Potential interactions between psychotropic drugs and alcohol and tobacco dependence

Abstract The aim of this study was to identify and analyze the potential interactions between psychotropic drugs and alcohol and tobacco addiction. A cross-sectional study was carried out on secondary data collection in a Center for Psychosocial Care in Alcohol and Other Drugs. Subjects aged 18 years old and over, with alcohol and tobacco dependence, who were taking psychotherapies were included. Medical records with the most recent prescriptions were reviewed. Potential interactions between psychotropic drugs and alcohol and tobacco were analyzed using the Micromedex database and stratified according to clinical risks and mechanisms of action. The Pearson's Chi-square test was used to find significant associations between the variables of interest. The significance level was set at 5%. Between the 2010-2018 period, 2,322 subjects were treated at the care center. Of these, 1,020 fulfilled the inclusion criteria, out of whom 515 (50.5%) were dependent on alcohol and 310 (30.4%) were dependent on tobacco. We found 1,099 potential interactions between psychotropic drugs and alcohol and 160 potential interactions between psychotropic drugs and tobacco. In relation to alcohol dependence, psychotropic drugs interacted largely with moderate clinical risk, and pharmacokinetic mechanisms of action. In relation to tobacco dependence, high clinical risk interactions and pharmacodynamic mechanisms of action predominated.

Prevalences of Stages of Change for Smoking Cessation in Adolescents and Associated Factors: Systematic Review and Meta-Analysis.

PURPOSE: To synthesize evidence on the prevalences of stages of change (Transtheoretical Model) for smoking cessation in adolescents and associated factors. METHODS: A systematic search of Web of Science (Thomson Reuters), SCOPUS (Elsevier), MEDLINE/PubMed, CINAHL (EBSCO) and PsycINFO (APA) was conducted to identify eligible studies. Two calibrated reviewers selected studies independently, extracted data, and appraised studies. A qualitative synthesis of the findings and meta-analysis of the prevalences of the stages of change for smoking cessation were carried out. A quality effects model was used to estimate the pooled prevalences. RESULTS: Eleven studies (N = 6469 adolescents) from five middle- to high-income countries were included in the review. Precontemplators accounted for 41% of smokers in earlier stages of change (95%CI: 34%-49%). In such a group, a lowered decisional balance, the lowest self-efficacy, and highest nicotine dependence were found (p < .05). CONCLUSIONS: A higher overall prevalence of adolescents in precontemplation stage for smoking cessation was observed. Such group displayed more unfavorable smoking-related behaviors and characteristics than adolescents in other stages. The evidence is limited due to the lack of studies in adolescents living in low-income countries.

Evidence of subgroups in smokers as revealed in clinical measures and evaluated by neuroimaging data: a preliminary study.

To date, fractionation of the nicotine addiction phenotype has been limited to that based primarily on characteristics of cigarette use, although it is widely appreciated that a variety of individual factors are associated with tobacco use disorder. Identifying subtypes of tobacco use disorder based on such factors may lead to better understanding of potential treatment targets, individualize treatments and improve outcomes. In this preliminary study, to identify potential subgroups, we applied hierarchical clustering to a broad range of assessments measuring personality, IQ and psychiatric symptoms, as well as various environmental and experiential characteristics from 102 otherwise healthy cigarette smokers. The identified subgroups were further compared on various resting-state fMRI measures from a subset (N = 65) of individuals who also underwent resting-state fMRI scanning. The clustering dendrogram indicated that smokers can be divided into three subgroups. Each subgroup had unique clinical assessment characteristics. The division yielded imaging differences between subgroups in the supplementary motor area/middle cingulate cortex and the cuneus. Regression analyses showed that amplitude of low frequency fluctuations in the supplementary motor area/middle cingulate cortex differed between groups and were negatively correlated with the Toronto Alexithymia Scale subscale Difficulty Describing Feelings.

Classifying and characterizing nicotine use disorder with high accuracy using machine learning and resting-state fMRI.

