Effects of abstinence from tobacco: Etiology, animal models, epidemiology, and significance: A subjective review

Department of Psychiatry, University of Vermont, Burlington, VT 05401-1419, USA.
Nicotine & Tobacco Research (Impact Factor: 3.3). 04/2007; 9(3):329-39. DOI: 10.1080/14622200701188927
Source: PubMed


This article updates a 1990 review of the effects of tobacco abstinence by reviewing (a) the etiology, (b) animal models, (c) the epidemiology, and (d) the clinical significance of tobacco abstinence effects. The author searched several databases to locate more than 3,500 citations on tobacco abstinence effects between 1990 and 2004. For brevity, the review does not evaluate these effects in regard to craving, hunger, or performance. Data collection and study conclusions were based on the author's subjective judgment. The most validated etiological model suggests that withdrawal is related to decreased dopaminergic activity, but how this relates to nicotine receptor changes is unclear. The two most validated animal models describe increases in intracranial self-stimulation thresholds or observable physical signs. Significant withdrawal symptoms occur in at least half of smokers when they try to quit. Withdrawal appears to produce clinically significant distress and impairment. Increases in depression after abstinence, but not other symptoms, prospectively predict relapse. In conclusion, the proposed neurobiological mechanisms by which withdrawal occurs leave several unanswered questions. Although animal models have been developed, how well they mimic withdrawal in humans is unclear. Tobacco withdrawal is common and can be distressing. Withdrawal-induced depression appears to undermine the smoker's ability to remain abstinent.

