Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence.
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ABSTRACT:
SUBMITTER: Liakoni E
PROVIDER: S-EPMC7967935 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence.
Liakoni Evangelia E Edwards Kathryn C KC St Helen Gideon G Nardone Natalie N Dempsey Delia A DA Tyndale Rachel F RF Benowitz Neal L NL
Clinical pharmacology and therapeutics 20181025 3
This study investigated the influence of the rate of nicotine metabolism, as indicated by the nicotine metabolite ratio (NMR), on tobacco dependence. We stratified 136 smokers on the basis of saliva NMR as fast (n = 65) and slow (n = 71) metabolizers. Two "loading cigarettes" were smoked after overnight, and a "reward cigarette" was smoked after 6 hours of daytime, abstinence. Blood nicotine concentrations, expired carbon monoxide, withdrawal/craving, and reward questionnaires were collected bef ...[more]
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Project description:INTRODUCTION:The rate of nicotine metabolism, estimated by the nicotine metabolite ratio (NMR), is an important determinant of tobacco dependence. This study investigated the effect of NMR on smoking behavior due to nicotine reinforcement during ad libitum smoking. AIMS AND METHODS:As part of a larger study, participants were stratified based on saliva NMR as fast and slow metabolizers. After smoking a cigarette and measuring nicotine blood concentrations, participants smoked as desired over a 90-minute period. Analysis included time to first cigarette, total number of cigarettes, total number of puffs, and weight of tobacco consumed. RESULTS:Sixty-one (48%) participants were fast metabolizers and 66 (52%) slow metabolizers by NMR. No significant differences were found regarding the smoking topography variables by NMR. Normal metabolizers by genotype (n = 79) had a shorter time to first cigarette than reduced metabolizers (n = 39; p = .032). Blacks smoked fewer cigarettes (p = .008) and took fewer total puffs (p = .002) compared with Whites. Among Whites, fast metabolizers by NMR had a shorter time to first cigarette compared with slow metabolizers (p = .014). Among fast metabolizers, Whites had, compared with Blacks, shorter latency to first cigarette (p = .003) and higher number of total puffs (p = .014) and cigarettes smoked (p = .014). Baseline cigarettes per day and nicotine elimination half-life significantly predicted topography outcomes. CONCLUSIONS:Saliva NMR did not predict cigarette reinforcement during a relatively brief period of ad libitum smoking. Differences were seen by race, with White fast metabolizers by NMR having shorter time to first cigarettes compared with slow metabolizers. IMPLICATIONS:After a 90-minute period of nicotine abstinence, NMR was not significantly associated with smoking reinforcement. Slow and fast metabolizers had similar time to first cigarette, number of cigarettes smoked, total number of puffs, and tobacco consumed; however, within-race differences show that within Whites, fast metabolizers had a faster time to first cigarette than slow metabolizers.
| S-EPMC7364822 | biostudies-literature
Project description:In the United States, the Food and Drug Administration (FDA) has initiated a public dialogue about reducing the nicotine content of cigarettes. A reduced-nicotine standard could increase withdrawal symptoms among current smokers. We examined the impact of switching smokers to cigarettes that varied in nicotine content on withdrawal symptoms over 6 weeks. A secondary analysis (N = 839) of a 10-site, double-blind clinical trial of nontreatment-seeking smokers was completed. Participants were instructed to smoke study cigarettes, containing 0.4 to 15.8 mg of nicotine/g of tobacco, for 6 weeks and were then abstinent overnight. Using latent growth curves, trajectories of individual withdrawal symptoms were compared between the reduced nicotine content (RNC) conditions and a normal nicotine content (NNC) condition. Path analyses compared symptoms after overnight abstinence. Relative to NNC cigarettes, participants smoking RNC cigarettes had increased anger/irritability/frustration and increased appetite/weight gain during the initial weeks, but the symptoms resolved by Week 6. Individuals who were biochemically verified as adherent with using only the 0.4 mg/g cigarettes had higher sadness levels (Cohen's d = .40) at Week 6 compared with the NNC condition, although symptoms were mild. After a post-Week 6 overnight abstinence challenge, some RNC conditions relative to NNC condition exhibited reduced withdrawal. Individuals who were biochemically confirmed as adherent to the lowest nicotine condition experienced only mild and transient symptom elevations. Thus, a reduced-nicotine standard for cigarettes produced a relatively mild and temporary increase in withdrawal among nontreatment-seeking smokers (ClinicalTrials.gov No. NCT01681875). (PsycINFO Database Record
| S-EPMC5986583 | biostudies-literature
Project description:Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction.
