Effects of nicotine dose, instructional set, and outcome expectancies on the subjective effects of smoking in the presence of a stressor.

The balanced placebo design (BPD) was used to evaluate the independent effects of nicotine dose and smoking-related expectancies on self-reported anxiety, urge to smoke, and withdrawal symptoms. After anxious mood was induced, participants smoked either a de-nicotinized cigarette or one with standard nicotine content. Nicotine dose was crossed with instructions that the cigarette was either de-nicotinized or standard. Nicotine cigarettes produced greater anxiety reduction than de-nicotinized cigarettes. Nicotine instructions attenuated anxiety only among those who held relevant expectancies. Nicotine dose and instructional set interacted such that either nicotine cigarettes or instructions that the cigarettes contained nicotine were sufficient to reduce urge to smoke. Implications of these findings and methodological issues regarding use of the BPD with cigarettes are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy.

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2×2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Influence of Instructions and Nicotine Dose on the Subjective and Reinforcing Effects of Smoking.

Subjective and reinforcing effects of smoking a cigarette were examined within a 2 x 2 modified balanced-placebo design, which manipulated instructions about nicotine content (i.e., told regular nicotine vs. told low nicotine) and actual nicotine dose (given a regular nicotine brand vs. a denicotinized brand). Most ratings of the nicotine content and reward value of cigarettes were higher for those told regular nicotine versus told low nicotine, and for those given regular nicotine versus given low nicotine. Nicotine and instructions did not affect craving, withdrawal, or smoke-reinforced responding, but instructions affected the number of puffs earned for those given low nicotine (i.e., placebo effect). Thus, verbal information (instructions) can influence some responses to smoking consistent with the presence of placebo and antiplacebo effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experimental analysis of the role of expectancy in nicotine withdrawal.

Manipulated the withdrawal symptoms experienced by 62 cigarette smokers during a 48-hr smoking abstinence period. Ss were randomly assigned to 1 of 4 expectancy manipulation groups (psychological complaints, somatic complaints, no complaints, and no-expectancy control), and withdrawal symptoms were measured during 48 hrs of ad libitum smoking and 48 hrs of abstinence. The expectancy manipulation consisted of placebo nicotine gum and specific instructions as to the type of withdrawal symptoms to expect during smoking abstinence. Ss instructed to expect no complaints during abstinence reported fewer somatic complaints and less mood disturbance than the no-expectancy controls. Ss instructed to expect somatic, but not psychological, complaints reported more numerous and severe somatic withdrawal symptoms than did Ss instructed not to expect such symptoms. Results suggest expectancy may play a role in nicotine withdrawal experiences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of transdermal nicotine on tobacco/nicotine abstinence and the effects of a concurrently administered cigarette in women and men.

Transdermal nicotine (TN) is an efficacious smoking cessation pharmacotherapy thought to work, in part, by attenuating the effects of tobacco/nicotine abstinence and the effects of concurrently smoked cigarettes. Clinical trials suggest that TN may be less efficacious for women. This study explored the possibility of TN-related gender differences in ≥8 hour abstinent smokers (54 women, 70 men) who completed four within-subject, double-blind, placebo-controlled sessions corresponding to 0, 7, 14, and 21 mg TN. In each approximately 6.5-hr long session participants smoked an own-brand cigarette 4 hours after TN administration and physiological and subjective outcomes were examined throughout each session. Results revealed that TN suppressed some signs and symptoms of tobacco abstinence and attenuated some effects of smoking, and these effects were not dependent on gender. Women were more sensitive to the direct effects of nicotine (e.g., ratings of Nauseous) and, independent of TN dose, self-administered less nicotine when smoking and rated smoking as less rewarding. Thus, although this study does not shed light on clinical observations that TN is less effective for women, results suggest that TN might need to be combined with other interventions to supplement its effects on tobacco/nicotine abstinence and concurrent smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Expectancy and pharmacology influence the subjective effects of nicotine in a balanced-placebo design.

The expectancy and pharmacological effects of nicotine (0.60 mg) on memory and the subjective effects of cigarettes were examined by using a balanced-placebo design (i.e., expect either nicotine or no nicotine and receive either nicotine or no nicotine). A total of 120 college students who smoke were assigned to 1 of the 4 experimental groups, then rated the cigarettes on a number of dimensions and completed questionnaires on smoking urges, tension, and energy. Participants also completed tests of memory as well as predictions of memory. Pharmacology played a stronger role than expectancy in most ratings of the cigarettes, but significant effects of expectancy did emerge for feelings of increased wakefulness, concentration, calming, cigarette satisfaction, and hunger reduction. The presence of nicotine significantly reduced smoking urges, but expectancy alone reduced tension after smoking. Neither variable produced significant effects on memory or memory predictions. These findings demonstrate that nonpharmacological factors can play an important role in the self-reported effects of nicotine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychological and pharmacological influences in cigarette smoking withdrawal: Effects of nicotine gum and expectancy on smoking withdrawal symptoms and relapse.

