Nicotine Withdrawal Symptoms Research Articles

Effect of activated peripheral κ-opioid receptors on the action of nicotine and its withdrawal in nicotine-dependent rats.

We studied the possibilities of modulating the effects of nicotine and its withdrawal in nicotine-dependent rats by peripheral injection of κ-opioid receptor agonist ICI 204,448. Injection of nicotine to rats previously treated with nicotine for 14 days reduced motor activity, suppressed metabolism, and increased food intake. In rats receiving ICI 204,448 after chronic administration of nicotine, food intake did not differ from that in control animals receiving isotonic NaCl solution. ICI 204,448 had virtually no effect on suppression of motor activity and metabolism. The rats receiving the last injection of nicotine 24 h prior to the experiment demonstrated an increase in metabolism, locomotor activity, and food intake. In these animals, ICI 204,448 completely abolished the effects of nicotine withdrawal. It was found that peripheral administration of compound ICI 204,448 did not significantly inhibit the effect of nicotine in nicotine-dependent rats, but abolished symptoms of nicotine withdrawal. It can be hypothesized that nicotine withdrawal syndrome is related to inhibition of dopamine release in the nucleus accumbens probably caused by enhanced κ-opioid activity in presynaptic terminals. Activation of peripheral κ-opioid receptors apparently suppressed (via vagal afferent pathways) central κ-opioid activity and reduced nicotine withdrawal symptoms in nicotine-dependent subjects.

Comparison of the Effectiveness of Virtual Cue Exposure Therapy and Cognitive Behavioral Therapy for Nicotine Dependence

Previous studies have reported promising results regarding the effect of repeated virtual cue exposure therapy on nicotine dependence. This study aimed to compare the effectiveness of virtual cue exposure therapy (CET) and cognitive behavioral therapy (CBT) for nicotine dependence. Thirty subjects with nicotine dependence participated in 4 weeks of treatment with either virtual CET (n=15) or CBT (n=15). All patients were male, and none received nicotine replacement treatment during the study period. The main setting of the CET used in this study was a virtual bar. The primary foci of the CBT offered were (a) smoking cessation education, (b) withdrawal symptoms, (c) coping with high-risk situations, (d) cognitive reconstruction, and (e) stress management. Daily smoking count, level of expiratory carbon monoxide (CO), level of nicotine dependence, withdrawal symptoms, and subjective craving were examined on three occasions: week 0 (baseline), week 4 (end of treatment), and week 12 (follow-up assessment). After treatment, the daily smoking count, the expiratory CO, and nicotine dependence levels had significantly decreased. These effects continued during the entire study period. Similar changes were observed in both virtual CET and CBT groups. We found no interaction between type of therapy and time of measurement. Although the current findings are preliminary, the present study provided evidence that virtual CET is effective for the treatment of nicotine dependence at a level comparable to CBT.

Multiple Risks for Patients Using the Transdermal Fentanyl Patch

Multiple Risks for Patients Using the Transdermal Fentanyl Patch

An fMRI Study prior and post acupuncture treatment during the first 24 hours of smoking cessation

Substance dependence or addiction is nowadays understood in a multifactorial etiological model, which includes psychological, neurobiological, genetic, social and environmental factors. The cigarette is a very efficient and highly engineered drug delivery system. When tobacco is smoked, nicotine rapidly reaches peak levels in the bloodstream and enters the brain. Recent research has shown how nicotine acts on the brain to produce a number of effects. Nicotine withdrawal symptoms include irritability, craving, depression, anxiety, cognitive and attention deficits, sleep disturbances, and increased appetite. These symptoms may begin within a few hours after the last cigarette, quickly driving people back to tobacco use. Many behavioral factors can also affect the severity of withdrawal symptoms. For some people, the feel, smell, and sight of a cigarette and the ritual of obtaining, handling, lighting, and smoking the cigarette are all associated with the pleasurable effects of smoking and can make withdrawal or craving worse. Acupuncture has been used in the treatment of nicotine dependence. This study will demonstrate the potential effects of acupuncture treatment for smoking cessation using the brain scanning method of fMRI to 10 heavy smokers and 5 non smokers. The fMRI has been applied prior and post acupuncture treatment during the first 24 hours of smoking cessation.

