Transdermal nicotine effects on attention

Nicotine has been shown to improve attentiveness in smokers and attenuate attentional deficits in Alzheimer’s disease patients, schizophrenics and adults with attention-deficit/hyperactivity disorder (ADHD). The current study was conducted to determine whether nicotine administered via transdermal patches would improve attentiveness in non-smoking adults without attentional deficits. The subjects underwent the nicotine and placebo exposure in a counterbalanced double-blind manner. Measures of treatment effect included the Profile of Mood States (POMS), Conners’ computerized Continuous Performance Test (CPT) of attentiveness and a computerized interval-timing task. The subjects were administered a 7 mg/day nicotine transdermal patch for 4.5 h during a morning session. Nicotine significantly increased self-perceived vigor as measured by the POMS test. On the CPT, nicotine significantly decreased the number of errors of omission without causing increases in either errors of commission or correct hit reaction time. Nicotine also significantly decreased the variance of hit reaction time and the composite measure of attentiveness. This study shows that, in addition to reducing attentional impairment, nicotine administered via transdermal patches can improve attentiveness in normal adult nonsmokers. Received: 11 June 1997/Final version: 13 March 1998     

The effects of nicotine on the attentional modification of the acoustic startle response in nonsmokers

RATIONALE AND OBJECTIVE: Research on nicotine and attention has mainly utilized samples of deprived smokers and tasks requiring volitional responses, raising the question of whether nicotine improves attention or simply alleviates withdrawal or improves motor speed. This study used the startle eyeblink reflex to assess nicotine effects on auditory attention in nonsmokers. MATERIALS AND METHODS: Sixty-seven healthy young adult nonsmokers completed a tone discrimination task. Acoustic startle probes were presented 60, 120, 240, or 4,500 ms after the onset of two-thirds of the tones and during intertrial intervals. Attention was assessed via (1) short-lead prepulse inhibition (PPI) of startle, a measure of early filtering; (2) long-lead prepulse facilitation (PPF) of startle, a measure of sustained processing; and (3) the modification of PPI and PPF by focused attention. Participants completed two laboratory sessions, once while wearing a 7-mg transdermal nicotine patch and once while wearing a placebo patch. Patches were administered in a double-blind procedure. RESULTS: Nicotine increased overall PPI, eta2(p)=0.09. Attention increased long-lead PPF, eta2(p)=0.25, but not short-lead PPI. Nicotine did not reliably enhance early or late controlled attentional processing in the sample overall. However, correlational analyses demonstrated that nicotine most improved attentional modification of short-lead PPI among participants with the weakest early attentional processing under placebo conditions. CONCLUSIONS: Nicotine enhanced early attentional filtering in general, and the effects of nicotine on early focused attention were dependent upon individual differences in placebo levels of attentional processing. The present data suggest that the effects of nicotine on attention extend beyond the alleviation of withdrawal and simple motor speeding.     

Effects of acute nicotine administration on resting EEG in nonsmokers

Smoking/nicotine has been shown to increase brain arousal states, yet previous studies have failed to distinguish between absolute improvements due to nicotine versus relief from withdrawal symptoms in smokers. This study examined the electrocortical response to nicotine in a nonsmoking population, in order to negate potential withdrawal symptoms. Twenty right-handed, nonsmoking participants were administered nicotine (6 mg) or placebo gum within a double-blind, repeated-measures design. In each session, EEG was recorded during a 2-min, resting, eyes-open condition. Nicotine administration (vs. placebo) resulted in significantly greater frontal (specifically left-frontal) alpha2 power. Similar to previous findings in smokers. The absence of slow-wave changes following nicotine in nonsmokers suggest that these previous results in smokers may be related to withdrawal state.     

The nicotine withdrawal assessment for youth: initial instrument validation and psychometric properties

Within the field of adolescent tobacco use, there does not exist a consistently used and validated measure of adolescent nicotine withdrawal symptoms. The purpose of this study was to evaluate the psychometric properties of the Nicotine Withdrawal Assessment for Youth (N-WAY), a new measure of adolescent nicotine withdrawal symptoms. Smokers and nonsmokers, ranging from 13 to 19 years old, were administered the N-WAY and other smoking information questionnaires in order to examine its reliability and validity. The N-WAY demonstrated satisfactory test-retest reliability (r=0.74-88) and internal consistency (Cronbach's α=0.90-0.92). Its total symptom score accurately discriminated current smokers from nonsmokers. The N-WAY was demonstrated to measure a construct different than nicotine dependence symptoms while correlates of nicotine withdrawal symptoms, such as number of daily cigarettes smoked and prior quit attempts, accurately predicted total N-WAY symptom and impact scores. Preliminary results indicate the N-WAY is a reliable and valid assessment of adolescent nicotine withdrawal symptoms among current smokers.     

Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms

Nicotine gum and transdermal nicotine have been shown to relieve withdrawal and double success rates over placebo in trials of smoking cessation. This study tested whether combining the two methods would relieve withdrawal more effectively compared to either treatment alone. Twenty-eight smokers served as their own controls in each of four conditions: active gum + active patch (double active), active gum + placebo patch (gum only active), placebo gum + active patch (patch active) and placebo gum+placebo patch (double placebo). This double placebo design controls sensory, psychological and ritual variables associated with each drug form. Withdrawal symptoms were rated four times daily for 3 days in each condition. Total baseline (smoking) withdrawal scores using visual analogue scales (VAS) averaged 101.1. During cessation, total withdrawal increased to 187.0 for the double placebo condition, 142.2 for the active gum/placebo patch treatment and 128.3 for the active patch/placebo gum treatment. The double active condition equalled smoking with score 99.2. All pairwise comparisons were significant (P<0.001) except between the two single active conditions and between smoking versus the double active condition. Significant time-of-day effects by treatment on withdrawal were observed for the double placebo condition (P<0.05) with less withdrawal in the morning. The findings suggest: 1) combining nicotine gum with transdermal nicotine may be superior to either treatment alone, 2) more symptoms may be nicotine specific (relieved by replacement) than previously thought.     

A low dose of subcutaneous nicotine improves information processing in non-smokers

Many studies have found that cigarette smoking or nicotine improves mental functioning in abstinent smokers. An unresolved issue is whether this improvement is due primarily to a direct facilitation of performance or to relief of the impairment caused by nicotine withdrawal. We evaluated the performance of 12 non-smokers before and twice (15 and 45 min) after a subcutaneous injection of 0.8 mg nicotine, 0.8 ml saline, and a control no treatment, on a choice reaction time (RT) task. Each treatment was given on a separate day; the control day was given on the first session. The order of nicotine and saline was balanced between subjects, and injections were given double-blind. The RT task manipulated stimulus and response processing. These manipulations consisted of two levels of stimulus complexity and two levels of response complexity, resulting in four task conditions. These manipulations along with latency measures of the event-related potential were used to identify the components of processing that mediated nicotine's effects on performance. During each active drug session blood nicotine levels, cardiovascular, and subjective responses were measured before and after each of the three tests (pre-drug, 15 min and 45 min post-drug). For the information processing measures only the comparisons of the pre- and 15-min post-test showed significant drug effects. Nicotine compared to saline significantly increased the number of responses at the fast end of the RT distribution. However, there were no changes in accuracy. Nicotine also speeded mean RT compared with saline or the control day, but the effects were only significant for the control-nicotine comparison. There was an interaction between effects of nicotine and the task variables, such that nicotine speeded P3 latency in the hardest task condition, while slowing it in the other task conditions. Nicotine significantly increased heart rate, which lasted for the entire session. Blood nicotine levels were lower than expected from a preliminary study in smokers and may have been responsible for the smaller than expected mean RT effects. These findings suggest that even a low dose of nicotine directly affects attention or stimulus processing components of information processing. This study also illustrates the importance of assessing both multiple components of information processing and nicotine levels when examining the effects of nicotine on cognition.     

ADHD medication reduces cotinine levels and withdrawal in smokers with ADHD

Individuals with ADHD may self-medicate with nicotine, the main psychoactive ingredient in tobacco smoke, in order to reduce symptoms and negative moods associated with ADHD. ADHD medication (e.g., methylphenidate and atomoxetine) may mimic some of the effects of nicotine and may aid smoking cessation in smokers with ADHD. The present study examined if ADHD medication reduces smoking and withdrawal in non-treatment seeking smokers with ADHD. Fifteen adult smokers with ADHD participated in the study, which consisted of an experimental phase and field monitoring phase to examine the acute and extended effects, respectively, of ADHD medication. During the experimental phase, smokers were asked to complete a Continuous Performance Task (CPT) and the Shiffman-Jarvik smoking withdrawal questionnaire during the following four conditions: (1) ADHD medication + cigarette smoking, (2) ADHD medication + overnight abstinence, (3) placebo + cigarette smoking, and (4) placebo + overnight abstinence. During the field monitoring phase, participants were asked to provide salivary cotinine samples and complete electronic diaries about smoking, smoking urge, ADHD symptoms, and stress in everyday life for two days on ADHD medication and for two days on placebo. Results of the experimental phase showed that ADHD medication improved task performance on the CPT and reduced withdrawal during overnight abstinence. During the field monitoring phase, ADHD medication reduced salivary cotinine levels compared to placebo. In addition, the electronic diary revealed that ADHD medication improved difficulty concentrating during no smoking events and stress. The findings of the present study suggest that, along with other strategies, ADHD medication may be used to aid smoking withdrawal and cessation in smokers with ADHD.     

