Dissociating nicotine and nonnicotine components of cigarette smoking

ArticleinPharmacology Biochemistry and Behavior 67(1):71-81 · October 2000with7 Reads
DOI: 10.1016/S0091-3057(00)00301-4
To dissociate the sensorimotor aspects of cigarette smoking from the pharmacologic effects of nicotine, smokers rated the subjective effects of nicotine-containing or denicotinized cigarettes, and intravenous (IV) nicotine or saline infusions. Three groups of participants (n=20 per group) received either: (1) continuous nicotine, (2) pulsed nicotine, or (3) saline. Each group was exposed to an IV condition once while smoking a denicotinized cigarette and once while not smoking, in a 3×2 mixed design. A fourth group (n=20) received saline while smoking their usual brand of cigarette. The dose and rate of nicotine administration were individualized based on previous measures of ad lib smoke intake. Denicotinized cigarette smoke significantly reduced craving and was rated significantly more satisfying and rewarding than the no-smoking conditions. IV nicotine reduced craving for cigarettes, and increased ratings of lightheadedness and dizziness. However, no significant satisfaction or reward was reported after IV nicotine. The combination of IV nicotine and denicotinized cigarette smoke produced effects similar to those of smoking the usual brand of cigarette. The results suggest that sensorimotor factors are critical in mediating the immediate subjective response to smoking, and that the immediate subjective effects of nicotine administered in doses obtained from cigarette smoking are subtle. Thus, addressing smokers' needs for both for the sensorimotor aspects of smoking as well as for the direct CNS effects of nicotine may be critical in enhancing smoking cessation treatment outcome.
    • "Whether these effects are nicotine-specific or a result of interactions between non-nicotine tobacco constituents and nicotine remains unknown. Intravenously administered nicotine has been found to reduce withdrawal symptoms (Rose et al., 2000), yet the extent to which these effects were due to expectancy versus nicotine pharmacology remains unclear, as expectancy was not manipulated independently of nicotine pharmacology. Other research suggests that nicotine-containing tobacco may be more effective than nicotine administered via NRT in reducing withdrawalrelated craving (Barrett, 2010 ), which is consistent with the possibility that non-nicotine tobacco constituents may contribute to withdrawal-relieving properties of smoking (Harris et al., 2010; Hoffman and Evans, 2013 ). "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Smoking cessation aids appear to be limited in their ability to prevent craving triggered by exposure to smoking-associated stimuli; however, the extent to which cue-induced cravings persist following denicotinized or nicotine-containing tobacco smoking is not known. Methods: Thirty (17 male) ⩾12-hour abstinent dependent smokers completed two sessions during which they smoked a nicotine-containing or denicotinized cigarette. Instructions regarding the nicotine content of the cigarette varied across sessions, and all participants were exposed to a neutral cue followed by a smoking cue after cigarette consumption. Craving was assessed before and after cigarette consumption and cue exposure. Results: Reduced intentions to smoke were associated with both nicotine expectancy (p<0.05) and nicotine administration (p<0.01), while reduced withdrawal-related craving was uniquely associated with nicotine administration (p<0.05). Smoking-associated stimuli increased craving regardless of nicotine expectancy or administration (p-values<0.001). Conclusions: While both nicotine pharmacology and expectancy appear to contribute to craving reduction associated with acute tobacco smoking, neither smoking-related nicotine administration nor expectation prevents increases in craving following exposure to smoking-associated stimuli. These findings suggest that cue-induced craving may be resistant to various pharmacological and psychological interventions.
