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.     

Negative affect, emotional acceptance, and smoking cessation

This article describes recent theoretical developments and empirical findings regarding the role of negative affect (NA) and emotion regulation in nicotine dependence and smoking cessation. It begins with a review of affect-based models of addiction that address conditioning, affect motivational, and neurobiological mechanisms and then describes the role of NA and emotion regulation in the initiation and maintenance of cigarette smoking. Next, the role of emotion regulation, coping skill deficits, depression, and anxiety sensitivity in explaining the relationship between NA and smoking relapse are discussed. We then review recent models of affect regulation, including emotional intelligence, reappraisal and suppression, and emotional acceptance, and describe implications for substance abuse and smoking cessation interventions. Finally, we point out the need for further investigations of the moderating role of individual differences in response to NA in the maintenance of nicotine dependence, and controlled randomized trials testing the efficacy of acceptance-based interventions in facilitating smoking cessation and relapse prevention.     

Reactivity to negative affect in smokers: The role of implicit associations and distress tolerance in smoking cessation

Avoidance of negative affect is one motivational factor that explains smoking cessation relapse during cessation attempts. This negative reinforcement model of smoking cessation and relapse has demonstrated the importance of one's ability to tolerate nicotine withdrawal symptoms, particularly negative affect states, in remaining abstinent from smoking. Distress tolerance and implicit associations are two individual constructs that may influence the strength of this relationship. In this pilot study the authors examined implicit associations related to avoidance and negative affect using a modified Implicit Association Test (IAT), a measure designed to examine implicit associations related to negative affect and avoidance, and the relationship of these associations to distress tolerance and smoking relapse. In total, 40 participants were recruited through community flyers as part of a larger smoking cessation study. Participants completed a brief smoking history, behavioral distress tolerance assessments, and the modified IAT. Smoking status was assessed via phone 3 days and 6 days post-quit date. Results from a Cox proportional hazard model revealed that implicit associations between avoidance and negative affect were significantly negatively correlated with time to relapse after a smoking cessation attempt, whereas the behavioral distress tolerance assessments did not predict time to relapse. This study provides novel information about the cognitive associations that may underlie avoidant behavior in smokers, and may be important for understanding smoking relapse when negative affect states are particularly difficult to tolerate. Authors discuss the importance of implicit associations in understanding smoking relapse and how they can be targeted in treatment.     

The relationship between cigarette smoking and impulsivity: A review of personality,behavioral, and neurobiological assessment

Impulsivity is a multi-dimensional construct that broadly encompasses impaired self-regulation. Studies comparing substance users and non-users, including cigarette smokers, consistently find that users are more impulsive than non-users. However, identifying the role of impulsivity in cigarette smoking initiation, maintenance, and relapse has been challenging because of variation in how impulsivity is defined and whether it is assessed as (1) a stable personality trait, (2) a behavior (either trait or state), or (3) a neurobiological process. Personality and behavioral assessments are typically weakly correlated or uncorrelated, but both types of impulsivity have been related to brain activity in the prefrontal cortex (PFC) and associated areas. This article provides a narrative review of research pertaining to the relationship between impulsivity and cigarette smoking, including smoking initiation, maintenance, and relapse, with respect to these three methods of impulsivity assessment. This review revealed that impulsivity is associated with all stages of tobacco use. Regarding initiation, research involving adolescents suggests that differences between adult smokers and non-smokers in self-reported impulsivity appear to pre-date smoking initiation, whereas behavioral impulsivity has not been as consistently associated with adolescent smoking. Conversely, chronic exposure to nicotine and acute nicotine deprivation may also increase impulsivity. Regarding maintenance and relapse, urgency, an aspect of impulsivity that refers to the tendency to act impulsively when experiencing negative affect, seems to play a particularly important role. In future research, investigators should define impulsivity precisely and provide a rationale for the type of assessment used. Targeting impulsivity reduction may facilitate successful smoking 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.     

