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)     

Positive reactions to tobacco predict relapse after cessation.

Among chronic smokers, individual differences in subjective reactions to smoking may characterize important facets of nicotine dependence that relate to abstinence-induced craving, withdrawal symptom profiles, and risk for relapse. Although the negative reinforcing properties of smoking have achieved prominent positions in models of relapse (Baker, Brandon, & Chassin, 2004), vulnerability to relapse risk may also arise from seeking positive reinforcement from smoking (Shiffman & Kirchner, 2009). In this study, 183 cessation-motivated smokers provided subjective craving, positive and negative reactions to standardized cigarettes following overnight abstinence. Level of craving, negative mood, and positive mood after overnight abstinence were significantly predictive of withdrawal on quit-day. Increased positive reactions to smoking were uniquely predictive of relapse after quitting (Hazard Ratio = 1.22, p     

Stress and drug-cue-induced craving in opioid-dependent individuals in naltrexone treatment.

Background: Naltrexone is a nonaddictive medication that blocks the euphoric effects of opioids. However, naltrexone treatment is associated with high rates of noncompliance and opioid relapse, possibly because it does not reduce stress and protracted withdrawal symptoms during early recovery. Prior clinical and preclinical research has indicated that both stress and drug-cue-related arousal response is associated with craving and vulnerability to relapse in a range of drug-using populations. Aims: To examine opioid craving and the subjective and cardiovascular response to stress and drug cues in naltrexone-treated opioid abusers. Method: Eleven men and three women engaged in naltrexone treatment for opioid dependence. They were exposed to personalized stress, drug-cue, and neutral-relaxing imagery in a single laboratory session. Subjective (craving, emotion) and cardiovascular (heart rate, systolic blood pressure, and diastolic blood pressure) measures were assessed. Results: Stress and drug-cue-related imagery significantly increased opioid craving, anxiety, and negative emotions and significantly decreased positive emotions compared to neutral imagery. Selective emotional responses were greater in the stress condition than in the drug-cue condition. Only stress-related imagery was associated with an increased cardiovascular response. Conclusions: Naltrexone-treated opioid abusers demonstrate vulnerability to stress and drug-cue-induced craving and arousal responses that may contribute to the high rates of noncompliance and relapse among opioid-dependent individuals undergoing naltrexone treatment. Pharmacological and behavioral interventions that specifically target the negative affectivity that co-occurs with drug-cue and stress-induced craving could be of benefit in improving naltrexone treatment outcomes in opioid dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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 and 8-hr period while participants smoked normally. Seven days later, participants were randomized to wear a 15-mg (16-hr) nicotine patch or 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. (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)     

EEG asymmetry and heart rate during experience of hypnotic analgesia in high and low hypnotizables

This study evaluates the effects of hypnotic analgesia and hypnosis on bilateral EEG activity recorded from frontal, central and posterior areas during three painful electrical stimulation conditions: waking, hypnosis/no-analgesia, hypnosis/analgesia. Eight high-hypnotizable and eight low-hypnotizable (right handed) subjects participated in the experiment. The following measures were obtained: pain and distress tolerance ratings; EEG spectral amplitudes for the frequency bands: delta (0.5-3.75 Hz), theta 1 (4-5.75 Hz), theta 2 (6-7.75 Hz), alpha 1 (8-9.75 Hz), alpha 2 (10-12.75 Hz), beta 1 (13-15.75 Hz), beta 2 (16-31.75 Hz), total band (0.5-31.75 Hz), '40-Hz' (36-44 Hz); cardiac interbeat interval (ms); mid-frequency and high-frequency peaks from power spectral analysis of heart period variability. During hypnosis/analgesia, high hypnotizable subjects displayed significant reductions in pain and distress scores compared to hypnosis/no-analgesia and waking conditions. In each experimental condition these subjects displayed significant lower total and beta 1 amplitudes compared to low hypnotizables. High hypnotizables, on central and posterior recording sites, during both hypnosis/analgesia and hypnosis/no-analgesia conditions also showed total and delta EEG amplitude reductions in both hemispheres and a theta 1 amplitude reduction in the left hemisphere. However, for total, delta and beta 1 bands in the hypnosis/analgesia condition the amplitude reduction was more pronounced in the right hemisphere as shown by hemispheric asymmetry in favor of the left hemisphere. Low hypnotizables, on posterior recording sites, displayed a delta amplitude reduction during hypnosis/no-analgesia and hypnosis/analgesia conditions. These subjects also showed, for all recording sites, a reduction in theta 1 amplitude during hypnosis/no-analgesia compared to the waking condition. Lows, however, failed in evidencing amplitude differences between hypnosis/no-analgesia and hypnosis/analgesia conditions. During hypnotic analgesia the hemispheric asymmetry found in high hypnotizables was parallel to a significant reduction in the spectral mid-frequency peak of heart period variability which indicated a decrease in the level of sympathetic activity. In contrast, during hypnosis/no-analgesia the EEG amplitude reduction was not paralleled by a decrease in sympathetic activity.     

