Nicotine gum: dose-related effects on cigarette smoking and subjective ratings

The effects of nicotine-containing chewing gum on cigarette smoking and subjective and physiological response were evaluated in eight normal volunteers. Isolated subjects smoked their regular brand of cigarettes freely in a naturalistic laboratory environment while watching television or reading. Before 90-min smoking sessions subjects chewed two pieces of placebo or nicotine-containing gum (0, 2, 4, or 8 mg) under double-blind conditions. Each subject received each treatment four times in a mixed order across days. Analysis of the chewed gum for remaining nicotine revealed that the mean delivered nicotine doses were 0, 1.02, 2.39, and 5.20 mg nicotine. Nicotine preloading produced dose-related increases in plasma nicotine, while producing dose-related decreases in various measures of cigarette smoking including number of cigarettes smoked, number of puffs taken, expired air carbon monoxide level, and ratings of smoking satisfaction. Nicotine preloading produced dose-related increases in ratings of gum dose-strength, while producing decreases in ratings of gum dose acceptability and liking. Heart rate and blood pressure were not significantly affected by nicotine gum. Taken together, the present results confirm that responses to nicotine in the gum preparation are orderly and related to dose, and the results suggest that the efficacy of treating tobacco dependence with nicotine gum may be enhanced by increasing the administered dose.     

Effects of oral pH on cigarette smoking.

Permeability of nicotine across the oral mucosa had been shown to be a direct linear function of alkalinity in the oral cavity. Here, oral pH in cigarette smokers was manipulated from pH 5 to 8 by rinses with Sorenson's and McIlvaine's buffers. As a alkalinity increased, cigarette taste was perceived as stronger, more bitter, and, in some cases, more upleasant; and heart-rate accelerated slightly. Nicotine self-administration and blood pressure were not influenced. Differential absorption of nicotine and cross-adaptation of sour to bitter taste are both discussed as explanations for the results.     

Effects of cigarette nicotine content and smoking pace on subsequent craving and smoking

Abstract Rationale. The relative contribution of sensory and pharmacological variables in regulating craving and smoking remains unclear. Rapid smoking procedures and denicotinized cigarettes can be used to further disentangle these factors, and to explore the relationship between craving and smoking. Objective. The present study examined the role of nicotine and sensory cues in mediating craving and smoking, and the relationship between craving and smoking. Methods. Participants (n=15) engaged in one session each of rapid smoking (up to nine cigarettes with puffs taken every 6 s) and normal paced smoking with nicotinized and denicotinized cigarettes (total of four sessions). During the next 3 h, craving and withdrawal assessments and smoking opportunities were scheduled every 15 min. Plasma nicotine levels were measured at baseline, immediately and 15 min after the smoking interventions, and subsequently at the time when the participant first chose to smoke. Results. Craving ratings were equally suppressed immediately after all conditions. After self-paced conditions, both types of cigarettes produced equivalent effects on latency to smoke. Latency to smoke was significantly longer after rapid smoking of nicotinized cigarettes compared to all other conditions. Finally, changes in craving were associated with choices to smoke. Conclusions. The sensory cues associated with smoking suppressed craving ratings regardless of the smoking pace or nicotine content. Only at high doses did nicotine levels play an additional role in acutely suppressing smoking behavior. Small elevations in craving ratings were associated with choices to smoke. Electronic Publication     

Sex differences in the subjective and reinforcing effects of cigarette nicotine dose

RATIONALE: Some research with novel nicotine delivery methods suggests that nicotine itself may be less reinforcing in women than in men. However, sex differences in the reinforcing effects of nicotine dose via cigarette smoking have received little attention. OBJECTIVES: Sex differences in the subjective and reinforcing effects of smoking were examined as a function of two cigarette nicotine "dose" levels (moderate - subjects' preferred brand, > or = 0.7 mg yield; low - Carlton "ultra-light", 0.1 mg yield). METHODS: Male and female smokers ( n = 30) participated in three sessions, the first two involving independent assessment (only one brand available), and the third involving concurrent assessment (both brands available), of subjective ratings (e.g. "liking") and reinforcement for the two cigarette brands. Subjects were blind to the brand of each cigarette, and subjects abstained overnight prior to each session. Reinforcement was determined by responses on a computer task to earn single puffs on the designated cigarette. RESULTS: Subjective ratings differed between the low versus moderate cigarette nicotine dose under both independent and concurrent assessment conditions, as expected. Notably, this dose difference was smaller in women than in men (i.e. significant sex by dose interactions). The dose effect on smoke reinforcement also was smaller in women than men, but only under the independent and not concurrent assessment condition. CONCLUSIONS: These results indicate that cigarette nicotine dose is a less important influence on the subjective and, under some conditions, reinforcing effects of smoking in women than in men.     

