Effects of a nicotine-enriched cigarette on nicotine titration,daily cigarette consumption,and levels of carbon monoxide,cotinine, and nicotine

To test whether cigarettes with low tar, low carbon monoxide, and medium nicotine yield produce less dangerous effects than cigarettes low in tar and CO but high in nicotine, 12 subjects were recruited to smoke nicotine-enriched cigarettes. The subjects smoked three types of cigarettes in the three experimental conditions: (1) their own brand; (2) cigarettes with 4.8 mg tar, 4.0mg CO, and 0.5 mg nicotine; (3) cigarettes with 5.8 mg tar, 4.1 mg CO, and 1.1 mg nicotine. Subjects monitored their daily consumption for 12 weeks; 4 weeks for each condition. During laboratory visits, the subjects smoked a cigarette while their heart rate and carbon monoxide in expired air were measured pre- and post-smoking. A blood sample was drawn and analyzed for nicotine and cotinine in each experimental condition. No significant differences in daily cigarette consumption were found, although a trend (P<0.07) in the direction of fewer nicotine-enriched cigarettes per day was found. Levels of CO varied significantly among the three conditions: The subjects' own brands yielded the highest level, while the nicotine-enriched cigarette yielded the lowest level. No differences were found for nicotine or cotinine levels. A second purpose of the experiment was to record the degree of nicotine titration displayed by individual smokers, tar and CO levels remained constant in the experimental cigarettes. No general titration effect was observed, although for daily consumption it approached significance. When the subjects' nicotine dependence, measured with a tolerance questionnaire, was taken into acount, a correlation with daily consumption was found (r=77, P<0.005). A cigarette with low tar and CO, but medium to high nicotine yield, would seem to produce less hazardous effects and is worthy of further investigation. The controversial question of whether smokers titrate for nicotine is a function of the individual's nicotine dependence.     

Effects of cigarette smoking on time estimation

Time estimation was measured in 33 heavy smokers, 34 non-smokers and 23 ex-smokers over two experimental sessions. All smokers abstained from smoking for 30 min prior to each session. Half of the smokers smoked a cigarette prior to time estimation measurement in the first session, whereas the remaining smokers smoked in the second one. Non-smokers and ex-smokers did not smoke. Results combined across the two sessions indicated no differences between smoking versus non-smoking conditions. However, a specific pattern of responses appeared in each experimental session. Separate analyses of results from each session revealed that, in the first session, smokers that smoked overestimated time in comparison with abstinent smokers, non-smokers and ex-smokers. In contrast, results of the second session showed no significant effects of smoking or abstinence. These results indicate that the effects of nicotine on time perception can be influenced by the repetition of the task and by the experimental situation. Data suggest that there may exist an interaction between the order of treatment (smoking versus non-smoking) and time estimation. Copyright © 1998 John Wiley & Sons, Ltd.     

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     

Nicotine and cotinine replacement when nicotine nasal spray is used to quit smoking

Nicotine nasal spray (NNS) is generally considered to be an effective smoking cessation aid, but all studies to date of NNS effectiveness have also utilized group therapy sessions or frequent laboratory visits to support their subjects’ stop smoking efforts. We studied 50 volunteers before they attempted to quit smoking and again at 1, 2 and 3 months after they received NNS to assist them in quitting smoking. No other stop smoking intervention was used, which more closely mimics the common practice of many individuals trying to stop smoking with the aid of a nicotine replacement product but without other supportive interventions. We found that 50% of the subjects quit smoking for the first month, 34% were still abstinent after 2 months and 32% quit smoking for 3 months. Those who quit smoking for the entire 3 months and who continued regular NNS use throughout had 67% cotinine replacement at the end of the first month, while another group which quit smoking for only the first month with the aid of NNS had 42% cotinine replacement at the end of that month. Our data confirm that NNS is an effective smoking cessation aid, but our abstinent rate at 3 months is slightly lower than in other studies in which group therapy was provided. Our data also indicate that higher NNS-induced cotinine replacement during the first month of quitting smoking (suggesting more frequent use of NNS) is associated with longer term quit-smoking success rate. Received: 4 June 1997/Final version: 19 December 1997     

Long-term nicotine substitution after application of a 16-hour nicotine patch in smoking cessation

Summary The purpose of the study was to examine long-term nicotine substitution and its variability during use of a nicotine patch. In two smoking cessation studies a 16-h nicotine patch, releasing 15 mg nicotine, was applied daily for 16 h over 12 weeks, to 167 smokers. Salivary cotinine was highly correlated with plasma cotinine (r = 0.93), and the concentration of cotinine in a single sample in the afternoon was well correlated with the AUC_cotinine over 24 h (r = 0.94). The salivary cotinine concentration after 1 week in 60 abstainers was 183 ng · ml^–. After 3, 6 and 12 weeks the cotinine concentrations were 86%, 79% and 59% of the 1-week value. The degree of nicotine compensation attained by the patch after 1 week was 52% (SD 24%) in subjects who succeeded in stopping smoking for at least 3 weeks. A quarter of the subjects achieved a compensation of less than 35% of their usual nicotine intake. Nicotine substitution with this 16-h nicotine patch was stable and the risk of overcompensation was small in this group of smokers.     