Varenicline and Cytisine Diminish the Dysphoric-Like State Associated with Spontaneous Nicotine Withdrawal in Rats

Tobacco addiction is characterized by a negative mood state upon smoking cessation and relapse after periods of abstinence. Clinical studies indicate that negative mood states lead to craving and relapse. The partial α4/α6/β2* nicotinic acetylcholine receptor (nAChR) agonists varenicline and cytisine are widely used as smoking cessation treatments. Varenicline has been approved in the United States for smoking cessation and cytisine is used in Eastern European countries. Despite the widespread use of these compounds, very little is known about their effects on mood states. These studies investigated the effects of varenicline, cytisine, and the cytisine-derivative 3-(pyridin-3′-yl)-cytisine (3-pyr-Cyt) on brain reward function in nicotine-naive and nicotine-withdrawing rats. The cytisine-derivative 3-pyr-Cyt is a very weak α4β2* nAChR partial agonist and like cytisine and varenicline has antidepressant-like effects in animal models. The intracranial self-stimulation (ICSS) procedure was used to investigate the effects of these compounds on brain reward function. Elevations in ICSS thresholds reflect a dysphoric state and a lowering of thresholds is indicative of a potentiation of brain reward function. It was shown that acute administration of nicotine and varenicline lowered ICSS thresholds. Acute administration of cytisine or 3-pyr-Cyt did not affect ICSS thresholds. Discontinuation of chronic, 14 days, nicotine administration led to elevations in ICSS thresholds that lasted for about 2 days. Varenicline and cytisine, but not 3-pyr-Cyt, diminished the nicotine withdrawal-induced elevations in ICSS thresholds. In conclusion, these studies indicate that varenicline and cytisine diminish the dysphoric-like state associated with nicotine withdrawal and may thereby prevent relapse to smoking in humans.     

Socially anxious smokers experience greater negative affect and withdrawal during self-quit attempts

Despite evidence of a strong and consistent relation between smoking and elevated social anxiety, strikingly little empirical work has identified mechanisms underlying the smoking-social anxiety link. Persons with elevated social anxiety may rely on smoking to cope with more severe nicotine withdrawal and post-quit negative mood states; yet, no known studies have investigated the relation of social anxiety to withdrawal severity. The current study examined the relation of social anxiety to post-quit nicotine withdrawal severity among 51 (33.3% female, M_age = 34.6) community-recruited smokers during the first two weeks following an unaided (i.e., no treatment) cessation attempt. Ecological momentary assessment was used to collect multiple daily ratings of withdrawal and negative mood states. Baseline social anxiety was related to increases in negative affect during the monitoring period and remained significantly related to post-quit withdrawal after controlling for negative affect, gender, lapses, and substance use. Persons with elevated social anxiety experience more severe post-quit withdrawal symptoms and increases in negative affect during a cessation attempt and may therefore benefit from intervention and treatment strategies geared toward helping them learn to cope with withdrawal and negative affect to improve cessation rates among these vulnerable smokers.     

Sex differences in affect-triggered lapses during smoking cessation: A daily diary study

IntroductionSmoking lapses during a cessation attempt are common and are thought to be a key predictor of full relapse. Positive and negative affective states have been hypothesized as important precipitants of lapses during quit attempts, although findings have been mixed. Accumulating evidence suggests that women may smoke more when experiencing negative affective states, while men may smoke more when experiencing positive affective states. The possibility that these sex differences may play a role in predicting lapses during a smoking cessation attempt, however, has not been well-investigated. In this study, we hypothesized that, during a quit attempt, negative affect would be more strongly associated with lapses among women, and positive affect would be more strongly associated with lapses among men.MethodWe conducted a prospective study in which male and female nicotine-dependent smokers (n = 60) made an unaided, ‘cold-turkey’ quit attempt. For fourteen days following the initiation of the quit attempt, participants completed daily diaries in which they recorded the degree to which states of ‘good mood’ and ‘bad mood’ preceded smoking lapses.ResultsConsistent with the study hypothesis, findings indicated that men reported higher good-mood-induced smoking lapses than women across the 14-day study interval. Conversely, while levels of bad-mood-induced smoking subsided over the 14-day interval among men, levels persisted among women.DiscussionResults further underscore the need to address sex-specific affective triggers when developing smoking cessation strategies.     