Prequit fMRI responses to pleasant cues and cigarette-related cues predict smoking cessation outcome.

The reasons that some smokers find it harder to quit than others are unclear. Understanding how individual differences predict smoking cessation outcomes may allow the development of more successful personalized treatments for nicotine dependence. Theoretical models suggest that drug users might be characterized by increased sensitivity to drug cues and by reduced sensitivity to nondrug-related natural rewards. We hypothesized that baseline differences in brain sensitivity to natural rewards and cigarette-related cues would predict the outcome of a smoking cessation attempt. Using functional magnetic resonance imaging, we recorded prequit brain responses to neutral, emotional (pleasant and unpleasant), and cigarette-related cues from 55 smokers interested in quitting. We then assessed smoking abstinence, mood, and nicotine withdrawal symptoms during the course of a smoking cessation attempt. Using cluster analysis, we identified 2 groups of smokers who differed in their baseline responses to pleasant cues and cigarette-related cues in the posterior visual association areas, the dorsal striatum, and the medial and dorsolateral prefrontal cortex. Smokers who showed lower prequit levels of brain reactivity to pleasant stimuli than to cigarette-related cues were less likely to be abstinent 6 months after their quit attempt, and they had higher levels of negative affect during the course of the quit attempt. Smokers with blunted brain responses to pleasant stimuli, relative to cigarette-related stimuli, had more difficulty quitting smoking. For these individuals, the lack of alternative forms of reinforcement when nicotine deprived might be an important factor underlying relapse. Normalizing these pathological neuroadaptations may help them achieve abstinence.

Rhodiola rosea L. extract and its active compound salidroside antagonized both induction and reinstatement of nicotine place preference in mice

Conventional pharmacological treatments for drug addiction aim to reduce three most important aspects: withdrawal syndrome, craving, and relapse. Pharmacological treatments currently available for the treatment of tobacco smoking are able to alleviate withdrawal symptoms but are not sufficiently effective in reducing craving and rarely effective to prevent relapse. Rhodiola rosea L., a well-known traditional oriental medicine with anxiolytic, antidepressive, antistress, and adaptogenic properties, has been recently shown to be effective in the prevention and treatment of nicotine-withdrawal symptoms. The present study used the conditioned place preference (CPP) model to systematically investigate, in mice, the effects of a R. rosea L. extract (RHO) and its active compound salidroside (SDS), on the reinforcing properties of nicotine and their efficacy in the vulnerability to reinstatement. To study the effects on the rewarding properties of nicotine, RHO (10, 15, and 20mg/kg) and SDS (0.2mg/kg) were tested both in the acquisition and expression of CPP induced by nicotine injection (0.5mg/kg). Moreover, the efficacy of RHO and SDS in preventing relapse induced by nicotine priming (0.1mg/kg, s.c.) and by restraint stress was also evaluated. Results showed the ability of RHO and salidroside to significantly reduce the rewarding properties of nicotine at all doses tested. RHO and SDS also suppressed both priming- and stress-induced reinstatement of CPP. The present study showed the positive effects of R. rosea L. in reducing rewarding properties and preventing relapse to nicotine and evidenced the important role of salidroside in the effects of the extract.

Effects of oxytocin on nicotine withdrawal in rats

Development of medications that attenuate symptoms of nicotine withdrawal may be useful for facilitating smoking cessation. The neuropeptide oxytocin (OXY) decreases withdrawal signs and other addiction-related effects of several drugs of abuse in animals, but has not been examined in a preclinical model of nicotine addiction. The goal of this study was to examine the effects of OXY on nicotine withdrawal in rats, measured as increases in somatic signs and elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during antagonist-precipitated withdrawal from a chronic nicotine infusion. Effects of OXY on baseline ICSS thresholds in non-dependent rats were also evaluated. OXY (0.06 – 1.0mg/kg, i.p.) blocked withdrawal-induced elevations in somatic signs in nicotine-dependent rats without affecting somatic signs in non-dependent rats. In contrast, OXY did not affect nicotine withdrawal-induced elevations in ICSS thresholds. Relatively high doses of OXY (0.75 or 2.0mg/kg) elevated baseline ICSS thresholds in non-dependent rats. These findings demonstrate that OXY blocks somatic signs but not elevations in ICSS thresholds during antagonist-precipitated nicotine withdrawal. The ability of higher OXY doses to elevate baseline ICSS thresholds in non-dependent rats may reflect an aversive and/or motoric effect. These data suggest that OXY-based medications may be useful for treating the somatic component of the nicotine withdrawal syndrome, but may not be effective in attenuating withdrawal-induced anhedonia.

