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

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

Effects of mecamylamine on human cigarette smoking and subjective ratings

Multiple measures of cigarette smoking, subjective effect and physiological effect were collected during 90-min test sessions in normal volunteers. Before sessions subjects received oral doses of mecamylamine (2.5, 5.0, 10, 20 mg) or placebo. Each dose and placebo was given three times in a randomized block sequence. Mecamylamine increased several measures of cigarette smoking, including number of cigarettes, number of puffs per cigarette, and expired air carbon monoxide level. Mecamylamine also produced modest, dose-related decreases in standing blood pressure and increases in standing heart rate. The subjective effects produced by mecamylamine were not characteristic of those of psychoactive drugs. Mecamylamine appears to have increased cigarette smoking by decreasing the effective dose level of nicotine available from cigarette smoking.     

Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance

This study investigated the smoking topography of marijuana and its effect on heart rate, subjective reports, and cognitive/psychomotor task performance. Male subjects (N = 12) with histories of moderate marijuana use smoked ad lib one cigarette containing 0, 1.3, or 2.7% delta 9-THC on separate days. Smoking topography measures revealed smaller puff and inhalation volumes and shorter puff duration for the high marijuana dose compared to the low dose. No other smoking behavior differed between the active doses. Heart rate was increased dose dependently over placebo levels. Active marijuana also increased subjective reports of drug effect over placebo, but not dose dependently. Significant memory impairment was observed on a forward and reverse digit span task, and performance was impaired on the digit symbol substitution task by the high, but not low, dose of marijuana. Performance on a divided attention task was not affected by marijuana. Thus, although subjects adjusted their smoking of cigarettes varying in THC content, dose-related effects of marijuana were obtained on several measures. The observed differences and individual variation in smoking topography measures suggest that precise control of smoking behavior would improve the accuracy of marijuana dose delivery.     

'Hangover' effects the morning after marijuana smoking

Thirteen male marijuana smokers participated in a study to determine whether marijuana smoked in the evening would result in measurable subjective or other behavioral effects the following morning. Subjects smoked either active (2.9% delta 9THC) or placebo (0.0% delta 9THC) marijuana cigarettes according to a standardized smoking regimen. Smoke inhalation was monitored by measuring expired air carbon monoxide (CO) levels before and after smoking. Acutely, active marijuana produced significant changes in heart rate, CO level, various measures of subjective effects, and behavioral tasks of card sorting, free recall and time production. When the test battery was repeated the following morning (approx. 9 h after smoking), significant changes were observed on two subjective effects scales and on the time production task after active, but not placebo, marijuana. These apparent 'hangover' effects were different from the acute effects of marijuana. The findings suggest that marijuana smoking can produce residual (hangover) effects the day after smoking. The precise nature and extent of these effects, as well as their practical implications, remain to be determined.     

Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects

Four healthy male subjects smoked two marijuana cigarettes or one marijuana cigarette and one placebo cigarette, or two placebo cigarettes on separate days in a random order crossover design. Each marijuana cigarette contained 2.8% delta-9-tetrahydrocannabinol (THC). Plasma hormones and THC were measured before and after each smoking session. Plasma LH was significantly depressed and cortisol was significantly elevated after smoking marijuana. Nonsignificant depressions of prolactin, FSH, testosterone and free testosterone and elevation of GH also occurred. Concurrent measures of subjective effects via subscales of the Addiction Research Center Inventory, Single Dose Questionnaire and a Visual Analog Scale were generally elevated. Significant impairment on a psychomotor performance task paralleled elevations in subjective effects, hormone effects and peak THC determinations. Although all the hormone effects were within normal basal ranges, interactions between these systems, and their effects on behavior cannot be discounted.     

The influence of nicotine dose and nicotine dose expectancy on the cognitive and subjective effects of cigarette smoking

This study investigated the independent and interactive effects of nicotine dose and nicotine dose expectancy on smoking outcomes using a 2 (given nicotine vs. placebo) × 2 (told nicotine vs. placebo) Balanced Placebo Design (BPD). Smokers (N = 148) completed the Rapid Visual Information Processing Task (RVIP) and measures of smoking urge, mood, and cigarette ratings (e.g., satisfying) after smoking a nicotine or placebo cigarette crossed with instructions that the cigarette contained either nicotine or no nicotine. Nicotine cigarettes (0.6 mg nicotine) produced better sustained attention performance than placebos as indicated by RVIP reaction time, hits, and sensitivity (A'). Nicotine cigarettes also produced better mood and greater rewarding subjective effects of the cigarettes on 11 of 11 dimensions compared to placebos. Nicotine instructions resulted in fewer RVIP false alarms, better mood, and greater rewarding subjective effects of the cigarettes on 9 of 11 dimensions compared to placebo instructions. Nicotine dose by nicotine dose expectancy interactions were also observed for urge and tension-anxiety, such that the dose expectancy manipulation produced differential effects only among those who smoked placebo cigarettes. In contrast a significant interaction for self-reported vigor-activity demonstrated that the dose expectancy manipulation produced effects only among those who smoked nicotine cigarettes. This study provides additional evidence that nicotine improves cognitive performance, and provides initial evidence that denicotinized cigarettes smoked under the guise that they contain nicotine influence cognitive performance, albeit with less robust effects than nicotine. These data may inform the development of expectancy-based interventions for tobacco dependence.     