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    • "To the best of our knowledge, only two studies have systematically evaluated the early time course of smoking withdrawal effects (Brown et al., 2013; Hendricks, Ditre, Drobes, & Brandon, 2006). However, these studies did not address the clinical significance of these symptoms (e.g., their relationships with quit attempt outcomes such as abstinence or later withdrawal symptoms; Hughes, 2007a), which could serve as predictors of treatment success and provide valuable information for clinicians in designing tailored interventions. Predictors of early withdrawal effects are also unknown. "
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    ABSTRACT: Although the early time course of smoking withdrawal effects has been characterized, the clinical significance of early withdrawal symptoms and their predictors are unknown. This study evaluated the relationships of early smoking withdrawal effects with quit attempt outcomes and the rate of nicotine metabolism. Eleven treatment-seeking smokers abstained from smoking for 4hr in the laboratory, before a quit attempt. Withdrawal measures included heart rate, sustained attention, and self-report. Following baseline assessment, withdrawal measures were administered every 30min. At the conclusion of the 4-hr early withdrawal session, participants received a brief smoking cessation intervention and then returned 1 week and 12 weeks later for outcome assessments that included biochemically confirmed smoking abstinence, cigarettes smoked in the past 24hr, and self-reported withdrawal symptoms. The rate of nicotine metabolism was estimated at intake using the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine) measured in saliva. Greater self-reported negative affect and concentration difficulty during early withdrawal, most notably anxiety, were related with poorer quit attempt outcomes. There was some indication that although a faster increase in craving and greater hunger during early withdrawal were associated with more favorable outcomes, a greater decrease in heart rate during this time was associated with poorer outcomes. Faster nicotine metabolism was related to a faster increase in anxiety but a slower increase in craving during early withdrawal. These findings lend support to the clinical significance of early smoking withdrawal effects. The rate of nicotine metabolism may be a useful predictor of early withdrawal symptoms.
    Nicotine & Tobacco Research 12/2013; 16(5). DOI:10.1093/ntr/ntt204 · 3.30 Impact Factor
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    • "Cessation of tobacco use produces a nicotine withdrawal syndrome characterized by negative affective (emotional) symptoms (e.g., depression, anxiety), cognitive deficits, weight gain, and somatic symptoms (Hughes, 2007a,b; Kenny and Markou, 2001; Paolini and De Biasi, 2011). Avoidance of nicotine withdrawal symptoms is thought to play a critical role in maintaining tobacco use (Baker et al., 2004; Hughes, 2007a; Koob and Le Moal, 2008; Markou, 2008; Paolini and De Biasi, 2011; Watkins et al., 2000a). Development of medications that attenuate the nicotine withdrawal syndrome may therefore be useful for facilitating smoking cessation. "
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    ABSTRACT: Development of medications that attenuate symptoms of nicotine withdrawal may be useful for facilitating smoking cessation. The neuropeptide oxytocin (OXY) decreases withdrawal signs and other addiction-related effects of several drugs of abuse in animals, but has not been examined in a preclinical model of nicotine addiction. The goal of this study was to examine the effects of OXY on nicotine withdrawal in rats, measured as increases in somatic signs and elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during antagonist-precipitated withdrawal from a chronic nicotine infusion. Effects of OXY on baseline ICSS thresholds in non-dependent rats were also evaluated. OXY (0.06 - 1.0mg/kg, i.p.) blocked withdrawal-induced elevations in somatic signs in nicotine-dependent rats without affecting somatic signs in non-dependent rats. In contrast, OXY did not affect nicotine withdrawal-induced elevations in ICSS thresholds. Relatively high doses of OXY (0.75 or 2.0mg/kg) elevated baseline ICSS thresholds in non-dependent rats. These findings demonstrate that OXY blocks somatic signs but not elevations in ICSS thresholds during antagonist-precipitated nicotine withdrawal. The ability of higher OXY doses to elevate baseline ICSS thresholds in non-dependent rats may reflect an aversive and/or motoric effect. These data suggest that OXY-based medications may be useful for treating the somatic component of the nicotine withdrawal syndrome, but may not be effective in attenuating withdrawal-induced anhedonia.
    Pharmacology Biochemistry and Behavior 11/2013; 116. DOI:10.1016/j.pbb.2013.11.002 · 2.78 Impact Factor
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    • "However, it is possible that the use of participants paid to abstain from smoking overnight may have attenuated the relationships between abstinence-related expectancies and withdrawal, as this research paradigm tends to yield muted withdrawal effects (Hughes 2007a). Thus, abstinence-related expectancies may prove even more potent predictors of longer-term withdrawal and withdrawal symptoms among those trying to cease cigarette use. "
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    ABSTRACT: Despite the decades-long emphasis on withdrawal in leading models of addiction, the causal mechanisms driving smoking withdrawal effects are not well known. This gap in the knowledge base has stalled theory and treatment development for smoking dependence. As cognitive factors have been largely neglected as predictors of withdrawal, the current study sought to examine how smokers' abstinence-related expectancies relate to withdrawal symptomatology. Adult smokers (N = 180; ≥10 cigarettes/day) participated in two counterbalanced experimental sessions involving either 16 h of abstinence or smoking as usual. At baseline, participants completed three withdrawal-related scales of the Smoking Abstinence Questionnaire (Withdrawal, Optimistic Outcomes, and Weight Gain scales), a self-report measure of smokers' abstinence-related expectancies. During experimental sessions, participants completed a number of instruments that covered the range of smoking withdrawal effects (i.e., negative affect, urge/craving to smoke, diminished positive affect, concentration difficulty, hunger, and physiological symptoms). Even after controlling for the influence of demographic characteristics and cigarette dependence, smokers' abstinence-related expectancies were meaningful predictors of abstinence-induced changes in various withdrawal symptoms (mean adjusted standardized β = 0.22). Stronger expectancies for withdrawal and weight gain predicted more severe withdrawal effects, whereas stronger expectancies for optimistic outcomes predicted less severe withdrawal effects. These findings are consistent with the notion that expectancies actively shape future experience and are the first to support the suggestion that smokers' abstinence-related expectancies may be causal agents of withdrawal symptomatology. Future research is required to more conclusively determine whether abstinence-related expectancies mold withdrawal effects.
    Psychopharmacology 06/2013; 230(3). DOI:10.1007/s00213-013-3169-7 · 3.88 Impact Factor
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