Bromocriptine reduces cigarette smoking.

AIMS: Animal studies have shown that nicotine releases dopamine, a neurotransmitter implicated in drug reinforcement. We hypothesized that bromocriptine would decrease smoking behavior in humans. DESIGN: The study was conducted double blind and subjects' order of dose exposure was randomized. PARTICIPANTS: The smoking behavior of 20 heavy smokers was recorded for 5 hours after ingesting placebo or one of two doses of bromocriptine (2.50 mg, 3.75 mg) over three sessions (one dose per session). FINDINGS: There was a significant negative linear trend by dosage indicating shorter total puffing time with increasing bromocriptine dosages (p < 0.02). Other significant negative linear trends by increasing dosage include fewer number of puffs, fewer number of cigarettes smoked and mean latency to smoke after 3 hours (expected CMAX on the drug (all ps < 0.05). There was a negative significant linear trend showing decreased plasma nicotine (p < 0.02) and cotinine (p < 0.005) with increasing dosages of bromocriptine. Shiffman/Jarvik Withdrawal Scale (SJWS) cigarette craving subscale scores decreased significantly across increasing dosages (linear trend p < 0.02). There was a significant negative linear trend (p < 0.05) on the Profile of Mood States (POMS) Vigor and Depression subscales, with subjects reporting decreased vigor and depression with increasing bromocriptine doses. No other mood effects were observed. CONCLUSION: These results support the hypothesis that dopaminergic mechanisms mediate cigarette smoking reinforcement.

Nicotine blood levels and subjective craving for cigarettes.

This study examined cigarette craving and blood nicotine levels in 11 male heavy smokers who were observed during 16 h of tobacco abstinence. Subjects rated their urge to smoke on a new brief 10-item questionnaire, Urge to Smoke (UTS), Schuh and Stitzer's four-item Visual Analog Scale (SSI), and a Strength of Urge to Smoke (SUTS) item. Testing occurred: 1) after 16 h (1700 h the night before to 0900 h the next morning) of abstinence from smoking; 2) after an ad lib smoking period following the 16 h abstinence; 3) every hour during 6 hours of abstinence; 4) and finally, after the 6 h abstinence, another ad lib smoking period. Thus, subjects smoked twice in each session. Blood plasma nicotine levels were measured before, after, and every 2 h during the 6-h abstinence period for a total of six measures. Blood pressure and heart rate were measured prior to each blood draw. There was a significant negative correlation between blood nicotine levels and craving for cigarettes on all craving questionnaires (rs = -0.55 to -0.78; ps < 0.002). Carbon monoxide was shown to correlate highly with nicotine blood levels (rs = 0.83 to 0.98 across subjects; ps < 0.001). Results are consistent with the hypothesis that "urge to smoke" reflects nicotine seeking in continuing smokers.

Associations between tobacco smoking and illicit drug use among methadone-maintained opiate-dependent individuals.

Tobacco chippers are individuals who smoke regularly yet are not nicotine dependent. In the present study, the authors examined the prevalence of tobacco chipping among methadone-maintained opiate abusers. Furthermore, the authors examined associations between tobacco and illicit substance use by comparing heavy smokers, tobacco chippers, and nonsmokers. Results demonstrate that tobacco chipping occurs among methadone-maintained individuals. Illicit substance use, measured through urine toxicology, was found to increase in a stepwise fashion from nonsmokers, to chippers, to heavy smokers. Smoking status (nonsmoker, chipper, heavy smoker) proved a more powerful predictor of cocaine and opiate use than daily methadone dose. Findings lend support to existing evidence suggesting associations between tobacco and opiate and cocaine use and strongly suggest that smoking cessation should be offered to all methadone-maintained individuals.

Nicotine reduces the frequency of anger reports in smokers and nonsmokers with high but not low hostility: an ambulatory study.