To determine the relative effects of expectancy and nicotine depletion on aversive withdrawal symptoms, we gave 109 smokers attempting to quit either nicotine gum or placebo within a balanced placebo design and monitored their withdrawal symptoms and smoking for 2 weeks. Subjects who believed they were getting nicotine gum reported less physical symptoms of withdrawal, showed less arousal, and smoked fewer cigarettes during the first week of quitting when compared with those who thought they were receiving placebo gum. The actual nicotine content of gum had no effect on withdrawal or relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transdermal nicotine-induced tobacco abstinence symptom suppression: Nicotine dose and smokers' gender.

An aversive tobacco abstinence syndrome, thought to reflect an underlying level of nicotine dependence, contributes to cigarette smokers' failed quit attempts. Nicotine replacement therapy (NRT) suppresses tobacco abstinence, but high relapse rates suggest room for improvement. Improving NRT's efficacy might begin with identifying factors that influence tobacco abstinence symptom suppression. Two such factors are smokers' gender and NRT dose. The purpose of this study was to determine the dose-related effects of transdermal nicotine (TN) on tobacco abstinence symptoms in 75 men and 53 women who regularly smoked cigarettes but who had abstained from smoking for at least 8-12 hr. Participants completed 4 double-blind, randomized 6.5-hr laboratory sessions that differed by TN dose (0, 7, 21, or 42 mg). Each session included blood sampling for plasma nicotine level, measurement of heart rate, participants' ratings of tobacco abstinence symptoms and effects of nicotine, and psychomotor performance. Increases in plasma nicotine level were related to TN dose and were independent of gender. TN-induced abstinence symptom suppression was dose-related for items assessing craving and urge to smoke and largely was independent of gender. TN increased heart rate and ratings of aversive side effects (e.g., nausea, lightheadedness) in a dose-related manner, and women were more sensitive at higher doses. Results from this laboratory study support the continued use of TN as a pharmacotherapy. Higher doses may ameliorate some abstinence symptoms, although the side effect profile, at least in the short term, may limit effectiveness, especially for women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The nicotine inhaler in smoking cessation

BACKGROUND: Nicotine replacement therapy has been shown to improve success rates in smoking cessation treatment. However, the available products cause adverse effects, which prevent some smokers from using them. A new method of delivering nicotine via inhaler supplies nicotine orally through inhalation from a plastic tube. This mode of delivering nicotine resembles smoking, as it includes handling and active inhalation. OBJECTIVES: To assess the efficacy and safety of the nicotine inhaler as an aid in smoking cessation. METHODS: A 1-year, randomized, double-blind, placebo-controlled study was conducted in a smoking cessation clinic. Two hundred forty-seven smokers who smoked at least 10 cigarettes per day and who had previously made a serious attempt to stop smoking using nicotine chewing gum were recruited through advertisements. Randomization to treatment or control conditions were made at the first group session, with 123 participants receiving nicotine inhalers and 124 receiving placebo inhalers. The inhalers were distributed at the second session and participants were allowed to use the inhalers for 6 months. MAIN OUTCOME MEASURE: Biochemically verified continuous abstinence from smoking after 2 and 6 weeks and at 3, 6, and 12 months. RESULTS: Significantly more participants who had used the nicotine inhalers were continuously abstinent compared with those who had used the placebo inhalers. The respective success rates after 12 months were 28% and 18% (P = .046). At 6 months, 20 participants (16%) in the nicotine group were still using the inhaler, compared with 4 (3%) in the control group (P < .001). CONCLUSION: The nicotine inhaler was an effective smoking cessation aid that produced a few mild and transient adverse effects.     

Effectiveness of a marijuana expectancy manipulation: Piloting the balanced-placebo design for marijuana.

