Severe Nicotine Withdrawal Research Articles

Efficacy of the QuitSure App for Smoking Cessation in Adult Smokers: Cross-Sectional Web Survey.

Cigarette smoking remains one of the leading causes of preventable death worldwide. A worldwide study by the World Health Organization concluded that more than 8 million people die every year from smoking, tobacco consumption, and secondhand smoke. The most effective tobacco cessation programs require personalized human intervention combined with costly pharmaceutical supplementation, making them unaffordable or inaccessible to most tobacco users. Thus, digital interventions offer a promising alternative to these traditional methods. However, the leading smartphone apps available in the market today have either not been studied in a clinical setting or are unable to match the smoking cessation success rates of their expensive offline counterparts. We would like to understand whether QuitSure, a novel smoking cessation app built by Rapidkart Online Private Limited, is able to bridge this efficacy gap and deliver affordable and effective smoking cessation at scale. Our objective was to do an initial exploration into the engagement, efficacy, and safety of QuitSure based on the self-reported experiences of its users. Outcomes measured were program completion, the effect of program completion on smoking behavior, including self-reported cessation outcomes, and negative health events from using the app. All QuitSure registered users who created their accounts on the QuitSure app between April 1, 2021, and February 28, 2022, were sent an anonymized web-based survey. The survey results were added to their engagement data on the app to evaluate the feasibility and efficacy of the app as a smoking cessation intervention. The data were analyzed using descriptive statistics (frequencies and percentages) and the χ2 test of independence. In total, 1299 users who had completed the QuitSure program submitted the survey and satisfied the inclusion criteria of the study. Of these, 1286 participants had completed the program more than 30 days before filling out the survey, and 1040 (80.1%, 95% CI 79.1%-82.6%) of them had maintained prolonged abstinence for at least 30 days after program completion. A majority of participants (770/891, 86.4%) who were still maintaining abstinence at the time of submitting the survey did not experience any severe nicotine withdrawal symptoms, while 41.9% (373/891) experienced no mild withdrawal symptoms either. Smoking quantity prior to completing the program significantly affected quit rates (P<.001), with heavy smokers (>20 cigarettes per day) having a lower 30-day prolonged abstinence rate (relative risk=0.91; 95% CI 90.0%-96.2%) compared to lighter smokers. No additional adverse events outside of known nicotine withdrawal symptoms were reported. The nature of web-based surveys and cohort selection allows for extensive unknown biases. However, the efficacy rates of survey respondents who completed the program were high and provide a case for further investigation in the form of randomized controlled trials on the QuitSure tobacco cessation program.

Cannabidiol Reduces Nicotine Withdrawal Severity and State Anxiety During an Acute E-cigarette Abstinence Period: A Novel, Open-Label Study.

Introduction: Despite efforts to curb nicotine use, 8.1 million adults in the United States use e-cigarettes. Notably, the majority of nicotine-containing e-cigarette users report wanting to quit in the near future, yet there is a dearth of research surrounding intervention efforts. Cannabidiol (CBD) has potential to facilitate e-cigarette quit attempts by decreasing withdrawal symptom intensity and anxiety during nicotine e-cigarette abstinence. Methods: This study employed an open-label, crossover design (n=20) to test the hypothesis that among daily nicotine-containing e-cigarette users, oral administration of 320 mg CBD would reduce self-reported nicotine withdrawal severity and state anxiety following a 4-h e-cigarette abstinence period compared to withdrawal and anxiety reported after abstinence in the absence of CBD. Results: After controlling for participants' positive CBD expectancies, results were consistent with hypotheses, suggesting CBD reduced both nicotine withdrawal symptom severity and state anxiety during e-cigarette abstinence. Conclusion: These preliminary findings suggest testing the impact of CBD on e-cigarette cessation attempts is warranted.

