Silver acetate interactions with nicotine and non-nicotine smoke components.

Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dose released and absolute bioavailability of nicotine from a nicotine vapor inhaler

In an open, randomized, three-way crossover study, 14 healthy smokers used one type of nicotine vapor inhaler intensely for 20 minutes every hour for 11 hours (12 administrations). Two different inhalation techniques were applied, shallow frequent sucking (buccal mode) and deep inhalations (pulmonary mode). The determination of nicotine was performed by capillary gas chromatography after single-step liquid-liquid extraction of the plasma sample. Nicotine was detected by means of a nitrogen-sensitive detector, giving high selectivity and sensitivity. The mean (+/- SD) nicotine dose released from each nicotine vapor inhaler unit was estimated at 4.00 +/- 0.60 mg (buccal mode) and 3.87 +/- 0.75 mg (pulmonary mode), inhaled with approximately 15 L of air. Mean (+/- SD) peak plasma level of the last dosing interval was 32.0 +/- 8.7 ng/ml and 34.2 +/- 8.9 ng/ml for the buccal and the pulmonary technique, respectively, achieved after 0.33 and 0.50 (median) hour, respectively. The mean (95% confidence interval [CI]) absolute bioavailability of nicotine was 51 (95% CI, 40 to 65) and 56 (95% CI, 47 to 67) when the buccal and pulmonary techniques were used, respectively. A significant correlation was found between systemically available dose and average steady-state nicotine plasma concentration. Based on the achievement of similar nicotine plasma levels, it may be concluded that the two modes of inhalation appear to be clinically equivalent.     

The influence of caffeine on nicotine's discriminative stimulus, subjective, and reinforcing effects.

Caffeine may acutely alter the discriminative stimulus and subjective effects of nicotine, perhaps explaining the association of coffee intake with smoking status. In this study, smokers were initially trained to discriminate 20 μg/kg nicotine by nasal spray from placebo (0). Then, generalization of nicotine discrimination was tested, using both 2- and 3-choice ("novel" option) procedures, across a range of doses (0-20 μg/kg) following pretreatment with 0, 2.5, and 5.0 mg/kg caffeine p.o. Nicotine reinforcement was assessed after the end of generalization testing using a choice procedure. Caffeine pretreatment did not alter nicotine discrimination and self-administration. Caffeine and nicotine influenced some subjective and cardiovascular responses, but there were no interaction effects except for diastolic blood pressure. These results do not support the notion that caffeine acutely alters nicotine's discriminative stimulus, subjective, or reinforcing effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The nicotine inhaler in smoking cessation

BACKGROUND: Nicotine replacement therapy has been shown to improve success rates in smoking cessation treatment. However, the available products cause adverse effects, which prevent some smokers from using them. A new method of delivering nicotine via inhaler supplies nicotine orally through inhalation from a plastic tube. This mode of delivering nicotine resembles smoking, as it includes handling and active inhalation. OBJECTIVES: To assess the efficacy and safety of the nicotine inhaler as an aid in smoking cessation. METHODS: A 1-year, randomized, double-blind, placebo-controlled study was conducted in a smoking cessation clinic. Two hundred forty-seven smokers who smoked at least 10 cigarettes per day and who had previously made a serious attempt to stop smoking using nicotine chewing gum were recruited through advertisements. Randomization to treatment or control conditions were made at the first group session, with 123 participants receiving nicotine inhalers and 124 receiving placebo inhalers. The inhalers were distributed at the second session and participants were allowed to use the inhalers for 6 months. MAIN OUTCOME MEASURE: Biochemically verified continuous abstinence from smoking after 2 and 6 weeks and at 3, 6, and 12 months. RESULTS: Significantly more participants who had used the nicotine inhalers were continuously abstinent compared with those who had used the placebo inhalers. The respective success rates after 12 months were 28% and 18% (P = .046). At 6 months, 20 participants (16%) in the nicotine group were still using the inhaler, compared with 4 (3%) in the control group (P < .001). CONCLUSION: The nicotine inhaler was an effective smoking cessation aid that produced a few mild and transient adverse effects.     

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)     

Greater sensitivity to subjective effects of nicotine in nonsmokers high in sensation seeking.

The personality characteristic of sensation seeking is associated with risk of smoking, perhaps because of greater initial sensitivity to nicotine. Young healthy nonsmokers (N?=?37) were administered 0, 10, and 20 μg/kg nicotine by nasal spray in 3 separate sessions, and subjective responses were assessed. Sensation-Seeking Scale (SSS) scores were then correlated with these responses. A comparison group of smokers (N?=?55) was included to determine whether sensation seeking was associated specifically with initial sensitivity to nicotine or with general sensitivity regardless of past nicotine exposure. SSS subscales, particularly Experience Seeking and Disinhibition, were correlated with subjective responses to nicotine in nonsmokers but generally not in smokers. These findings indicate that sensation seeking is associated with greater initial sensitivity to nicotine's subjective effects and may provide directions for further study of individual-differences characteristics that predispose people to the risk of becoming smokers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do adolescent smokers experience withdrawal effects when deprived of nicotine?

