Effects of methadone on human cigarette smoking and subjective ratings

In order to study possible interactions between opioids and cigarette smoking, we examined the effects of oral methadone administration on the smoking behavior of five male methadone-maintenance patients. Isolated subjects smoked their regular brand of cigarettes ad libitum in a naturalistic laboratory environment while reading or watching television. Ninety minutes before each daily 2-hr smoking session subjects received either placebo, dextromethorphan (a taste blind) or one of three doses of methadone, 0.5, 1.0 or 2.0 times their regular maintenance dose (40-60 mg). Each subject received each treatment five times, in a mixed order across days. Methadone pretreatment resulted in a dose-related increase in the number of cigarettes smoked per session (from a mean of 2.8 after placebo to 5.6 after the high dose of methadone). The total time spent puffing during the session increased from a mean of 27 sec after placebo to 74 sec after the high dose of methadone. CO levels in expired air (a measure of actual smoke inhalation) showed corresponding dose-related increases. Methadone administration also resulted in dose-related decreases in pupil diameter and increases in subjective ratings of smoking satisfaction and dose-strength. Dextromethorphan had no significant effects on any measure of smoking behavior or subjective response. The results demonstrate that methadone can produce substantial increases in cigarette smoking and may have implications regarding the proposed role of endogenous opioids in the smoking process.     

Cigarette brand-switching: effects on smoke exposure and smoking behavior

This study examined the effects of cigarette yield (Federal Trade Commission-determined deliveries of nicotine, tar and CO) on both biological exposure to smoke constituents and smoking behaviors. Smokers (N = 10) of high-yield cigarettes were switched in random order among five different commercially available cigarette brands with nicotine yields of 0.1, 0.4, 0.7, 1.1 (altered brand) and 1.0 (usual brand) mg and smoked each cigarette type for 5 days while a wide variety of assessments were performed. Steady-state cotinine and CO levels were substantially lower after 5 days of smoking ultra-low yield cigarettes (cotinine, 152 ng/ml; CO, 25 ppm) than when smoking usual-brand high-yield cigarettes (cotinine, 252 ng/ml; CO, 38 ppm). Both CO and nicotine boost (acute exposure) were related to yield. However, relative between-yield differences in all nicotine and CO exposure measures were smaller than predicted from Federal Trade Commission yield ratings. Substantial yield-related alterations were observed in smoking behavior. Subjects smoked more cigarettes and took larger and more closely spaced puffs when smoking low- as compared with high-yield cigarettes. The amount of tobacco burned per day was similar across all yield conditions. However, filter vent-blocking of ultra-low yield cigarettes did not appear to occur on a consistent basis. Subjective reports indicated poor acceptability of lower-yield cigarettes. We conclude that switching to lower-yield cigarettes brings about substantial alterations in smoking behavior which are at least partially responsible for the observed biological compensation associated with these cigarettes.     

Marijuana smoking: effect of varying delta 9-tetrahydrocannabinol content and number of puffs.

The purpose of this study was to determine marijuana dose-effects on subjective and performance measures over a wider dosage range than previously reported using technology which allowed for specification of both the volume and delta 9-tetrahydrocannabinol (THC) content of smoke delivered, and to relate these effects to plasma THC levels. Seven male community volunteers, who were moderate users of marijuana, smoked 4, 10 or 25 puffs from cigarettes containing either 1.75 or 3.55% THC on 6 separate days. Postsmoking plasma THC levels were systematically related to both number of puffs and cigarette THC content. Maximal THC levels occurred immediately after smoking and ranged from 57 to 268 ng/ml. These plasma levels provided a measure of systemic delivery when a known volume and THC content of marijuana smoke was inhaled. Orderly dose-related increases were also observed for heart rate, expired air carbon monoxide and subjective report of drug effects. The 25-puff, 3.55%-THC condition produced greater plasma THC levels than previously reported and reliably impaired performance on a battery of psychomotor and cognitive tasks with substantial individual differences noted in the degree of performance impairment. Puff number/THC content combinations producing comparable plasma THC levels resulted in similar subjective effects and performance impairment. This study provided a comprehensive assessment of the pharmacological effects of smoked marijuana over a wider and more precisely controlled dosage range than has been accomplished previously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nicotine chewing gum on cigarette smoking and subjective and physiologic effects