Two studies were conducted to determine the anger-attenuating effects of nicotine as a function of trait hostility. The 1st study examined the effects of nicotine on diary ratings of anger during a 24-hr period in a natural setting in 30 smokers and 30 nonsmokers. Participants took part in 2 monitoring sessions involving the administration of a nicotine patch and a placebo patch. Participants were categorized as high or low on trait hostility on the basis of their scores on the Cook-Medley Hostility scale. Administration of the nicotine patch, compared with the placebo patch, resulted in a significant reduction in diary reports of anger from 24% to 13% in high-hostile participants. In low-hostile participants, nicotine had no effect on reports of anger during the day. The anger-palliative effects of nicotine were greatest among participants more frequently reporting anger on the placebo-patch day. These effects were independent of smoking status and gender. The 2nd study, which was restricted to high-hostile smokers (n = 19) and nonsmokers (n = 23), found that, compared with a placebo patch, administration of nicotine resulted in significant reductions in reports of anger in smokers and nonsmokers. The results of these 2 studies clearly link nicotine to reduced reports of anger in high-hostile individuals.

Mentholated cigarette smoking and lung-cancer risk.

PURPOSE: Menthol smoking may lead to a greater increase in lung-cancer risk than smoking of nonmentholated cigarettes. Mentholation of cigarettes adds additional carcinogenic components to cigarette smoke and increases retention times for cigarette smoke in the lungs. Only two epidemiologic studies have been conducted on menthol smoking and lung cancer, and their results are conflicting. Of note, African American males have much higher rates of lung cancer than Caucasian males despite smoking fewer cigarettes per day. Because the consumption of menthol cigarettes is much more frequent among African Americans, it is of interest to examine the possible association between menthol smoking and lung-cancer risk in this population. METHODS: We examined the association between menthol cigarette smoking and lung-cancer risk among smokers by comparing 337 incident cases of lung cancer with 478 population controls enrolled in a case-control study of lung cancer. Information on smoking history and other known and potential risk factors for lung cancer, including dietary intake, was obtained by in-person interviews. RESULTS: The adjusted odds ratios did not differ appreciably between smokers of mentholated cigarettes versus exclusive nonmentholated cigarette smokers in the overall study group of smokers. The odds ratio (OR) for 32 pack-years or more of mentholated vs. nonmentholated cigarettes was 0.90 (95% confidence interval (CI) = 0.38-2.12) in African Americans and 1.06 (95% CI = 0.47-2.36) in Caucasians, and did not differ for either ethnic group (p = 0.98). CONCLUSIONS: Our results suggest that the lung-cancer risk from smoking mentholated cigarettes resembles the risk from smoking non-mentholated cigarettes. Our data do not support the hypothesis that the increased risk of lung cancer among African Americans is due to the increased prevalence of menthol smoking.

The effects of dopaminergic D2 stimulation and blockade on smoking behavior.

Researchers have hypothesized that dopamine mediates the reinforcing effects of stimulant drugs, including nicotine. Three experiments tested whether manipulating dopamine would alter human smoking behavior. Experiments used double-blind, repeated measures designs. In Experiment 1, 4 participants were given haloperidol (a dopamine antagonist; placebo, 0.5, and 1.0 mg) on 3 occasions. The smoking rate was faster in the 1.0 mg versus the placebo condition. In Experiment 2, 12 participants were given haloperidol (2.0 mg) and placebo on 2 occasions. The intercigarette interval was shorter at the expected time of peak drug concentration. In Experiment 3, 5 participants were given bromocriptine (a dopamine agonist, 2.5 mg) and placebo on 2 occasions. The smoking rate was significantly slower with bromocriptine. These results suggest that blockade of D2 receptors increases smoking whereas their stimulation decreases smoking.

Interest in smoking cessation among methadone maintained outpatients.

The prevalence of cigarette smoking among opiate abusers is extremely high and tobacco related diseases are a major factor associated with morbidity and mortality for this group. Yet, many treatment providers remain reluctant to address smoking cessation with their clients due in part to the belief that substance abusers are not interested in quitting smoking. The present study examined self-reported interest in smoking cessation among methadone maintenance clients (N = 120) in four clinics in Los Angeles. Fifty-eight percent of subjects rated themselves as 'Somewhat' or 'Very Interested' in a smoking cessation program. Overall subjects appeared to accurately perceive the personal risks from tobacco smoking. In conclusion we find that clients in methadone maintenance treatment programs evidence a high level of interest in quitting smoking and may well be suited for a highly structured smoking cessation intervention.

Pain inhibition, nicotine, and gender.