Cigarette smoking continues to be a leading cause of preventable morbidity and mortality. Although the majority of smokers report making a quit attempt in the past year, smoking cessation rates remain modest. Thus, developing accurate, data-driven methods that can classify and characterize the neural features of nicotine use disorder (NUD) would be a powerful clinical tool that could aid in optimizing treatment development and guide treatment modifications. This investigation applied support vector machine-based classification to resting-state functional connectivity (rsFC) data from individuals diagnosed with NUD (n = 108; 63 male) and matched nonsmoking controls (n = 108; 63 male) and multi-dimensional scaling to visualize the heterogeneity of NUD in individual smokers based on rsFC measures. Machine-based learning models identified five resting-state networks that played a role in distinguishing smokers from controls: the posterior and anterior default mode networks, the sensorimotor network, the salience network and the right executive control network. The classification method constructed classifiers with an average correct classification rate of 88.1 percent and an average area under the curve of 0.93. Compared with controls, individuals with NUD had weaker functional connectivity measures within these networks (P < 0.05, false discovery rate corrected). Further, multi-dimensional scaling visualization demonstrated that controls were similar to each other whereas individuals with NUD had less similarity to controls and to other individuals with NUD. Our findings build upon previous literature demonstrating that machine learning-based approaches to classifying rsFC data offer a valuable technique to understanding network-level differences in nicotine-related neurobiology and extend previous findings by improving classification accuracy and demonstrating the heterogeneity in resting-state networks of individuals with NUD.

Types of Smokers Who Seek Smoking Cessation Treatment According to Psychopathology.

Psychopathology and psychological distress have been shown to be related to poor smoking cessation outcomes and abstinence maintenance. Thus, it is important to identify individuals with high levels of psychopathology before undergoing smoking cessation treatment in order to increase their likelihood of success. OBJECTIVE: The primary aim of the present study was to analyze whether we could classify smokers by using self-reported measures of psychopathology. In addition, a secondary aim was to examine if there were significant differences among the groups of smokers regarding sociodemographic information, nicotine dependence, and cessation rates at the end of treatment and at 6- and 12-month follow-ups. METHODS: Participants were 281 smokers seeking smoking cessation treatment. Participants were classified into different smoking groups by using a 2-step cluster analysis based on baseline scores on the Restructured Clinical (RC) scales of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF), Beck Depression Inventory-II (BDI-II), and State-Trait Anxiety Inventory (STAI). RESULTS: Smokers were classified into 3 groups according to levels of psychopathology: Low (n = 158), Intermediate (n = 78), and High (n = 45). Smokers in the High Group were more likely to present higher levels of psychopathology and to continue smoking at the end of treatment when compared with the two other clusters. In addition, smokers classified in this group were more likely to be nicotine dependent and from a low social class. CONCLUSIONS: A subgroup of smokers can be easily identified through self-report measures of psychopathology. Furthermore, these individuals were more likely to continue smoking at the end of treatment. This suggests that this group with high levels of psychopathology might benefit from future interventions that are more intensive or cessation treatments targeted to their specific characteristics.

Framing Tobacco Dependence as a "Brain Disease": Implications for Policy and Practice.

INTRODUCTION: Like other forms of drug dependence, tobacco dependence is increasingly being described as a "chronic brain disease." The potential consequences of this medical labelling have been examined in relation to other addictions, but the implications for tobacco control have been neglected. Some have posited that biomedical conceptions of addiction will reduce stigma and increase uptake of efficacious treatments. Others have countered that it could increase stigma, reduce treatment seeking, and deter unassisted quitting. We explored how smokers respond to the labelling of smoking as a brain disease. METHODS: Semi-structured interviews with 29 Australian smokers recruited using purposive sampling. Thematic analysis was used to analyze the results. RESULTS: Most participants questioned the accuracy of the brain disease label as applied to smoking. They believed that smoking was not a chronic disease because they perceived smoking to be an individual's choice. In addition, many believed that this label would increase the stigma that they already felt and, did not want to adopt a "sick role" in relation to their smoking. CONCLUSIONS: Describing smoking as a brain disease is more likely to alienate smokers than to engage them in quitting. The application of overly medical labels of smoking are inconsistent with smokers own conceptualizations of their smoking, and may have unintended consequences if they are widely disseminated in healthcare settings or antismoking campaigns. IMPLICATIONS: The participants in this project believed that biomedical labels of smoking as a "brain disease" or a "chronic disease" were discordant their existing understandings of their smoking. Explanations of addiction that downplay or ignore the role of choice and autonomy risk being perceived as irrelevant by smokers, and could lead to suspicion of health professionals or an unwillingness to seek treatment.

