and restlessness may aid in the design of smoking cessation interventions.     

Prospective examination of effects of smoking abstinence on cortisol and withdrawal symptoms as predictors of early smoking relapse

This study addressed the hypothesis that exaggerated mood and cortisol changes during the first 24h of smoking abstinence are associated with early relapse. Salivary cortisol levels and mood reports were measured during 24-h ad libitum smoking and the first 24-h abstinence period of a quit attempt. Seventy-two habitual smokers (34 women and 38 men) who were interested in smoking cessation participated. Cotinine concentrations in saliva and expired carbon monoxide were measured before and after abstinence and 1 week after the quit date to verify smoking status. Abstinence produced significant withdrawal symptoms in all participants and reduced cotinine and carbon monoxide levels. While participants showed the expected diurnal changes in cortisol levels, those who relapsed within the first week post quitting exhibited a greater drop in morning cortisol concentrations during abstinence relative to their ad libitum smoking levels. Participants who relapsed reported greater withdrawal symptoms, craving for cigarettes, and distress, and they also reported greater reduction in positive affect during the first 24-h period of abstinence than those who maintained abstinence. These results support the hypothesis that early relapse is associated with exaggerated mood and adrenocortical perturbations observed during the first day of abstinence.     

Reduction of abstinence-induced withdrawal and craving using high-dose nicotine replacement therapy

Rationale Decreasing withdrawal and craving during smoking cessation is a major aim of cessation medications. Prior studies have shown that Nicotine Replacement Therapy (NRT) decreases withdrawal symptom severity but have relied on retrospective reports and lacked robust measures of baseline symptoms or symptoms during unmedicated abstinence. Objectives and methods We tested the effect of high-dose (35 mg) nicotine patch on withdrawal and craving during abstinence using real-time assessment with electronic diaries during ad libitum smoking, a brief period of experimentally directed trial abstinence, and the first 3 days of cessation. Subjects were 324 smokers randomized to high-dose nicotine patches or placebo. Results Treatment with active patches reduced withdrawal and craving during cessation and completely eliminated deprivation-related changes in affect or concentration. Conclusion High-dose NRT reduces withdrawal symptoms and craving and can eliminate some symptoms entirely. Saul Shiffman and Stuart Ferguson consult exclusively for GlaxoSmithKline Consumer Healthcare on matters relating to existing smoking cessation products. Dr. Shiffman also has an interest in a new smoking cessation product, and is a founder of invivodata, inc., which provides electronic diaries for clinical trials.     

Melatonin treatment attenuates symptoms of acute nicotine withdrawal in humans

Nicotine withdrawal is typically associated with negative changes in mood and performance, which often lead to relapse. We tested whether an oral 0.3-mg dose of melatonin administered 3.5 h after the nicotine withdrawal, and increasing circulating melatonin concentrations within the physiological range, affects the symptoms of acute 10-h (0800-1800 h) nicotine withdrawal in regular smokers. Self-reported ratings of mood, sleepiness, and cigarette craving were assessed hourly, using 17 visual analog scales (VAS). Computerized Four-Choice Reaction Time (FCRT) and Simple Auditory Reaction Time (SART) tests were used to assess performance every 2 h. Saliva samples were collected hourly, and salivary melatonin levels were measured using supersensitive radioimmunoassay. Compared with the placebo, melatonin treatment significantly reduced self-ratings of "anxious," "restless," "tense," "irritable," "angry," "depressed, " "impatient," and "craving for cigarettes." Melatonin treatment did not significantly change the responses on the performance tests used. These data suggest that melatonin can help to counteract the acute effects of smoking cessation on mood.     

Symptoms of Depression and Smoking Behaviors Following Treatment with Transdermal Nicotine Patch

Subscales from the Center for Epidemiologic Studies Depression Scale (CESD), assessed prior to treatment, were examined as predictors of withdrawal, craving, and affect during the first week of abstinence, as well as smoking abstinence during the first week of abstinence and at the end of treatment. The negative affect and somatic features CESD subscales were related to higher levels of nicotine withdrawal. The relationship between the interpersonal disturbance CESD subscale and nicotine withdrawal approached significance. This study suggests the need to examine novel psychological mechanisms that may account for the relationship between depression symptoms and smoking cessation.     

