How I Learned That Cigarettes Were Addictive--1970s to 1980s: A Personal History.

OBJECTIVE: This is a personal history of how I came to view cigarette smoking as an addiction to nicotine. I discuss working with Stanley Schachter and Murray Jarvik. Although I note the importance of Michael Russell (as do many colleagues), I draw attention to the considerable effect on my work of Edward Brecher through his 1972 book, Licit and Illicit Drugs. I give examples of the influence of the makers and sellers of nicotine-containing gum on my career in Canada and the United States as well as on the careers of several important colleagues. Ted Klein, who did public relations for nicotine-replacement products, is noted as an important figure in the tobacco control movement of the time, especially for those doing behavioral and smoking cessation research.

Advances in smoking cessation pharmacotherapy: Non-nicotinic approaches in animal models.

The landscape of worldwide tobacco use is changing, with a decrease in traditional smoking and an exponential rise in electronic cigarette use. No new nicotine cessation pharmacotherapies have come to market in the last 10 years. The current therapies that have been approved by the United States Food and Drug Administration for nicotine cessation include nicotine replacement therapy, varenicline, a nicotinic acetylcholine receptor partial agonist, and the atypical antidepressant bupropion. Nicotine replacement therapy and varenicline both act on nicotinic acetylcholine receptors. Bupropion inhibits the dopamine transporter, the norepinephrine transporter, and the nicotinic acetylcholine receptors to inhibit smoking behavior. Notwithstanding these treatments, rates of successful nicotine cessation in clinical trials remain low. Recent pharmacological approaches to improve nicotine cessation rates in animal models have turned their focus away from activating nicotinic acetylcholine receptors. The present review focuses on such pharmacological approaches, including nicotine vaccines, anti-nicotine antibodies, nicotine-degrading enzymes, cannabinoids, and metformin. Both immunopharmacological and enzymatic approaches rely on restricting and degrading nicotine within the periphery, thus preventing psychoactive effects of nicotine on the central nervous system. In contrast, pharmacologic inhibition of the enzymes which degrade nicotine could affect smoking behavior. Cannabinoid receptor agonists and antagonists interact with the dopamine reward pathway and show efficacy in reducing nicotine addiction-like behaviors in preclinical studies. Metformin is currently approved by the Food and Drug Administration for the treatment of diabetes. It activates specific intracellular kinases that may protect against the lower metabolism, higher oxidation, and inflammation that are associated with nicotine withdrawal. Further studies are needed to investigate non-nicotinic targets to improve the treatment of tobacco use disorder. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.

Evaluation of nicotine patch adherence measurement using self-report and saliva cotinine among abstainers in a smoking cessation trial.

BACKGROUND: Adherence to nicotine patches relates to cessation. This is the first study to examine the validity of self-reported nicotine patch adherence relative to saliva cotinine. METHODS: We used data from 198 clinical trial participants who received 11 weeks of nicotine patches, self-reported patch use, had saliva cotinine 1-week after the start of treatment assessed, and were not smoking when saliva was collected (CO < 6). Self-reported patch adherence was defined as: 3-day (before saliva collection), 7-day (before saliva collection), 3-week use (7 days before, and 14 days after, saliva collection), and 11-week use (7 days before, and 10 weeks after, saliva collection). Analyses, including receiver operating characteristic curves, considered differences in nicotine metabolism. Sensitivity, specificity and positive (PPV) and negative predictive value (NPV) assessed optimal cotinine cut-point for adherence. RESULTS: Self-reported 7-day (r = 0.13) and 3-week (r = 0.13) patch use marginally correlated with week 1 cotinine (p's = 0.08) but not 3-day or 11-week. Significant area under the curve (AUC) values of 0.67 (95 %CI: 0.55-0.79) and 0.72 (95 %CI: 0.57-0.88) were found using 7-day self-report for the overall sample and for slow metabolizers (p's<0.01), but not for normal metabolizers. Optimal 1-week cotinine cut-points using 7-day self-report were 170 ng/mL (overall) and 184 ng/mL (slow), with sensitivity = 0.56-0.62, specificity = 0.69-0.78, PPV = 0.96-0.97, and NPV = 0.13-0.14. CONCLUSIONS: Among CO-confirmed abstainers, self-reported patch use and saliva cotinine assessed 1-week into treatment, were modestly correlated and optimal cotinine cut-point differed by rate of nicotine metabolism. Seven-day patch use may be a more valid self-report measure of patch adherence based on cotinine than 3-day, 3-week, or 11-week. Rate of nicotine metabolism may affect this relationship.

Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial.

RATIONALE: Given that tetrahydrocannabinol (THC) and nicotine have similar effects on negative affect (NA), we hypothesized that a 7-mg nicotine patch (NP) would reduce NA-related cannabis (CAN) withdrawal symptoms in cannabis-dependent (CD) individuals who were not nicotine dependent. OBJECTIVE: We sought to determine whether NP reduces NA across 15 days of CAN abstinence in two groups: non-tobacco smokers (NTS) and light tobacco smokers (LTS). METHODS: CD participants (N = 127; aged 18-35) who used CAN at least 5 times/week for the past 12 + months were randomized to (1) NP or (2) a placebo patch (PP) and received $300 for sustained biochemically verified CAN abstinence. Of those randomly assigned, 52 of 63 NP, and 56 of 64 PP maintained biochemically verified CAN abstinence and 51 NP and 50 PP participants complied with all aspects of the study. Affect and other withdrawal symptoms were measured every 48 h across 15 days of CAN abstinence. RESULTS: After controlling for age, tobacco use, baseline THC concentration, and baseline measurements of the dependent variable, NP reduced NA symptoms across the 15-day treatment relative to PP. Differences in NA and CAN withdrawal symptoms were not moderated by tobacco user status. CONCLUSIONS: The findings provide the first evidence that NP may be able to attenuate NA-related withdrawal symptoms in individuals with cannabis use disorder who are not heavy users of tobacco or nicotine. CLINICAL TRIALS REGISTRY: NCT01400243 http://www.clinicaltrials.gov.

2018 Langley Award for Basic Research on Nicotine and Tobacco: Bringing Precision Medicine to Smoking Cessation.

INTRODUCTION: Large segments of the world population use combustible cigarettes, and our society pays a high price for smoking, through increased healthcare expenditures, morbidity and mortality. The development of combustible cigarette smoking requires the initiation of smoking and a subsequent chain of behavioral transitions from experimental use, to established regular use, to the conversion to addiction. Each transition is influenced by both environmental and genetic factors, and our increasing knowledge about genetic contributions to smoking behaviors opens new potential interventions. METHODS: This review describes the journey from genetic discovery to the potential implementation of genetic knowledge for the treatment of tobacco use disorder. RESULTS AND CONCLUSIONS: The field of genetics applied to smoking behaviors has rapidly progressed with the identification of highly validated genetic variants that are associated with different smoking behaviors. The large scale implementation of this genetic knowledge to accelerate smoking cessation represents an important clinical challenge in precision medicine.

Trends in Attempts to Quit Smoking in England Since 2007: A Time Series Analysis of a Range of Population-Level Influences.