Activation of GABAergic Neurons in the Interpeduncular Nucleus Triggers Physical Nicotine Withdrawal Symptoms

Chronic exposure to nicotine elicits physical dependence in smokers, yet the mechanism and neuroanatomical bases for withdrawal symptoms are unclear. As in humans, rodents undergo physical withdrawal symptoms after cessation from chronic nicotine characterized by increased scratching, head nods, and body shakes. Here we show that induction of physical nicotine withdrawal symptoms activates GABAergic neurons within the interpeduncular nucleus (IPN). Optical activation of IPN GABAergic neurons via light stimulation of channelrhodopsin elicited physical withdrawal symptoms in both nicotine-naive and chronic-nicotine-exposed mice. Dampening excitability of GABAergic neurons during nicotine withdrawal through IPN-selective infusion of an NMDA receptor antagonist or through blockade of IPN neurotransmission from the medial habenula reduced IPN neuronal activation and alleviated withdrawal symptoms. During chronic nicotine exposure, nicotinic acetylcholine receptors containing the β4 subunit were upregulated in somatostatin interneurons clustered in the dorsal region of the IPN. Blockade of these receptors induced withdrawal signs more dramatically in nicotine-dependent compared to nicotine-naive mice and activated nonsomatostatin neurons in the IPN. Together, our data indicate that therapeutic strategies to reduce IPN GABAergic neuron excitability during nicotine withdrawal, for example, by activating nicotinic receptors on somatostatin interneurons, may be beneficial for alleviating withdrawal symptoms and facilitating smoking cessation.

The detox strategy in smoking comprising nutraceutical formulas of non-hydrolyzed carnosine or carcinine used to protect human health

The increased oxidative stress in patients with smoking-associated disease, such as chronic obstructive pulmonary disease, is the result of an increased burden of inhaled oxidants as well as increased amounts of reactive oxygen species generated by various inflammatory, immune and epithelial cells of the airways. Nicotine sustains tobacco addiction, a major cause of disability and premature death. In addition to the neurochemical effects of nicotine, behavioural factors also affect the severity of nicotine withdrawal symptoms. For some people, the feel, smell and sight of a cigarette and the ritual of obtaining, handling, lighting and smoking a cigarette are all associated with the pleasurable effects of smoking. For individuals who are motivated to quit smoking, a combination of pharmacotherapy and behavioural therapy has been shown to be most effective in controlling the symptoms of nicotine withdrawal. In the previous studies, we proposed the viability and versatility of the imidazole-containing dipeptide-based compounds in the nutritional compositions as the telomere protection targeted therapeutic system for smokers in combination with in vitro cellular culture techniques being an investigative tool to study telomere attrition in cells induced by cigarette smoke (CS) and smoke constituents. Our working therapeutic concept is that imidazole-containing dipeptide-based compounds (non-hydrolyzed carnosine and carcinine) can modulate the telomerase activity in the normal cells and can provide the redox regulation of the cellular function under the terms of environmental and oxidative stress and in this way protect the length and the structure of telomeres from attrition. The detoxifying system of non-hydrolyzed carnosine or carcinine can be applied in the therapeutic nutrition formulations or installed in the cigarette filter. Patented specific oral formulations of non-hydrolyzed carnosine and carcinine provide a powerful manipulation tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection from telomere attrition associated with smoking. It is demonstrated in this work that both non-hydrolyzed carnosine and carcinine are characterized by greater bioavailability than pure l-carnosine subjected to enzymatic hydrolysis with carnosinase, and perform the detoxification of the α,β-unsaturated carbonyl compounds present in tobacco smoke. We argue that while an array of factors has shaped the history of the 'safer' cigarette, it is the current understanding of the industry's past deceptions and continuing avoidance of the moral implications of the sale of products that cause the enormous suffering and death of millions that makes reconsideration of 'safer' cigarettes challenging. In contrast to this, the data presented in the article show that recommended oral forms of non-hydrolyzed carnosine and carcinine protect against CS-induced disease and inflammation, and synergistic agents with the actions of imidazole-containing dipeptide compounds in developed formulations may have therapeutic utility in inflammatory lung diseases where CS plays a role.