This is the first controlled prospective study of the effects of nicotine deprivation in adolescent smokers. Heart rate and subjective withdrawal symptoms were measured over and 8-hr period while participants smoked normally. Seven days later, participants were randomized to wear a 15-mg (16-hr) nicotine patch or placebo patch for 8 hr, and they refrained from smoking during the session. Those wearing the placebo experienced a decrease in heart rate across sessions and an increase in subjective measures of nicotine withdrawal. Those wearing the active patch also reported significant increases for some subjective symptoms. Expectancy effects were also observed. The findings indicate that adolescent smokers experience subjective and objective changes when deprived of nicotine. As in previous research with adults, expectancies concerning the effects of nicotine replacement also influenced perceptions of withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Effects of Nicotine on Attention and Working Memory in Never-Smokers.

The subjective and physiological effects of nicotine in nicotine-naive individuals are consistent across studies, though the cognitive effects are variable: Positive, negative, or no effects have been reported. Assessing specific cognitive processes (e.g., alerting, orienting, executive function, and phonological and visuospatial working memory) may help reduce this variability. This within-subject study (N = 20) was designed to assess the effect of nicotine gum (0, 2, or 4 mg) on subjective, physiological, and cognitive measures. Dose-dependent increases in dysphoria and heart rate were observed, though nicotine did not influence any aspect of attention or working memory. Future studies should take into account the difference in effect sizes for cognitive versus physiological/subjective measures and maximize power (e.g., increase sample size) accordingly. (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?     

Subjective effects of transdermal nicotine among nonsmokers.

The subjective experience of nicotine, which may be influenced by personality traits as well as environmental factors, may be important for understanding the factors associated with the initiation and maintenance of nicotine dependence. The present study examined the effects of 7 mg transdermal nicotine among a relatively large sample (n = 91; 44 women) of college-aged nonsmokers. Using a placebo controlled, double-blind, within-subjects design, nicotine’s effects were examined at rest and again after participants completed a sustained attention task. Sex and personality factors (Behavioral Inhibition and Behavioral Approach; BIS/BAS Scales; Carver & White, 1994) were examined as potential moderators. Overall, the effects of nicotine were generally modest and unpleasant. In the context of the cognitive task, nicotine increased nausea and negative affect but reduced fatigue, relative to placebo. In contrast, effects of nicotine during the initial 4 hr of patch administration, in which participants were in their natural environments, were moderated by individual differences in behavioral approach. Neither behavioral inhibition nor gender reliably moderated any subjective effects of nicotine. The present work suggests transdermal nicotine exerts only modest, mostly negative effects among nonsmokers. Future work should examine both contextual and personality moderators in large samples of participants who are exposed to nicotine through multiple routes of administration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic voluntary nicotine drinking enhances nicotine palatability in rats.

Examined the response of rats to nicotine (NI) solutions with the brief-exposure, taste reactivity (TR) test, and a 2-bottle, 24-hr preference test. Naive nondeprived Ss were administered intraoral infusions of distilled water and 1 μg/ml, 5 μg/ml, 10 μg/ml, 25 μg/ml, 50 μg/ml, and 100 μg/ml NI. NI solutions up to a concentration of 50 μg/ml elicited a number of ingestive TR responses similar to that by water. Ingestive responses significantly decreased and aversive TR responses significantly increased in response to 100 μg/ml nicotine. On the basis of these results, 2-bottle preferences for water vs 1 μg/ml, 5 μg/ml, and 0 μg/ml (water control group) NI were measured in 3 groups of naive Ss. Ss initially showed an equal preference for 0 μg/ml and 1 μg/ml NI. After 16 days of exposure, however, Ss developed a significant preference for 1 μg/ml NI. The preference ratio for 5 μg/ml NI significantly increased during the experiment, but the preference ratio remained significantly less than that for 1 μg/ml and 0 μg/ml NI solutions. Last, TR responses elicited by intraoral infusions of 1 μg/ml and 5 μg/ml NI were then measured in these Ss having had the 2-bottle experience. Ss showing a 2-bottle preference for the 1 μg/ml NI solution displayed significantly more ingestive TR responses to 1 μg/ml and 5 μg/ml NI than did the control Ss. Data indicate that prolonged voluntary access to NI results in an increased preference for NI and modifies the immediate oral/gustatory reactivity of the Ss to NI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amphetamine lowers brain stimulation reward (BSR) threshold in alcohol-preferring (P) and non-preferring (NP) rats: Regulation by D? and D? receptors in the nucleus accumbens.