WISDM Primary and Secondary Dependence Motives: Associations With Smoking Rate, Craving, and Cigarette Effects in the Natural Environment.

INTRODUCTION: The Wisconsin Inventory of Smoking Dependence Motives (WISDM) is a multidimensional measure of smoking motives that was developed to facilitate research aiming to refine the nomological network surrounding tobacco dependence. Recent evidence suggests that a composite of four subscales, termed the Primary Dependence Motives (PDM), may represent core features of advanced addiction, while the remaining nine subscales (Secondary Dependence Motives; SDM) represent instrumental motives for cigarette use that may be relevant at any stage of smoking. METHODS: A sample of 255 smokers (all regular alcohol users) participated in an ecological momentary assessment study in which they monitored smoking behavior and related experiences for 21 days. Multilevel regression analyses tested how PDM and SDM predicted daily smoking rate, cigarette craving, and appraisals of pleasure and relief of unpleasant feelings from smoking. RESULTS: When PDM and SDM were entered simultaneously, only PDM was related to daily cigarette count, and only SDM predicted reports of craving and relief from unpleasant feelings from smoking. SDM was associated with reports of greater pleasure from smoking and PDM was associated with lower pleasure ratings. The Fagerström Test for Nicotine Dependence (FTND) was related to daily smoking rate and craving, but WISDM composites contributed incremental prediction. CONCLUSIONS: The findings confirm that PDM indexes heavier use that is relatively unrelated to immediate consequences of smoking. SDM is not uniquely related to smoking heaviness, but is associated with craving and reports of pleasure and relief of unpleasant feelings derived from smoking during ad lib use. IMPLICATIONS: This study extends the evidence for the distinction between the WISDM PDM and SDM. PDM scores are associated with heavier smoking and are relatively unrelated to immediate consequences of smoking. SDM is more strongly related to craving and reports of smoking-derived pleasure and relief of unpleasant feelings during ongoing use in daily life.

Tabaquismo intermitente, ¿la nueva forma de consumo? / Intermittent smoking: the new form of consumption?

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Assessment of the Tobacco Dependence Screener Among Smokeless Tobacco Users.

INTRODUCTION: Variants of the Fagerström Tolerance Questionnaire and Fagerström Test for Nicotine Dependence (FTND) are widely used to study dependence among smokeless tobacco (ST) users. However, there is a need for a dependence measure which is based on the clinical definition of dependence and is easy to administer. The Tobacco Dependence Screener (TDS), a self-administered 10-item scale, is based on the Diagnostic and Statistical Manual, fourth edition (DSM-IV) and ICD-10 definitions of dependence. It is commonly used as a tobacco dependence screening tool in cigarette smoking studies but it has not been evaluated for dependence in ST users. The purpose of this study is to evaluate the TDS as a measure of tobacco dependence among ST users. METHODS: Data collected from a community-based sample of exclusive ST users living in Oklahoma (n = 95) was used for this study. TDS was adapted to be used for ST dependence as the references for smoking were changed to ST use. Concurrent validity and reliability of TDS were evaluated. Salivary cotinine concentration was used as a criterion variable. Overall accuracy of the TDS was assessed by receiver's operating characteristic (ROC) curve and optimal cutoff scores for dependence diagnosis were evaluated. RESULTS: There was no floor or ceiling effect in TDS score (mean = 5.42, SD = 2.61). Concurrent validity of TDS as evaluated by comparing it with FTND-ST was affirmative. Study findings showed significant association between TDS and salivary cotinine concentration. The internal consistency assessed by Cronbach's alpha indicated that TDS had acceptable reliability (α = 0.765). TDS was negatively correlated with time to first chew/dip and positively correlated with frequency (number of chews per day) and years of ST use. Results of logistic regression analysis showed that at an optimal cutoff score of TDS 5+, ST users classified as dependent had significantly higher cotinine concentration and FTND-ST scores. CONCLUSIONS: TDS demonstrated acceptable reliability and concurrent validity among ST users. These findings are consistent with the results of previous cigarette smoking studies evaluating TDS. A self-administered tobacco dependence measure for ST users based on a clinical definition of dependence is an effective tool in research setting. IMPLICATIONS: ST dependence research is still evolving. This is the first study of the TDS among ST users providing preliminary evidence about some of the psychometric properties of the scale. Similar to cigarette smokers, TDS is an effective measure of ST dependence. Study showed moderate reliability and affirmative concurrent validity of the TDS among ST users.