Discrimination and insomnia: Examining depressive symptoms and nicotine withdrawal through a serial mediation model in a sample of smokers

Insomnia is a common sleep disorder associated with poor health outcomes. Individuals from racially underrepresented groups as well as women tend to report more severe insomnia symptoms, and frequent experiences of discrimination have been found to drive such disparities. Smokers commonly experience sleep problems since nicotine can alter the sleep-wake cycle. Discrimination is associated with increased nicotine dependence, and such discrimination may also intensify tobacco withdrawal, specifically mood and cognitive-related aspects of withdrawal. The potential impact of discrimination on withdrawal symptoms and related mood symptoms like depression may lead to increases in insomnia symptoms. However, no studies to date have evaluated the indirect association of discrimination with insomnia severity through nicotine withdrawal and depressive symptoms. Therefore, this cross-sectional survey of n = 110 non-Hispanic Black and White current smokers (48.2 % Black, 69.1 % women) investigated these associations through a serial mediation model. Controlling for race, gender, nicotine dependence levels, and income, multivariate analyses supported a significant indirect effect of discrimination on insomnia severity through depressive symptoms. Analyses supported the hypothesized serial mediation model whereby discrimination is positively associated with depressive symptoms, which in turn are linked to more severe nicotine withdrawal, leading to greater insomnia severity. Smokers encountering frequent experiences of discrimination might be at increased risk of suffering insomnia as a result of their increased depressive and withdrawal symptoms. Future work is necessary to understand the role of depressive symptoms in these associations as well as possible implications for smoking relapse and success of smoking cessation programs.

Characterizing nicotine withdrawal in smokers experiencing homelessness

ObjectiveThe rate of cigarette smoking among persons experiencing homelessness is five times the national prevalence, and these smokers experience difficulty quitting. Nicotine withdrawal may be a barrier to initiating and sustaining successful smoking cessation, but its time course is poorly characterized in this population. We hypothesize that withdrawal symptoms will be elevated and related to treatment outcomes. MethodsThis secondary data analysis characterized nicotine withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Severity Index, during a quit attempt in treatment-seeking smokers experiencing homelessness who enrolled in a randomized smoking cessation trial. Participants (N = 70) reported MNWS symptoms three times prior to the scheduled quit date and twice weekly for 4 weeks post–quit date. We also examined the relation of pre-quit symptoms to treatment outcomes (quit day smoking status, patch adherence, duration of abstinence, and percent negative CO samples submitted). ResultsEndorsement of withdrawal symptoms was highest prior to the quit date and decreased over time with increases at weeks 3 to 4; a sizable percentage (20% to 35%) of participants endorsed symptoms throughout the 4 week post–quit period. Severity for most symptoms was at its lowest 2–3 weeks post–quit date, then increased in weeks 3 and 4. Anticipatory withdrawal was inversely related to nicotine patch adherence (p = .01), but not the abstinence-based treatment outcomes (ps > 0.05). ConclusionsContinued withdrawal symptom endorsement throughout treatment and increases in severity noted 3 to 4 weeks post–quit date suggest possible targets for intervention as part of smoking cessation counseling for smokers experiencing homelessness. Anticipatory withdrawal symptoms (prior to the quit date) were common and predictive of poor adherence to cessation aids.

Pain characteristics and nicotine deprivation as predictors of performance during a laboratory paradigm of smoking cessation.