Differences in the mesolimbic dopamine (DA) pathway that regulates alcohol preference may also increase sensitivity to the reinforcing effects of other drugs of abuse. In the present study, the curve-shift (rate-frequency) paradigm was used to quantify the interaction of amphetamine with the rewarding effects of lateral hypothalamic brain stimulation reward (BSR) in alcohol-preferring (P) and -nonpreferring (NP) rats. The role of D? and D? DA receptors of the nucleus accumbens (NAcc) in mediating the reward-potentiating effects of amphetamine was also determined. Animals were tested with randomly administered amphetamine (0.25, 0.75, 1.25 mg/kg ip), DA-receptor antagonists (SCH 23390 [2.0 μg, 5.0 μg]; eticlopride [2.0 μg, 5.0 μg]), or a combination of the 2 (SCH 23390 [2.0 μg, 5.0 μg] + 0.75 mg/kg amphetamine; eticlopride [2.0 μg, 5.0 μg] + 0.75 mg/kg amphetamine). Amphetamine produced comparable dose-related leftward shifts in the rate-frequency function for both P and NP rats, with a greater than 60% reduction observed in BSR threshold. On intervening days, baseline threshold was unaltered between tests and similar between rat lines. Unilateral infusion in the NAcc of either the D? or D? receptor antagonist produced rightward shifts in the rate-frequency function of amphetamine, completely reversing-attenuating its reward-enhancing effects. The results demonstrate that amphetamine produces similar threshold-lowering effects in both P and NP rats and that the reward-potentiating effects of amphetamine do not correlate with alcohol preference under the conditions of the present study. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinforcing effects of nicotine as a function of smoking status.

The authors compared acute nicotine self-administration among 4 groups varying in current or past dependence: dependent smokers, nondependent smokers, ex-smokers who had quit at least I year ago, and nonsmokers. Nicotine (0 vs. 12 μg/kg/8 sprays) available by nasal spray was self-administered with a choice procedure. Self-administration also was related to participant characteristics (sex, alcohol and caffeine intake, sensation-seeking score) and to subjective responses to initial nicotine spray exposure. Nicotine self-administration was similar between dependent and nondependent smokers but was greater in those groups than in ex-smokers and nonsmokers, who did not differ from each other. Self-administration was unrelated to most other participant characteristics. In nonsmokers, self-administration was related directly to pleasurable effects but inversely to aversive effects. Few effects were related to self-administration in the other groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The separate and combined effects of nicotine and alcohol on working memory capacity in nonabstinent smokers.

Research indicates that nicotine and alcohol are often used on the same occasion. However, the reasons for their concurrent use are not well understood. We hypothesized that one reason smokers use tobacco when they drink alcohol is to compensate for alcohol’s negative effects on processing capacity with nicotine’s enhancement of processing capacity. As such, the present study tested this theory by using an independent groups design to examine the separate and combined acute effects of alcohol and nicotine on working memory (WM) capacity. Nonabstinent daily smokers (n = 127) performed the counting span task (CSPAN) after consuming either an alcohol (men: 0.8 g/kg; women: 0.7 g/kg) or placebo beverage and smoking either nicotinized (1.14 mg nicotine, 15.9 mg tar) or denicotinized (.06 mg nicotine, 17.9 mg tar) cigarettes. Analyses revealed that smokers who smoked the nicotinized cigarettes performed significantly worse on the CSPAN task than smokers who smoked the denicotinized cigarettes. Although there was no main effect of alcohol on WM performance, women exhibited better WM performance than men after consuming alcohol whereas men performed better than women on the WM task after consuming the placebo beverage. Findings also revealed no interaction between the two substances on WM performance. Taken together, results suggest that nicotine impairs nonabstinent smokers’ verbal WM capacity and that gender moderates the effects of alcohol on WM. Furthermore, the present findings failed to support the notion that nicotine compensates for alcohol-related decrements in working memory capacity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naltrexone alteration of the nicotine-induced EEG and mood activation response in tobacco-deprived cigarette smokers.