Smoking cessation in peri- and postmenopausal women: a review

A substantial portion of smokers are peri- or postmenopausal women. Cigarette smoking and menopause have overlapping negative health consequences and may act synergistically to contribute to worse health outcomes in this population. Little is known about issues specific to peri- and postmenopausal women attempting to quit smoking; however, it can be hypothesized that they face unique challenges in quitting smoking. Particularly, negative affect and vasomotor menopausal symptoms may make smoking cessation particularly challenging in this group of women. Peri- and postmenopausal women are also more prone to weight gain following smoking cessation, and concerns about postcessation weight gain may contribute to reduced motivation to quit smoking or to relapse to smoking. Recent evidence suggests that estrogen level may be positively associated with nicotine reward, which may aid in the smoking cessation efforts of postmenopausal women while possibly contributing to worse outcomes in perimenopausal women. Unfortunately, no known studies have compared premenopausal women with peri- or postmenopausal women on smoking cessation outcome variables. Studies in postmenopausal women indicate that hormone therapy (HT) use does not affect nicotine withdrawal, smoking cessation outcomes, or weight gain following smoking cessation; however, a lack of randomized trials limits the strength of these conclusions. Evidence of the effects of HT on mood following smoking cessation is conflicting. Further research is needed to identify the unique factors influencing smoking cessation in peri- and postmenopausal women and to develop and test interventions that target these variables in a way that improves cessation rates among this population.     

Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial

Rationale Fluoxetine improves affect in clinical syndromes such as depression and premenstrual dysphoric disorder. Little is known about fluoxetines influence on mood changes after quitting smoking, which often resemble sub-clinical depression.Objectives The present study, a re-analysis of previously published data (Niaura et al. 2002), examined fluoxetines effect on changes in negative and positive affect following quitting smoking.Methods Adult smokers (n=175) without clinically significant depression were randomized on a double-blind basis to receive fluoxetine hydrochloride (30 or 60 mg daily) or placebo for 10 weeks in combination with cognitive-behavioral therapy (CBT) for smoking cessation. We postulated that fluoxetine would beneficially influence post-cessation changes in positive and negative affect.Results Mood change across treatment was analyzed using mixed linear modeling controlling for initial level of nicotine dependence, plasma fluoxetine metabolites, and change in cotinine (a nicotine metabolite) at each visit. Relative to placebo, those on 60 mg fluoxetine experienced an elevation in positive affect that increased across time [t(526)=2.50, P=0.01], and a reduction in negative affect that returned to baseline across time [t(524)=2.26, P=0.02]. There were no differences between 30 mg and placebo on changes in positive or negative affect.Conclusions Results indicate that 60 mg of fluoxetine improves both positive and negative mood states after quitting smoking and that diminished positive affect may be an overlooked affective response to smoking cessation.     

Blockade of CRF1 receptors in the central nucleus of the amygdala attenuates the dysphoria associated with nicotine withdrawal in rats

The majority of smokers relapse during the acute withdrawal phase when withdrawal symptoms are most severe. The goal of the present studies was to investigate the role of corticotropin-releasing factor (CRF) and noradrenergic transmission in the central nucleus of the amygdala (CeA) in the dysphoria associated with smoking cessation. It was investigated if blockade of CRF1 receptors, blockade of α1-adrenergic receptors, or stimulation of α2-adrenergic receptors in the CeA diminishes the deficit in brain reward function associated with nicotine withdrawal in rats. Nicotine dependence was induced by implanting minipumps that delivered a nicotine solution. Withdrawal was precipitated with the nicotinic acetylcholine receptor antagonist mecamylamine. A discrete-trial intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In all the experiments, mecamylamine elevated the brain reward thresholds of the rats chronically treated with nicotine and did not affect the brain reward thresholds of the saline-treated control rats. Intra-CeA administration of the CRF1 receptor antagonist R278995/CRA0450 completely prevented the mecamylamine-induced elevations in brain reward thresholds in the nicotine-treated rats and did not affect the brain reward thresholds of the saline-treated control rats. R278995/CRA0450 has also been shown to block sigma-1 receptors but there is no evidence that this could affect negative mood states. Intra-CeA administration of the α1-adrenergic receptor antagonist prazosin or the α2-adrenergic receptor agonist clonidine did not affect the brain reward thresholds of the nicotine or saline-treated rats. These studies suggest that CRF1 receptor antagonists may diminish the dysphoria associated with smoking cessation by blocking CRF1 receptors in the CeA.     

Preventing relapse in the treatment of nicotine addiction: current issues and future directions.

