Sensory blockade of smoking satisfaction

Cigarette smokers were presented with controlled doses of cigarette smoke to determine whether the resulting reduction in cigarette craving depended upon perceiving the sensory qualities of the smoke. Cigarette craving was assessed before and after inhaling controlled doses of smoke in two conditions: (1) Local anesthesia of the upper and lower respiratory airways, induced by mouth rinsing, gargling and inhalation of a mist containing the topical anesthetic lidocaine; and (2) no-anesthesia control, in which all solutions were saline. A sham smoking procedure was presented in both conditions. Craving and ad lib smoking behavior were also assessed 30 minutes after controlled smoking. The results indicated that smoke, as opposed to sham puffs, significantly reduced reports of cigarette craving, and local anesthesia significantly blocked this immediate reduction in craving produced by smoke inhalation. Puffs were also rated as less desirable in the anesthesia condition. Thirty minutes after smoking, craving was no different in the anesthesia and saline control conditions. However, craving as well as smoking intake in both conditions was less when smoke had been given previously than in the sham smoking control. These results suggest that sensory cues accompanying inhalation of cigarette smoke are important determinants of immediate smoking satisfaction. However, the sustained effects of smoke intake on subsequent smoking behavior (30 min later) may be mediated by processes other than sensory stimulation of the respiratory tract, such as plasma nicotine levels.     

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     

Deprivation state but not nicotine content of the cigarette affects responding by smokers on a progressive ratio task

In two experiments, we used a progressive ratio schedule to explore factors associated with smoking motivation. In study 1, smokers who had abstained for more than 8 h bar-pressed for longer to obtain puffs on a cigarette than did non-deprived smokers. Neither group, however, showed nicotine-induced improvements in performance on an attention-demanding task. In the second study, two groups of minimally deprived smokers worked on the progressive ratio task for puffs of either a standard or an ultralow nicotine cigarette. The amount of work expended for puffs was the same for both cigarettes. The groups were also indistinguishable in terms of their subjective experience of the impact of smoking. These results suggest that the addition of nicotine to the cigarette may not have an immediate impact on the effort expended for a puff on that cigarette, and that short term changes in craving may be observed independent of satiety effects associated with nicotine ingestion. We conclude that the progressive ratio task is a useful and sensitive measure of desire to smoke, although the two experiments highlight the complexity of the relationship between subjective, objective and behavioural measures of smoking and nicotine ingestion in humans. Received: 14 October 1997/Final version: 18 May 1998     

Smoking environment cues reduce ability to resist smoking as measured by a delay to smoking task

Introduction: Environments associated with smoking may promote lapse and relapse in smokers attempting to quit. Here we examined the effects of exposure to visual smoking environment cues on smoking urge and the ability to resist smoking, as measured with a delay-to-smoking task in which monetary contingencies are provided for resisting smoking. Methods: Adult daily smokers (n = 22) completed two experimental sessions, each following 6 h smoking abstinence. Sessions differed only in the type of cue participants were exposed to (smoking environments vs. nonsmoking environments). Participants completed subjective ratings of smoking urge, withdrawal and other reactions (i.e. craving, affect). Behavioral outcomes on the delay-to-smoking task included latency to first cigarette, number of cigarettes smoked and average number of puffs per cigarette. Results: Across cue exposure sessions, 64% of participants initiated smoking (no effect of condition was observed). However, exposure to smoking environments as compared to the nonsmoking environments resulted in greater craving, faster initiation of smoking, and more smoked cigarettes. Greater craving was associated with a shorter time to initiate smoking, but this effect did not differ across sessions. In contrast, withdrawal was more strongly associated with number of cigarettes smoked during smoking environment sessions. Conclusion: Together, these results suggest smoking environments increase smoking urge and promote smoking behavior. Further research is necessary to examine the specific and interactive effects of smoking-related environments on real-world smoking lapse and relapse.     

Little evidence that “denicotinized” menthol cigarettes have pharmacological effects: an EEG/heart-rate/subjective-response study