Determinants of plasma concentrations of nicotine and cotinine during cigarette smoking and transdermal nicotine treatment

Objective: Interindividual variability in plasma concentrations of nicotine and its proximate metabolite, cotinine, is considerable during smoking and transdermal nicotine treatment, even among individuals taking in nominally similar doses of nicotine. This report explores the determinants of this variability and the utility of baseline (smoking) plasma concentrations to predict concentrations during transdermal nicotine treatment. Methods: Data were analysed from a smoking cessation study (n = 466), and from a pharmacokinetic study (n = 12). Multiple regression models examined the relationships of plasma concentrations to individual characteristics such as smoking pattern, absorbed dose of nicotine, and pharmacokinetic parameters. Results: Plasma concentrations of nicotine and cotinine were highly variable in both studies. Indirect estimates of plasma clearance (baseline plasma concentration divided by cigarettes per day) together with other factors could account for 18 to 33% of the variability during transdermal nicotine treatment in the smoking cessation study. In contrast, 75 to 99% was accounted for by direct measurements of plasma clearances and systemic dose of nicotine in the pharmacokinetic study. Conclusion: Plasma concentrations of nicotine and cotinine during transdermal nicotine treatment are poorly predicted by clinical history or baseline plasma concentrations. This is a result of inadequate characterisation of highly variable individual pharmacokinetic parameters and absorbed dose of nicotine. Considering the interindividual variability of plasma nicotine and cotinine concentrations together with the lack of clinical end-points for transdermal nicotine dosing, it seems logical to investigate the utility of a therapeutic drug monitoring approach for transdermal nicotine treatment – particularly for high dose regimens (> 22 mg per 24 hours). Received: 7 May 1996 / Accepted in revised form: 21 August 1996     

香烟中的尼古丁对吸烟行为的影响

长期吸烟可引起多种身体疾病,香烟的广泛使用严重危害了公众的健康。早期香烟相关研究的关注点在焦油上,它是香烟的主要有害物质,但研究表明减少焦油的轻型香烟并没有达到减少危害的效果。近期研究逐渐把关注点放到了吸烟的成瘾性上,也就是香烟中的尼古丁。尼古丁通过影响大脑神经化学的复杂作用建立和维持烟草成瘾,长期使用会导致生理和心理依赖。许多研究分别采用逐级降低和立即降低香烟中的尼古丁含量的方式,也有一部分研究以调整香烟尺寸的方式即细支烟,来研究香烟中的尼古丁含量对改变吸烟行为的作用,进而达到减少危害的目的。     

Lack of effect of cimetidine on cigarette smoking

Summary The efficacy of cimetidine as a treatment that could reduce smoking in heavily dependent smokers has been determined. In a randomised, double-blind, double-crossover experiment, 43 heavy smokers were divided into two groups, one receiving cimetidine 400 mg orally three times a day, and the other receiving placebo for two weeks followed by the alternative treatment (placebo or cimetidine).No significant difference in the mean alveolar carbon monoxide, nicotine or cotinine levels was found between the two treatment groups compared to baseline. Since the alveolar carbon monoxide level reflects the intensity of smoking behaviour, the results suggest that no change in smoking behaviour occurred in the subjects.Contrary to our previous findings that cimetidine decreased the total body clearance of nicotine by 30% in a population of non-smokers, in the heavily dependent smokers, cimetidine did not appear to alter nicotine elimination. One possible explanation for the discrepancy is that tobacco smoking is known to induce nicotine metabolism and the induction might have offset any effect of cimetidine on nicotine elimination.Cimetidine does not appear to be a useful treatment leading to a reduction or cessation of cigarette smoking.     

Effects of smoking abstinence and nicotine abstinence on heart rate,activity and cigarette craving under field conditions

In a field study heart rate, activity, cigarette consumption, craving for cigarettes, saliva cotinine and subjective ratings were assessed in 12 female subjects, smoking medium tar/medium nicotine cigarettes (TN). The habituated cigarettes were compared with a nearly nicotine-free/medium tar (0·08 mg/9·3 mg) cigarette ( Tn ) and with abstinence. Two recording periods of 3 days each were conducted in two consecutive weeks. Heart rate was highest with the Tn cigarettes, 8 bpm lower on abstinence days and in between with the Tn cigarettes. A characteristic increase in heart rate and activity before cigarette lighting appeared with the TN and the Tn cigarettes and with button pressing indicating smoking desire on abstinence days. This response is attributed to an anticipative activation preceding lighting a cigarette. Subjective ratings assessing the craving to smoke differed between abstinence and the smoking condition but not between the two cigarette types, whereas saliva cotinine was significantly higher with the TN than with the Tn cigarettes or abstinence. Cigarette consumption was similar with both cigarette types, but taste and strength were rated better for the TN than the Tn cigarettes. It is concluded that heart rate and saliva cotinine depend on the amount of nicotine absorbed, whereas subjective craving is reduced by smoking independently of the actual nicotine yield of the cigarette.     