Although smoking-cessation rates have continued to increase, the vast majority of smokers who quit eventually relapse. Between 1974 and 1985, over 1.3 million smokers quit during each of those years. However, 75% to 80% of those individuals resumed smoking within six months. This article describes the dynamic phenomenon of smoking relapse within the context of cyclical episodes of smoking and quitting during an individual's lifetime. Theories of the determinants of smoking relapse are reviewed and methods designed to prevent relapse are described. Smoking relapse is discussed in terms of three aspects of tobacco addiction: (1) biological-addiction mechanisms, (2) conditioning processes, and (3) cognitive-social learning factors. The major determinants of smoking relapse are reviewed, including nicotine withdrawal, stress, weight gain, social influences, conditioning factors, causal attributions, and environmental variables. A transtheoretical-developmental model is explored in the longitudinal investigation of the natural history of slips (lapses) and relapse episodes. Relapse prevention interventions are described that emphasize self-awareness, self-regulation, self-efficacy, affect regulation, social support, and lifestyle balance. Recent developments in pharmacological adjuncts to treatment are also examined. It is concluded that innovative relapse prevention methods need to be designed for hard-core smokers with histories of cessation failures, substance abuse and/or psychiatric impairment. These and other recommendations for future research on smoking relapse and relapse prevention are discussed.     

Preventing relapse in the treatment of nicotine addiction: current issues and future directions

Although smoking-cessation rates have continued to increase, the vast majority of smokers who quit eventually relapse. Between 1974 and 1985, over 1.3 million smokers quit during each of those years. However, 75% to 80% of those individuals resumed smoking within six months. This article describes the dynamic phenomenon of smoking relapse within the context of cyclical episodes of smoking and quitting during an individual's lifetime. Theories of the determinants of smoking relapse are reviewed and methods designed to prevent relapse are described. Smoking relapse is discussed in terms of three aspects of tobacco addiction: (1) biological-addiction mechanisms, (2) conditioning processes, and (3) cognitive-social learning factors. The major determinants of smoking relapse are reviewed, including nicotine withdrawal, stress, weight gain, social influences, conditioning factors, causal attributions, and environmental variables. A trans-theoretical-developmental model is explored in the longitudinal investigation of the natural history of slips (lapses) and relapse episodes. Relapse prevention interventions are described that emphasize self-awareness, self-regulation, self-efficacy, affect regulation, social support, and lifestyle balance. Recent developments in pharmacological adjuncts to treatment are also examined. It is concluded that innovative relapse prevention methods need to be designed for hard-core smokers with histories of cessation failures, substance abuse and/or psychiatric impairment. These and other recommendations for future research on smoking relapse and relapse prevention are discussed.     

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.     

Smoking Cessation Leads to Reduced Stress,but Why?

Recent longitudinal studies have demonstrated that smoking cessation leads to reduced feelings of stress. This finding is not predicted by either of the two main models for smoking behavior. The nicotine resource model (Warburton) states that nicotine is used to cope with external stressors, and predicts that smokers will suffer from increased stress when they quit smoking. The deprivation reversal model (Schachter), suggests that smoking reverses the deleterious effects of deprivation; cessation will then lead to a period of increased stress, followed by a return to baseline. Although the stress/cessation data agree with neither model, they are consistent with a third explanation, namely that smoking causes stress. This model states that acute nicotine deprivation (i.e., between cigarettes) leads to increased stress. Smokers then use cigarettes to reverse these withdrawal effects and “normalize” their mood. This model explains some paradoxical aspects of the smoking/mood relationship. First, why smokers are calmed by smoking, yet report high average levels of stress. Second, why stress levels become reduced after smoking cessation; this is because the former smoker no longer suffers from the adverse mood effects of acute nicotine depletion.     

The alternative five-factor model of personality, nicotine dependence and relapse after treatment for smoking cessation

Personality is one of several factors that have been related to the initiation, maintenance and cessation of smoking. This paper aims to analyze the relationship between the alternative five-factor model of personality (AFFM), nicotine dependence (ND), nicotine use (NU) and cessation after twelve months of a cognitive–behavioral therapy combined with medication. In this prospective study, a sample of 103 smokers who were taking part in a workplace smoking cessation intervention, answered the Zuckerman–Kuhlman Personality Questionnaire. ND and NU were measured with the Fagerström Test for the Nicotine Dependence (FTND) and the number of cigarettes smoked per day (CPD), respectively. Tobacco cessation was self-reported at twelve months follow-up and biologically confirmed. Results varied according to gender. In men, low scores on Sociability predicted high ND and large number of CPD. In addition, low scores on Sensation Seeking and high scores on Impulsivity predicted also a high smoking rate at baseline. No personality traits were found to explain ND in women, but high Impulsivity–Sensation Seeking and General Activity predicted high CPD. Predictors of cessation also differed by gender. Apart from FTND level, high levels on Impulsivity predicted relapse in males. In women, high levels on Sociability predicted relapse. This model correctly classified two thirds of abstainers and relapsers for men and three fourths for women at 12 months. Furthermore an interaction between personality and gender was observed. The AFFM appears to have a substantial power for predicting cessation. Personality assessment when beginning treatment for smoking cessation could allow incorporating strategies to improve outcomes.     