    Full-text · Article · Apr 2016
    • "Some researchers have expressed doubts that regular smoking and tobacco use are evidence of addiction to nicotine per se (Dar and Frenk 2004; 2007; Robinson and Pritchard 1992). These reservations arise from a number of observations including the difficulty or inconsistency of establishing nicotine self-administration in laboratory animals (Dar and Frenk 2002; Griffiths et al. 1979; Le Foll and Goldberg 2009; Koffarnus and Winger 2015; Goodwin et al. 2015), the relatively limited success of nicotine replacement therapies for smoking cessation (Etter and Stapleton 2006; Hughes et al. 2003; McClure and Swan 2006) , the lack of consistent mood-elevating or Beuphoric^ effects of nicotine ( Hughes et al. 2000; Kalman and Smith 2005), and the observation that denicotinized cigarettes are able to reduce cigarette craving and withdrawal (Rose et al. 2000; Shahan et al. 1999). Although the reinforcing effects of nicotine in nicotine users have been demonstrated (e.g., Harvey et al. 2004; Le Foll and Goldberg 2009; Perkins 2004 ), these effects appear relatively inconsistent. "
    [Show abstract] [Hide abstract] ABSTRACT: Rationale: Global tobacco-related mortality dwarfs that of all other drugs. Nicotine is believed to be the primary agent responsible for tobacco use and addiction. However, nicotine is a relatively weak and inconsistent reinforcer in nonhumans and nicotine reinforcement has not been demonstrated in never-smokers. Objectives: This study investigated the discriminative, subjective, and reinforcing effects of nicotine in never-smokers. Methods: Eighteen never-smokers (<50 lifetime nicotine exposures) participated in a double-blind study. During a drug discrimination phase, volunteers ingested oral nicotine and placebo capsules (quasi-random order) at least 2 h apart and rated subjective effects repeatedly for 2 h after ingestion in daily sessions. Blocks of 10 sessions were continued until significant discrimination was achieved (p ≤ 0.05, binomial test; ≥8 of 10). Following discrimination, nicotine choice was tested by having volunteers choose which capsule set to ingest on each daily session. Successive blocks of 10 sessions were conducted until choice for nicotine or placebo met significance within each volunteer (≥8 of 10 sessions). Results: All 18 volunteers significantly discriminated nicotine from placebo; the lowest dose discriminated ranged from 1.0 to 4.0 mg/70 kg. Nine volunteers significantly chose nicotine (choosers) and nine significantly chose placebo (nicotine avoiders). The choosers reported predominately positive nicotine subjective effects (e.g., alert/attentive, good effects, liking), while avoiders tended to report negative effects (e.g., dizzy, upset stomach, disliking). Both choosers and avoiders attributed their choice to the qualitative nature of drug effects. Conclusions: These results provide the first evidence that nicotine can function as a reinforcer in some never-smokers.
    Full-text · Article · Sep 2015
    • "Thus, an initially aversive sensory experience becomes reinforcing and has the potential to improve the smoker's experience. Further supporting the notion that smoking cues themselves are reinforcing, it has been shown that smoking cues are readily self-administered in humans [26]. Animal models also have demonstrated a similar effect of nicotine on enhancing the reinforcing properties of nicotine-associated cues. in rats, lever pressing for a naturally rewarding visual stimulus was greatly enhanced with either contingent or noncontingent presentations of nicotine, but not of sucrose [27,28] . "
    [Show abstract] [Hide abstract] ABSTRACT: Mentholated cigarettes gained popularity in the 1950s and were often marketed as “healthy” cigarettes, attributable to their pleasurable mint flavor and cooling sensation in the mouth, lungs, and throat. While it is clear that nicotine is the primary psychoactive component in tobacco cigarettes, recent work has suggested that menthol may also play a role in exacerbating smoking behavior, despite original health claims. Recent evidence highlights four distinct biological mechanisms that can alter smoking behavior: 1) menthol acts to reduce the initially aversive experiences associated with tobacco smoking; 2) menthol can serve as a highly reinforcing sensory cue when associated with nicotine and promote smoking behavior; 3) menthol's actions on nicotinic acetylcholine receptors may change the reinforcing value of nicotine; and 4) menthol can alter nicotine metabolism, thus increasing nicotine bioavailability. The purpose of this review is to highlight and evaluate potential biological mechanisms by which menthol can alter smoking behavior.
    Full-text · Article · Sep 2015
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