AIM: To quantify population-level associations between quit attempts and factors that have varied across 2007-2017 in England. METHODS: Data from 51 867 past-year smokers participating in the Smoking Toolkit Study (a monthly cross-sectional survey of individuals aged 16+) were aggregated over an 11-year period. Time series analysis was undertaken using ARIMAX modeling. The input series were: (1) prevalence of smoking reduction using (a) e-cigarettes and (b) nicotine replacement therapy; (2) prevalence of roll-your-own tobacco use; (3) prevalence of (a) smoking and (b) non-daily smoking; (4) mass media expenditure; (5) average expenditure on smoking; (6) characteristics in the form of (a) prevalence of high motivation to quit, (b) average age, (c) proportion from lower social grades, and (d) average number of cigarettes smoked; and (7) implementation of tobacco control policies. RESULTS: There was a decline in the prevalence of quit attempts from 44.6% to 33.8% over the study period. The partial point-of-sale ban was associated with a temporary increase in quit attempt prevalence (Badjusted = 0.224%; 95% confidence interval [CI] 0.061 to 0.388). Quit attempts were positively associated with the prevalence of high motivation to quit (Badjusted = 0.165%;95% CI 0.048 to 0.282) and negatively associated with the mean age of smokers (Badjusted = -1.351%; 95% CI -2.168 to -0.534). All other associations were nonsignificant. CONCLUSION: Increases in the prevalence of high motivation to quit was associated with higher prevalence of attempts to quit smoking, while an increase in the mean age of smokers was associated with lower prevalence. The introduction of the partial point-of-sale ban appeared to have a temporary positive impact. IMPLICATIONS: This study provides insight into how monthly changes in a wide range of population-level factors are associated with changes in quit attempts over an extended time period in a country with a strong tobacco control climate. The findings suggest a need for intervention or policy to stimulate quit attempts in older smokers. Otherwise, increases in the mean age of a smokers appears likely to undermine wider efforts to promote quit attempts in a population.

Impact of Adding Telephone-Based Care Coordination to Standard Telephone-Based Smoking Cessation Counseling Post-hospital Discharge: a Randomized Controlled Trial.

BACKGROUND: Cessation counseling and pharmacotherapy are recommended for hospitalized smokers, but better coordination between cessation counselors and providers might improve utilization of pharmacotherapy and enhance smoking cessation. OBJECTIVE: To compare smoking cessation counseling combined with care coordination post-hospitalization to counseling alone on uptake of pharmacotherapy and smoking cessation. DESIGN: Unblinded, randomized clinical trial PARTICIPANTS: Hospitalized smokers referred from primarily rural hospitals INTERVENTIONS: Counseling only (C) consisted of telephone counseling provided during the hospitalization and post-discharge. Counseling with care coordination (CCC) provided similar counseling supplemented by feedback to the smoker's health care team and help for the smoker in obtaining pharmacotherapy. At 6 months post-hospitalization, persistent smokers were re-engaged with either CCC or C. MAIN MEASURES: Utilization of pharmacotherapy and smoking cessation at 3, 6, and 12 months post-discharge. KEY RESULTS: Among 606 smokers randomized, 429 (70.8%) completed the 12-month assessment and 580 (95.7%) were included in the primary analysis. Use of any cessation pharmacotherapy between 0 and 6 months (55.2%) and between 6 and 12 months (47.1%) post-discharge was similar across treatment arms though use of prescription-only pharmacotherapy between months 6-12 was significantly higher in the CCC group (30.1%) compared with the C group (18.6%) (RR, 1.61 (95% CI, 1.08, 2.41)). Self-reported abstinence rates of 26.2%, 20.3%, and 23.4% at months 3, 6, and 12, respectively, were comparable across the two treatment arms. Of those smoking at month 6, 12.5% reported abstinence at month 12. Validated smoking cessation at 12 months was 19.3% versus 16.9% in the CCC and C groups, respectively (RR, 1.13 (95% CI, 0.80, 1.61)). CONCLUSION: Supplemental care coordination, provided by counselors outside of the health care team, failed to improve smoking cessation beyond that achieved by cessation counseling alone. Re-engagement of smokers 6 months post-discharge can lead to new quitters, at which time care coordination might facilitate use of prescription medications. TRIAL REGISTRATION: NCT01063972.

Effects of motivation phase intervention components on quit attempts in smokers unwilling to quit: A factorial experiment.