The ability of nicotine to decrease sensitivity to pain in humans has been a subject of dispute. Decreased sensitivity has been demonstrated in studies involving men, whereas the effect has been less obvious or absent in studies involving predominantly, or entirely, women. To determine whether there are gender differences in nicotine's hypoalgesic actions, ratings of electrocutaneous stimulation were obtained from 30 male and 44 female smokers and nonsmokers under placebo and nicotine conditions. Nicotine increased the pain threshold and tolerance ratings of men but had no effect on the pain ratings of women. Among men, there was no effect of smoking history, suggesting that the changes in pain perception reflect a direct pain-inhibitory effect of nicotine rather than a relief from acute nicotine withdrawal. Nicotine had no effect on mood or task ratings, indicating that the antinociceptive effects observed were not due to nicotine's putative mood effects.

Olfactory thresholds for nicotine and menthol in smokers (abstinent and nonabstinent) and nonsmokers.

Nonsmokers and smokers were compared for olfactory sensitivity to two odors associated with cigarettes: nicotine and menthol. Smokers were tested twice--while nonabstinent, and after 16-20 h of smoking abstinence. Smokers showed a higher olfactory threshold for nicotine than did nonsmokers, but the same threshold for menthol. Furthermore, when the smokers were abstinent, they showed a lower olfactory threshold for nicotine than when they were nonabstinent, but again, the same threshold for menthol. These results suggest a nicotine specific olfactory deficit in smokers that is reduced during abstinence.

Contingency management for tobacco smoking in methadone-maintained opiate addicts.

Seventeen methadone-maintained cigarette smokers received 4 weeks of contingency management (CM) as a stop-smoking intervention. Results indicated that CM patients significantly reduced breath CO levels from baseline to completion of treatment and that 23.4% of patients maintained 1 week or more of continued smoking abstinence. Results indicated a link between smoking abstinence and reduced cocaine use, although not reduced opiate use, which raised questions about possible shared biological and psychological mechanisms for tobacco and cocaine use.

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial.

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation but absolute success rates are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safety and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8-32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO < or = 8 ppm; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.

Enhanced lexical processing of smoking stimuli during smoking abstinence.

In a group of heavy smokers, overnight abstinence from smoking facilitated the perception of briefly presented smoking words. Subjects in the nicotine-abstinent condition accurately identified significantly more smoking-related words than food-related or neutral words. However, a group tested in a non-abstinent condition showed no significant differences in ability to identify the three different word types. Smokers deprived of cigarettes were also significantly better able to categorize smoking words than non-abstinent subjects. These results demonstrate an abstinence-based facilitation of processing smoking-related stimuli at the semantic level, consistent with the hypothesis that smoking-related concepts are activated, or primed, during deprivation from nicotine.

Menthol vs nonmenthol cigarettes: effects on smoking behavior.

OBJECTIVES: The purpose of this study was to examine intraindividual differences in smoking behavior between smoking regular and mentholated cigarettes. METHODS: Healthy male smokers (n = 29) smoked either a regular or a mentholated cigarette in two separate sessions 1 week apart. Commercial brands with comparable tar, nicotine, and CO content were used. Smoking behavior was constrained by fixed 15-second interpuff intervals, but puff volume and number of puffs were unconstrained. RESULTS: When smoking the non-mentholated brand of cigarettes, participants smoked 22% more puffs and had 13% higher mean volumes per puff than they did when smoking the mentholated brand of cigarettes. The aggregate 39% excess exposure to cigarette smoke in the regular-cigarette condition was not accompanied by commensurate excesses in expired carbon monoxide or in physiological measures normally correlated with nicotine exposure. CONCLUSIONS: These findings parallel differences in physiological correlates of exposure to nicotine found in cross-sectional comparisons of African-American and White smokers and are consistent with the results of emerging laboratory investigations.

Mentholated cigarettes decrease puff volume of smoke and increase carbon monoxide absorption.

The influence of mentholated vs. regular cigarettes on selected chemical and topographic parameters was measured in 20 smokers in a pulmonary function laboratory. Half the subjects were black and half were white; half were menthol and half regular smokers. All subjects smoked both types of cigarettes, one on each of 2 days. Compared to regular cigarettes, mentholated cigarettes produced a significantly greater boost in carbon monoxide measured as both blood carboxyhemoglobin and end-expired carbon monoxide, despite the fact that mentholated cigarettes decreased average and total cumulative puff volumes and increased mean puff flow rates of inhaled smoke. These chemical and topographic differences were independent of race. No significant differences in depth of inhalation of the smoke or in the amount of insoluble smoke particulates delivered to or retained in the respiratory tract were noted between the two types of cigarettes. Mentholation of cigarettes may decrease volume of smoke inhaled but appears to increase exposure of smokers to toxic effects of carbon monoxide.