Pilot Investigation of Changes in Readiness and Confidence to Quit Smoking After E-Cigarette Experimentation and 1 Week of Use

This study examined changes in smokers' readiness and confidence to quit smoking, smoking behavior, nicotine withdrawal symptoms, and tobacco product preference following electronic cigarette (EC) experimentation and 1 week of ad libitum use. Current cigarette smokers, with no prior use of ECs and uninterested in quitting, completed 3 study phases: baseline assessment (N = 20), experimentation (N = 19), and ad libitum use (N = 16). Baseline assessment consisted of completion of assessment measures and exhaled carbon monoxide measurements. Experimentation phases consisted of four, 75-min sessions in which participants completed assessment measures and sampled 3 EC brands and their own brand of cigarette (OBC). Ad libitum use included participants selecting and being provided their preferred EC brand from the experimentation phase to be used "as you want" for 1 week. Outcome measures included readiness and confidence to quit smoking, nicotine withdrawal symptoms, product preference/satisfaction, and smoking behavior items. Readiness and confidence to quit increased significantly during the experimentation period and continued to increase during ad libitum use. There were no significant differences in reported effectiveness in reducing smoking urges and cravings between OBC and EC though OBC were rated as more enjoyable and satisfying. During ad libitum use, regular cigarette smoking decreased by approximately 44% from baseline levels with overall tobacco use (EC + OBC) remaining the same. Among a small convenience sample of unmotivated cigarette smokers, EC experimentation and 1 week of ad libitum use increased readiness and confidence to quit regular cigarettes and reduced regular cigarette smoking.

Effects of Smoking Abstinence on Cigarette Craving, Nicotine Withdrawal, and Nicotine Reinforcement in Smokers With and Without Schizophrenia

Schizophrenia is associated with a high prevalence of cigarette smoking. The aims of this study were to compare smokers with schizophrenia (SS) and control smokers without psychiatric illness (CS) on (a) cigarette craving and nicotine withdrawal symptom severity during a 72-hr smoking abstinence period; (b) nicotine reinforcement, before and after abstinence; and (c) latency to smoking lapse following abstinence. We also explored mediators of smoking lapse in SS and CS. SS (n = 28) and CS (n = 27) underwent a nicotine versus denicotinized cigarette puff choice task before and after a 72-hr period of smoking abstinence that was experimentally controlled by providing cash reinforcement contingent on biochemical verification of abstinence. Twenty-four hours after the second choice task, participants could receive a low-value reinforcer if they had continued to abstain since the previous day. Those who remained abstinent were recontacted a week later to determine time of their smoking lapse. SS reported more severe cigarette craving and nicotine withdrawal symptoms throughout the 72-hr abstinence period, had greater nicotine preference after abstinence, and lapsed back to smoking significantly sooner than CS. The relationship between group and smoking lapse latency was mediated by baseline depression and nicotine withdrawal symptom severity but not by effects of abstinence on craving or nicotine reinforcement. Overall, these results indicate that negative affect is a key contributor to poor smoking cessation outcomes among those with schizophrenia.

Korean American Women's Experiences with Smoking and Factors Associated with Their Quit Intentions.

This study explored Korean American women's experiences with smoking and tested the theory of planned behavior to identify factors associated with their intentions to quit smoking. It employed a mixed-methods research design, using qualitative and quantitative data. Participants were recruited via a combination of random (N = 49) and convenience (N = 45) sampling techniques. Women in this study initiated smoking at age of 23 on average, and nearly half smoked at indoor houses. They initiated smoking out of curiosity about the effect and belief that smoking would relieve their stress. Reasons for continued smoking were (a) to avoid nicotine withdrawal symptoms, (b) to cope with life stressors, including acculturative stress, and (c) to fulfill one's destiny as a lifetime smoker. Many attempted to quit due to health issues and pregnancy. Fear of disclosure and limited English proficiency were found to be major barriers to seeking help for quitting. Past-year quit attempt(s), attitudes toward quitting, and perceived family norm favoring quitting explained 25% of the variance in intentions to quit smoking (F [3,90] = 11.58, P < 0.001). Findings suggest that gender- and culture-specific intervention strategies are needed to assist Korean American women in smoking cessation.