Our study was conducted to assess the effects of multiple doses of nicotine chewing gum on a variety of measures of cigarette smoking, affect, and physiologic response. Cigarette smokers resided on a research unit for the duration of the study, during which time their smoking behavior was measured during nine 12-hour test sessions. At the start of each session and every 2 hours thereafter, subjects received oral doses of nicotine (2 or 4 mg) or placebo in the form of a chewing gum (nicotine polacrilex). Each dose of active drug and placebo was given for three sessions in a randomized block sequence. Total number of puffs per day was significantly decreased at both the 2 and 4 mg doses when compared with placebo, and the total number of cigarettes smoked per day was significantly decreased at the 4 mg dose. There were dose-related changes in certain subjective effects: Self-reported ratings of dose strength were directly related to dose, desire to smoke tended to be inversely related to dose, and prominent measures of abuse liability did not change. The only cardiovascular measure that was significantly changed by nicotine dose was systolic blood pressure, which showed an attenuation of the diurnal pattern as the dose increased.     

Inhaled smoke volume, puffing indices and carbon monoxide uptake in asymptomatic cigarette smokers

Nine asymptomatic smokers each smoked one cigarette of their usual brand on four separate occasions. The inhaled smoke volume was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded by using an electronic smoking analyser and flowhead/cigarette holder. The expired air carbon monoxide concentration was measured immediately before and within 5 min of finishing smoking. The inhaled smoke percentage (total inhaled smoke volume/total puff volume) averaged 46% to 85% in different subjects. Neither the mean inhaled smoke volume per puff nor the total inhaled smoke volume per cigarette was significantly correlated with any of the puffing indices. Smokers took significantly smaller and shorter puffs, left longer between puffs and inhaled less smoke as the cigarette was smoked (P less than 0.01), although the proportion of the puff which was subsequently inhaled did not change significantly. There was no significant intra-subject difference in any index from one visit to another.     

Nicotine intake and dose response when smoking reduced-nicotine content cigarettes

OBJECTIVES: The progressive reduction of the nicotine content of cigarettes has been suggested as a way to wean smokers from nicotine and tobacco. As a first step in evaluating this strategy, we studied smokers smoking cigarettes containing tobacco with differing nicotine content. METHODS: Twelve healthy smokers participated in a semiblinded, within-subject, crossover study. Subjects were asked to smoke 1 of their usual brand of cigarette and then on 5 subsequent occasions to smoke a research cigarette, each with differing nicotine content. The research cigarettes contained 0.6 to 10.1 mg nicotine per cigarette. Plasma nicotine and blood carboxyhemoglobin levels, as well as subjective and cardiovascular responses, were measured after smoking. Systemic nicotine intake per cigarette was estimated by use of plasma nicotine concentrations over time and clearance data from the general population. RESULTS: Systemic nicotine intake (0.26-1.47 mg per cigarette) varied with nicotine content of the cigarette (r = 0.82, P < .001). Compensation when smoking single low-nicotine content cigarettes ranged from -1% (95% confidence interval, -23% to 21%) to 34% (95% confidence interval, -39% to 107%) for 1-mg to 8-mg research cigarettes. Carbon monoxide intake and estimated tar exposure were similar across cigarettes. Low-nicotine content cigarettes were rated as being of lower quality and less satisfying than the 12-mg research cigarette or the usual brand (P < .05 for both comparisons). Cigarette smoking increased heart rate and decreased skin temperature, but the nicotine dose-response curve flattened at higher doses, with a maximal response being observed in cigarettes at a nicotine content level of about 8 mg. CONCLUSIONS: Our study suggests that reduced-nicotine content cigarettes are reasonable candidates for trying to reduce the level of nicotine addiction in smokers. The flat nicotine dose-cardiovascular response curve is consistent with other studies demonstrating tolerance to the cardiovascular effects of nicotine.     