Rationale: A substantial portion of cigarette smokers prefer menthol-flavored cigarettes. To date, however, no studies have examined whether menthol in cigarettes has central pharmacological effects. Objective: We investigated psychophysiological and subjective effects of smoking menthol versus non-menthol cigarettes in both menthol and non-menthol smokers. To assess these effects independently of the immediate effects of nicotine, all cigarettes employed were “denicotinized” (FTC nicotine yield = 0.06 mg). Methods: The psychophysiological measures were EEG and heart rate (HR). The subjective measures assessed mental alertness, muscular relaxation, anxiety/nervousness, and how much a participant wanted to smoke one of his usual brand of cigarettes. Menthol and non-menthol smokers participated in a single session in which each participant smoked both a menthol and a non-menthol denicotinized cigarette (order balanced across participants). The psychophysiological and subjective measures were recorded before and after smoking each cigarette. Results: Out of 48 F-ratios spanning 22 analyses of variance involving the critical interaction between pre-/post-smoking and menthol/non-menthol cigarette, only one unambiguously fit a “pharmacological” pattern, a result indistinguishable from a type-I statistical error. We report evidence that menthol smokers may be chronically less aroused and more sensitive to the effects of nicotine than non-menthol smokers. Conclusions: We found little evidence that menthol in cigarettes has central pharmacological effects. Received: 27 July 1998/Final version: 26 October 1998     

U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking

Rationale: The role of endogenous opiate systems in cigarette smoking remains unclear. In laboratory animals, opiate antagonists block many of the effects of nicotine, but in humans they do not consistently alter smoking behavior. Objective: This study explored the effects of naltrexone, alone and in combination with nicotine, on smoking behavior. Methods: In a double-blind, double-dummy, within-subjects design, 19 regular smokers received four treatments of 1 week duration: naltrexone tablet (50 mg) plus placebo skin patch, placebo tablet plus nicotine skin patch (21 mg/24 h), naltrexone tablet plus nicotine skin patch, and placebo tablet plus placebo skin patch. During each treatment, subjects rated their responses to nicotine-containing and denicotinized cigarettes in the laboratory, and to their own brand of cigarette smoked ad libitum outside the laboratory. Results: Pretreatment with the nicotine patch attenuated smoking-induced decreases in craving, negative affect, and rates of ad lib smoking, and potentiated the aversiveness of a cigarette. Naltrexone reversed these effects of the nicotine patch, and produced negative effects on mood. Conclusions: The blockade of nicotine’s effects by naltrexone supports a role for opioid mechanisms in cigarette smoking. Received: 9 October 1997/Final version: 3 December 1998     

Sex differences in the influence of nicotine dose instructions on the reinforcing and self-reported rewarding effects of smoking

Rationale Compared to men, the smoking behavior of women may be less responsive to nicotine and more responsive to nonpharmacological factors, perhaps including verbal information (e.g., dose instructions). Objective This study compared the influence of the presence vs absence of dose instructions on the subjective and reinforcing effects of nicotine via cigarette smoking in men and women. Methods Subjects (n=120) abstained overnight from smoking and were randomly assigned to one of four groups. Half of the subjects received nicotine cigarettes (Quest 1, yield of 0.6 mg), and the other half received denicotinized cigarettes (“denic”; Quest 3, yield of 0.05 mg). Furthermore, half of each subsample was accurately instructed they were receiving a “normal nicotine” or a “no nicotine” cigarette, while the other half received no instructions. Subjects completed baseline measures of craving and mood (positive and negative affect), took two puffs from the cigarette after receiving dose instructions or no instructions, and then rated the cigarette's “reward” value (liking, satisfying) and other characteristics. They also repeated the craving and mood measures. Subjects then smoked more of that same brand ad libitum over the next 30 min to measure reinforcement (puff number and latency to first puff). Results Overall, nicotine increased reward, other cigarette ratings, and positive affect, but did not affect craving or smoking behavior. However, results varied by sex. Dose instructions enhanced the effects of nicotine on smoking reward and reinforcement in women, while instructions tended to dampen or even reverse these effects of nicotine in men (i.e., interaction of sex×nicotine×instructions). Conclusions In women but not in men, the influence of nicotine on smoking reward and reinforcement is enhanced by accurate verbal information about the cigarette's nicotine dose. These results are consistent with the notion that the smoking behavior of women, relative to men, may be more responsive to nonpharmacological factors.     

Acute psychomotor,subjective and physiological responses to smoking in depressed outpatient smokers and matched controls