The effect of bupropion on nicotine craving and withdrawal

Rationale and objectives: Bupropion has demonstrated efficacy for smoking cessation. Given the importance of nicotine craving and withdrawal in the smoking cessation process, the current study examined the effects of bupropion on these parameters during smoking abstinence. Methods: During a 2-day Baseline phase with ad lib smoking, 91 non-depressed smokers (who were not trying to quit permanently) were administered measures of nicotine craving, withdrawal symptoms, and timed measures of cognitive performance five times daily. Participants were then assigned randomly to a 14-day treatment regimen with bupropion 300 mg/day, bupropion 150 mg/day, or placebo. Thereafter, the above measures were re-administered during 3 days of abstinence on a closed research ward. Results: Relative to placebo, 300 mg bupropion significantly reduced abstinence-associated increases in rated depression, difficulty concentrating, and irritability, and attenuated a decrease in positive affect. The results also suggested that bupropion might have a positive effect on performance measures during the withdrawal period. No effects were observed on craving, anxiety, restlessness, or hunger. The lack of findings on craving measures may be explained by a floor effect; except on the first day of abstinence, neither drug nor placebo groups showed much craving elevation during abstinence. Conclusions: Study results indicate that bupropion ameliorates some nicotine withdrawal symptoms. Received: 24 February 1999 / Final version: 15 August 1999     

Smoking environment cues reduce ability to resist smoking as measured by a delay to smoking task

Introduction: Environments associated with smoking may promote lapse and relapse in smokers attempting to quit. Here we examined the effects of exposure to visual smoking environment cues on smoking urge and the ability to resist smoking, as measured with a delay-to-smoking task in which monetary contingencies are provided for resisting smoking. Methods: Adult daily smokers (n = 22) completed two experimental sessions, each following 6 h smoking abstinence. Sessions differed only in the type of cue participants were exposed to (smoking environments vs. nonsmoking environments). Participants completed subjective ratings of smoking urge, withdrawal and other reactions (i.e. craving, affect). Behavioral outcomes on the delay-to-smoking task included latency to first cigarette, number of cigarettes smoked and average number of puffs per cigarette. Results: Across cue exposure sessions, 64% of participants initiated smoking (no effect of condition was observed). However, exposure to smoking environments as compared to the nonsmoking environments resulted in greater craving, faster initiation of smoking, and more smoked cigarettes. Greater craving was associated with a shorter time to initiate smoking, but this effect did not differ across sessions. In contrast, withdrawal was more strongly associated with number of cigarettes smoked during smoking environment sessions. Conclusion: Together, these results suggest smoking environments increase smoking urge and promote smoking behavior. Further research is necessary to examine the specific and interactive effects of smoking-related environments on real-world smoking lapse and relapse.     

Postcessation cigarette use: the process of relapse

One hundred twenty-nine chronic smokers successfully completed a smoking cessation program composed of behavioral counseling and aversive smoking. During the two-year follow-up period, 92 of these subjects reported smoking. The progression from subjects' first cigarette to full relapse was examined via standardized telephone interviews. The latency between subjects' initial postcessation smoking episode and subsequent return to daily smoking was related to pretreatment confidence level, affective state at the time of the first cigarette, and origin of the first cigarette. Neither affective reaction nor coping response execution after the initial cigarette was related to the rate of relapse. Results are discussed in terms of current theory and treatment implications.     

Modeling the effect of alcohol on smoking lapse behavior

Objective

The primary aim of this project was to examine the role of alcohol use in smoking lapse behavior, as alcohol consumption is a known risk factor for poor smoking cessation outcomes.

Materials and methods

We have developed a novel human laboratory model to examine two primary aspects of alcohol-mediated tobacco relapse: (1) Does alcohol facilitate the initiation of the first cigarette? (2) Once the first cigarette is initiated, does alcohol facilitate subsequent smoking? Using a within-subject design, 16 daily smokers who were also heavy social drinkers received a priming drink (0.03 g/dl or taste-masked placebo) and then had the option of initiating a tobacco self-administration session or delaying initiation by 5-min increments for up to 50 min in exchange for monetary reinforcement. Subsequently, the tobacco self-administration session consisted of a 1-h period in which subjects could choose to smoke their preferred brand of cigarettes using a smoking topography system or receive monetary reinforcement for cigarettes not smoked. Alcohol craving, tobacco craving, subjective reactivity to alcohol, and nicotine withdrawal were assessed as secondary outcomes.

Results

Results demonstrated that after consuming the alcohol beverage, subjects were less able to resist the first cigarette and initiated their smoking sessions sooner, and smoked more cigarettes compared to the placebo beverage. These findings have implications for smoking cessation in alcohol drinkers and model development to assess smoking lapse behavior.     

Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues.

Exposure to smoking cues increases craving for cigarettes and can precipitate relapse. Whereas brain imaging studies have identified a distinct network of brain regions subserving the processing of smoking cues, little is known about the influence of individual difference factors and withdrawal symptoms on brain cue reactivity. Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerstr?m test of nicotine dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.     