Designation of obesity as a disease: lessons learned from alcohol and tobacco.

Obesity is a leading cause of preventable death in the USA. The American Medical Association recently recognized obesity as meeting the definition of a chronic disease. This declaration had the intention of improving screening and long-term treatment and is historically similar to the designation of tobacco and alcohol dependence as a chronic disease. Nevertheless, it has ignited a nationwide debate in both academia and public opinion. The current article reviews the implications of treating obesity as a chronic disease, comparing the similarities in pathophysiology of obesity and other addictions, and discusses the pros and cons of this designation as it pertains to health care workers and patients.

Paciente fumador con enfermedad cardiovascular: efectividad de vareniclina en la práctica clínica / A patient who smokes with cardiovascular disease: effectiveness of varenicline the clinical practice

Objetivos. El objetivo principal de este estudio es evaluar la efectividad y seguridad de vareniclina como tratamiento para dejar de fumar en un grupo de fumadores con enfermedad cardiovascular (EVC), en la práctica clínica. Material y métodos. Se ha revisado nuestra base de datos y se han incluido las historias clínicas que consignan ECV estable (>2 meses). Se trata de un estudio descriptivo, longitudinal con recogida retrospectiva de los datos. Se han incorporado a 180 pacientes todos tratados con vareniclina, a dosis estándar de 1 mg cada 12 h, durante 12 semanas, más apoyo psicológico y material de autoayuda. En total se llevaron a cabo 7 visitas (Basal, 2ª y 4ª semanas; 2º, 3º y 6º mes, y, finalmente, a la 52ª semana). Tambien se realizaron llamadas telefónicas, la manifestación verbal de abstinencia se confirmó con la medición del CO en aire espirado (<10 ppm). Resultados. La edad media de los participantes fue de 58 años, con predominio de varones (78%). Edad media de inicio 15,5 años, consumo medio de cigarrillos 25/día. Media en el test de Richmond 8,1; y en el test Fagerström 7,5 puntos. El 83% encendía el 1er cigarrillo en menos de media hora. Las tasas de abstinencia a las 12 s (52%); a las 24 s (44%) y a las 52 s (37%). La tasa de abandonos debido a la presencia de efectos adversos fue del 7,6%. Los efectos indeseados más frecuentes fueron, respectivamente: náuseas, cefalea, insomnio, vómitos y sueños anormales. Conclusiones. Los participantes presentan un consumo elevado de cigarrillos/día y una severa dependencia. Alta motivación, con elevada puntuación en el test de Richmond. Vareniclina se ha mostrado como un tratamiento farmacológico efectivo para conseguir el cese en fumadores con EVC estable, y el fármaco es, generalmente, bien tolerado, presentando un aceptable perfil de seguridad en el paciente con ECV estable (AU)

Objectives. The principal objective of this study is to evaluate effectiveness and safety of Varenicline as a smoking cessation treatment in a group of smokers with cardiovascular disease (CVD) in the clinical practice. Material and methods. A review was made of our database and the clinical records that achieved stable CVD (>2 months) were included. This is a descriptive, longitudinal study with retrospective collection of the data. A total of 180 patients, all treated with varenicline, at standard dose of 1 mg every 12 h, for 12 weeks, plus psychological support and self-help material were incorporated. In all, 7 visits (baseline, 2nd and 4th weeks; 2nd, 3rd and 6th month and finally at 52 weeks) were carried out. Telephone calls were also made; the oral manifestation of abstinence was confirmed with measurement of CO in expired air (<10 ppm). Results. Mean age of the participants was 58 years, with predominance of males (78%). Mean age at onset was 15.5 years, mean consumption of cigarettes 25/day. Mean on the Richmond test 8.1 and on the Fagerstrom test 7.5 points. A total of 83% smoked the 1st cigarette in less than half an hour. Abstinence rates at 12 w (52%); at 24 w (44%) and at 52 w (37%). Drop-out rate due to presence of adverse effects was 7.6%. The most frequent undesired effects were, respectively: nauseas, headache, insomnia, vomits and unusual dreams. Conclusions. The participants had an elevated use of cigarettes/day and severe dependence. High motivation, with high score on the Richmond test. Varenicline has proven to be an effective drug treatment to achieve smoking cessation in smokers with stable CVD, and the drug is generally well tolerated, with an acceptable safety profile in patients with stable CVD (AU)

Classifying a smoker scale in adult daily and nondaily smokers.