Rationale Cigarette smoking is highly prevalent in people diagnosed with depression, and depressed smokers are less likely to quit. Examining depressed smokers’ responses to smoking will help determine the role of depression in maintaining cigarette smoking. Objectives To determine the psychomotor, subjective and physiological effects of cigarette smoking in currently depressed smokers versus matched controls. Materials and methods Fourteen currently depressed smokers and 14 never-depressed smokers, matched in age, gender, nicotine dependence and daily cigarette consumption, smoked three cigarettes at half-hourly intervals. All smokers were non-deprived. Self-reported mood and craving for cigarettes, performance on a simple reaction time task, expired-air carbon monoxide, heart rate and blood pressure were assessed before and after smoking each cigarette. Smoking topography was also assessed. Results Depressives and controls did not differ in terms of dependence on cigarettes or expired-air carbon monoxide. Topographic and cardiovascular measures were similar in depressed and control participants, suggesting that they smoke cigarettes in a similar manner. However, depressives displayed enhanced reaction time performance after the first cigarette. Positively reinforced craving was reduced after smoking each cigarette but returned to baseline levels within 30 min in depressed but not in control smokers. Depressed smokers also displayed higher levels of negatively reinforced craving. Both depressives and controls reported improved positive mood after smoking. Conclusions Cigarette smoking in non-deprived depressed smokers enhances psychomotor performance and the reduction of positively reinforced craving in depressed smokers after smoking is transient, suggesting that enhanced craving may play a role in the maintenance of smoking in depression.     

Peer modeling effects in the smoking behavior of teenagers

Modeling influences on adolescent smoking behavior were investigated. Twenty-eight male and twenty-eight female teenagers were exposed to each of three experimental conditions: a male smoking confederate, a female smoking confederate, and no model present. The order of each of these half-hour long conditions was counterbalanced across subjects. Three aspects of smoking behavior were directly observed: number of cigarettes smoked, number of puffs per cigarette, and duration of each cigarette. The presence of a smoking model increased the number of people who smoked and the number of cigarettes smoked and decreased the number of puffs per cigarette. The sex of the model did not affect the smoking behavior of either male or female subjects. Boys tended to smoke more cigarettes than girls (p < .06) and boys took significantly more puffs per cigarette than did girls in the model present conditions. The results provide experimental confirmation that modeling influences teenagers' smoking behavior, but the rate of smoking in the absence of a model demonstrates that modeling effects cannot account for the maintenance of smoking.     

Mecamylamine does not precipitate withdrawal in cigarette smokers

Mecamylamine is an antihypertensive that acts via nicotinic antagonism and has been suggested as an aid in smoking cessation. Nicotine dependent patients may not accept mecamylamine if it precipitates withdrawal, as it does in nicotine dependent rats. This study examined mecamylamine’s effects using procedures designed to measure precipitated withdrawal symptoms in humans. Ten cigarette smokers (mean of 37.5 cigarettes/day) and ten non tobacco-using subjects participated in three 6-h sessions. After a 2-h baseline period in which smokers smoked one cigarette every 30 min, oral mecamylamine (0, 10, or 20 mg randomly ordered across sessions) was administered (double-blind). No smoking was allowed for the remainder of the session. Mecamylamine reduced blood pressure and increased heart rate relative to placebo in both the smokers and the non-tobacco users. No reliable direct subjective effects of mecamylamine were observed. Smokers’ subjective reports of cigarette craving and tobacco withdrawal increased, and DSST performance was disrupted over the last 4 h of each session. Effects were independent of dose (placebo versus active). These results suggest that up to 20 mg mecamylamine will not precipitate nicotine withdrawal and that this medication would be acceptable for use in smoking cessation. Received: 20 April 1996/Final version: 3 June 1996     

Social interaction and smoking topography in heavy and light smokers.

The effects of social interaction on the topography of smoking behavior of heavy and light cigarette smokers was investigated. Smoking behavior was analyzed via closed circuit television monitoring during periods of informal interpersonal conversation and periods of isolation. Number of cigarettes smoked, number of puffs, cigarette duration, interpuff interval, puff duration, percent of tobacco burned, time with cigarette in mouth, and time with cigarette in hand were analyzed. Heavy and light smokers were affected differentially by the social conditions. Light smokers took more frequent and longer puffs when smoking alone with social interaction functioning to decrease the total amount of smoke inhaled. Heavy smokers were unaffected by the social conditions.     

Effects of cigarette nicotine content on smoking behavior of baboons

Human cigarette smokers modify the way in which they smoke cigarettes of differing nicotine content, apparently to maintain nicotine exposure at a preferred level. The effects of changing from moderate to high or low nicotine content cigarettes were examined in 11 baboons (superspecies Papio cynocephalus) trained to smoke cigarettes for water rewards. Relative to the moderate nicotine content cigarette, the animals took significantly (p < .05) more puffs on the high nicotine content cigarette, and the puffs on the high nicotine cigarette were significantly larger in volume. The animals made the same number of puffs, relative to the moderate nicotine content cigarette, on the low nicotine content cigarette, but the volume of the puffs was significantly smaller. The cotinine output in urine varied significantly and was directly related to cigarette nicotine content; cotinine is the primary metabolite of nicotine. Baboons, like people, prefer high nicotine content cigarettes. Nonhuman primates also regulate nicotine exposure by modification of their puffing behavior. These results indicate that the nonhuman primate also can be used as a model for the investigation of the behavioral aspects of cigarette smoking.     