BACKGROUND: Smoking reduction treatment is a promising approach to increase abstinence amongst smokers initially unwilling to quit. However, little is known about which reduction treatment elements increase quit attempts and the uptake of cessation treatment amongst such smokers. METHODS: This study is a secondary analysis of a 4-factor randomized factorial experiment conducted amongst primary care patients (N = 517) presenting for regular healthcare visits in Southern Wisconsin who were unwilling to quit smoking but willing to cut down. We evaluated the main and interactive effects of Motivation-phase intervention components on whether participants: 1) made a quit attempt (intentional abstinence ≥24 h) by 6- and 26-weeks post-study enrollment and, 2) used cessation treatment. We also evaluated the relations of quit attempts with abstinence. The four intervention components evaluated were: 1) Nicotine Patch vs. None; 2) Nicotine Gum vs. None; 3) Motivational Interviewing (MI) vs. None; and 4) Behavioral Reduction Counseling (BR) vs. None. Intervention components were administered over 6 weeks, with an option to repeat treatment; participants could request cessation treatment at any point. RESULTS: Nicotine gum significantly increased the likelihood of making a quit attempt by 6 weeks (23% vs. 15% without gum; p < .05). Conversely, nicotine patch reduced quit attempts when used with BR. Patch also discouraged use of cessation treatment (15.8% vs. 23% without patch; p < .05). Aided vs. unaided quit attempts produced abstinence in 42% vs. 10% of participants, respectively. CONCLUSION: Nicotine gum is a promising Motivation-phase intervention that may spur quit attempts amongst smokers initially unwilling to quit.

Smoking Cessation Pharmacotherapy Based on Genetically-Informed Biomarkers: What is the Evidence?

INTRODUCTION: Pharmacogenomic studies have used genetic variants to identify smokers likely to respond to pharmacological treatments for smoking cessation. METHODS: We performed a systematic review and meta-analysis of primary and secondary analyses of trials of smoking cessation pharmacotherapies. Eligible were trials with data on a priori selected single nucleotide polymorphisms, replicated non-single nucleotide polymorphisms, and/or the nicotine metabolite ratio. We estimated the genotype × treatment interaction as the ratio of risk ratios (RRR) for treatment effects across genotype groups. RESULTS: We identified 18 trials (N = 9017 participants), including 40 active (bupropion, nicotine replacement therapy [NRT], varenicline, or combination therapies) versus placebo comparisons and 16 active versus active comparisons. There was statistical evidence of heterogeneity across rs16969968 genotypes in CHRNA5 with regard to both 6-month abstinence and end-of-treatment abstinence in non-Hispanic black smokers and end-of-treatment abstinence in non-Hispanic white smokers. There was also heterogeneity across rs1051730 genotypes in CHRNA3 with regard to end-of-treatment abstinence in non-Hispanic white smokers. There was no clear statistical evidence for other genotype-by-treatment combinations. Compared with placebo, NRT was more effective among non-Hispanic black smokers with rs16969968-GG with regard to both 6-month abstinence (RRR for GG vs. GA or AA, 3.51; 95% confidence interval [CI] = 1.19 to 10.30) and end-of-treatment abstinence (RRR for GG vs. GA or AA, 5.84; 95% CI = 1.89 to 18.10). Among non-Hispanic white smokers, NRT effectiveness relative to placebo was comparable across rs1051730 and rs169969960 genotypes. CONCLUSIONS: We did not identify widespread differential effects of smoking cessation pharmacotherapies based on genotype. The quality of the evidence is generally moderate. IMPLICATIONS: Although we identified some evidence of genotype × treatment interactions, the vast majority of analyses did not provide evidence of differential treatment response by genotype. Where we find some evidence, these results should be considered preliminary and interpreted with caution because of the small number of contributing trials per genotype comparison, the wide confidence intervals, and the moderate quality of evidence. Prospective trials and individual-patient data meta-analyses accounting for heterogeneity of treatment effects through modeling are needed to assess the clinical utility of genetically informed biomarkers to guide pharmacotherapy choice for smoking cessation.

Age Moderates Smokers' Subjective Response to Very-Low Nicotine Content Cigarettes: Evidence from a Randomized Controlled Trial.