INTRODUCTION: Smoker identity, or the strength of beliefs about oneself as a smoker, is a robust marker of smoking behavior. However, many nondaily smokers do not identify as smokers, underestimating their risk for tobacco-related disease and resulting in missed intervention opportunities. Assessing underlying beliefs about characteristics used to classify smokers may help explain the discrepancy between smoking behavior and smoker identity. This study examines the factor structure, reliability, and validity of the Classifying a Smoker scale among a racially diverse sample of adult smokers. METHODS: A cross-sectional survey was administered through an online panel survey service to 2,376 current smokers who were at least 25 years of age. The sample was stratified to obtain equal numbers of 3 racial/ethnic groups (African American, Latino, and White) across smoking level (nondaily and daily smoking). RESULTS: The Classifying a Smoker scale displayed a single factor structure and excellent internal consistency (α = .91). Classifying a Smoker scores significantly increased at each level of smoking, F(3,2375) = 23.68, p < .0001. Those with higher scores had a stronger smoker identity, stronger dependence on cigarettes, greater health risk perceptions, more smoking friends, and were more likely to carry cigarettes. Classifying a Smoker scores explained unique variance in smoking variables above and beyond that explained by smoker identity. CONCLUSIONS: The present study supports the use of the Classifying a Smoker scale among diverse, experienced smokers. Stronger endorsement of characteristics used to classify a smoker (i.e., stricter criteria) was positively associated with heavier smoking and related characteristics. Prospective studies are needed to inform prevention and treatment efforts.

A new nicotine dependence score and a new scale assessing patient comfort during smoking cessation treatment.

Smoking is considered the leading preventable cause of morbidity and mortality. The pharmacological management of nicotine withdrawal syndrome enables better cessation rates. In our smoking cessation program, we have developed a data collection system, which includes two new instruments: a score that assesses nicotine dependence in smokers of < 10 cigarettes/day; and a patient comfort scale to be used during smoking cessation treatment. Here, we describe the two instruments, both of which are still undergoing validation.

Avaliação dos parâmetros hematológicos, oxigenação periférica e capacidade respiratória em fumantes / Assessment of hematological parameters, peripheral oxygenation and respiratory capacity in cigarette smokers

As substâncias encontradas no cigarro agem sobre vários órgãos e sistemas, constituindo um fator de risco para doenças vasculares. Frequentemente, a concentração de cotinina tem sido usada como marcador bioquímico de exposição ao tabaco. O objetivo desse estudo foi verificar a influência do hábito de fumar nos parâmetros hematológicos, oxigenação periférica, capacidade respiratória e concentração de cotinina urinária. Vinte não fumantes e vinte fumantes com dependência de nicotina classificada como acima de moderada foram comparadas quanto aos parâmetros estudados. O volume globular , a concentração de hemoglobina corpuscular média e a contagem de monócitos foram maiores em fumantes (p=0,007 e p = 0,028, respectivamente ), bem como a concentração de cotinina urinária (p< 0,001). O aumento no valor do volume globular e na concentração de cotinina urinária ocorreu de maneira dose-dependente. Os outros parâmetros não se mostraram diferentes entre os dois grupos. O hábito de fumar traz diversas consequências aos indivíduos, incluindo alterações nos parâmetros hematológicos que podem estar relacionados a complicações vasculares.

Degree of dependence influences the effects of smoking on psychomotor performance and working memory capacity.