Effects of ventilated cigarette holders on cigarette smoking by humans

Heavy cigarette smokers individually attended daily 3-h test sessions which were run in specially designed cigarette smoking evaluation rooms. Subjects were required to use the cigarette holder provided, and were required to extinguish each cigarette 4 min after the first puff on the cigarette. Other than these restrictions, subjects were allowed to smoke ad libitum. The concentration of delivered tobacco product was varied from 100 to 10% across sessions by using graded commercially available ventilated cigarette holders. As concentration of tobacco product was decreased, rate of puffing and total number of puffs showed robust compensatory increases. Number of cigarettes increased only moderately in response to decreases in tobacco product concentration. There was little change in subjective ratings of strength on smoking satisfaction. Finally, expired air carbon monoxide (CO) values and cigarette butt weights were relatively stable across the four ventilation conditions. These later findings suggest that a significant degree of compensation had occurred in response to the concentration manipulations.     

Evaluation of a low to middle tar/medium nicotine cigarette designed to maintain nicotine delivery to the smoker

A specific objective of this 6-week crossover study was to determine how 21 regular smokers of middle tar cigarettes changed their smoking behaviour and uptake of smoke constituents, when switching to either lower tar cigarettes capable of delivering amounts of nicotine similar to a conventional middle tar cigarette (maintained nicotine product), or to conventional low tar/low nicotine cigarettes. Subjects visited the laboratory every 2 weeks for detailed assessment of their smoking behaviour. Weekly per capita consumption was similar for all three cigarettes. They were smoked with variable intensities (low tar > maintained nicotine > middle tar), the tendency being for larger puff volumes, faster puffing and increased puff duration with the low tar cigarettes. The maintained nicotine cigarette was preferred to the middle tar cigarette, although acceptability ratings of the three cigarettes only differed marginally. The nicotine absorbed from the maintained nicotine and middle tar cigarettes was similar and significantly greater than the levels achieved from the low tar cigarettes. Intake of carbon monoxide into the mouth and absorption into the blood stream was lower for the maintained nicotine cigarette than for the middle tar cigarette, with the low tar cigarette occupying an intermediate position. Derived estimates of tar intake suggested reduced intake of tar into the respiratory tract (around 25%) from the maintained nicotine product relative to the middle tar product. The possible advantages of switching to maintained nicotine cigarettes is discussed.     

Effects of cotinine on cigarette self-administration

Previous studies have shown that cotinine, a metabolite of nicotine, antagonizes some of the effects of nicotine. One study showed that cotinine eliminates the beneficial effects of the nicotine patch in reducing cigarette withdrawal symptoms. The purpose of this study was to examine the effects of various doses of cotinine on cigarette self-administration. Subjects were randomly assigned to one of three doses of cotinine fumarate (40, 80 and 160 mg) and placebo, each for a period of 10 days, in a randomized order. Outcome variables included measures of nicotine intake and subjective responses to smoked cigarettes. Results showed no differences in the number of cigarettes smoked, carbon monoxide levels, and weights of cigarette butts across the various doses of cotinine and placebo. However, higher nicotine serum levels were observed in the 160 mg cotinine fumarate condition compared to placebo and to 40 mg cotinine fumarate. No systematic effects of cotinine on subjective responses to cigarettes were observed. Cotinine appears potentially to have a selective modulatory effect on nicotine withdrawal symptoms but not on cigarette smoking. Received: 2 September 1997 / Final version: 30 December 1997     

一种测定香烟烟气或尼古丁气雾环境中大鼠体内尼古丁摄入量的简单方法

目的：探讨大鼠暴露于香烟烟气或尼古丁雾化环境中，体内尼古丁实际摄入量的测定方法。方法：考察氰化钾-巴比妥酸法测定尿中尼古丁代谢产物柯廷宁的可靠性。给大鼠缓慢恒速静脉输注不同浓度的尼古丁溶液1h，作为大鼠体内摄入尼古丁量的参照，收集大鼠60h的全部尿液并测定柯廷宁（cotinine）含量作为尼古丁的排出量，两者之间建立标准曲线。将大鼠置于香烟烟气或尼古丁气雾暴露箱中1h，收集大鼠60h的全部尿液并测定柯廷宁含量，根据建立的标准曲线推算大鼠体内尼古丁的实际摄入量。结果：给大鼠缓慢恒速输注不同浓度的尼古丁溶液和大鼠的柯廷宁排出量之间有良好的线性关系，能够根据柯廷宁的排出量推算尼古丁的摄入量。结论：用氰化钾-巴比妥法测定柯廷宁尿中含量能达到药物代谢技术要求。     