Effect of nicotine on the tobacco withdrawal syndrome

This study tested the ability of nicotine to alleviate the tobacco withdrawal syndrome. Signs and symptoms of tobacco withdrawal were measured in 100 smokers who fulfilled DSM-III criteria for tobacco dependence and a past history of tobacco withdrawal. After 2 evenings of baseline measurement, subjects were randomly assigned to receive either nicotine or placebo gum in a double blind manner. Subjects then stopped smoking, chewed gum freely, and returned on the 1st, 2nd, and 4th evenings of abstinence for further measurement. Nicotine reduced the increase in irritability, anxiety, difficulty concentrating, restlessness, impatience, and somatic complaints that subjects reported after cessation. Reductions in these withdrawal symptoms by nicotine were confirmed by ratings of significant others and by subjects' scores on the Profile of Mood States. Nicotine did not reduce the increases in cigarette craving, hunger, eating, insomnia, tremulousness, or supine heart rate after cessation. The effects of nicotine occurred immediately and persisted throughout the study. Although many subjects correctly identified their drug group, the efficacy of the gum was independent of subjects' identifications of drug. The relief of tobacco withdrawal by nicotine gum suggests that the tobacco withdrawal syndrome is caused, in part, by nicotine deprivation.This study was funded by a grant from Merrell Dow Pharmaceuticals, Inc. and by funds for psychiatric research from the State of Minnesota     

Effects of nicotine on novelty detection and memory recognition performance: double-blind, placebo-controlled studies of smokers and nonsmokers

Rationale  Dependent smokers exhibit deficits in attentional and memory processes when smoking abstinent as compared to when satiated. While nicotine replacement therapy improves attention during abstinence, it is unclear whether this is due to the alleviation of withdrawal-related deficits or inherent beneficial effects of nicotine. Objectives  The primary aim of these studies was to test whether nicotine exerts a beneficial effect on novelty detection and whether such effects occur in nonsmokers as well as habitual smokers. Materials and methods  In two parallel, double-blind, placebo-controlled studies, 24 smokers (study 1) and 24 nonsmokers (study 2) were tested in two counterbalanced sessions: once while wearing a nicotine patch (smokers = 14 mg; nonsmokers = 7 mg) and once while wearing a placebo patch. On each day, participants performed three content-specific oddball tasks (perceptual, semantic, and emotional) that required them to press a button whenever they saw a novel target (20% of stimuli) embedded in a stream of common nontarget stimuli (80% of stimuli). Recognition memory for targets was subsequently tested. Reports of mood, smoking withdrawal, patch side effects, and blind success were collected in each session. Results  Among smokers, compared to placebo, nicotine decreased target reaction time during all oddball tasks. Among nonsmokers, nicotine increased target detection accuracy and subsequent memory recognition. Nicotine’s enhancement on each respective measure was not task-content specific in either sample. Conclusions  These data suggest that acute nicotine administration may exert direct beneficial effects on novelty detection and subsequent memory recognition in both smokers and nonsmokers. Moreover, these effects are not content-specific.     

Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: results of a preliminary study

Rationale Individuals with attention deficit hyperactivity disorder (ADHD) smoke at higher rates than the general population; however, little is known about the mechanisms underlying this comorbidity. Objective This study evaluated the effects of overnight abstinence on withdrawal symptoms and cognitive performance in adult smokers with and without ADHD. Materials and methods Individuals smoking ≥15 cigarettes per day were recruited from the community and underwent an evaluation to establish a diagnosis of ADHD (n = 12) or not (n = 14). Withdrawal symptoms, mood, craving, cognitive performance, and smoking cue reactivity were measured during two laboratory sessions—in a ‘Satiated’ condition participants smoked up to and during the session while in an ‘Abstinent’ condition, participants were required to be smoking abstinent overnight and remain abstinent during the session. Results The effects of abstinence on ADHD and non-ADHD smokers did not differ for withdrawal symptom severity, mood, craving or cue reactivity. Significant Group × Condition interactions were observed for measures of attention and response inhibition on the Conners’ CPT. For reaction time (RT) variability and errors of commission, the ADHD group exhibited greater decrements in performance after overnight abstinence compared to the non-ADHD group. The effects of abstinence on other cognitive measures (e.g., rapid visual information processing task, cued Go/No-Go task) did not differ between the two groups. Conclusion This preliminary study is the first to systematically evaluate the effects of acute smoking abstinence in adult smokers diagnosed with ADHD. Individuals with the disorder may smoke at higher rates due to greater worsening of attention and response inhibition after abstinence.     

Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease

Rationale: Acute nicotine injections have been found to improve attentional performance in patients with Alzheimer’s disease (AD), but little is known about chronic nicotine effects. Objective: The present study was undertaken to evaluate the clinical and neuropsychological effects of chronic transdermal nicotine in Alzheimer’s disease subjects over a 4-week period. Methods: The double-blind, placebo controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. Patients wore the nicotine patch (Nicotrol^®) for 16?h a day at the following doses: 5?mg/day during week 1, 10?mg/day during weeks 2 and 3 and 5?mg/day during week 4. The eight subjects had mild to moderate AD and were otherwise healthy. Results: Nicotine significantly improved attentional performance as measured by the Conners’ continuous performance test (CPT). There was a significant reduction in errors of omission on the CPT which continued throughout the period of chronic nicotine administration. The variability of hit reaction time (reaction time for correct responses) on the CPT was also significantly reduced by chronic nicotine. Nicotine did not improve performance on other tests measuring motor and memory function. Conclusions: The sustained improvement in attention found in this study with nicotine dermal patches is encouraging. However, the lack of detected effects of nicotine treatment on other cognitive and behavioral domains in this study leaves questions concerning the clinical impact of nicotinic treatment in Alzheimer’s disease. The modest size of this study limited statistical power which may have been needed to detect more subtle but clinically significant cognitive effects. Higher doses of nicotine, other nicotinic ligands or combination treatment of nicotine with other therapies may be efficacious for producing broader therapeutic effects.     

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     

Withdrawal symptoms over time among adolescents in a smoking cessation intervention: Do symptoms vary by level of nicotine dependence?

Nicotine dependence may be expressed differently in teens than in adults. Thus, it may not be sufficient to build diagnostic and cessation treatment strategies for teens based on adult-derived clinical and research data. This is the first study to prospectively examine the development of withdrawal symptoms by level of nicotine dependence among adolescent smokers. Forty-seven adolescent smokers completed nicotine withdrawal symptoms measures during 10 weeks of cessation treatment. Nicotine dependence was assessed at baseline using the mFTQ. Change in withdrawal symptoms over time by level of nicotine dependence was examined via mixed model ANOVA. Nicotine withdrawal in daily adolescent smokers was strongly and prospectively associated with the level of nicotine dependence. Craving was rated as the most problematic symptom at the baseline assessment. The results of this study may help guide the development of future research on diagnostic and cessation treatment strategies for teens.     

Nicotine self-administration and withdrawal: modulation of anxiety in the social interaction test in rats

RATIONALE: Most smokers report smoking has an anxiolytic effect, which may contribute to nicotine dependence. OBJECTIVE: To examine effects in the social interaction test (SI) of anxiety after 4 weeks' self-administered nicotine (15 infusions of 0.03 mg/kg, totalling 0.45 mg/kg per day), and after 24 and 72 h of withdrawal. The effect of exposure to the operant chamber on withdrawal responses was also examined. METHODS: Animals were trained to self-administer saline or nicotine and after 4 weeks they were tested in SI after their daily self-administration session. Animals were retested after 24 and 72 h withdrawal, when they were either taken directly from the home cage or were tested 5 min after a 30-min exposure to the operant chamber. RESULTS: Compared with the saline control group, the animals that had been self-administering nicotine for 4 weeks showed decreased social interaction with no decrease in locomotor activity, indicating a significant anxiogenic effect of the nicotine infusions. There was no change in social interaction after 24 and 72 h withdrawal from chronic nicotine, regardless of whether or not the rats were exposed to the operant chamber just prior to being tested. CONCLUSIONS: Nicotine self-administration is not maintained because of its anxiolytic effect, but despite, or because of, its anxiogenic effect. There was no evidence of an anxiogenic response after either 24 or 72 h of withdrawal and thus increased anxiety on withdrawal from nicotine does not seem to contribute to nicotine self-administration.     

Attention-deficit/hyperactivity disorder (ADHD) symptoms, craving to smoke, and tobacco withdrawal symptoms in adult smokers with ADHD

Background

Tobacco withdrawal symptoms may be confounded with attention-deficit/hyperactivity disorder (ADHD) symptoms among smokers with ADHD.