Effects of the nicotinic antagonist mecamylamine on inspection time

RATIONALE: Several lines of evidence suggest that nicotinic acetylcholine receptors (nAchRs) are involved in speed of information processing, and inspection time appears to be particularly sensitive to nicotinic manipulation. OBJECTIVE: The present study sought to examine the effects of the nAchR antagonist mecamylamine on inspection time. Furthermore, the extent to which the anticholinesterase donepezil would reverse the effects of mecamylamine on inspection time was also examined. METHODS: A double-blind, repeated measures design was employed. Subjects (n = 6) received placebo, mecamylamine (20 mg PO) or mecamylamine (20 mg PO) and donepezil (5 mg PO). Inspection time and physiological measures were then assessed. RESULTS: The mecamylamine condition and the mecamylamine and donepezil condition were associated with an increase in heart rate, when compared to the placebo condition. There was a significant slowing of inspection time in the mecamylamine condition; compared to placebo, which was partly reversed by donepezil. CONCLUSIONS: The slowing of inspection time following mecamylamine is consistent with the role of nAchRs in speed of information processing, and add to the evidence that IT may in part index nAchR system integrity.     

d-Amphetamine increases choice of cigarette smoking over monetary reinforcement

RATIONALE: Psychomotor stimulants previously have been found to increase the frequency of cigarette smoking, but it is unclear whether this is due to a non-specific increase in general activity or a specific increase in the reinforcing effects of smoking. OBJECTIVES: To investigate whether d-amphetamine increases the relative reinforcing effects of cigarette smoking. METHODS: Ninety minutes after d-amphetamine (7.5, 15 mg/70 kg) or placebo administration, 13 male and female subjects participated in 3-h sessions during which they could make a maximum of 20 choices between cigarette smoking (two puffs per choice), earning money ($0.25 per choice), or neither. In separate sessions, using the same subjects, the effects of d-amphetamine on the frequency of ad libitum smoking was assessed. RESULTS: During choice sessions, d-amphetamine dose-dependently increased smoking choices from 4.2 +/- 0.6 to 5.7 +/- 0.6. During sessions in which subjects smoked ad libitum, d-amphetamine increased number of cigarettes smoked from 2.8 +/- 0.4 to 3.8 +/- 0.6. Breath carbon monoxide (CO) levels, a measure of smoke exposure, showed corresponding dose-related increases. CONCLUSIONS: These results are consistent with previous findings that d-amphetamine increases smoking and provide evidence that this effect is due to a drug-produced increase in the relative reinforcing effects of cigarette smoking.     

Assessing the senok,sory role of nicotine in cigarette smoking

Thirty-two subjects were tested in five double-blind sessions (16 subjects in the morning following overnight smoking abstention, and 16 in the afternoon following ad-lib smoking). In each session, subjects smoked one of five experimental (EX) cigarettes having the following FTC nicotine/‘tar’ yields in mg: 0.08/8.5, 0.17/9.1, 0.37/9.8, 0.48/9.8, and 0.74/10.4. In a sixth session, subjects smoked a 0.71/8.6 commercial ‘light’ (CL) cigarette that was their usual brand. Before and after smoking, subjects subjectively rated their desire to smoke a cigarette of their usual brand and had blood smaples drawn. Following smoking subjects rated the cigarette on a variety of sensory dimensions; they also rated smoking satisfaction. Analysis of variance indicated that nicotine played an important sensory role for a variety of dimensions related to cigarette taste and sensory impact but not perceived draw. Principal-components analyses indicated that sensory factors were at least as important as nicotine pharmacology (indirectly indexed by the preto post-smoking rise in blood nicotine concentration) when considering smoking’s overall effects on satisfaction, product acceptance, and reduction in desire to smoke. A preliminary version of these data was presented at the International Symposium on Nicotine. The Effects of Nicotine on Biological Systems II, Montreal, July 21–24, 1994. The authors thank Drs. Brad Ingebrethsen, Deborah Pritchard, and two anonymous reviewers for comments on earlier drafts.     