Intravenous nicotine replacement suppresses nicotine intake from cigarette smoking

Insofar as smokers regulate body levels of nicotine, nicotine replacement is expected to suppress the desire to smoke a cigarette. Our study was designed to test the hypothesis that i.v. replacement of nicotine will suppress daily intake of nicotine from ad libitum cigarette smoking and to compare the physiological effects of prolonged exposure to nicotine infused i.v. to the effect of smoking cigarettes throughout the day. Eight subjects received a 14-hr infusion of deuterium-labeled nicotine dosed to achieve levels of nicotine similar to those while smoking cigarettes for each individual (average, 33.1 mg; range, 17.7-49.9 mg) or saline (placebo). Cigarette smoking was permitted as desired. Nicotine infusion did not significantly affect the number of cigarettes smoked or the amount of tobacco burned, but nicotine intake from cigarette smoking was suppressed in all but one subject by an average of 24.6% (range, 4.0-51.2%). Down-regulation of levels of nicotine while smoking in response to infusion of nicotine was imprecise, which may be a result of psychosocial factors influencing smoking behavior along with the development of tolerance to toxic effects of nicotine as a consequence of prolonged exposure to nicotine. Intravenous nicotine and cigarette smoking increased average heart rate and blood pressure throughout the day and 24-hr urinary epinephrine excretion to a similar extent. Despite higher levels of nicotine when subjects smoked during infusion of nicotine, there were no additional nicotine-related effects. No adverse effects were noted; most subjects could not distinguish nicotine from saline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of increasing urinary pH on cigarette smoking

We evaluated the effects of increasing urinary pH on sensitive automated measures of cigarette smoking behavior. Urine was alkalized by oral doses of 50 or 75 mg/kg sodium bicarbonate. Measurements of cigarette smoking behavior included the number of cigarettes smoked and automated measures of puff frequency and duration. The sodium bicarbonate resulted in little or no change in the number of cigarettes smoked, but in five of the seven subjects frequency and duration of cigarette puffs after sodium bicarbonate decreased 10% to 15%. The small decreases in cigarette smoking brought about by sodium bicarbonate cannot be expected to have significant overall effects.     

Smoked marijuana effects on tobacco cigarette smoking behavior

The effects of marijuana smoke exposure on several measures of tobacco cigarette smoking behavior were examined. Eight healthy adult male volunteers, who smoked both tobacco and marijuana cigarettes, participated in residential studies, lasting 10 to 15 days, designed to measure the effects of marijuana smoke exposure on a range of behavioral variables. Tobacco cigarettes were available throughout the day (9:00 A.M. until midnight). Each day was divided into a private period (9:00 A.M. to 5:00 P.M.), during which subjects were socially isolated, and a social period (5:00 P.M. to midnight), during which subjects could interact. Under blind conditions, subjects smoked placebo and active marijuana cigarettes (0%, 1.3%, 2.3%, or 2.7% delta 9-tetrahydrocannabinol) four times daily (9:45 A.M., 1:30 P.M., 5:00 P.M. and 8:30 P.M.). Each subject was exposed to both placebo and one active dose over 2- to 5-consecutive-day intervals, and dose conditions (i.e., placebo or active) alternated throughout the study. Active marijuana smoking significantly decreased the number of daily tobacco smoking bouts, increased inter-bout intervals and decreased inter-puff intervals. Marijuana decreased the number of tobacco smoking bouts by delaying the initiation of tobacco cigarette smoking immediately after marijuana smoking, whereas decreases in inter-puff intervals were unrelated to the time of marijuana smoking. No consistent interactions between marijuana effects and social or private periods (i.e., time of day) were observed.     