| S-EPMC4573778 | biostudies-literature
Project description:ImportanceGiven the actions of varenicline tartrate and bupropion hydrochloride sustained-release (SR) on neurobiological targets related to affect and reward, it is thought that the modulation of nicotine withdrawal symptoms may contribute to their effectiveness.ObjectiveTo assess the relative efficacy of varenicline and bupropion SR plus intensive counseling on smoking cessation and emotional functioning.Design and settingPlacebo-controlled randomized clinical trial at a university medical center.ParticipantsIn total, 294 community volunteers who wanted to quit smoking.InterventionsTwelve weeks of varenicline, bupropion SR, or placebo plus intensive smoking cessation counseling (10 sessions, for a total of approximately 240 minutes of counseling).Main outcome measuresProlonged abstinence from smoking and weekly measures of depression, negative affect, and other symptoms of nicotine withdrawal.ResultsSignificant differences were found in abstinence at the end of treatment and through the 3-month postquit follow-up visit, favoring both active medications compared with placebo. At the 6-month postquit follow-up visit, only the varenicline vs placebo comparison remained significant. Varenicline use was also associated with a generalized suppression of depression and reduced smoking reward compared with the other treatments, while both active medications improved concentration, reduced craving, and decreased negative affect and sadness compared with placebo, while having little effect (increase or decrease) on anxiety and anger. No differences were noted in self-reported rates of neuropsychiatric adverse events.Conclusions and relevanceIn a community sample, varenicline exerts a robust and favorable effect on smoking cessation relative to placebo and may have a favorable (suppressive) effect on symptoms of depression and other affective measures, with no clear unfavorable effect on neuropsychiatric adverse events.Trial registrationclinicaltrials.gov Identifier: NCT00507728.
| S-EPMC4128024 | biostudies-literature
Project description:ImportanceSmoking cigarettes during pregnancy can impair maternal and child health, and pregnant individuals have increasingly used electronic cigarettes (e-cigarettes) for various reasons, including quitting smoking.ObjectiveTo assess smoking abstinence rates among pregnant individuals who used e-cigarettes compared with those who used nicotine replacement therapy (NRT).Design, setting, and participantsThis cohort study is a secondary data analysis of phase 8 of the US Pregnancy Risk Assessment Monitoring System, conducted between 2016 and 2020. Eligible participants included pregnant individuals who smoked combustible cigarettes within the 3 months before pregnancy and either used e-cigarettes or NRT during pregnancy. Data analysis was conducted from March 2022 to April 2023.ExposuresCombustible cigarette use within 3 months before pregnancy and use of either e-cigarettes or NRT during pregnancy.Main outcomes and measuresThe primary outcome was the individual's self-reported smoking abstinence status during the last 3 months of pregnancy. Weighted percentages were reported and weighted multivariable logistic regression models were used to examine the association of e-cigarette use vs NRT with smoking abstinence. A propensity score was used to control for confounding by sociodemographics, pregnancy characteristics, prepregnancy smoking intensity, depression, behavioral support, and hookah use.ResultsThe cohort included 1329 pregnant individuals (759 ≥25 years [60.2%]; 766 non-Hispanic White individuals [79.8%]) of whom 781 had an education level of high school or lower (61.4%), and 952 had an annual household income of $48 000 or less (81.5%). Of the 1329 individuals, 890 (unweighted percentage, 67.0%) were existing e-cigarette users, 67 (unweighted percentage, 5.0%) were new e-cigarette users, and 372 (unweighted percentage, 28.0%) were NRT users. Compared with individuals who used NRT during pregnancy, individuals who used e-cigarettes had a higher rate of smoking abstinence in late pregnancy (456 individuals [50.8%] vs 67 individuals [19.4%]; propensity score adjusted odds ratio [OR], 2.47; 95% CI, 1.17-5.20; P = .02). In the secondary analysis stratified by the timing of e-cigarette use initiation, existing users of e-cigarettes who initiated before pregnancy had a higher smoking abstinence rate than NRT users (446 users [53.1%] vs 67 users [19.4%]; adjusted OR, 2.61; 95% CI, 1.23-5.51; P = .01). However, new e-cigarette users who initiated use during pregnancy had a similar smoking abstinence rate in late pregnancy when compared with NRT users (10 users [20.6%] vs 67 users [19.4%]; adjusted OR, 1.13; 95% CI, 0.22-5.87; P = .88).Conclusions and relevanceThese findings suggest that individuals who used e-cigarettes during pregnancy had a higher smoking abstinence rate in late pregnancy than individuals who used NRT, especially for those who initiated e-cigarette use before pregnancy, indicating that replacement of cigarettes with e-cigarettes during pregnancy may be a viable strategy for harm reduction.