Manipulation of cigarette craving through rapid smoking: efficacy and effects on smoking behavior

Craving is thought to play an important role in maintaining regular smoking patterns in current smokers, and in leading to relapse in smokers attempting to quit. Within the scientific community however, the concept is surrounded by controversy. In an effort to 1) identify interventions that can reliably influence cigarette cravings, and 2) assess the relationship between cigarette craving and smoking behavior, effects of aversive rapid smoking (up to nine cigarettes with puffs taken every 6 s) on self-reported craving and subsequent smoking behavior were compared to effects of self-paced smoking or no smoking. Subjects (n = 14) engaged in a rapid, self-paced or no smoking procedure at the start of three separate sessions. Craving levels, measured repeatedly during the next 3 h of no smoking, were significantly lower after rapid smoking than after either self-paced or no smoking. Measures of subsequent smoking behavior (latency to first cigarette, number of cigarettes, number of puffs) did not differ systematically across conditions. Thus, craving was reliably suppressed by aversive rapid smoking, but craving scores did not predict actual smoking behavior. Received: 2 April 1998/Final version: 7 August 1998     

An investigation of cigarette smoking behavior and nicotine dependence among Chinese opiate addicts

To explore the characteristics of nicotine dependence among Chinese opiate addicts, a survey was conducted among 357 opiate addicts in Drug Detoxification and Rehabilitation Center from 4 different provinces by using a self-designed questionnaire and Fagerström Test for Nicotine Dependence (FTND). Among the 357 opiate addicts, 355 (99.4%) had the history of cigarette smoking and the mean cigarette smoked per day were 19.1, 34.9, 21.5 and 21.5 sticks during the time of before drug taking, addiction phase, abstinence period and after abstinence respectively. Among 347 smokers with FTND score, 67.2% were severe nicotine dependence (FTND score ≥ 7.0). The lower education degree, injection, poly-drug use and 3 or more relapse were dependently associated with the severe nicotine dependence, and the adjusted odds ratio (OR) were 3.8 (1.5–10.0), 2.3 (1.3–4.0), 3.7 (2.1–6.5) and 1.9 (1.1–3.4) respectively. This study exhibited high rate of cigarette smoking in Chinese opiate addicts and the majority had severe nicotine dependence and suggested that a comprehensive intervention of cigarette smoking should be paid attention to during substance abuse treatment in China.     

Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level

Acute administration of mecamylamine, a centrally active nicotinic cholinergic agonist, has been shown to increase amount of smoking as indicated by smoking topography (e.g., puff rate, puff duration), expired carbon monoxide changes, and other inferential measures. In the present study, subjects showed significantly greater increases in plasma nicotine following smoking of two high-nicotine research cigarettes when pretreated with mecamylamine than when pretreated with placebo, even though no significant differences in puff volume or puff number were detected. Interestingly, none of our subjects reported nausea, although some achieved plasma nicotine levels at which nausea would typically be expected. We attribute the observed increases in nicotine intake to compensatory behavior designed to overcome mecamylamine's blocking effects.     

Effects of heroin self-administration on cigarette smoking

Cigarette smoking increased during heroin self-administration in comparison to drug-free and methadone detoxification conditions in eight heroin addicts given naltrexone placebo (P<0.01) and three heroin addicts given buprenorphine placebo. Cigarette smoking was stable across conditions for one subject who did not use heroin during naltrexone blockade of heroin effects. Five subjects smoked significantly more (P<0.01) during the hour following a heroin injection than during the preceding hour, and two subjects in the same group smoked significantly less following a heroin injection (P<0.05). Subjects smoked significantly more during the evening and night when self-administering heroin than during baseline conditions (P<0.05), but subjects did not sleep significantly less during heroin self-administration. The peak of the intercigarette interval distribution remained between 16–30 min during baseline and heroin conditions. However, the increased smoking during heroin use appeared to reflect a higher rate of smoking rather than a generalized increase across intercigarette intervals. These data extend previous findings, that alcohol consumption is associated with increased cigarette smoking, to IV heroin self-administration.     