Although smokers with co-occurring pain report expectations for experiencing greater nicotine withdrawal and difficulty quitting, limited work has examined the role of pain in cessation-related outcomes. The goal of this study was to examine clinically relevant pain characteristics (pain persistence, pain intensity, pain-related disability) as predictors of withdrawal and smoking lapse/relapse outcomes using a laboratory paradigm of cessation. Participants (N = 120 daily cigarette smokers; 48% male; Mage = 36.17, SD = 12.16; MCigarettes Per Day = 20.51, SD = 6.99) were randomized to either nondeprived or 12-hr nicotine deprivation conditions prior to an experimental study visit. Upon arrival to the laboratory, participants completed measures of pain characteristics and nicotine withdrawal symptoms. Primary outcomes included nicotine withdrawal scores and analogues of smoking lapse (latency to initiating smoking) and relapse (number of cigarettes smoked). We hypothesized that smokers with greater pain persistence, pain intensity, and pain-related disability would endorse more severe nicotine withdrawal and greater lapse/relapse behavior, and that these positive associations would be stronger among those who were nicotine deprived. Results indicated that, above and beyond the effect of nicotine deprivation, persistent pain predicted more severe nicotine withdrawal, and that greater pain-related disability predicted quicker latency to lapse during the laboratory paradigm. Contrary to expectation, nicotine deprivation did not moderate effects of pain characteristics on withdrawal or lapse/relapse outcomes. Clinical implications include that different pain processes may influence different cessation outcomes, and that smokers in pain may benefit from the provision of pharmacological aids to better control withdrawal symptoms. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Smoking dependence and anxio-depressive disorders in Tunisian smokers attending the smoking cessation clinic in a university hospital

BackgroundSmokers with comorbid anxio-depressive disorders are more prone to progress to a more severe level of dependence and to experience more severe nicotine withdrawal symptoms than smokers without anxio-depressive disorders.Aim of the studyTo determine the relationship between tobacco dependence and anxio-depressive disorders as well as assessing their impact on the withdrawal.MethodsWe conducted a cross-sectional study among attendees of the smoking cessation clinic of Sahloul University Hospital, Sousse, Tunisia, from December 2009 to May 2015. The monitoring of the attendees was performed through retrieving the records until May 2016 in order to verify their smoking cessation status at 1 year.ResultsOverall, 534 smokers were included. We identified 315 smokers (59%) presenting an anxio-depressive disorder. Based on the HAD scale, we found 231 patients (43.4%) with anxiety disorders, 200 (37.6%) patients with depressive disorders, and 116 (21.8%) patients with anxio-depressive disorder.In multivariate analysis, only a high number of consultation was associated with a better rate of tobacco cessation at 6 months. However, no factor was found linked to the relapse at 1 year.ConclusionAccording to our results, only a high number of consultation was revealed as an independent factor of withdrawal for anxio-depressed smokers. It is necessary to simultaneously use the nicotinic substitutions and anxio-depressive treatment to ensure the tobacco cessation.

Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers.

This double-blind, placebo controlled study examined whether menthol inhaled from an electronic cigarette (e-cigarette) would change subjective and withdrawal alleviating effects of intravenous nicotine in young adult smokers. A total of 32 menthol-preferring smokers and 25 non-menthol-preferring smokers participated in the study that consisted of a random sequence of three different inhaled menthol conditions (0.0%, 0.5%, and 3.2%) across three test sessions (a single menthol condition per session). In each test session (performed at least 24 hours apart), a random order of saline, and two different nicotine infusions of 0.25 mg and 0.5 mg/70 kg of bodyweight were administered, one hour apart, concurrent with menthol inhalation. While menthol did not alter the positive subjective effects of nicotine, menthol significantly enhanced aversive effects of nicotine in non-menthol-preferring smokers and reduced smoking urges in menthol-preferring smokers. In addition, menthol-preferring smokers reported blunted positive subjective responses to nicotine and less severe nicotine withdrawal after overnight nicotine deprivation. Finally, compared to non-menthol-preferring smokers, menthol-preferring smokers had a significantly lower baseline nicotine metabolite ratio indicating slower nicotine metabolism within our sample of menthol-preferring smokers. Our findings did not support an enhancement of nicotine's positive subjective effects from inhaled menthol. However, as compared to non-menthol-preferring smokers, menthol-preferring smokers had blunted positive subjective responses to nicotine and reduced overnight withdrawal severity that may be partly due to inhibition of nicotine metabolism from chronic exposure to inhaled menthol. Collectively, these results reveal a more complex and nuanced role of inhaled menthol in smokers than previously recognized.