Nicotine nasal spray and vapor inhaler: abuse liability assessment

Acute subjective and physiological effects were examined to provide information relevant to abuse liability of new nicotine delivery systems. Subjects (n = 12) were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from nicotine-containing cigarettes (0.1 mg per puff), 0, 1, 2 or 4 nasal sprays (0.5 mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013 mg nicotine per inhalation) in a within-subject single blinded design. While smokers clearly liked cigarette puffs, there was much less evidence of liking produced by either nasal spray or vapor inhaler; only modest elevations on a measure of good drug effects were observed. The novel delivery products engendered unpleasant effects of burning throat and nose, watery eyes, runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increase was dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with the latter device. Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products. Received: 28 May 1996 / Final version: 25 October 1996     

Natural observations of smoking behavior: are there sex, age, context- or activity-related differences?

We unobtrusively observed 1979 people smoking one to three cigarettes in a variety of everyday activities. There were gender differences only with respect to group size and composition, and the time the cigarette was in the mouth. For most measures the correlations between behaviors were higher for men than women. There were few significant age differences in smoking behavior. We classified the activities of smokers into six broad categories: study, passive watching, active-involvement, eating and drinking (non-alcohol), waiting rooms and alcohol-related. There were significant differences in all measures (except time in mouth) as a function of the activity categories. Generally, smokers that were actively involved or passively watching had cigarettes lit for longer than smokers actively involved. Generally smokers that were actively involved took fewer puffs per cigarette than other smokers. Number of puffs per cigarette for all activity categories was lower than that reported from laboratory studies.     

Naltrexone administration affects ad libitum smoking behavior

Endogenous opioid peptides have been implicated in the reinforcement of smoking and opioid antagonists have been examined to determine their role in smoking behavior. To date, the relationship between smoking behavior and chronic opiate antagonist administration during ad libitum smoking has not been investigated. The purpose of this study was to examine the relationships between naltrexone, an opiate antagonist administered orally, and smoking behavior and mood states during ad libitum smoking. A repeated measures experimental design was used. Normal adult male and female volunteers, admitted to the Clinical Research Center, were randomly assigned to naltrexone-treated (n = 22) or placebo-control (n = 21) groups in a double-blind manner. Day 1 was considered acclimation to the unit and day 2 was baseline, or pre-drug administration. On days 3, 4, and 5, subjects received 50 mg naltrexone or a placebo at 0700 and 1600 hours. Plasma nicotine and expired air carbon monoxide levels were measured daily at 1900 hours. Number of cigarettes smoked, mood states, withdrawal symptomatology and self-reported satisfaction with smoking were also quantified daily. Results indicated that plasma nicotine levels (P = 0.005), number of cigarettes smoked daily (P = 0.003) and self-reported satisfaction with smoking (P = 0.043) were significantly lower among those treated with naltrexone, compared to the placebo-control group. Expired air carbon monoxide levels did not differ between the two groups. In addition, mood states and withdrawal symptoms did not differ between groups. These findings suggest that endogenous opioid peptides influence specific smoking behavior variables. Received: 7 November 1997/ Final version: 7 April 1998     

Temporal effects of nicotine nasal spray and gum on nicotine withdrawal symptoms

Nicotine nasal spray and nicotine gum have been found to be effective in relieving nicotine withdrawal symptoms. In this randomized single-blind study, 91 cigarette smokers were randomly assigned to a single 1 mg dose of active nicotine nasal spray (n = 29), active 4 mg nicotine gum (n = 31), saline placebo nasal spray (n = 16) or placebo gum (n = 15). Following overnight abstinence, subjects repeatedly completed visual analog scales for assessing nicotine withdrawal symptoms over 30 min preceding (time -30 min to time 0) and 120 min following a single dose of study medication. This sequence was performed 3 times during the day. Nicotine withdrawal symptoms were assessed on a 41-point visual analog scale (1 = no withdrawal, 41 = extreme withdrawal). At the initial session only, blood samples for serum nicotine levels were taken at baseline, then at 5, 10, 30 and 120 min following study drug administration. The mean (± SD) age of the subjects was 38.6 (±10.1) years, 48% were females, smoking rate was 24.5 (±7.8) cigarettes per day, and years of smoking was 19.9 (±10.0). A single 1 mg dose of nicotine nasal spray provided more immediate relief for craving for a cigarette compared to a single 4 mg dose of nicotine gum. Serum venous nicotine levels for the active nicotine nasal spray and nicotine gum were comparable at 5 and 10 min while the levels were higher for nicotine gum at 30 and 120 min. Changes in withdrawal symptoms were not found to be related to serum venous nicotine levels. Our findings provide a rationale for the as needed use of nicotine nasal spray to control withdrawal symptoms, possibly in combination with other medications with longer acting effects. Received: 18 February 1998/Final version: 1 May 1998     