Rapid smoking of menthol and nonmenthol cigarettes by black and white smokers.

White subjects took significantly more puffs of cigarette smoke before stopping than did black subjects in a modified, controlled-dose rapid smoking procedure. Paradoxically, however, no racial differences were detected for changes in carbon monoxide levels, or changes in cardiovascular variables (systolic and diastolic blood pressure, and heart rate). Due to the cooling and topical anesthetic properties of menthol, it was hypothesized that menthol and regular cigarette smokers would take more puffs from menthol cigarettes than from regular cigarettes before stopping in the controlled-dose rapid smoking procedure. However, no difference was observed for the number of puffs taken from regular as opposed to menthol cigarettes (cigarette type condition) and no differences were found for Cigarette Preference (regular smokers vs. menthol smokers).

Nicotine abstinence produces content-specific Stroop interference.

Adult, male smokers were randomly assigned to be nicotine abstinent for 12 h (n = 10) or to smoke normally for the same period of time (n = 10). Performance on a modified version of the Stroop (1935) color-naming task, where subjects named the color of ink in which each of a series of words was written, showed that abstinent smokers took significantly longer to color-name words related to cigarette smoking (e.g., Lighter) than to color-name neutral control words (e.g., Pennant). Non-abstinent smokers showed a significant difference in the opposite direction. These results suggest that nicotine abstinence decreases the ability to ignore the meaning of smoking-related information. This finding supports the hypothesis that abstinence produces a content-specific shift in attentional focus. The present pattern of results cannot be explained by a general decrease in cognitive function due to nicotine abstinence.

Beneficial effects of nicotine.

Nicotine in tobacco brings illness and death to millions of people. Yet nicotine in its pure form has the potential to be a valuable pharmaceutical agent. Nicotine fairly specifically binds to the cholinergic nicotinic gating site on cationic ion channels in receptors throughout the body. This action stimulates the release of a variety of neurotransmitters including especially catecholamines and serotonin. When chronically taken, nicotine may result in: (1) positive reinforcement, (2) negative reinforcement, (3) reduction of body weight, (4) enhancement of performance, and protection against; (5) Parkinson's disease (6) Tourette's disease (7) Alzheimers disease, (8) ulcerative colitis and (9) sleep apnea. The reliability of these effects varies greatly but justifies the search for more therapeutic applications for this interesting compound.

Transdermal nicotine and smoking behavior in psychiatric patients.

The authors used a double-blind crossover design to observe the effect of transdermally administered nicotine on the smoking behavior of 13 psychiatric patients who were not trying to stop smoking. The patients smoked significantly fewer cigarettes while receiving nicotine than while receiving placebo. These data suggest that transdermally administered nicotine can be a useful adjunct in treating nicotine-addicted psychiatric patients in a non-smoking environment.

Combined use of alcohol and nicotine gum.

This study evaluated the effects of chewing nicotine gum immediately before and just after drinking a moderate amount of alcohol. Four research questions were addressed. First, does chewing nicotine gum prior to drinking alcohol attenuate the increased craving to smoke that is typically associated with alcohol use? Second, does drinking prior to chewing reduce the gum's effectiveness? Third, are significant side effects observed with nicotine gum, and is their severity affected by alcohol use? Finally, can we identify subjects who are more likely to respond well to the gum on the basis of smoking history or pattern or other descriptive-demographic, psychologic, or historical variables? Smokers who had abstained for at least 12 h were studied in a fully crossrandomized experimental design that contrasted nicotine gum (before or after drinking) versus sugarless gum, and alcohol versus a no-alcohol comparison condition. Nicotine gum use was associated with significantly greater immediate reduction in craving to smoke, regardless of whether it preceded or followed alcohol, but the effects were weak and short-lived in either case. Moderate use of alcohol after chewing the gum eliminated virtually all of its beneficial effects. Mild side effects were common with nicotine gum, but equally so regardless of alcohol use. A small battery of demographic and historical variables failed to identify those subjects who responded well to nicotine gum.