Affect regulation, nicotine addiction, and smoking cessation

Numerous investigators have examined the role of negative affective states and affect regulation in the initiation and development of cigarette smoking behavior, smoking cessation, and relapse prevention. Affect regulation refers to any attempt to alleviate negative mood states by means of pharmacologic-, cognitive-, behavioral- or environmental-change methods. The psychological construct/process of affect regulation is examined in relation to (1) the initiation, development, and maintenance of the cigarette smoking habit; (2) the process of quitting smoking; and (3) the long-term maintenance of smoking abstinence versus relapse. Various psychosocial factors and physiological mechanisms are explored that have been hypothesized to be links between negative mood states, nicotine addiction, and smoking cessation. Implications for smoking cessation treatment are discussed in the areas of (1) the use of pharmacologic agents, such as clonidine, in the reduction of nicotine withdrawal symptoms; (2) nicotine replacement therapy; and (3) skills-training approaches to smoking cessation and relapse prevention.     

Affect regulation, nicotine addiction, and smoking cessation.

Numerous investigators have examined the role of negative affective states and affect regulation in the initiation and development of cigarette smoking behavior, smoking cessation, and relapse prevention. Affect regulation refers to any attempt to alleviate negative mood states by means of pharmacologic-, cognitive-, behavioral- or environmental-change methods. The psychological construct/process of affect regulation is examined in relation to (1) the initiation, development, and maintenance of the cigarette smoking habit; (2) the process of quitting smoking; and (3) the long-term maintenance of smoking abstinence versus relapse. Various psychosocial factors and physiological mechanisms are explored that have been hypothesized to be links between negative mood states, nicotine addiction, and smoking cessation. Implications for smoking cessation treatment are discussed in the areas of (1) the use of pharmacologic agents, such as clonidine, in the reduction of nicotine withdrawal symptoms; (2) nicotine replacement therapy; and (3) skills-training approaches to smoking cessation and relapse prevention.     

Gender differences in acute tobacco withdrawal: effects on subjective, cognitive, and physiological measures

Gender differences in tobacco withdrawal are of considerable clinical importance, but research findings on this topic have been mixed. Methodological variation in samples sizes, experimental design, and measures across studies may explain the inconsistent results. The current study examined whether male (n = 101) and female (n = 102) smokers (> or =15 cigarettes/day) differed in abstinence-induced changes on a battery of self-report measures (withdrawal, affect, craving), cognitive performance tasks (attention, psychomotor performance), and physiological responses (heart rate, blood pressure, brain electroencephalogram). Participants attended 2 counterbalanced laboratory sessions, 1 following 12 hr of abstinence and the other following ad libitum smoking. Results showed that women reported greater abstinence-induced increases in negative affect, withdrawal-related distress, and urge to smoke to relieve withdrawal distress. In contrast, both genders reported similar abstinence-induced changes in positive affect and urge to smoke for pleasure. Men and women exhibited generally similar abstinence-induced changes in physiological and cognitive performance measures. In addition, gender did not moderate the association between withdrawal symptoms and baseline measures of smoking behavior and dependence. Abstinence-induced changes in withdrawal distress mediated the effect of gender on latency until the 1st cigarette of the day at trend levels ( p < .10). These findings suggest that there are qualitative gender differences in the acute tobacco withdrawal syndrome that may underlie gender-specific smoking patterns.     

Effect of high-dose nicotine patch on craving and negative affect leading up to lapse episodes

Rationale

Nicotine patches have been reliably demonstrated to improve smoking cessation outcomes but most users still lapse, and then relapse, during treatment. While patch has been shown to alleviate background cravings, its effects on cue-induced cravings — which have been linked to the occurrence of lapse events — are poorly understood.

Objectives

Here we investigate the effect of nicotine patch on the intensity of craving and negative affect experienced during the hours immediately preceding lapse episodes.

Methods

Participants were 185 smokers who had quit in the context of a randomized, double-blind trial of high-dose (35 mg) nicotine patch and who lapsed at least once during the first 5 weeks of treatment. Participants used electronic diaries to monitor their smoking, affect, and craving during their cessation attempt.

Results and conclusions

The data suggest that developments on the lapse day — either external events or changes in internal states — caused craving and negative affect to rise, cumulating in the lapse. Nicotine is known to lower background craving and negative affect, but the difference between patch and placebo appeared to dissipate in the hours immediately preceding lapse episodes. Understanding the process by which these symptoms "spike" prior to a lapse — and developing treatments to counter it — are worthy research endeavors.