Objective

(1) To assess overlap between ADHD symptoms and tobacco/nicotine withdrawal symptoms and craving; (2) to assess the relationship between craving or withdrawal symptoms and the effect of osmotic-release oral system methylphenidate (OROS-MPH) on ADHD symptoms; (3) to assess the association of ADHD symptoms, craving, and withdrawal symptoms with abstinence.

Methods

Secondary analysis of a randomized, placebo controlled smoking cessation trial assessing the efficacy of OROS-MPH taken in addition to nicotine patch among individuals with ADHD. ADHD symptoms, withdrawal symptoms, and craving were assessed at baseline and 2, 4 and 6 weeks after a target quit day.

Results

Withdrawal symptoms and craving showed limited and modest overlap with ADHD symptoms prior to abstinence but more extensive and stronger correlation after quit day. Compared to placebo, OROS-MPH reduced ADHD symptoms; this effect was attenuated by controlling for withdrawal symptoms, but not by craving. Craving, but not ADHD symptoms and withdrawal symptoms, was associated with abstinence during the trial.

Conclusion

When treating smokers with ADHD (1) craving, rather than tobacco withdrawal symptoms or ADHD symptoms may be the more effective therapeutic smoking cessation targets; (2) careful distinction of craving, withdrawal symptoms, and ADHD symptoms when assessing withdrawal phenomena is needed.     

Effects of atomoxetine on subjective and neurocognitive symptoms of nicotine abstinence

Nicotine dependence has been linked to attention-deficit hyperactivity disorder (ADHD) symptoms in both clinical and general populations. This behavioural pharmacology study used a within-subject, double-blind, crossover design to test the effects of atomoxetine, a medication for ADHD, on nicotine abstinence symptoms. Fifty non treatment-seeking smokers (>/=15 cigarettes/day) completed a baseline session when they were smoking as usual and then two laboratory testing sessions after overnight abstinence and treatment with 7 days of either atomoxetine (1.2 mg/kg) or placebo. During each laboratory session, participants completed subjective measures of abstinence symptoms and performed neurocognitive tasks. In mixed effects models, atomoxetine, compared with placebo, was found to be associated with a reduction in abstinence-induced subjective withdrawal symptoms. Atomoxetine was also associated with significant reductions in self-reported smoking urges amongst smokers who scored high on a baseline measure of smoking for stimulation. However, atomoxetine had no effect on any of the cognitive tasks employed in the study. Thus, atomoxetine may reduce cravings to smoke among smokers who use nicotine to increase arousal.     

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.     

Nicotine and ADHD: Cognitive Association

ABSTRACT

Nicotine remains one of the most highly addictive substances. Although the percentage of smokers has declined in the United States, the prevalence of smoking in individuals with Attention Deficit Hyperactivity Disorder (ADHD) persists. To better understand the neuro-biological basis of this comorbidity, we have focused on a prospective preclinical design.

The Spontaneously Hypertensive Rat (SHR) has been extensively utilized as an animal model of ADHD with research supporting face, construct, and predicative validity measures. The contribution of the dopaminergic system is of major interest primarily due to the successful use of methylphenidate and other stimulants in treatment. However, much consideration has been given to dopamine's role in the reward and addiction aspects of nicotine use in ADHD.

The current study was designed to assess the role of dopamine in the prefrontal cortex, a region critical to cognition, after exposure to chronic nicotine. Nicotine was chronically delivered to SHR and control animals via alzet mini pump. Dopamine was measured via microdyalsis, in freely moving animals, on either day 4 or 11 of chronic nicotine exposure.

Our findings suggest that prefrontal cortex dopamine levels increased two-fold in the ADHD animals compared with controls, suggesting that the use of nicotine by ADHD sufferers may be associated with cognitive enhancement. This current preclinical study support reports illustrating that cognitive aspects were most closely linked to tobacco use in adolescence with ADHD.     

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     

Do adolescent smokers experience withdrawal effects when deprived of nicotine?

This is the first controlled prospective study of the effects of nicotine deprivation in adolescent smokers. Heart rate and subjective withdrawal symptoms were measured over an 8-hr period while participants smoked normally. Seven days later, participants were randomized to wear a 15-mg (16-hr) nicotine patch or a placebo patch for 8 hr, and they refrained from smoking during the session. Those wearing the placebo experienced a decrease in heart rate across sessions and an increase in subjective measures of nicotine withdrawal. Those wearing the active patch also reported significant increases for some subjective symptoms. Expectancy effects were also observed. The findings indicate that adolescent smokers experience subjective and objective changes when deprived of nicotine. As in previous research with adults, expectancies concerning the effects of nicotine replacement also influenced perceptions of withdrawal.