Reactivity to negative affect in smokers: The role of implicit associations and distress tolerance in smoking cessation

Avoidance of negative affect is one motivational factor that explains smoking cessation relapse during cessation attempts. This negative reinforcement model of smoking cessation and relapse has demonstrated the importance of one's ability to tolerate nicotine withdrawal symptoms, particularly negative affect states, in remaining abstinent from smoking. Distress tolerance and implicit associations are two individual constructs that may influence the strength of this relationship. In this pilot study the authors examined implicit associations related to avoidance and negative affect using a modified Implicit Association Test (IAT), a measure designed to examine implicit associations related to negative affect and avoidance, and the relationship of these associations to distress tolerance and smoking relapse. In total, 40 participants were recruited through community flyers as part of a larger smoking cessation study. Participants completed a brief smoking history, behavioral distress tolerance assessments, and the modified IAT. Smoking status was assessed via phone 3days and 6days post-quit date. Results from a Cox proportional hazard model revealed that implicit associations between avoidance and negative affect were significantly negatively correlated with time to relapse after a smoking cessation attempt, whereas the behavioral distress tolerance assessments did not predict time to relapse. This study provides novel information about the cognitive associations that may underlie avoidant behavior in smokers, and may be important for understanding smoking relapse when negative affect states are particularly difficult to tolerate. Authors discuss the importance of implicit associations in understanding smoking relapse and how they can be targeted in treatment.

Ear Acupressure for Smoking Cessation: Study Protocol for a Randomised Controlled Trial

Background: Smoking is the largest preventable cause of death and disease worldwide but smokers often fail to quit due to nicotine withdrawal symptoms. Current available pharmaceutical therapies may assist with smoking cessation but may have side effects. Ear acupressure (EAP) and ear acupuncture have been used for smoking cessation, and some positive results have been reported. The aim of the study is to assess the efficacy and safety of EAP in assisting individuals to quit smoking and/or support them in the management of nicotine withdrawal symptoms. Methods: This study will be a randomised, single-blind, sham-controlled study conducted at RMIT University in Melbourne, Australia. Adult smokers will be randomly assigned to receive EAP specifically for smoking cessation or nonspecific EAP treatments. After a 2-week run-in, participants will be treated once a week for 8 weeks and followed up for 12 weeks. The primary outcome measures will be 7 day point-prevalence cessation rate by self-report validated by expired carbon monoxide and nicotine withdrawal symptoms measured by the Mood and Physical Symptoms Score questionnaire. Secondary outcomes will be self-reported usage of nicotine replacement therapies, cigarette consumption, body weight change and quality of life. The safety end point will be self-reported adverse events associated with EAP. Intention-to-treat analysis will be applied. Discussion: Findings from this study will determine if this EAP intervention alone can be an effective and safe therapy to assist with smoking cessation and the management of nicotine withdrawal symptoms.

Neural Bases of Pharmacological Treatment of Nicotine Dependence - Insights from Functional Brain Imaging: A Systematic Review