The neural mechanisms contributing to the arousal-eliciting actions of smoking and nicotine involve multiple neurotransmitter systems. The current study examined the role of opioid neurotransmission in modulating the neuroelectric- and mood-activating response to acute nicotine administration in overnight tobacco-deprived smokers. In a randomized, double-blind, placebo-controlled design involving 18 (10 male, 8 female) overnight tobacco-abstinent smokers, spectrally analyzed electroencephalographic (EEG) activity and subjective reports of mood, euphoria, and smoking withdrawal were assessed in response to nicotine gum (4 mg) after pretreatment with placebo or with 50 mg of the opioid antagonist naltrexone. In addition to reducing withdrawal symptoms and increasing euphoria ratings, as well as subjective alertness in male participants, nicotine induced an EEG arousal response consisting of diffuse slow wave (delta, theta) amplitude reductions, frontal fast alpha wave amplitude increments, and elevations in beta wave amplitude, which were greater in female than in male smokers. Naltrexone attenuated the alerting and euphoric actions of nicotine but did not affect nicotine's ameliorating effects on withdrawal symptoms. Nicotine-induced frontal reductions in delta and global reductions in theta were prevented by naltrexone pretreatment, as were increases in anterior recordings of relative fast alpha. These findings suggest that the opioid system is involved in nicotine-induced subjective and neuroelectric arousal and implicate opioid-cholinergic interactions in the elicitation of these arousal responses to nicotine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Placebo cigarettes in smoking research.

This review outlines the development and use of placebo cigarettes in smoking research. Research on effects of smoking has been disadvantaged by the lack of an adequate placebo condition. Recently, tobacco-based denicotinized cigarettes have been used in smoking research to distinguish effects of smoking due to the delivery of nicotine, other components of tobacco smoke, and the sensory process of smoking. Placebo cigarettes do not increase heart rate and blood pressure or produce electroencephalogram changes ordinarily associated with nicotine. However, placebo cigarettes reduce subjective measures of tobacco craving, desire to smoke, and tobacco withdrawal. These findings indicate that the effects of cigarette smoking are dependent on the delivery of nicotine, tar, other compounds of tobacco smoke, and the sensory stimuli. The next generation of research may begin to investigate the mechanisms that modulate these placebo effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological dose effects of a freon, trifluoromethane (FC-23), compared to N2O

Animal studies show FC-23 to be a promising magnetic resonance imaging indicator of regional cerebral blood flow. In a Phase 1, dose ranging (investigative new drug) study, neuropsychological (NP) tests, subjective ratings, and intensive physiological monitoring were used to determine the maximum tolerated concentration of FC-23 for human application. Five normal healthy male volunteers were exposed to concentrations of FC-23 between 10% and 60% [randomly interleaved with exposures to both room air and 40% nitrous oxide (N2O)] in a within-subjects, double-blind design. Analyses of individual cases and ranked group data showed that individuals tolerated the 30% concentration of FC-23 according to established criteria. Planned comparisons indicated that inhalation of FC-23 produced smaller NP changes and fewer negative symptoms than 40% N2O but poorer NP performance and more negative symptoms than room air. This study indicated that FC-23 is not inert and that humans do not tolerate concentrations suitable for current MRI technology. NP and subjective data assisted in characterizing the sedative effect of FC-23.     

Effects of alcohol intoxication on anger experience and expression among partner assaultive men.

The author investigated the acute effects of alcohol intoxication on anger experience and expression among 46 maritally violent (MV) and 56 maritally nonviolent (NV) men randomly assigned to receive alcohol, placebo, or no alcohol. Participants completed an anger-arousing articulated thoughts in simulated situations (ATSS) paradigm and imagined marital conflict scenarios. Anger experience was operationalized as subjective ratings of anger experienced during ATSS, and anger expression was measured as ATSS anger statements and aggression verbalizations. MV men given alcohol articulated significantly more aggressive verbalizations than all other groups, with high trait anger and increased anger experience predicting more aggressive verbalizations. Thus, alcohol may exert proximal effects on abusive behavior among individuals already prone to respond to conflict with increased anger. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Transdermal Nicotine During Imaginal Exposure to Anxiety and Smoking Cues in College Smokers.

In a 2 (patch) × 2 (smoking) × 2 (anxiety) mixed design, 52 undergraduate smokers randomly received a nicotine (21 mg) or placebo patch. After a 4-hr nicotine absorption/deprivation period, participants imagined several scenarios varying in cue content: (a) anxiety plus smoking, (b) anxiety, (c) smoking, and (d) neutral. Although smoking urge increased in both the nicotine and placebo conditions after the absorption/deprivation period, those who received the placebo reported significantly greater urge. During the cue reactivity trials, a significant Patch × Smoking × Anxiety interaction effect was observed for urge. However, participants who received nicotine still experienced moderate urges, indicating that nicotine did not attenuate cue-elicited urge. Transdermal nicotine did not diminish anxiety during the absorption/deprivation period or in response to the cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)