Intravenous nicotine and caffeine: subjective and physiological effects in cocaine abusers

The subjective and physiological effects of intravenously administered caffeine and nicotine were compared in nine subjects with histories of using caffeine, tobacco, and cocaine. Subjects abstained from tobacco cigarette smoking for at least 8 h before each session. Dietary caffeine was eliminated throughout the study; however, to maintain consistency with the nicotine intake, subjects were administered caffeine (150 mg/70 kg b.i.d.) in capsules, with the last dose administered 15 to 18 h before each session. Under double-blind conditions, subjects received placebo, caffeine (100, 200, and 400 mg/70 kg), and nicotine (0.75, 1.5, and 3.0 mg/70 kg) in mixed order. Physiological and subjective data were collected before and repeatedly after drug or placebo administration. Compared with the highest dose of caffeine, the highest dose of nicotine produced greater subjective ratings on a number of scales. At doses that produced comparable ratings of drug effect (1.5 mg/70 kg of nicotine and 400 mg/70 kg of caffeine), both drugs produced similar increases in ratings of good effect, liking, high, stimulated, and bad effect. Nicotine showed a somewhat faster time to peak subjective effects than caffeine (2 versus 4 min). Subjective ratings that differentiated caffeine and nicotine were ratings of rush, blurry vision, and stimulant identification (elevated by nicotine) and ratings of unusual smell and/or taste (elevated by caffeine). Both caffeine and nicotine decreased skin temperature and increased diastolic blood pressure; however, caffeine decreased whereas nicotine increased heart rate. The study documents both striking similarities and some notable differences between caffeine and nicotine, which are among the most widely used mood-altering drugs.     

Effects of tobacco and non-tobacco cigarette smoking on endothelium and platelets

Endothelial damage and platelet activation may mediate increased cardiovascular morbidity and mortality in tobacco cigarette smokers. Our study was designed to determine whether acute effects of tobacco smoking on endothelium and platelets could be avoided by the substitution of non-tobacco cigarettes. Twenty healthy nonsmokers smoked two tobacco cigarettes in 20 minutes and on another occasion (separated by 1 week) smoked two cigarettes made from wheat, cocoa, and citrus plants. Mean endothelial cell counts from venous blood before and after smoking tobacco cigarettes were 2.3 and 4.8 and before and after smoking non-tobacco cigarettes counts were 2.5 and 3.0. Mean platelet aggregate ratios before and after smoking tobacco cigarettes were 0.80 and 0.65 and before and after smoking non-tobacco cigarettes they were 0.81 and 0.78. Much greater effects of tobacco smoking on endothelial cell counts and platelet aggregate ratios suggest the possibility that non-tobacco cigarette smoking may be less harmful to the cardiovascular system than is tobacco cigarette smoking.     

Cigarette smoking as a risk for cardiovascular disease. Part VI. Compensation with nicotine availability as a single variable

In a biochemical investigation of human smoking behavior with filter cigarettes with high draw resistance that varied only in nicotine yield, we attempted to determine which nicotine levels provide desired nicotine intake with a minimum of physiologic and biochemical consequences. Twelve prescreened subjects were divided into two study groups and supplied with cigarettes that varied in nicotine delivery. Both groups were initially monitored while smoking their usual cigarette. At the following visit, smokers in group 1 received incremental increases and smokers in group 2 received incremental decreases in nicotine levels in assigned cigarettes. All subjects were monitored upon first exposure, after 1 week of acclimatization to each experimental cigarette, and upon return to their usual brands. Subjects in both groups were unable to compensate fully for their nicotine uptake from the lowest nicotine cigarette. In subjects in group 1, new nicotine baselines began to develop after 1 week of acclimatization to cigarettes containing 0.9 and 1.3 mg nicotine. New baseline nicotine levels were also noted in subjects receiving decreases in nicotine (group 2) after smoking the cigarette containing 1.3 mg nicotine for 1 week. Carboxyhemoglobin concentrations did not differ from those measured after the usual-brand cigarettes. Plasma cotinine concentrations increased as nicotine content per cigarette increased, except when subjects smoked a 1.3 mg nicotine cigarette. Plasma thiocyanate levels did not vary in either group. Systolic and diastolic blood pressures were generally not different from control values.     