Cigarette nicotine content as a determinant of human smoking behavior

Summary Measures of smoking rate and psychological effects of cigarettes with varying nicotine content were made in 15 subjects. While subjects did perceive differences in strength and quality of the experimental lettuce cigarettes as compared to their own brands, their smoking rates did not decrease differentially over the nicotine gradient. The decrement in smoking due to the experimental cigarettes persisted when subjects resumed smoking their own cigarettes. However, the smoking that did occur in the absence of both tobacco and nicotine indicates that the habit itself often exhibits functional autonomy from the physiological effects of nicotine.     

The effect of smoking/nicotine on response selection

Nicotine taken by ad lib smoking or other routes of administration has been reported to shorten reaction time (RT) in many cognitive tasks. Most of these tasks have used visually presented stimuli and require a simple motor response such as a button press. The reliance on this type of RT task makes it difficult to determine the specific stage(s) affected by smoking/nicotine. Event‐related potential studies indicate that visual perceptual processing is faster after smoking/nicotine. However, recent studies indicated that the magnitude of this enhancement is not sufficient to explain the total improvement in RT performance due to smoking/nicotine. These studies suggest that a significant performance‐enhancement effect may occur after the decision or classification of stimuli is completed. The next logical step in the information processing chain is response selection. We examined the effect of smoking/nicotine on response selection in a stimulus‐response compatibility task. In this double‐blind study, easy response‐selection RTs were facilitated by smoking/nicotine but difficult response‐selection RTs were not. Copyright © 1999 John Wiley & Sons, Ltd.     

Effects of graded smoke inhalation on subsequent cigarette smoking behavior

Five smokers smoked a cigarette ad libitum one minute after inhaling either 0, 2, 4, 8 or 12 puffs of tobacco smoke according to a standardized smoking regimen. Heart rate and expired air carbon monoxide levels increased in a linear manner with increasing number of pretreatment puffs. Subjects took fewer puffs on, and spent less time smoking, and puffing on, the cigarette as the number of pretreatment puffs increased. The duration of individual puffs decreased with successive puffs as the cigarette was smoked, but was not affected by the puff pretreatments. Intervals between successive puffs (interpuff intervals) generally increased over the first half, and leveled off or decreased over the second half of the cigarette. Interpuff intervals occurring early in the cigarette tended to increase after the 12-puff pretreatment. The results are consistent with the suggestion that the observed increase in interpuff interval as a cigarette is smoked is the result of a satiation process.     

Relative effects of nicotine and coffee on cigarette smoking

The relative influence of nicotine and coffee on cigarette consumption was examined in a laboratory setting. During the first half hour of the experimental session, subjects were either preloaded with two cigarettes or nicotine deprived. During the subsequent hour, subjects were given two cups of either coffee or water, and number of cigarettes smoked during this period was assessed. Results showed a significant preload effect, with non-preloaded subjects smoking an average of .88 cigarettes per hour more than preloaded subjects. A nonsignificant increase in smoking was found for the coffee condition. The implications of these findings for relative effects of pharmacological and environmental events on smoking are discussed.     

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.     

Effects of smoking different doses of nicotine on human aggressive behavior

A new methodology was employed to study the effects of drugs on human aggressive behavior in a laboratory situation. The effects of not smoking, smoking a low nicotine dose (0.42 mg/cigarette), and smoking a high nicotine dose (2.19 mg/cigarette) on human nonaggressive and aggressive responding was determined. A nonaggressive response, which resulted in the accumulation of money, was continuously available to the subject. Two different aggressive responses were also available: the ostensible subtraction of money from, and the ostensible presentation of a 1-s blast of white noise to a (fictitious) person. Aggressive responding was elicited by subtracting money from the research subjects, which was attributed to a fictitious person paired with the research subject randomly each day. Nicotine, administered with experimental cigarettes, produced dose-dependent decreases in both types of aggressive responding elicited by low or high frequency subtractions of money attributed to another person. Generally, the more aggressive response option, i.e., subtraction of money from another person, decreased more following nicotine administration. Smoking the same doses of nicotine increased nonaggressive monetary reinforced responding. This indicates that the suppressant effect of nicotine on aggressive responding was not due to a nonspecific depressant action.Portions of these data have been previously reported at a regional meeting of the International Society for Research on Aggression held in Boston, MA, in August, 1981.