Wheel running during chronic nicotine exposure is protective against mecamylamine-precipitated withdrawal and up-regulates hippocampal α7 nACh receptors in mice.

Evidence suggests that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanisms mediating this effect are unclear. We investigated, in a mouse model, the effect of exercise intensity during chronic nicotine exposure on nicotine withdrawal severity, binding of α4β2*, α7 nicotinic acetylcholine (nAChR), μ-opioid (μ receptors) and D2 dopamine receptors and on brain-derived neurotrophic factor (BDNF) and plasma corticosterone levels. Male C57Bl/6J mice treated with nicotine (minipump, 24mg·kg-1 ·day-1 ) or saline for 14days underwent one of three concurrent exercise regimes: 24, 2 or 0h·day-1 voluntary wheel running. Mecamylamine-precipitated withdrawal symptoms were assessed on day 14. Quantitative autoradiography of α4β2*, α7 nAChRs, μ receptors and D2 receptor binding was performed in brain sections of these mice. Plasma corticosterone and brain BDNF levels were also measured. Nicotine-treated mice undertaking 2 or 24h·day-1 wheel running displayed a significant reduction in withdrawal symptom severity compared with the sedentary group. Wheel running induced a significant up-regulation of α7 nAChR binding in the CA2/3 area of the hippocampus of nicotine-treated mice. Neither exercise nor nicotine treatment affected μ or D2 receptor binding or BDNF levels. Nicotine withdrawal increased plasma corticosterone levels and α4β2* nAChR binding, irrespective of exercise regimen. We demonstrated for the first time a profound effect of exercise on α7 nAChRs in nicotine-dependent animals, irrespective of exercise intensity. These findings shed light onto the mechanism underlining the protective effect of exercise on the development of nicotine dependence. This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

Need for medication to complement catecholamines in smoking cessation of hardcore smokers.

Many smokers find it difficult to stop smoking without assistance. The antidepressants bupropion and nortriptyline can aid smoking cessation. The main aim of this study was to understand the pathophysiology of smoking cessation better based on biological backgrounds. We investigated the following biological markers for any alterations during smoking cessation in the absence of pharmacotherapy: the dopamine metabolite homovanillic acid (HVA), the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and brain-derived neurotrophic factor (BDNF). Assessment and blood sampling were performed at a baseline (the start) time point and at a critical time point during smoking cessation. Seven of 30 smokers quit during a 16-week follow-up period; these smokers were defined as remission group from tobacco dependence. The remaining 23 smokers were categorized as hardcore smokers. The smoking group was compared with 23 non-smokers matched for age and gender. We compared blood levels of biological markers in each of the three groups. The hardcore smoker group showed significant decreases in HVA and MHPG levels between baseline and the critical time point (p=0.018 and p=0.033, respectively). However, the remission from tobacco dependence group exhibited no significant changes in any of the biomarkers examined. They had lower scores on the Minnesota nicotine withdrawal scale than the hardcore smoker group (p=0.002). The hardcore smoker group had higher MHPG and BDNF levels than the non-smoker group (p=0.002 and p<0.001, respectively). Hardcore smokers experience severe nicotine withdrawal symptoms. Nicotine withdrawal is associated with catecholamine deficiency. The resulting withdrawal symptoms make quitting difficult for hardcore smokers. These hardcore smokers may require medication to compensate for the catecholamine deficit. Non-nicotinic medications such as bupropion, nortriptyline, or varenicline may be required to bolster the catecholamine deficit in hardcore smokers.

A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke.