Nicotine dependence is difficult to treat, and the biological mechanisms that are involved are not entirely clear. There is an urgent need to develop better drugs and more effective treatments for clinical practice. A critical step towards accelerating progress in medication development is to understand the neurobehavioral effects of pharmacotherapies on clinical characteristics associated with nicotine dependence. This review sought to summarize the functional magnetic resonance imaging (fMRI) literature on smoking cessation with the aim to better understand the neural processes underlying the effects of nicotinic and non-nicotinic pharmacological smoking cessation treatments on specific symptoms of nicotine dependence and withdrawal. We conducted a search in Pubmed, Web of Science and PsycINFO databases with the keywords 'fMRI' or 'functional magnetic resonance imaging' and 'tobacco' or 'nicotine' or 'smok*'. The date of the most recent search was May 2012. The original studies that were included were those of smokers or nicotine-dependent individuals, published in the English language, with pharmacological treatment for nicotine dependence and use of fMRI with blood oxygen level-dependent (BOLD) imaging or continuous arterial spin labelling (CASL). No date limit was applied. Two of the authors read the abstracts of all studies found in the search (n = 1,260). The inclusion and exclusion criteria were applied, and 1,224 articles were excluded. In a second step, the same authors read the remaining 36 studies. Nineteen of the 36 articles were excluded. The results were tabulated by the number of individuals and their mean age, the main sample characteristics, smoking status, study type and methodology, and the main fMRI findings. Seventeen original fMRI studies involving pharmacological treatment of smokers were selected. The anterior and posterior cingulate cortex, medial and lateral orbitofrontal cortex, ventral striatum, amygdala, thalamus and insula are heavily involved in the maintenance of smoking and nicotine withdrawal. The effects of varenicline and bupropion in alleviating withdrawal symptoms and decreasing smoking correlated with modulation of the activities of these areas. Nicotine replacement therapy seems to improve cognitive symptoms related to withdrawal especially by modulating activities of the default-network regions; however, nicotine replacement does not necessarily alter the activities of neural circuits, such as the cingulate cortices, that are associated with nicotine addiction. The risk of bias in individual studies, and across studies, was not assessed, and no method of handling data and combining results of studies was carried out. Most importantly, positron emission tomography (PET) studies were not included in this review. fMRI studies delineate brain systems that contribute to cognitive deficits and reactivity to stimuli that generate the desire to smoke. Nicotinic and non-nicotinic pharmacotherapy may reduce smoking via distinct neural mechanisms of action. These findings should contribute to the development of new medications and discovery of early markers of the therapeutic response of cigarette smokers.

Effects of bupropion on cognitive performance during initial tobacco abstinence

BackgroundBupropion may aid tobacco abstinence by quickly relieving symptoms of nicotine withdrawal, perhaps including impaired cognitive performance. We examined whether bupropion would attenuate abstinence-induced cognitive deficits on the first day of a brief quit attempt, when smokers are most likely to relapse. MethodsSmokers (N=24) with high quit interest were recruited for within-subjects cross-over test of bupropion vs placebo on ability to abstain during separate short-term practice quit smoking attempts. After introduction to working memory (N-back) and sustained attention (continuous performance task; CPT) tasks during the pre-quit smoking baseline, performance on these tasks was assessed after abstaining overnight (CO<10ppm) on the first day of each quit attempt, while on bupropion and on placebo. ResultsCompared to placebo, bupropion after abstinence improved correct response times for working memory (p=.01 for medication by memory load interaction) and for one measure of sustained attention (numbers, but not letters; p<.05). DiscussionBupropion may attenuate some features of impaired cognitive performance due to withdrawal on the first day of a quit attempt. Future studies could examine whether this effect of bupropion contributes to its efficacy for longer-term smoking cessation.

Effect of Varenicline on Individual Nicotine Withdrawal Symptoms: A Combined Analysis of Eight Randomized, Placebo-Controlled Trials

Concerns exist that varenicline may cause neuropsychiatric side effects. Some of these symptoms (e.g., depression, irritability) have been measured in clinical trials using nicotine withdrawal scales. This study assessed the effect of varenicline on neuropsychiatric and other symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). We analyzed weekly individual MNWS symptom ratings in 8 randomized double-blind, placebo-controlled smoking cessation trials funded by Pfizer with similar methodology (n = 2,403 varenicline; n = 1,434 placebo). Ratings for the past 24hr were obtained prior to quitting and starting treatment and at Weeks 1-6 and 11 after the quit date. In repeated measures analyses controlling for baseline values, ratings for 5 neuropsychiatric symptoms (depressed mood, irritability, anxiety, difficulty concentrating, and restlessness) and urge to smoke were lower (p < .01) for varenicline than placebo at each timepoint. Worsening in scores from 0-2 (baseline) to 4 was less frequent on varenicline than placebo for all ratings except appetite- (significantly more frequent for varenicline, p < .0001) and sleep-related items. Repeated measures analysis for individuals with low levels of exhaled carbon monoxide revealed similar patterns except for a nonsignificant difference for increased appetite. Use of varenicline while trying to quit smoking reduces and does not increase neuropsychiatric symptoms such as depressed mood and irritability measured on the MNWS in smokers without current psychiatric disorders. It is associated with increases in sleep disturbance and appetite although the latter appears due to enabling more subjects to abstain from smoking.