Effects of caffeine on tobacco withdrawal

Smoking cessation increases caffeine blood levels, and this has been hypothesized to cause some of the symptoms of tobacco withdrawal (e.g., anxiety and insomnia). To test this hypothesis, 10 coffee drinkers who smoked cigarettes were entered into a completely within-subjects experimental design in which the effects of caffeine dose (0, 50, and 100 mg/coffee serving) and smoking status (smoking versus abstinence) were examined over a 4-day period. Self-reported and observed measures of tobacco withdrawal, caffeine withdrawal, and intoxication, as well as psychomotor tasks and vital signs, were completed daily; blood was drawn at the end of each period. Temporary abstinence produced typical withdrawal symptoms but did not significantly increase caffeine blood levels. Caffeine did not increase the severity of symptoms but did decrease the severity of withdrawal-induced hunger. These findings suggest that, in the absence of increased blood levels, caffeine does not increase the severity of tobacco withdrawal.     

Smoking behaviour in young families: Do parents take practical measures to prevent passive smoking by the children?

Objective - To investigate smoking behaviour in young families.

Design - Cross-sectional study.

Setting - Mother and child health centres in Oslo, Norway.

Subjects - the families of 1046 children attending the health centres for 6-weeks-, 2- or 4- year well child visits.

Main outcome measures - Daily smoking, smoking quantity and practical measures taken by the parents to prevent passive smoking among the children as assessed by parental reports.

Results - in 48% of the families at least one adult was smoking. 33% of the smoking parents smoked more than ten cigarettes per day. 47% of the smoking families reported that they did not smoke indoors.

Conclusions - the parents were less likely to smoke if they were more than 35 years of age, had a child aged less than one year, had' a spouse/co-habitee or had a long education. Smoking parents smoked less if they had a spouse/co-habitee, had a child aged less than one year or had few children. Smoking parents were more often careful and did not smoke indoors if they had a child aged less than one year, had a spouse/co-habitee, did not have a smoking spouse/co-habitee or smoked a low number of cigarettes per day.     

Evaluation of methods to estimate cigarette smoke uptake

Exposure to tobacco smoke is measured by a variety of invasive and noninvasive techniques. Our purpose was to examine how well some of these measures correlated when obtained simultaneously from the same subjects. On three occasions, six subjects were studied while they were smoking a single cigarette after 24 hr of abstinence. There were positive correlations between increases in heart rate and plasma nicotine concentrations and between percentage carboxyhemoglobin and exhaled carbon monoxide. Although residual cotinine was readily detected in samples of plasma before the subjects smoked, there was an increase in mean levels, with a peak approximately 1 hr after smoking. Urinary concentrations of nicotine, cotinine, and nicotine-1'-N-oxide and thiocyanate levels in plasma and saliva were essentially unchanged by smoking a single cigarette. Data on smoke generation and nicotine retention in cigarette butts correlated poorly with all other measures of smoke uptake.     

Sensory mechanisms in the upper respiratory tract affect the inhalation of cigarette smoke in man

Cigarette puffing parameters (puff volume, puff duration, number of puffs, total smoking time) and inhaled smoke volume (by a radiotracer technique) have been measured in a group of 11 asymptomatic smokers, once after topical anaesthesia of the upper airways and once without anaesthesia. Topical anaesthesia significantly reduced the mean inhaled smoke volume per puff for the group from 41.1 ml to 30.6 ml (P less than 0.05) and the total inhaled smoke volume from 575 ml to 528 ml (P = 0.05), but cigarette puffing parameters were unchanged. It is concluded that stimulation of upper airway sensory receptors, probably sensitive to nicotine, may be an important mechanism in determining the amount of cigarette smoke inhaled by smokers.     