Placebo cigarettes in a spaced smoking paradigm

Existing evidence supports the notion that nicotine delivery and recentness of smoking mediate the effects of smoking, including decreases in tobacco craving. However, smoking placebo (denicotinized) cigarettes decreases tobacco craving after overnight abstinence. The present study tested whether the recentness of smoking was an important determinant in the ability of a placebo cigarette to reduce tobacco craving. Placebo (0.07 mg nicotine) and conventional (1.1 mg nicotine) cigarettes were used in a spaced smoking paradigm. In six experimental sessions lasting 240 min, subjects smoked either a placebo or conventional nicotine cigarette in intervals of either 30, 60, or 240 min. Heart rate (HR), exhaled carbon monoxide (CO) levels, and subjective (Schuh-Stitzer, QSU) measures of tobacco craving were obtained throughout the spaced smoking paradigm. HR and CO levels increased after smoking both types of cigarettes. Increasing the interval since the last cigarette significantly (p<0.001) increased the baseline values of tobacco craving. Smoking either the placebo or the conventional cigarette caused a significant (p<0.01) reduction in the craving score after smoking. However, the nicotine yield of the cigarette did not influence these patterns. It is concluded that acute tobacco cravings can be repeatedly diminished with cigarettes that do not deliver nicotine.     

Acute and Residual Effects of Marijuana in Humans

Marijuana continues to be the most commonly abused illicit drug in the United States. Because many people abuse marijuana during the evening and on weekends and then go to work or school the next day, more research is needed on the residual effects of marijuana. The current study sought to examine both acute and residual subjective, physiologic, and performance effects of smoking a single marijuana cigarette. Ten healthy male volunteers who reported recent use of marijuana resided on a residential research ward. On three separate days, subjects smoked one NIDA marijuana cigarette containing either 0%, 1.8%, or 3.6% Δ⁹-tetrahydrocannabinol (THC) according to a paced puffing procedure. Subjective, physiologic, and performance measures were collected prior to smoking, five times following smoking on that day, and three times on the following morning. Subjects reported robust subjective effects following both active doses of marijuana, which returned to baseline levels within 3.5 h. Heart rate increased and the pupillary light reflex decreased following active dose administration with return to baseline on that day. A new finding was that marijuana smoking acutely produced decrements in smooth pursuit eye tracking. Although robust acute effects of marijuana were found on subjective and physiological measures, and on smooth pursuit eye tracking performance, no effects were evident the day following administration, indicating that the residual effects of smoking a single marijuana cigarette are minimal.     

Effects of food deprivation on responses to marijuana in humans

The effects of 24h of food deprivation on subjective, physiological and cognitive responses to marijuana were studied in 8 male marijuana smokers. A within-subjects design was used in which subjects smoked active (1.3% THC) and placebo (0.0% THC) marijuana in both a fed and a fasting state. Each of the four experimental conditions - Fed/Active, Fed/Placebo, Fast/Active, Fast/Placebo - was enacted twice according to a randomized block design. A controlled smoking regimen was employed which held inhaled volume of marijuana smoke constant across feeding conditions. Smoke inhalation was monitored by measuring expired-air carbon monoxide (CO) levels before and after smoking. Heart rate and subjective effects of marijuana were assessed before, during and after smoking. A measure of memory performance, free recall, was also assessed after smoking. CO absorption from both placebo and active marijuana did not differ across feeding conditions, indicating that smoke dose was similar across feeding conditions. Typical effects of marijuana, such as elevated heart rate, impaired memory and increased "high" ratings were obtained after smoking active marijuana, but fasting had no effect on the drug response. Lack of a food deprivation effect on marijuana subjective effects and memory performance was noted not only in all subjects, but also in a subset of subjects (n=6) whose physiological states provided verification of their fasting state in Fast sessions.     