| S-EPMC10498331 | biostudies-literature
Project description:IntroductionThe study objectives were to examine smoking abstinence and reinstatement effects on subjective experience and cognitive performance among adolescent smokers.MethodsAdolescents (aged 14-17 years, 60 daily smokers and 32 nonsmokers) participated. Participants completed baseline assessments (Session 1) and returned to the laboratory 1-3 days later to repeat assessments (Session 2); half of the smokers were randomly assigned to 15-17 hr tobacco abstinence preceding Session 2.ResultsDuring Session 2, abstaining smokers reported significantly greater increases in withdrawal symptoms, smoking urges, and negative affect compared with smokers who did not abstain and compared with nonsmokers. Smoking reinstatement reversed abstinence effects, returning to baseline levels for smoking urges and negative affect. Abstaining smokers showed significantly enhanced cognitive performance on two of six tasks (two-letter search compared with nonabstaining smokers; serial reaction time compared with nonsmokers); smoking reinstatement resulted in significant decrements on these two tasks relative to nonabstaining smokers.DiscussionEffects of smoking abstinence and reinstatement on self-report measures are consistent with earlier research with adolescent as well as adult smokers and may help to elucidate the motivational underpinnings of smoking maintenance among adolescent smokers. Effects found on cognitive performance were contrary to hypotheses; further research is needed to understand better the role of cognitive performance effects in smoking maintenance among adolescents.
| S-EPMC2902909 | biostudies-literature
Project description:IntroductionThe major aim of this study was to test whether abstinence from e-cigarettes causes withdrawal symptoms in former smokers.MethodsWe conducted an unblinded, within-participants, pre-post clinical trial in which 109 former smokers who were current daily electronic cigarette (e-cigarette) users used their own e-cigarette for 7 days followed by 6 days of biologically confirmed abstinence engendered via an escalating contingency payment system. Participants monitored symptoms of nicotine withdrawal daily via an Interactive Voice Response system. They also attended three laboratory visits per week for carbon monoxide and cotinine testing to verify abstinence.ResultsHalf of participants completely abstained for a week. All the Diagnostic and Statistical Manual, Fifth Edition (DSM-5) tobacco withdrawal symptoms, craving for e-cigarettes, craving for tobacco cigarettes, and the four possible new withdrawal symptoms (anhedonia, impulsivity, mood swings, and positive affect) increased during abstinence. Weight increased and heart rate decreased with abstinence. Symptoms showed the prototypical inverted U time pattern of a withdrawal state. The magnitude of withdrawal appeared to be somewhat less than that in a prior study of abstinent daily tobacco cigarette smokers. More severe withdrawal on the first 2 days of abstinence did not predict abstinence on the last day of the study.ConclusionsFormer smokers who are daily e-cigarette users transfer physical dependence on tobacco cigarettes to dependence on e-cigarettes. The severity of withdrawal from e-cigarettes appears to be only somewhat less than that from daily tobacco cigarette use. Replication tests that include placebo controls, testing for pharmacological specificity, and including never-smokers, non-daily e-cigarette users and dual users are indicated.ImplicationsOur results indicate e-cigarettes can maintain physical dependence. This adverse effect should be included in any risk vs. benefit calculation. Also, potential and current e-cigarette users should be informed that abrupt cessation of e-cigarettes can cause withdrawal symptoms.Trial registrationNCT02825459.