Nicotine withdrawal in chippers and regular smokers: Subjective and cognitive effects.

From previous studies, chippers (very light, long-time cigarette smokers) seem not to be nicotine dependent, despite decades of smoking. The effect of tobacco deprivation on chippers' withdrawal reactions was examined. Matched groups of 26 chippers and 25 regular smokers were studied while abstaining or smoking for 2-day blocks, with assessments administered 5 times daily by palm-top computers. As hypothesized, chippers showed no changes as a result of nicotine deprivation. In contrast, regular smokers demonstrated distinct changes in craving, mood, arousal, and sleep disturbance. The computers also tested participants' cognitive performance. Unlike chippers, regular smokers' performance on complex tasks was slower under deprivation; the effect could not be explained by changes in motor performance or simple reaction time. Results suggest performance may have been improved by nicotine rather than worsened by withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behaviour-related effects of nicotine on slow EEG waves in basal nucleus-lesioned rats

The basal magnocellular nucleus is assumed to play a crucial role in cholinergic activation of the cortical EEG. The aim of this study was to establish whether intraperitoneally applied nicotine may counteract the power asymmetry of the slow waves in the cortical EEG of both hemispheres after an unilateral lesion in the basal nucleus. In 17 rats the basal nucleus (substantia innominata/ventral pallidum) was unilaterally lesioned by ibotenic acid. The lesion produced unilateral power increases of all frequencies up to 20 Hz in the frontal EEG that increased with higher arousal level. Additionally, synchronized spike and wave discharges appeared in the frontal EEG. The results indicate that the basal nucleus suppresses especially the delta EEG waves in the frontal motor cortex during motor active behaviour. Nicotine (0.1 and 1 mg/kg) partially counteracts the power asymmetry of frontal slow waves (2-6 Hz) only during exploratory sniffing but not during grooming and waking immobility. Physostigmine (1 mg/kg) was also effective during exploratory sniffing. The results may indicate a role of nicotinic mechanisms in the information input component of exploratory behaviour.     

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)     

Effects of tobacco smoking and abstinence on middle latency auditory evoked potentials

OBJECTIVE: To evaluate the effects of tobacco cigarette smoking and overnight abstinence on middle latency auditory evoked potentials among smokers and nonsmokers. METHODS: Groups of 9 to 10 adult male and female nonsmokers and smokers participated in the study. Each person volunteered for two laboratory sessions conducted in the early afternoon on 2 separate days. Smokers abstained from tobacco products 6 to 15 hours before the abstinent session and maintained their usual smoking behavior before the smoking session. The nonsmokers had a similar laboratory experience but sham smoked by means of inhaling air. Middle latency auditory evoked potentials were recorded from Cz to both ears as reference. RESULT: The latencies of the Na and Pa potentials during the smoking session were significantly (p < 0.01) shorter than those in abstinent smokers and nonsmokers. After smoking, peak-to-trough amplitudes for the V-Na, Na-Pa, and Pa-Nb potentials were larger than those after abstinence and significantly larger than those among nonsmokers. CONCLUSIONS: The shorter latencies of the middle latency brain wave components in the smoking session suggest faster processing of sensory information after cigarette smoking. Larger Pa amplitudes after cigarette smoking suggest a higher arousal level than that among partially abstinent smokers and nonsmokers.     