Although alcohol and nicotine administration studies have demonstrated that manipulating subjects’ expectancies regarding drug content affects drug response, research with marijuana has not adequately studied drug expectancy effects. The present pilot study was the first to evaluate the credibility and effect of expectancy manipulation on subjective measures and smoking patterns using a marijuana administration balanced-placebo design (BPD). In a 2 × 2 instructional set (told delta-9-tetrahydrocannabinol [THC] vs. told no THC) by drug (smoked marijuana with 2.8% THC vs. placebo) between-subjects design, the authors examined the effect of marijuana expectancy manipulation and the pharmacologic effect on affective and physiologic measures, cigarette ratings, and smoking behavior with 20 marijuana smokers (mean age = 20 years; 25% female). Large main effects of expectancy were found on ratings of cigarette potency, strength, taste, smell, and satisfaction, and observed smoking behavior. Pharmacologic effects were particularly evident for self-reported physical reactions to marijuana and cigarette potency and satisfaction ratings. This study demonstrated the feasibility of the BPD research with marijuana and yielded promising results for future studies examining the independent and combined effects of marijuana pharmacology and expectancies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute effects of nicotine content in cigarettes on coronary flow velocity and coronary flow reserve in men

We investigated the acute effects of smoking on coronary flow reserve in terms of the nicotine content of cigarettes in 21 smokers. Coronary flow velocity was measured with a Doppler flow wire. Subjects smoked cigarettes containing >1 mg nicotine (n = 8, group 1) or <1 mg (n = 6, group 2). Subjects in the control group mimicked smoking without a cigarette (n = 7). Coronary flow reserve decreased after smoking in group 1, but not in group 2 or the control group. This reduction may have mediated nicotine or some other unknown substances influenced by smoking.     

Smoking behavior and smoking history of tobacco chippers.

Nicotine produces dependence in almost all cigarette smokers. 65 chippers (anomalous smokers who smoke regularly but at very low levels [1–5 cigarettes/day]) were compared with 72 matched regular smokers (20–40 cigarettes/day). Despite having smoked an average of 46,000 cigarettes in 19 yrs of smoking, chippers demonstrated little sign of nicotine dependence. They reported frequent casual abstinence from smoking without withdrawal symptoms, smoked their 1st cigarette of the day hours after waking, and scored low on a modified Fagerstrom Tolerance Questionnaire, a measure of tobacco dependence. Although most chippers had never smoked heavily, a small subgroup of chippers reported previous extended periods of heavy smoking, which suggests that some people may be able to overcome dependence while continuing to smoke. These "converted chippers" could not be distinguished from "native chippers" on the basis of their current smoking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of cigarette smoking on perception of thermal pain.

The effects of cigarette smoking on pain perception were evaluated in 18 healthy smokers. Thermal pain stimuli were used to assess pain detection threshold and tolerance and to collect subjective ratings of the intensity and unpleasantness of painful stimuli. After overnight abstinence, pain perception was evaluated before and after 3 experimental treatments. Participants smoked normal cigarettes, smoked denicotinized cigarettes, or remained abstinent. Smoking normal cigarettes produced relative increases in pain tolerance compared with abstinence. Smoking denicotinized cigarettes produced intermediate effects on tolerance not different from the other 2 treatments. Effects were not detected for pain threshold or subjective pain ratings. Results suggest that cigarette smoking can have antinociceptive effects, which may depend both on nicotine and on other factors associated with smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cigarette smoking, nicotine addiction, and relaxation.

Shock endurance was used to measure the amount of anxiety experienced in a stressful situation by nonsmokers, smokers allowed to smoke cigarettes containing low levels or moderately high levels of nicotine, and smokers not allowed to smoke. Ss were 51 university students. Smokers deprived of cigarettes and those who smoked cigarettes containing low levels of nicotine behaved more anxiously than nonsmokers and Ss allowed to smoke high-nicotine cigarettes, but the high-nicotine smokers behaved no less anxiously than nonsmokers. Results support the hypothesis that the calming effect of smoking is due to the action of nicotine in ending withdrawal symptoms in addicted smokers rather than to a sedative property of cigarette smoking. (12 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy

This review discusses the known cardiovascular effects of smoking and the effects of nicotine without tobacco smoke and interprets the available data on cardiovascular risk during nicotine replacement therapy (NRT). Nicotine gum and patches are now approved for over the counter sale in the United States. Smokers with cardiovascular disease are advised to seek physician counseling before using nicotine products, but information regarding the safety of these products in such patients is not readily available to most physicians. Nicotine may contribute to cardiovascular disease, presumably by hemodynamic consequences of sympathetic neural stimulation and systemic catecholamine release. However, there are many potential cardiovascular toxins in cigarette smoke other than nicotine. The doses of nicotine obtained by regular cigarette smoking generally exceed those delivered by NRTs, and the cardiovascular effects of nicotine are, in general, more intense when delivered rapidly by cigarette smoking than the slower delivery by transdermal nicotine or nicotine gum. Because the dose-cardiovascular response relation for nicotine is flat, the effects of cigarette smoking in conjunction with NRT are similar to those of cigarette smoking alone. Cigarette smoking increases blood coagulability, a major risk factor for acute cardiovascular events, whereas transdermal nicotine does not appear to do so. Clinical trials of NRT in patients with underlying, stable coronary disease suggest that nicotine does not increase cardiovascular risk. At worst, the risks of NRT are no more than those of cigarette smoking. The risks of NRT for smokers, even for those with underlying cardiovascular disease, are small and are substantially outweighed by the potential benefits of smoking cessation.     

Cocaine use can increase cigarette smoking: Evidence from laboratory and naturalistic settings.

Two studies examined the effects of cocaine use on cigarette smoking. Study 1 was conducted with 10 healthy volunteers under controlled laboratory conditions. Participants received double-blind doses of intranasal cocaine HCI (100 mg) or placebo in separate sessions, with each being followed by a 3-hr period of monitored cigarette smoking. Latency to the first cigarette and the mean interval between cigarettes was significantly shorter and the total number of cigarettes smoked was greater after cocaine than placebo administration. Study 2 was conducted by using urine specimens from 9 ambulatory cocaine-dependent patients. Urine cotinine (nicotine metabolite) levels on days when urinalysis testing indicated recent cocaine use were compared with levels on days when urinalysis testing indicated no recent use. Cotinine levels were significantly higher on cocaine-positive days, indicating that cocaine use was associated with greater cigarette smoking. Overall results provide evidence that acute cocaine administration can increase cigarette smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of nicotine on negative affect among more impulsive smokers.

In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N=70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity × Condition (nicotinized vs. de-nicotinized) × Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High-dose transdermal nicotine and naltrexone: Effects on nicotine withdrawal, urges, smoking, and effects of smoking.

Although treatment with transdermal nicotine replacement (TNR) has improved smoking abstinence rates, higher doses of TNR could improve effects on urge to smoke, nicotine withdrawal, and reinforcement from smoking, and naltrexone might further reduce reinforcement and urges. A laboratory investigation with 134 smokers using a 3 × 2 parallel-group design evaluated the effects of TNR (42-mg, 21-mg, or 0-mg patch) as crossed with a single dose of naltrexone (50 mg) versus placebo on urge to smoke, withdrawal, and responses to an opportunity to smoke (intake, subjective effects) after 10 hr of deprivation. Urge and withdrawal were assessed both prior to and after cigarette cue exposure. Only 42 mg TNR, not 21 mg, prevented urge to smoke, heart rate change, and cue-elicited increase in withdrawal. Both 21 and 42 mg TNR blocked cue-elicited drop in heart rate and arterial pressure. Naltrexone reduced cue-elicited withdrawal symptoms but not urges to smoke or deprivation-induced withdrawal prior to cue exposure. Neither medication significantly affected carbon monoxide intake or subjective effects of smoking except that 42 mg TNR resulted in lower subjective physiological activation. No interaction effects were found, and no results differed by gender. Results suggest that starting smokers with 42 mg TNR may increase comfort during initial abstinence, but limited support is seen for naltrexone during smoking abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The acute effects of nicotine on positive and negative affect in adolescent smokers.

Although adolescent cigarette smoking remains a critical public health concern, little is known about the reinforcing mechanisms governing smoking in this vulnerable population. To assess predictions derived from both positive and negative reinforcement models of drug use, the authors measured the acute effects of nicotine, as administered via tobacco cigarettes, on both positive and negative affect in a group of 15- to 18-year-old smokers. A matched group of nonsmokers served as a comparison group. Findings revealed that whereas adolescents who smoked a cigarette experienced reductions in both positive and negative affect, the observed reductions in negative affect were moderated by nicotine content of the cigarette (high yield vs. denicotinized), level of nicotine dependence, level of baseline craving, and smoking expectancies pertinent to negative affect regulation. Nonsmokers experienced no change in affect over the 10-min assessment period, and no interaction effects were observed for positive affect. Overall, the findings conform to a negative reinforcement model of nicotine effects and strongly suggest that, even among young light smokers, nicotine dependence and resultant withdrawal symptomatology may serve as motivating factors governing smoking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)