Withdrawal from chronic nicotine and subsequent sensitivity to nicotine challenge on contextual learning

Nicotine withdrawal is associated with numerous symptoms including impaired hippocampus-dependent learning. Theories of nicotine withdrawal suggest that nicotinic acetylcholine receptors (nAChRs) are hypersensitive during withdrawal, which suggests enhanced sensitivity to nicotine challenge. Research indicates that prior exposure to nicotine enhances sensitivity to nicotine challenge, but it is unclear if this is due to prior nicotine exposure or specific to nicotine withdrawal. Therefore, the present experiments examined if prior nicotine exposure or nicotine withdrawal altered the effects of nicotine challenge on hippocampus-dependent learning. C57BL/6J mice were trained and tested in contextual conditioning following saline or nicotine challenge either during (24h after cessation) or after (14 days after cessation) a period of nicotine withdrawal symptoms. Nicotine challenge produced a greater enhancement of contextual conditioning relative to control withdrawal state in mice withdrawn from chronic nicotine for 24h compared to 14 days and corresponding saline controls. These experiments support the suggestion that during periods of abstinence, smokers may perceive tobacco providing a large boost in cognition.

Cigarette craving and withdrawal symptoms during temporary abstinence and the effect of nicotine gum

It is widely believed that nicotine withdrawal symptoms appear within a few hours of stopping smoking, but few data exist documenting their emergence in naturalistic settings. In several countries, nicotine replacement products are licensed for relief of withdrawal symptoms during temporary abstinence, but again, there are no data supporting this from naturalistic settings. To examine the emergence of cigarette craving and withdrawal symptoms during temporary abstinence in a naturalistic setting while using either nicotine or placebo gum. Double-blind, randomised, placebo-controlled study in which 132 dependent smokers abstained for 6 h with the assistance of either nicotine (2 mg, n = 42 or 4 mg, n = 24) or placebo (n = 66) gum while travelling on a non-smoking train. Outcome measures were ratings of craving and mood withdrawal symptoms prior to treatment and at regular intervals during abstinence. In a multivariate analysis of all symptoms, there was no interaction between treatment and time [F(21,110) = 1.28, p = 0.20, η²(p)= 0.20] nor an effect of treatment [F(7,124) = 0.45, p = 0.87, η²(p)= 0.03]. There was an effect of time [F(21,110) = 11.59, p < 0.001, η²(p)= 0.69) and univariate analyses revealed that the majority of symptoms increased linearly throughout the period of abstinence with detectable onsets typically between the first 60 and 180 min of abstinence. Smokers who temporarily abstain in naturalistic settings experience craving and withdrawal symptoms that emerge linearly over the first 6 h of abstinence. Changes in craving and several mood withdrawal symptoms can be detected within the first 3 h. Nicotine gum may not have an acute effect on the development of these symptoms.

Anhedonia and Anxiety Sensitivity: Prospective Relationships to Nicotine Withdrawal Symptoms During Smoking Cessation

The aim of the present investigation was to explore the main and interactive effects of anhedonic depressive symptoms and anxiety sensitivity in terms of the individual components of nicotine withdrawal symptoms experienced on quit day as well as throughout the initial 14 days of cessation. Participants included 65 daily cigarette smokers (38 women; Mage = 46.08 years, SD = 9.12) undergoing psychosocial-pharmacological cessation treatment. Results indicated that, after controlling for the effects of participant sex and nicotine dependence, anhedonic depression symptoms, but not anxiety sensitivity, significantly predicted quit day levels of mood-based nicotine withdrawal symptoms. Conversely, anxiety sensitivity, but not anhedonic depression symptoms, was significantly related to the change in most nicotine withdrawal symptoms over time. Finally, our results revealed a significant interaction between anxiety sensitivity and anhedonic depression symptoms related to the slope of certain withdrawal symptoms over time. Specifically, among participants with higher levels of anxiety sensitivity, greater levels of anhedonic depression symptoms were related to greater increases in withdrawal symptoms over time for two of the nine anxiety-relevant components of nicotine withdrawal (restlessness and frustration). Among high anxiety-sensitivity persons, compared with those low in anxiety sensitivity, anhedonic depression symptoms may be more relevant to the experience of some withdrawal symptoms being more intense and persistent during the early phases of quitting.