Nicotine dependence, depression, and the moderating role of goal cognitions.

The authors examined the moderating role of goal cognitions in the process of nicotine dependence in young adult smokers. A college sample of 85 male and 78 female smokers completed measures of nicotine dependence and psychological distress. They also provided cognitive evaluations for goals related to smoking cessation on scales measuring self-efficacy, value, planning, self-reward, self-criticism, self-monitoring, social comparison, and positive and negative goal-based arousal. As has been previously established, depression had a direct and significant effect on nicotine dependence. Moreover, significant interactions between goal cognitions and depression provided evidence for the hypothesized moderating effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear reactivity to bodily sensations among heavy smokers and nonsmokers.

Individuals who smoke are more likely to experience panic attacks and develop panic disorder than those in the general population. One possible explanation is that smokers may experience a heightened fear response to somatic disturbances. To date, few laboratory studies have tested this hypothesis directly. The present study examined 24 adult heavy smokers (10 females) in 12-hr nicotine withdrawal and 24 adult nonsmokers (12 females) on subjective and physiological reactivity to a 4-min carbon dioxide rebreathing challenge. Results indicate that, despite an attenuated acceleration in respiration during the challenge, smokers experienced a significantly greater increase in self-reported panic symptoms than nonsmokers. In addition, smokers reported significantly greater trait levels of suffocation fear prior to the challenge. Findings are discussed with respect to the role of smoking in panic vulnerability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacotherapy for smoking cessation: Unvalidated assumptions, anomalies, and suggestions for future research.

Questions several assumptions about the rationale for pharmacological therapies for smoking cessation, including whether (1) future smokers will be those more dependent on nicotine and thus in greater need of nicotine replacement or other pharmacotherapy, (2) transdermal nicotine and nicotine gum work by reducing withdrawal symptoms, and (3) clonidine works by decreasing sympathetic arousal. After describing currently available pharmacotherapies, the article also describes several unexpected findings that need to be taken into consideration by clinicians: (1) Transdermal nicotine is effective when given without psychological therapy, (2) transdermal nicotine and nicotine gum do not consistently decrease postcessation weight gain, (3) high level of nicotine dependence does not consistently predict better response to transdermal nicotine, and (4) clonidine is effective in women but not in men. The article poses other questions for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Manipulating smoking motivation: Impact on an electrophysiological index of approach motivation.

A chief goal of this research was to determine whether stimuli and events known to enhance smoking motivation also influence a physiological variable with the potential to index approach motivation. Asymmetry of electroencephalographic (EEG) activity across the frontal regions of the 2 hemisphere (left minus right hemisphere activation) was used to index approach motivation. In theory, if EEG asymmetry sensitively indexes approach dispositions, it should be influenced by manipulations known to affect smoking motivation, that is, exposure to smoking cues and tobacco deprivation. Seventy-two smokers participated in this research and were selectively exposed to a smoking-anticipation condition (cigarettes plus expectation of imminent smoking) following either 24 hr of tobacco withdrawal or ad libitum smoking. Results indicated that EEG asymmetry was increased by smoking anticipation and that smoking itself reduced EEG asymmetry. Results also suggested that smoking anticipation increase overall (bihemispheric) EEG activation. Results were interpreted in terms of major theories of drug motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterizing nicotine withdrawal in pregnant cigarette smokers.

Maternal smoking is a leading preventable cause of poor pregnancy outcomes and infant morbidity and mortality. Whereas pregnancy has been thought of as a "window of opportunity" when women are more motivated to change health behaviors such as smoking, only 20% of pregnant women quit smoking upon learning they are pregnant and remain abstinent at the end of the pregnancy. Greater understanding of possible obstacles to smoking during pregnancy, such as nicotine withdrawal, is needed. The symptoms of nicotine withdrawal have been well characterized in nonpregnant smokers, but there has been only 1 report conducted during pregnancy, and that was a retrospective study. The aim of the present study was to characterize nicotine withdrawal and craving in pregnant cigarette smokers. These data were collected as part of prospective clinical trials assessing the efficacy of voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum. The authors examined results from the Minnesota Nicotine Withdrawal Scale (J. R. Hughes & D. K. Hatsukami, 1998) in 27 abstainers (reported no or very low levels of smoking, which was confirmed biochemically) and 21 smokers (smoked at >80% of their baseline smoking level) during the first 5 days of a cessation attempt. Abstainers reported more impatience, anger, and difficulty concentrating than did smokers. The results also suggest that pregnant smokers generally may have elevated baseline levels of withdrawal, which need to be considered in the design and analysis of future studies. (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)     

Measures of affect and nicotine dependence predict differential response to smoking cessation treatments.