Nicotine withdrawal symptoms contribute to relapse in smokers, thereby prolonging the harm caused by smoking. To investigate the molecular basis for this phenomenon, we conducted a genome-wide association study of DSM-IV nicotine withdrawal in a sample of African American (AA) and European American (EA) smokers. A combined AA and EA meta-analysis (n=8021) identified three highly correlated single nucleotide polymorphisms (SNPs) in the protocadherin (PCDH)-α, -β and -γ gene cluster on chromosome 5 that were associated with nicotine withdrawal (P<5 × 10-8). We then studied one of the SNPs, rs31746, in an independent sample of smokers who participated in an intravenous nicotine infusion study that followed overnight smoking abstinence. After nicotine infusion, abstinent smokers with the withdrawal risk allele experienced greater alleviation of their urges to smoke, as assessed by the Brief Questionnaire on Smoking Urges (BQSU). Prior work has shown that the PCDH-α, -β and -γ genes are expressed in neurons in a highly organized manner. We found that rs31746 mapped to a long-range neuron-specific enhancer element shown previously to regulate PCDH-α, -β and -γ gene expression. Using Braincloud mRNA expression data, we identified a robust and specific association between rs31746 and PCDH-β8 mRNA expression in frontal cortex tissue (P<1 × 10-5). We conclude that PCDH-α, -β and -γ gene cluster regulatory variation influences the severity of nicotine withdrawal. Further studies on the PCDH-α, -β and -γ genes and their role in nicotine withdrawal may inform the development of novel smoking cessation treatments and reduce the harm caused by tobacco smoking.

Correlates of nicotine withdrawal severity in smokers during a smoke-free psychiatric hospitalization

Psychiatric hospitals are increasingly adopting smoke-free policies. Tobacco use is common among persons with mental illness, and nicotine withdrawal (NW), which includes symptoms of depression, anxiety, anger/irritability, and sleep disturbance, may confound psychiatric assessment and treatment in the inpatient setting. This study aimed to characterize NW and correlates of NW severity in a sample of smokers hospitalized for treatment of mental illness in California. Participants (N=754) were enrolled between 2009 and 2013, and averaged 17 (SD=10) cigarettes/day prior to hospitalization. Though most (70%) received nicotine replacement therapy (NRT) during hospitalization, a majority (65%) reported experiencing moderate to severe NW. In a general linear regression model, NW symptoms were more severe for women, African American patients, and polysubstance abusers. Though invariant by psychiatric diagnostic category, greater NW was associated with more severe overall psychopathology and greater cigarette dependence. The full model explained 46% of the total variation in NW symptom severity (F [19, 470]=23.03 p<0.001). A minority of participants (13%) refused NRT during hospitalization. Those who refused NRT reported milder cigarette dependence and stated no prior use of NRT. Among smokers hospitalized for mental illness, NW severity appears multidetermined, related to cigarette dependence, demographic variables, psychiatric symptom severity, and other substance use. Assessment and treatment of NW in the psychiatric hospital is clinically warranted and with extra attention to groups that may be more vulnerable or naïve to cessation pharmacotherapy.

Chronic Pain Status, Nicotine Withdrawal, and Expectancies for Smoking Cessation Among Lighter Smokers

Chronic pain and tobacco smoking are both highly prevalent and comorbid conditions, and chronic pain may pose a barrier to smoking cessation. The objective of this study was to test associations between chronic pain status and several smoking-related factors that have previously been shown to predict cessation outcomes. Daily smokers (N = 205) were recruited from the general population to complete an online survey of pain and tobacco smoking. Results indicated that smokers with chronic pain (vs. no chronic pain) consumed more cigarettes per day, scored higher on an established measure of tobacco dependence, reported having less confidence in their ability to quit, and endorsed expectations for experiencing greater difficulty and more severe nicotine withdrawal during future cessation attempts. Mediation analyses further indicated that the inverse association between chronic pain and abstinence self-efficacy was indirectly influenced by past cessation failures. These findings suggest that individuals with chronic pain may constitute an important subgroup of tobacco smokers who tend to experience lower confidence and greater difficulty when attempting to quit. Future research would benefit from replicating these findings among older and more diverse samples of heavier tobacco smokers, and extending this work to the study of prospective relations between chronic pain status and cessation-relevant processes/outcomes over the course of a quit attempt.