Design considerations for a pilot trial using a novel approach for evaluating smoking-cessation medication in methadone-maintained smokers

The prevalence of smoking in methadone-maintained (MM) patients is over 80% and smoking-abstinence rates are strikingly low, even with the use of first-line smoking-cessation medications. Research has found that cigarettes increase the reinforcing properties of methadone; this interaction may be an additional, daily, challenge to smoking cessation in MM-smokers. This paper describes a novel approach in which patients who experience a particular barrier to achieving smoking abstinence are selected, and the impact of smoking-cessation medications on the identified barrier is evaluated. This is a 7-week, outpatient, randomized, within-subject, placebo-controlled, crossover trial with a follow-up visit at week 8. MM-smokers, who smoke ≥ 40% of their total daily cigarettes in the 4-h post-methadone-dosing period, as assessed with a Quitbit electronic cigarette lighter, will be recruited from a methadone program in Cincinnati, Ohio. Eligible participants will be randomized to receive four interventions (nicotine nasal spray (1 mg per dose, up to 40 times per day), placebo nicotine nasal spray, varenicline (2 mg/day), and varenicline placebo) in one of four orders to mitigate potential order effects. The primary outcome analysis will consist of two sets of statistical analyses, one comparing the effect of nicotine nasal spray to its placebo, and one comparing the effect of varenicline to its placebo, on the proportion of daily cigarettes smoked during the 4-h post-methadone-dosing period. This trial is of interest both as an efficient, precision-medicine-based approach to testing smoking-cessation interventions and as a specific strategy for identifying effective smoking-cessation treatment for MM-smokers.     

Smoking behavior and desire to quit among low-income female caregivers.

The purpose of this study was to examine smoking behavior and the desire to quit among low-income women. Two hundred and eight women caregivers were surveyed about their smoking status, exposure to environmental tobacco smoke in the home, and desire to quit smoking. Most of the smokers (74%) wanted to quit smoking. With a logistic regression model, the number of years smoked was the only significant predictor variable for the dependent variable of thoughts about quitting when age, years of smoking, number of children, marital status, number of smokers in the home, cigarettes smoked per day, and money spent per week on cigarettes were entered as independent variables. The fewer years smoked the more likely the women wanted to quit.     

Smoking: knowledge, attitudes, habits and degree of dependence of young adults in Salvador

This study was aimed at evaluating the degree of smoking dependence and to characterize social demographic data, habits and attitudes of young smokers. Answered the questionnairel02 students from Salvador, State of Bahia, of which 11 were smokers. Their mean age and the age in which they first smoked were 18.2 and 13.4 years respectively. Most of them were male, in the first year of senior high school, of brown skin color and had close relatives who smoke. The majority of those young smokers had been advised about the risks of smoking at home and in school, but few had knowledge about the benefits of quitting. Almost half of them had been smoking for more than three years and had started to smoke out of curiosity. More than half of them smoked one cigarette per day, with low levels of nicotine, bought the cigarettes in shops, and wanted and tried to quit smoking, but never succeeded. The degree of dependence was low for most of them. This study offers hints for nurses to act against smoking with young adults.     

Reactions to cigarettes as a function of nicotine and "tar".

Experiments carried out to examine the effects of nicotine and "tar" on the extent of and subjective reactions to cigarette smoking. It was confirmed that smokers rate commercial, low-nicotine cigarettes as less "strong" and less "satisfying" than their usual brands. Since such cigarettes deliver reduced amounts of tar as well as of nicotine, an experiment to distinguish between the two was carried out with special cigarettes. Ratings of "strength" were directly related to nicotine but were not affected by tar. The numbers of cigarettes smoked fell slightly as their estimated delivery of nicotine increased, but tar had no effect on this index. The urinary excretion of nicotine was correlated with the rated yields of nicotine for the different cigarettes, but there was also evidence that subjects tended to adjust their manner of smoking so as to titrate their doses of nicotine. The results are interpreted as indicating a role for nicotine, but not for tar, in the maintenance of cigarette smoking behavior, and as support for the view that less harmful cigarettes should have a high yield of nicotine relative to tar.