Comparison of subjective,pharmacokinetic, and physiological effects of marijuana smoked as joints and blunts

Recent increases in marijuana smoking among the young adult population have been accompanied by the popularization of smoking marijuana as blunts instead of as joints. Blunts consist of marijuana wrapped in tobacco leaves, whereas joints consist of marijuana wrapped in cigarette paper. To date, the effects of marijuana smoked as joints and blunts have not been systematically compared. The current within-subject, randomized, double-blind, placebo-controlled study sought to directly compare the subjective, physiological, and pharmacokinetic effects of marijuana smoked by these two methods. Marijuana blunt smokers (12 women and 12 men) were recruited and participated in a 6-session outpatient study. Participants were blindfolded and smoked three puffs from either a blunt or a joint containing marijuana with varying Δ⁹-tetrahydrocannabinol (THC) concentrations (0.0, 1.8, and 3.6%). Subjective, physiological (heart rate, blood pressure, and carbon monoxide levels) and pharmacokinetic effects (plasma THC concentration) were monitored before and at specified time points for 3 h after smoking. Joints produced greater increases in plasma THC and subjective ratings of marijuana intoxication, strength, and quality compared to blunts, and these effects were more pronounced in women compared to men. However, blunts produced equivalent increases in heart rate and higher carbon monoxide levels than joints, despite producing lower levels of plasma THC. These findings demonstrate that smoking marijuana in a tobacco leaf may increase the risks of marijuana use by enhancing carbon monoxide exposure and increasing heart rate compared to joints.     

Antinociceptive, subjective and behavioral effects of smoked marijuana in humans

The purpose of this study was to determine whether marijuana produced dose-dependent antinociception in humans and, if so, whether endogenous opiates modulate this effect. A total of five male regular marijuana users participated in three test sessions during which they smoked cigarettes containing 0% (placebo) and 3. 55% Delta(9)-tetrahydrocannabinol (Delta(9)-THC) (active). Each of four controlled smoking bouts per session, spaced at 40-min intervals, consisted of nine puffs from active and placebo cigarettes (three cigarettes, three puffs per cigarette, one puff per min). During successive bouts, participants smoked 0, 3, 6 and 9 (0, 3, 9 and 18 cumulative) puffs from active marijuana cigarettes, with the remainder of puffs from placebo cigarettes. Test sessions were identical, except for naltrexone 0, 50 or 200 mg p.o. (randomized, double-blind) administration 1 h before the first smoking bout on the different days. Before smoking, between smoking bouts and postsmoking, participants completed an assessment battery that included antinociceptive (finger withdrawal from radiant heat stimulation), biological, subjective, observer-rated signs and performance measures. Marijuana produced significant dose-dependent antinociception (increased finger withdrawal latency) and biobehavioral effects. Naltrexone did not significantly influence marijuana dose-effect curves, suggesting no role of endogenous opiates in marijuana-induced antinociception under these conditions.     

Tetrahydrocannabinol content and differences in marijuana smoking behavior

Changes in smoking behavior in response to a change in marijuana potency were measured in marijuana users. A marijuana cigarette containing 1.2% or 3.9% tetrahydrocannabinol (THC) was smoked on separate days by ten experienced users. Puff volume, duration and number, interpuff interval, inhalation volume and duration were averaged for each cigarette. The high potency cigarettes were smoked with more puffs and longer interpuff intervals, but also with greater inhaled volumes of air, thereby diluting the marijuana smoke.     

Effects of ethanol on cigarette smoking by volunteers without histories of alcoholism

The effects of ethanol on cigarette smoking were assessed in volunteer research subjects who had histories of light to moderate social drinking. Five subjects participated individually in daily 90-min sessions that were conducted in rooms equipped to permit automatic monitoring of cigarette smoking behavior. Each subject was tested at four dose levels of ethanol and placebo, which were given orally on a double-blind basis, 30 min prior to sessions. Dose order was according to a random block sequence in which each dose was given in each of five blocks of five sessions. Data from five alcoholic subjects who were similarly tested at only one ethanol dose level were used for comparison. For the nonalcoholic group, ethanol doses that produced reliable changes in group scores on various psychometric instruments produced no significant change in smoking behavior. There were differences among the nonalcoholic subjects, however, in that smoking was significantly decreased by ethanol in two subjects, was increased by ethanol in two subjects, and was unchanged in the fifth subject. For the alcoholic group, ethanol produced reliable changes in psychometric measures and significant increases in cigarette smoking. Within- and between-group analyses of results suggest that the effect of ethanol on cigarette smoking may be related to prior history of alcoholic beverage consumption.     