Socially anxious smokers experience greater negative affect and withdrawal during self-quit attempts

Despite evidence of a strong and consistent relation between smoking and elevated social anxiety, strikingly little empirical work has identified mechanisms underlying the smoking-social anxiety link. Persons with elevated social anxiety may rely on smoking to cope with more severe nicotine withdrawal and post-quit negative mood states; yet, no known studies have investigated the relation of social anxiety to withdrawal severity. The current study examined the relation of social anxiety to post-quit nicotine withdrawal severity among 51 (33.3% female, Mage=34.6) community-recruited smokers during the first two weeks following an unaided (i.e., no treatment) cessation attempt. Ecological momentary assessment was used to collect multiple daily ratings of withdrawal and negative mood states. Baseline social anxiety was related to increases in negative affect during the monitoring period and remained significantly related to post-quit withdrawal after controlling for negative affect, gender, lapses, and substance use. Persons with elevated social anxiety experience more severe post-quit withdrawal symptoms and increases in negative affect during a cessation attempt and may therefore benefit from intervention and treatment strategies geared toward helping them learn to cope with withdrawal and negative affect to improve cessation rates among these vulnerable smokers.

Low Carbohydrate and Moderately Fat-Reduced Diets Similarly Affected Early Weight Gain in Varenicline-Treated Overweight or Obese Smokers.

Weight gain is common when stopping smoking. This study compared the effect of advising smokers to follow a diet low in carbohydrates versus a usual fat-reduced diet on weight gain and nicotine withdrawal. In a randomized clinical trial, 122 men and women smokers with body mass index 25-40kg/m(2) were assigned low-carbohydrate versus moderately fat-reduced diets. Within a week thereafter all participants started treatment with a 12-week course of varenicline 10 days prior to the target quit date. Brief dietary and motivational counseling was given at all visits. Self-reported abstinence was validated. Protein intake in the low-carbohydrate versus fat-reduced diets was 26.4% of total energy versus 20.0%, fat 38.2% versus 30.1%, and carbohydrates 29.0% versus 41.7% (all P < .001). Mean weight changes for the low-carbohydrate versus fat-reduced groups were -1.2 (SD 2.2) versus -0.5 (SD 2.0) kg, -0.2 (SD 3.3) versus 0.5 (SD 2.6) kg, and 2.2 (SD 4.5) versus 2.1 (SD 3.9) kg at 4, 12, and 24 weeks after the target quit date, respectively (not statistically significant). Smoking abstinence rates did not differ between diets. In the combined groups, point prevalence abstinence rates were 71.0% at 12 weeks and 46.3% at 24 weeks. The Minnesota Nicotine Withdrawal Symptoms score was lower in the fat-reduced group compared with the low-carbohydrate group at weeks 4 and 12. In overweight or obese smokers using varenicline a low-carbohydrate diet was no better than a fat-reduced diet in reducing weight gain but may result in more severe nicotine withdrawal symptoms. Compared to previous studies, cessation rates with varenicline were not impaired by dietary counseling. The study implies that a popular low-carbohydrate diet does not result in greater weight loss than a moderately fat-reduced diet in overweight and obese smokers who are attempting to quit smoking with the aid of varenicline. Dietary counseling combined with varenicline treatment did not appear to unfavorably influence quit rates compared to previous studies in smokers not selected for overweight or obesity. Notably, the withdrawal symptoms score was lower in the fat-reduced dietary group than the low-carbohydrate group, suggesting a venue for further study.