Acute pharmacodynamic tolerance to the subjective effects of cigarette smoking

A brief feeling state questionnaire was completed before and after each cigarette, over a day of smoking. Feelings of stress/anxiety demonstrated a pattern of repetitive vacilation over the day, with high stress before smoking, reduced stress after smoking, and stress levels increasing again between cigarettes. There was no evidence of acute pharmacodynamic tolerance, with cigarettes leading to altered feelings of anxiety/stress over the whole day of smoking. Self-rated feelings of arousal also demonstrated a pattern of vacilation over the day, with low arousal pre-smoking, increased arousal post-smoking, but arousal levels reducing again between cigarettes. The ANOVA drug × time interaction was significant, with the greatest arousal change following the first cigarette of the day. However, later cigarettes led to similar amounts of arousal change over the rest of day, thus questioning whether acute pharmacodynamic tolerance was occurring. Instead, the heightened arousal response to the first cigarette of the day may reflect the influence of two other factors. Firstly, overnight deprivation, with the first cigarette of the day leading to the greatest increase in plasma nicotine. Secondly, low early-morning arousal with its associated potential for increased arousal. Overall, therefore, there was little indication of acute pharmacodynamic tolerance to the subjective effects of nicotine. Cigarettes were associated with altered feelings of stress and arousal, over the whole day of smoking.     

Influencing cigarette smoking with nicotine antagonists

Antagonists of nicotine have been used in an attempt to resolve the continuing controversy about the role of nicotine as the primary reinforcer in cigarette smoking. Mecamylamine, an antagonist which readily penetrates to the central nervous system, increased the rate of cigarette smoking by about 30% in laboratory tests; this was accompanied by reduced blood pressure, impaired performance of a digit symbol substitution test, improved hand steadiness, and by dysphoria. The increased smoking may be regarded as self-titration with nicotine, an interpretation which receives some support from results obtained with pentolinium, an antagonist with predominantly peripheral actions. In the doses used, pentolinium did not affect smoking rate, blood pressure, or hand steadiness, but it impaired digit symbol performance and induced dysphoria. The different results with mecamylamine and pentolinium support previous evidence that the action of nicotine in the central nervous system has a small but clearly demonstrable role as a primary reinforcer of the smoking habit.A preliminary account of this work has appeared previously (Jarvik, in press).     

Effects of exercise on craving and cigarette smoking in the human laboratory

Exercise is increasingly being pursued as a treatment to reduce cigarette smoking. The efficacy of clinical, exercise-based cessation interventions may be enhanced by conducting laboratory studies to determine maximally effective conditions for reducing smoking, and the mechanisms through which the effects on smoking are achieved. The main purpose of this study was to assess whether the effects of exercise on two components of craving (anticipated reward from smoking, anticipated relief from withdrawal) mediated the relationship between exercise and delay (in min) to ad libitum smoking. Experiment 1 (N = 21) assessed the effects of exercise intensity (inactivity, low, moderate) on craving components up to 60 min post-exercise. Because moderate-intensity exercise most effectively reduced craving on the reward component, all participants exercised at a moderate intensity in Experiment 2. Using an ABAB within-subjects design, Experiment 2 (N = 20) evaluated whether the effects of moderate-intensity exercise on reward and relief components of craving mediated the relationship between exercise and participants' delays (in min) to ad libitum smoking. Delays were significantly longer after exercise (M = 21 min) versus inactivity (M = 4 min), and the effects of exercise on delay were mediated through the reward component of craving. Future research should continue to explore the mechanisms through which exercise influences behavioral indices of smoking in the human laboratory. Additionally, given the benefits uniquely afforded by exercise-based cessation interventions (e.g., improving mood and other health outcomes), implementing these interventions in clinical settings may contribute substantially to improving public health.     

Effect of cigarette smoking on prepulse inhibition of the acoustic startle reflex in healthy male smokers

The present study investigated the effects of cigarette smoking on prepulse inhibition (PPI) of the acoustic startle reflex in healthy men. Cigarette smoking in a group of overnight smoking-deprived smokers increased PPI as compared to the smoking-deprived condition. This finding is consistent with previous animal studies showing that nicotine increases PPI of the acoustic startle reflex. In addition, cigarette smoking also reduced startle amplitude during the first 6–7 min of the post-smoking session. Received: 4 March 1996 / Final version: 17 June 1996     

Effects of response requirement and the availability of an alternative reinforcer on cigarette smoking by schizophrenics