OBJECTIVE: Exploration of the variable effect of the degree of smoking dependence on psychomotor performance and working memory capacity. METHODS: This is a randomized, controlled, prospective study conducted in the Department of Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq from 15 January 2011 to 25 February 2011. After third stage male medical students completed the Fagerstrom Test for Nicotine Dependence questionnaire, we randomly selected a sample of 32 students and divided them into 3 groups: 10 participants with zero score (non-smokers), 11 participants with a score of 5 or less (light smokers), and 11 participants with a score of 6 or more (heavy smokers). Choice reaction time and flicker fusion were measured by the Leeds psychomotor performance test battery, and working memory capacity was measured by the N-back working memory test. RESULTS: We found significant improvement in ascending flicker fusion test in heavy smokers in comparison with non-smokers (p=0.005, confidence interval [CI] 0.99-6), and light smokers (p=0.053, CI 0.39-4.5). Heavy smokers significantly deteriorated in the 3-back task in comparison with non-smokers (p=0.006, CI 4-25.8), and light smokers (p=0.009, CI 3-24.4). No significant changes were seen between groups in the descending critical flicker fusion, the components of choice reaction time, and in 1-, 2- back working memory tests. CONCLUSION: Heavy smoking (high nicotine) enhances arousal, but impairs working memory capacity.

[When does nicotine dependence begin?]. / Kiedy zaczyna sie uzaleznienie od nikotyny?

Tobacco use leads in short time to nicotine dependence. Mechanisms of this process remain still not quite understood, of importance is also a question: When does nicotine dependence begin? The present review reports commonly used definition of nicotine dependence (according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition and International Statistical Classification of Diseases and Health Related Problems Tenth Revision), as well as its limited value in detecting first symptoms of this process. The review presents also the concept, which links the beginning of dependence with diminished autonomy (i.e., autonomy theory), results of studies supporting this concept, and neurophysiologic model of sensitization-homeostasis for nicotine dependence development. Further, despite phenomenon of sensitization has not been demonstrated in humans, results of animal studies arguing for sensitization-homeostasis theory are presented in the article. Usefulness of the Hooked on Nicotine Checklist in diagnosing first nicotine dependence symptoms in adolescents is also pointed out.

What does it take to be a smoker? Adolescents' characterization of different smoker types.

INTRODUCTION: Studies have demonstrated that clinical- and research-based definitions of who a smoker is and what constitutes smoking often differ from adolescent-derived definitions, which can be problematic for effective intervention and prevention efforts. We investigated how adolescents define different smoker types (nonsmoker, smoker, regular smoker, addicted smoker, heavy smoker, experimental smoker, casual smoker, and social smoker) using multiple indicators of smoking behaviors, including frequency, amount, place, and length of time cigarette smoking, and whether differences exist by smoking experience. METHODS: Quantitative and qualitative methods were used to analyze data from a cohort of adolescents (N = 372) in northern California. RESULTS: We found differences in how adolescents characterized smoker types based on their own smoking experience. Ever-smokers tended to have a greater flexibility in determining what constituted nonsmoking and heavy smoking, while never-smokers had much narrower definitions. Results also indicated that adolescents may mistakenly associate nicotine addiction with a high frequency and amount of cigarette use as 74.3% characterized an addicted smoker as having smoked for a few years or more. In addition, there was a considerable amount of overlap in definitions between different smoker types, particularly among the smoker-regular smoker, addicted smoker-heavy smoker, and casual smoker-social smoker pairs. CONCLUSION: Health communication strategies for youth smoking prevention need to address the wide variability and overlap in how adolescents define different smoker types. Greater attention should be directed to understanding the nuances of how adolescents define smoking in order to maximize the effectiveness of youth-centered smoking prevention and cessation messages.

Hardcore smokers in Norway 1996-2009.

INTRODUCTION: The aim of this study was to investigate changes in the relative proportion of hardcore smokers (HCS) in Norway for the years 1996-2009. METHODS: Data were derived from Statistics Norway's annually cross-sectional representative samples of the adult population. The total sample size of smokers each year was between 250 and 500. The outcome measure was HCS, defined by their intention not to quit smoking and absence of attempts to quit during the last 12 months. Logistic regression analysis was conducted to estimate the association between time (survey year) and the number of HCS. RESULTS: We identified three groups of smokers: occasional smokers, daily non-HCS, and HCS. The relative proportion of HCS declined in the period 1996-2009, from 30% to 23%. A model adjusted for gender, age, educational level, and the use of snus (smokeless tobacco) showed the same downward trend. CONCLUSIONS: Within this sample of Norwegian smokers, the relative share of HCS is not increasing. This knowledge is important for tobacco prevention policy. The result does not support a hardening hypothesis regarding changes in the size of the group of HCS. Further analysis is needed to investigate individual resistance to smoking cessation.