Case Report: Nicotine Replacement Therapy (NRT) in Hospitalized Surgical Patient

Hospital surgical services are often reluctant to offer nicotine replacement therapy (NRT) to inpatients due to concerns that nicotine leads to vasoconstriction and impaired wound healing. However, multiple potential health benefits result from offering NRT to hospitalized surgical patients who use tobacco products. A 28-year-old female patient, hospitalized following a motor vehicle accident, experienced severe nicotine withdrawal symptoms and a strong desire to smoke. After a Tobacco Treatment Specialist (TTS) consultation, the Physical Medical and Rehabilitation service at the hospital began her on NRT with positive outcomes. The patient experienced decreased cravings and withdrawal symptoms, as well as an increased desire to remain tobacco free after discharge. More surgical patients may have an increased commitment to remain tobacco free after discharge, if their withdrawal symptoms are treated during hospitalization using NRT.

FKBP5 variation is associated with the acute and chronic effects of nicotine.

Stress and hormones released in response to stress influence the effects of nicotine and the severity of nicotine withdrawal. Here, we systematically examine the contribution of a stress response gene, FKBP5, to the acute and chronic behavioral effects of nicotine in smokers. Subjects were European- and African-American (EA and AA) heavy smokers who participated in an intravenous (IV) nicotine administration study (total n=169). FKBP5 rs3800373 genotype was analyzed for association to several outcomes, including nicotine withdrawal and the acute subjective, heart rate (HR), blood pressure and plasma cortisol responses to IV nicotine. Nicotine withdrawal was also examined in relation to rs3800373 allele frequencies in an independent cohort of EA and AA current smokers (n=3821). For a subset of laboratory subjects FKBP5 mRNA (n=48) expression was explored for an association to the same outcomes. The rs3800373 minor allele was associated with less severe nicotine withdrawal in laboratory subjects and the independent cohort of smokers. The rs3800373 minor allele was also associated with lower subjective ratings of negative drug effects in response to IV nicotine. Low FKBP5 mRNA expression was associated lower cortisol levels, lower subjective ratings of negative drug effects and a blunted HR response to nicotine. Stress hormone regulation via FKBP5 warrants further investigation as a potential contributor to the effects of nicotine withdrawal, which occurs commonly, and has an important role in the maintenance of smoking behavior and relapse following a quit attempt.

Nicotine Withdrawal and Dependence Among Smokers With a History of Childhood Abuse

Previous studies have found that those with a history of childhood abuse are more likely to smoke cigarettes than those without a history of abuse. Mechanisms underlying this greater prevalence are unclear. We examined whether current smokers with a history of childhood abuse reported greater levels of nicotine dependence and more severe nicotine withdrawal symptoms. We analyzed data from a 2-wave, national, random-digit-dial survey of adult cigarette smokers (n = 751). We examined whether childhood physical, emotional, and sexual abuse were associated with greater levels of nicotine dependence. Among those who made a quit attempt (n = 368), we examined whether abuse was associated with more severe withdrawal symptoms recalled during the 14 months between surveys. For both dependence and withdrawal, we tested a mediation pathway through current serious mental illness (SMI). All 3 types of childhood abuse were associated with more severe withdrawal symptoms. These associations were partially mediated by SMI. Sexual abuse and physical abuse were directly associated with dependence, whereas emotional abuse was indirectly associated with dependence through SMI. All 3 forms of childhood abuse were associated with both dependence and withdrawal. The greater prevalence of smoking found among those with a history of childhood abuse may be explained by heightened vulnerability to nicotine dependence and withdrawal and may be partially due to comorbid mental illness.