The relationship between self-efficacy and nicotine withdrawal severity among adult smokers

Cigarette smokers who have low confidence in their ability to resist temptations to smoke or to quit smoking altogether (i.e., low quitting-related self-efficacy) are more likely to relapse during an attempt to quit smoking. Therefore, it is important to understand what factors influence quitting-related self-efficacy, especially during early abstinence when relapse is most likely to occur. Social cognitive theory suggests two competing hypotheses: (1) negative emotional and physiological states, such as those associated with the nicotine withdrawal syndrome, will reduce self-efficacy related to smoking cessation; and (2) low self-efficacy will increase an individual's susceptibility to arousal, such as the negative emotions and physiological responses associated with nicotine withdrawal. The current preliminary study prospectively examined the association between nicotine withdrawal severity and self-efficacy in 21 adult, heavy smokers (23.8% female) at three time points during the first 48?h of abstinence from smoking cigarettes. Results indicated that withdrawal severity did not predict self-efficacy. Instead, self-efficacy after 24?h of abstinence showed a trend toward predicting withdrawal severity at 48?h of abstinence. Findings suggest the possibility that low self-efficacy may be associated with an increase in nicotine withdrawal severity, and also suggest the presence of a dynamic relationship between self-efficacy and nicotine withdrawal.     

Smoking history, nicotine dependence, and changes in craving and mood during short-term smoking abstinence in alcohol dependent vs. control smokers

Objective

The goal of this study was to compare lifetime cigarette smoking, severity of nicotine dependence, and subjective effects of short-term tobacco abstinence in abstinent alcohol dependent (AD) and control smokers.

Method

AD (n = 119) and control (n = 55) ever-smokers were compared on tobacco use history and nicotine dependence. Negative affect and craving to smoke were examined in a subsample of currently smoking AD (N = 34) and control (N = 19) participants during a 6-h period of tobacco abstinence using the Profile of Mood States (POMS) and the Questionnaire on Smoking Urges-Brief (QSU-B).

Results

Although AD smokers did not differ from controls on heaviness of smoking, they were more likely to meet lifetime criteria for nicotine dependence. AD smokers also reported more withdrawal symptoms and were more likely to endorse withdrawal-related depressed mood during past smoking reduction or abstinence periods. During short-term abstinence, AD smokers were more likely to report high craving to smoke for negative affect relief within the first 150 min of tobacco abstinence, but did not differ from controls on overall craving to smoke or withdrawal-related negative affect on the POMS.

Conclusions

Results support previous findings that AD smokers have a greater prevalence of nicotine dependence and more severe nicotine withdrawal, with a greater propensity toward withdrawal-related depressed mood. These results, along with our novel finding that greater craving to smoke in abstaining smokers with AD is specific to negative affect-related craving, suggest that negative reinforcement may be a particularly salient factor in the maintenance of tobacco use among individuals with AD.     

Effect of nicotine on negative affect among more impulsive smokers

In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N=70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity x Condition (nicotinized vs. de-nicotinized) x Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation.     

Nicotine delivery systems

Over the past 20 years, medicinal nicotine has been used to aid smoking cessation, and has led to a significant increase in the number of smokers who successfully quit. This review describes currently available medicinal nicotine products, which include nicotine patch, gum, lozenge, nasal spray, inhaler and sublingual tablet, including their pharmacokinetics and recommended dosing. New developments in nicotine delivery that could further increase cessation rates include high-dose patches, rapid release gum, combined patch and acute forms, and several novel channels for nicotine delivery, such as nicotine drink, straw, lollipop and a pulmonary inhaler. New applications of existing and novel medicinal nicotine products may include relapse prevention, nicotine maintenance, temporary withdrawal management, reduced smoking and gradual quitting.