| S-EPMC7171279 | biostudies-literature
Project description:IntroductionUse of e-cigarettes among never-smokers has substantially increased; yet there are few descriptions of the consequences of such use. We assessed whether adult never-smokers can have withdrawal from cessation of e-cigarettes.MethodsIn an un-blinded pre-post clinical trial, 30 never-smoker daily e-cigarette users used their own nicotine-containing e-cigarette for 7 days followed by 6 days of biologically confirmed abstinence. Participants monitored symptoms of nicotine withdrawal nightly via an Interactive Voice Response system. They attended three lab visits/week to provide expired carbon monoxide and urine samples to determine compliance.FindingsAbstinence increased all the DSM5 symptoms of tobacco withdrawal and this occurred in the majority of participants. The increase in severity of withdrawal was small and rarely impaired functioning.ConclusionsOur finding suggests that withdrawal symptoms can occur in never-smokers who stop e-cigarettes abruptly. However, the severity of withdrawal appears to be small and may not be of clinical or regulatory significance. Although our sample size was small and thus replication tests of our results are indicated, it may be prudent to warn never-smokers that withdrawal symptoms may occur.ImplicationsThis study indicates that withdrawal symptoms can occur in never-smokers who are daily e-cigarette users. However, the severity of withdrawal from e-cigarette abstinence in never-smokers appears to be small and may not be of clinical or regulatory significance. Given our small sample size, replication of our results is warranted. Nevertheless, it might be prudent to warn never-smokers of addiction to e-cigarettes.Clinical Trial Registration = NCT02825459.
| S-EPMC7171287 | biostudies-literature
Project description:BackgroundThe purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research.MethodsA seven-member translation committee conducted the translation process using the following methodology: production of two independent forward translations; comparison and reconciliation of the translations; backward translation of the first reconciled version; comparison of the original WSWS and the backward version leading to the production of the second reconciled version; pilot testing and review of the translation, and finalization.ResultsLinguistic and conceptual issues arose during the process of translating the instrument, particularly pertaining to the title, instructions, and some of the items of the scale. In addition, the researchers had to find culturally acceptable equivalents for some terms and idiomatic phrases. Notable among these include expressions such as "irritability", "feeling upbeat", and "nibbling on snacks", which had to be replaced by culturally acceptable expressions. During cognitive debriefing and clinician's review processes, the Malay translated version of WSWS was found to be easily comprehensible, clear, and appropriate for the smoking withdrawal symptoms intended to be measured.ConclusionsWe applied a rigorous translation method to ensure conceptual equivalence and acceptability of WSWS in Malay prior to its utilization in research and clinical practice. However, to complete the cultural adaptation process, future psychometric validation is planned to be conducted among Malay speakers.
| S-EPMC2882374 | biostudies-literature
Project description:BackgroundIndividuals who report more depressive symptoms consistently demonstrate higher rates of nicotine dependence and less successful smoking cessation than do individuals who report fewer depressive symptoms. Nicotine withdrawal and smoking urges are two potential factors that may account for the differences observed between these two groups. This study assessed whether elevated depression symptoms among nicotine dependent smokers are associated with changes in withdrawal and urges to smoke when undergoing smoking cessation treatment.MethodData on 81 nicotine dependent smokers were collected as part of a smoking cessation randomized trial that compared standard and contingency management treatment across one baseline week and four treatment weeks. Linear mixed model analyses were conducted with high and low depression scores predicting changes in withdrawal and urge ratings from a baseline week and four treatment weeks.ResultsParticipants with elevated depression symptoms reported more intense nicotine withdrawal and smoking urges throughout treatment. Further, participants with greater depressive symptoms exhibited an increase in smoking urges at the start of treatment, compared with a gradual decline in urges among participants with fewer depressive symptoms.ConclusionsSmokers with elevated depressive symptoms experience significantly elevated discomfort during smoking cessation efforts in the form of increased withdrawal and craving. This discomfort has the potential to make quitting smoking more difficult. Clinical Trial Identifier: NCT00865254.
| S-EPMC4988686 | biostudies-literature