History of marijuana use and tobacco smoking topography in tobacco-dependent adolescents

Adolescent tobacco smokers have higher rates of marijuana (MJ) use than nonsmokers. Because MJ smoking typically involves deeper inhalation and longer breathholding than tobacco smoking, we hypothesized greater puff volume, longer puff duration and puff interval, and higher puff velocity during tobacco smoking among (1) MJ-using teens; (2) teens whose onset of MJ smoking occurred before tobacco (MBT). One hundred and three tobacco-dependent adolescents presented for smoking cessation treatment (66.0% female, 71.0% European American, mean age 15.3+/-1.25 years) smoked one cigarette of their own brand in the laboratory prior to study entry. Topography and associated physiological measures among current recreational (<5 days in a 14-day period) MJ users (n=25), current heavy (>/=5 days in a 14-day period) MJ users (n=22) and current non-MJ-smoking teens (n=56) were compared. There were no differences in tobacco smoking topography or physiological measures by recent MJ-smoking history or by order of substance initiation. Significantly more African American than European American adolescent smokers reported MJ use before tobacco. Our findings in adolescent smokers are consistent with results from adult studies in which history of MJ smoking was not associated with changes in tobacco smoking topography.     

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.     

d-Amphetamine increases choice of cigarette smoking over monetary reinforcement

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

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.     

Comparative effects of tobacco smoking and nasal nicotine

OBJECTIVE: Compare the electroencephalographic (EEG) and cardiovascular effects of tobacco smoking and nasal nicotine in the same subjects. METHODS: Eleven volunteer smokers were studied after >10 h of overnight tobacco deprivation. Quantitative EEG was used to measure brain electrical changes produced by four different treatments. Each subject smoked a low (0.08 mg) and average nicotine (1 mg) yield cigarette on one test day and received placebo and nicotine nasal spray (0.5 mg/spray) on a second day in a counterbalanced design. EEG activity was measured from 16 scalp electrodes and analyzed as delta, theta, alpha (1), alpha (2), beta (1), and beta (2) frequency bands. Heart rate (HR), blood pressure (BP), and plasma venous nicotine concentrations (VNC) were monitored during both sessions. EEG data from all 16 channels at each of six frequencies were compared over 10 min using repeated measures ANOVA analysis. Changes in HR, BP, and VNC from baseline were compared using ANOVA followed by post hoc Scheffe's test. RESULTS: Smoking an average nicotine delivery cigarette resulted in highly significant decreases in alpha (1) activity, significant increases in alpha (2) activity, and significant increases in both HR and VNC compared to all other conditions. CONCLUSION: When smokers are allowed to pace themselves, cigarette smoking is far more effective than nasal nicotine in activating the EEG and increasing HR and VNC. This lack of equivalent physiological effects may explain the low success rate when nicotine nasal spray is used by those trying to quit smoking.     

Effects of single doses of alcohol and caffeine on cigarette smoke puffing behavior

Puffing behavior (number of puffs, puff duration, puff volume, peak pressure, peak flow, peak latency, and puff interval) and pre- to postsmoking delta tidal CO difference were measured in female subjects in order to assess separate and combined effects of ethanol and caffeine. The subjects smoked two cigarettes of their habitual brand in a preliminary familiarizing session and in each of the subsequent four test sessions. The treatments administered after smoking the first cigarette in the test sessions were: alcohol placebo and caffeine placebo; alcohol placebo and caffeine; alcohol and caffeine placebo; alcohol and caffeine. Test-retest reliability across the first cigarette of each session (which was not smoked under the influence of the treatments) was remarkably high for all the puffing parameters. Ethanol in the dose of 0.7 g/kg intensified cigarette smoking of the second cigarette by increasing delta tidal CO, average puff volume, and total puff volume per cigarette, whereas 0.5 g/kg ethanol and 5 mg/kg caffeine given alone or combined with ethanol failed to influence puffing behavior consistently.     

"Paradoxical" effects of smoking on subjective stress versus cardiovascular arousal in males and females.

Cigarette smoking has sometimes been found to decrease subjective stress while simultaneously increasing cardiovascular arousal, contrasting effects referred to as the "nicotine paradox." The present study assessed acute effects of cigarette smoking on subjective stress vs. cardiovascular arousal in minimally deprived male and female smokers who smoked (n = 16) or sham smoked (unlit cigarette, n = 15) and a comparison group of male and female nonsmokers (n = 12) who sham smoked only. All subjects participated in two sessions (high- or low-challenge computer task) in which they smoked or sham smoked prior to each of two 20-min task trials. Results showed reduced subjective stress in smoking smokers compared with sham-smoking smokers during the high- but not low-challenge task. However, this stress reduction occurred only immediately after smoking and dissipated midway through each trial. In males, smoking appeared to reduce stress below that of nonsmokers, while smoking in females attenuated stress only partially to the level of nonsmokers. In contrast with the attenuated stress effects, cardiovascular arousal (especially heart rate) was increased immediately after smoking during both tasks and did not appear to be directly related to subjective changes. These findings suggest that the stress-reducing effects of smoking may be transient, situationally specific, partly gender dependent, and dissociated from the effects of smoking on cardiovascular arousal.