Role of abstinence and visual cues on food and smoking craving

This study was designed to examine the relationship between cravings for food and cravings for cigarettes by presenting smoking-related or food-related visual cues to smokers who were either smoking-deprived or food-deprived. Fifteen regular cigarette smokers participated in this four-session, within-subject study in which they rated their craving for cigarettes and craving for food under four conditions: after abstaining from smoking, after abstaining from eating, after abstaining from both smoking and eating, or after no abstinence. We found that before presentation of the cues, overnight smoking abstinence increased craving for cigarettes, and overnight food abstinence increased craving for food. In each condition, presentation of cues further increased craving for the object of deprivation: smoking cues further increased craving for cigarettes after smoking abstinence, and food cues further increased craving for food after abstaining from food. Smoking abstinence did not affect craving for food, but food abstinence modestly increased smoking craving. These results indicate that craving for cigarettes or food is specifically increased by both deprivation from the substance and by presentation of substance-related cues.     

Effects of d-amphetamine and smoking abstinence on cue-induced cigarette craving

In this study, the authors investigated the effects of the indirect dopamine agonist d-amphetamine (AMPH) on cue-induced cigarette craving in smokers. Abstinent or nonabstinent cigarette smokers (N=21) rated their cravings for cigarettes and for food (control) after pretreatment with AMPH (15 mg) or placebo and before and after viewing blocks of smoking-related, food-related, and neutral pictures. Before the cues were presented, AMPH increased cigarette craving and decreased food craving. Smoking and food cues increased craving for cigarettes and for food, respectively. AMPH also further increased cigarette craving (and decreased food craving) after cue presentation, but it did so regardless of cue type (food or smoking). Smoking abstinence markedly increased craving regardless of cue presentation or drug condition. These results suggest that both AMPH and smoking abstinence can increase cigarette craving, but they do not appear to specifically affect responses to conditioned smoking-related cues.     

Modeling the effect of alcohol on smoking lapse behavior

Objective

The primary aim of this project was to examine the role of alcohol use in smoking lapse behavior, as alcohol consumption is a known risk factor for poor smoking cessation outcomes.

Materials and methods

We have developed a novel human laboratory model to examine two primary aspects of alcohol-mediated tobacco relapse: (1) Does alcohol facilitate the initiation of the first cigarette? (2) Once the first cigarette is initiated, does alcohol facilitate subsequent smoking? Using a within-subject design, 16 daily smokers who were also heavy social drinkers received a priming drink (0.03 g/dl or taste-masked placebo) and then had the option of initiating a tobacco self-administration session or delaying initiation by 5-min increments for up to 50 min in exchange for monetary reinforcement. Subsequently, the tobacco self-administration session consisted of a 1-h period in which subjects could choose to smoke their preferred brand of cigarettes using a smoking topography system or receive monetary reinforcement for cigarettes not smoked. Alcohol craving, tobacco craving, subjective reactivity to alcohol, and nicotine withdrawal were assessed as secondary outcomes.

Results

Results demonstrated that after consuming the alcohol beverage, subjects were less able to resist the first cigarette and initiated their smoking sessions sooner, and smoked more cigarettes compared to the placebo beverage. These findings have implications for smoking cessation in alcohol drinkers and model development to assess smoking lapse behavior.     

Compensation and effective smoking by different nicotine dependent smokers

The role of nicotine in smoking behavior was studied in a compensation experiment. Fourteen smokers were recruited and their dependence on nicotine was measured by a Tolerance Questionnaire. Each subject smoked four cigarettes, two with high nicotine content and two with low. Recordings were made of the number of puffs, interpuff intervals and puff duration by means of a thermistor inserted into a wooden cigarette holder. A composite “Smoking Score” was calculated for each cigarette smoked. Data analysis showed that the more dependent subjects smoked more effectively than less dependent subjects and that weaker cigarettes were smoked more effectively than stronger cigarettes. Compensatory smoking and nicotine dependence covaried. The results were discussed in light of recent efforts to offer the public weaker cigarettes.