Cigarette smoking and other forms of drug abuse are more prevalent among schizophrenics than the general population. Despite the clinical importance of this problem, there has been relatively little experimental study of schizophrenic drug use. We examined under controlled laboratory conditions the effects of response requirement and the availability of an alternative (monetary) reinforcer on cigarette smoking by schizophrenics. Subjects were six heavy smokers with diagnoses of schizophrenia or schizoaffective disorder. Before each session, subjects provided carbon monoxide samples indicating recent smoking abstinence. During 3-h sessions, subjects obtained opportunities to smoke (2 puffs/opportunity) under a fixed ratio (FR) schedule of reinforcement, which varied across sessions from FR50 to FR6400. In half of the sessions, subjects also were able to earn a small amount of money ($0.25/ratio completed) under an FR400 schedule. Increasing the response requirement for smoking decreased smoking and increased smoking-maintained responding. The availability of the monetary reinforcer decreased smoking and smoking-maintained responding by approximately half. These results are consistent with those seen previously in community volunteers without major mental illness studied under the same experimental conditions, suggesting that smoking by these two populations is controlled, at least in part, by a common set of determinants. Received: 20 April 1998/Final version: 20 January 1999     

The effects of cigarette smoking on overnight performance

Fifteen healthy smokers and 15 non-smokers were enrolled into this study investigating the effects of smoking on overnight performance. Subjects arrived at the test centre at 1930 hours and were assessed at baseline (2000 hours) and at 2200, 0000, 0200, 0400, 0600, and 0800 hours on a battery of tests (including Critical Flicker Fusion, CFF; Choice Reaction Time, CRT; Compensatory Tracking Task, CTT; Short Term Memory Task, STM; and the Line Analogue Rating Scale, LARS). Results showed that the performance of the smokers was more consistent with baseline measures than that of the non-smokers, which became more impaired throughout the night on a number of tasks [CFF (P < 0.005), Total Reaction Time (TRT, P < 0.05), CTT (P < 0.05) and the Reaction Time (RT) aspect of the CTT task (P < 0.0005)]. The Recognition Reaction Time (RRT) aspect of the CRT task showed that the performance of the non-smokers became more impaired from baseline (P < 0.005), while that of the smokers remained at baseline levels until 0400 hours, when it deteriorated to become comparable to that of the non-smoking controls. Subjective sedation ratings (LARS) resulted in comparable levels of impairment for both study groups (P < 0.00005). Findings from the STM task failed to reach significance. These data suggest that when performance is being measured overnight, smokers show little or no impairment, whilst the performance of non-smokers showed performance decrements. Received: 29 May 1997/Final version: 22 September 1997     

抽烟对异丙酚有效靶浓度的影响

目的:观察抽烟对异丙酚有效靶浓度的影响。方法:选择择期在全麻下行上腹部手术的男患者50例,其中抽烟患者24例为A组,非抽烟患者26例为B组,在BIS监测下观察两组患者在插管前、插管后、切皮前、切皮后、术中探查、术毕时的异丙酚效应靶浓度、心率和平均动脉压。结果:两组患者的一般情况比较差异无显著性(P>0.05)。除切皮前,抽烟患者的异丙酚有效靶浓度均较非抽烟患者高(P<0.01或P<0.05),而其它各时间点的血流动力学指标无差异(P>0.05)。结论:长期抽烟使患者手术时对异丙酚的反应性降低,效应室有效靶浓度明显高于非抽烟患者,而对手术期间血流动力学无明显影响。     

Nil effect of cigarette smoking on ranitidine pharmacokinetics

Ranitidine (150 mg) was administered to smoking and non-smoking healthy male volunteers. Statistical analysis on the calculated pharmacokinetics parameters showed that the differences were insignificant.     

No effect of cigarette smoking on electroencephalographic nonlinearity

The Gaussian surrogate-date procedure was applied to the measurement of the effect of cigarette smoking on the dimensional complexity of normal, resting EEG. Evidence of significant nonlinearity in the EEG was obtained, replicating previous results. However, unlike EEG dimensional complexity, EEG nonlinearity (difference between original and surrogate data) was not affected by smoking. This indicates that, under resting conditions, smoking/nicotine may have a modulating effect on input from the reticular activating system, with such input having a global, linearizing effect on cortical dynamics. Nonlinear dynamics resulting from intracortical processes appear not to be affected.