126 smokers were randomly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies (skills training or support) and 1 of 2 nicotine exposure strategies (nicotine gum or rapid smoking). Counseling and nicotine strategies were completely crossed: All 4 combinations resulted in equivalent 1-yr abstinence rates. Skills training produced higher initial cessation and more coping responses posttreatment than did support. Rapid smoking, but not nicotine gum, produced tachycardia to the taste of cigarettes posttreatment, consistent with cigarette aversion. The treatments were differentially effective among subpopulations of smokers: Ss high in pretreatment negative affect responded best to support counseling; those low in pretreatment negative affect responded best to skills training. Self-reports of pretreatment craving predicted response to the nicotine-exposure treatments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nitric oxide mediates mecamylamine- and naloxone-precipitated nicotine withdrawal

A nitric oxide synthase inhibitor blocked nicotine abstinence signs and increased weight loss in male, nicotine-dependent rats during withdrawal precipitated by the nicotinic receptor antagonist mecamylamine or the opioid receptor antagonist naloxone. These results indicate that nitric oxide systems mediate important aspects of the expression of nicotine physical dependence and suggest the potential use of nitric oxide synthase inhibitors as aids in tobacco smoking cessation.     

Effects of chronic nicotine treatment and withdrawal on hypothalamic proopiomelanocortin gene expression and neuroendocrine regulation

Considerable evidence suggest that some responses to smoking and nicotine are mediated by forebrain beta-endorphinergic opioid mechanisms. It has also been demonstrated that nicotine stimulates rat tuberoinfundibular dopaminergic activity. Since we have proposed that interactions between mediobasohypothalamic (MBH) dopaminergic and beta-endorphinergic mechanisms have a key role in neuroendocrine integration, we investigated the effects of chronic nicotine treatment and withdrawal on: (1) MBH concentrations of proopiomelanocortin (POMC, precursor for beta-endorphin biosynthesis) mRNA; (2) MBH concentrations of tyrosine hydroxylase (TH, rate limiting enzyme in catecholamine biosynthesis) mRNA; (3) corresponding serum prolacin, corticosterone, luteinizing hormone (LH), and testosterone concentrations. POMC and TH mRNA levels were measured by RNase protection/solution hybridization assay; serum hormone levels were measured by radioimmunoassay. Adult male rats received subcutaneous injections of either nicotine or saline during the dark period of each day on an increasing frequency (1-3 injections/day) and dosage (0.4-0.5 mg nicotine/kg body weight) schedule over 4 weeks. The rats were sacrificed after 4 weeks treatment and at 1, 3, 7, 14 and 21 days withdrawal. Chronic daily nicotine administration induced significant changes in serum corticosterone, serum prolactin, MBH TH mRNA, and MBH POMC mRNA concentrations that tended to persist through day 3 of withdrawal; serum prolactin and MBH POMC mRNA concentrations were suppressed whereas serum corticosterone and MBH TH mRNA concentrations were stimulated. None of the parameters were significantly different from control levels following 7 or more days of withdrawal from nicotine, except for a significant decrease of MBH POMC mRNA concentrations on day 21. Chronic daily nicotine or withdrawal did not significantly alter serum LH or testosterone concentrations. These results suggest that chronic nicotine inhibited POMC gene expression and thus, probably, biosynthesis of beta-endorphin and other opiomelanocortins. We hypothesize that suppression of forebrain beta-endorphin synthesis in response to long-term nicotine exposure produces a chronically opioid deficient condition which may play an important role in maintaining nicotine self-administration and in mediating some changes during the nicotine withdrawal syndrome.