Anxiety and smoking cessation outcomes in alcohol-dependent smokers

Anxiety-related characteristics, including anxiety sensitivity and trait anxiety, are elevated in individuals with alcohol and nicotine dependence and associated with greater difficulties with quitting smoking. However, little is known about how anxiety-related characteristics are related to smoking cessation outcomes in alcohol-dependent smokers. The present study, part of a larger smoking cessation clinical trial, examined associations between anxiety sensitivity, trait anxiety, nicotine withdrawal symptoms, smoking urges, and smoking cessation outcomes in a sample of 83 alcohol-dependent smokers. Participants were enrolled in concurrent alcohol and tobacco treatment as part of a substance-abuse intensive outpatient program. Smoking cessation treatment was administered in a 3-week cognitive-behavioral format that included 8 weeks of open-label nicotine patch treatment. Information on nicotine withdrawal, smoking urges, and CO-confirmed smoking consumption rates was collected at baseline, quit date, end of behavioral treatment, and at a 1-month follow-up. Higher levels of anxiety sensitivity were associated with more smoking urges due to anticipation of negative affect relief at quit date. Higher levels of trait anxiety were associated with more smoking urges due to positive reinforcement and anticipation of relief of negative affect at quit date, as well as more severe nicotine withdrawal symptoms at the end of treatment. Levels of anxiety sensitivity and trait anxiety were not associated with Cox regression survival times to relapse. These results indicate that for alcohol-dependent smokers, levels of anxiety sensitivity and trait anxiety are important to consider in the assessment and treatment of nicotine dependence.

Panic Attack History and Anxiety Sensitivity in Relation to Cognitive-Based Smoking Processes Among Treatment-Seeking Daily Smokers

Empirical research has found that panic attacks are related to increased risk of more severe nicotine withdrawal and poor cessation outcome. Anxiety sensitivity (AS; fear of anxiety and related sensations) has similarly been found to be related to an increased risk of acute nicotine withdrawal and poorer cessation outcome. However, research has yet to examine the relative contributions of panic attacks and AS in terms of cognitive-based smoking processes (e.g., negative reinforcement smoking expectancies, addictive and negative affect-based reduction smoking motives, barriers to cessation, problem symptoms experienced while quitting). Participants (n = 242; 57.4% male; M (age) = 38.1) were daily smokers recruited as a part of a larger randomized control trial for smoking cessation. It was hypothesized that both panic attacks and AS would uniquely and independently predict the studied cognitive-based smoking processes. As hypothesized, AS was uniquely and positively associated with all smoking processes after controlling for average number of cigarettes smoked per day, current Axis I diagnosis, and participant sex. However, panic attack history was only significantly related to problem symptoms experienced while quitting smoking. Although past research has demonstrated significant associations between panic attacks and certain aspects of cigarette smoking (e.g., severity of nicotine withdrawal; lower abstinence rates, and negative affect reduction motives), the present findings suggest that AS may be more relevant to understanding beliefs about and motives for smoking behavior as well as perceptions of cessation-related difficulties.

A lack of association between severity of nicotine withdrawal and individual differences in compensatory nicotine self-administration in rats

Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced-nicotine tobacco products. Factors contributing to individual variability in compensation are poorly understood. The objective of this study was to examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction. Rats were trained for ICSS and NSA (0.06mg/kg per infusion). After stabilization, effects of reducing the nicotine unit dose to 0.03mg/kg per infusion were examined. Following reacquisition of NSA (0.06mg/kg per infusion), effects of antagonist-precipitated withdrawal and saline extinction (spontaneous withdrawal) were examined. Reducing the NSA unit dose produced partial compensation as indicated by the increased infusion rates, but a 35% mean decrease in daily nicotine intake. The magnitude of compensation varied considerably among rats. Dose reduction did not elicit withdrawal in rats as a group, although there were substantial increases in ICSS thresholds in some animals. Intracranial self-stimulation thresholds were consistently elevated during precipitated and spontaneous withdrawal, confirming that rats were nicotine-dependent. Individual differences in compensation were not correlated with changes in ICSS thresholds during dose reduction, precipitated withdrawal, or spontaneous withdrawal. In a secondary analysis, greater precipitated withdrawal severity predicted greater initial nicotine seeking during extinction. Severity of nicotine withdrawal was not related to the degree of compensation in this protocol. These data do not support a role for nicotine withdrawal in individual differences in compensation during reduced nicotine exposure, but do suggest that withdrawal may contribute to nicotine seeking during early abstinence.