INTRODUCTION: Reducing the level of nicotine in cigarettes is a regulatory strategy that has the potential to greatly improve public health. If nicotine levels are reduced in all commercially available cigarettes, current smokers might find it easier to quit and young people might be less likely to become dependent. However, it is not yet known whether age moderates subjective or behavioral responses to low-nicotine cigarettes. METHODS: Recently, a large, multisite randomized clinical trial was conducted to compare the effects of cigarettes differing in nicotine content (either usual-brand or research cigarettes containing 15.8, 5.2, 2.4, 1.3, or 0.4 mg nicotine/g tobacco) across 6 weeks of exposure. In this secondary analysis, we tested whether age moderated smokers' subjective (measures of psychological reward, smoking satisfaction) and behavioral (cigarettes smoked per day, smoking topography, and nicotine exposure) responses to cigarettes varying in nicotine content after 2 and 6 weeks of use, while controlling for baseline dependence and demographic factors. RESULTS: Results indicated that younger adults (age 18-24) who smoked cigarettes with 2.4-0.4 mg/g nicotine reported significantly less smoking satisfaction and psychological reward, and smoked fewer cigarettes per day, than older adults (25+ years) after 2 weeks of use. No differences in topography were observed at either time point. After 6 weeks of use, differences had diminished on all measures. CONCLUSIONS: The reduced positive effects of reduced-nicotine content cigarettes in young adults suggests that this regulatory policy may reduce smoking reinforcement in this vulnerable population. IMPLICATIONS: As the FDA considers reducing the level of nicotine in cigarettes to make them less addictive, understanding the potential impact of this policy on young people is of crucial importance. We found that young adults had significantly lower positive subjective effects to very-low nicotine content (VLNC) cigarettes and smoked fewer VLNC cigarettes than older adults after 2 weeks of use, indicating that this policy may reduce smoking reinforcement more quickly in young adults. These data add to the growing body of evidence on the potential for this policy to positively affect public health.

Stillbirth Among Women Prescribed Nicotine Replacement Therapy in Pregnancy: Analysis of a Large UK Pregnancy Cohort.

INTRODUCTION: We aimed to compare risk of stillbirth between maternal smokers and those prescribed nicotine replacement therapy (NRT) during pregnancy. AIMS AND METHODS: We conducted a cross-sectional analysis on a pregnancy cohort of 220,630 singleton pregnancies ending in live or stillbirth between 2001 and 2012 from The Health Improvement Network UK general practice database. Women were categorized into three groups: NRT (prescribed during pregnancy or 1 month before conception); smokers; and controls (nonsmokers without a pregnancy NRT prescription). We calculated Odds ratios (OR) and corresponding 95% confidence intervals (CI) for stillbirth in the NRT group and smokers compared to controls. RESULTS: A total of 805 pregnancies ended in stillbirth (3.6/1000 births). Absolute risks of stillbirth in NRT and smoker groups were both 5/1000 births compared with 3.5/1000 births in the control group. Compared with the control group, the adjusted odds of stillbirth in the NRT group was not statistically significant (OR = 1.35, 95% CI 0.91 to 2.00), although it was similar in magnitude to that in the smokers group (OR = 1.41, 95% CI 1.13 to 1.77). CONCLUSIONS: We found no evidence of a statistically significant association between being prescribed NRT during pregnancy and odds of stillbirth compared with nonsmoking women. Although our study had much larger numbers than any previously, an even larger study with biochemically validated smoking outcome data and close monitoring of NRT use throughout pregnancy is required to exclude effects on findings of potential exposure misclassification.

Level of Alcohol Consumption and Successful Smoking Cessation.

INTRODUCTION: The negative association between heavy alcohol use and likelihood of successful smoking cessation is well established. However, evidence on the effects of moderate alcohol consumption on smoking cessation is sparse. This analysis evaluated the association between alcohol use and smoking and the interaction of alcohol use and use of pharmacotherapy interventions in relation to smoking cessation. METHODS: Data from adults (n = 923) recruited through a smoking cessation website between November 2011 and March 2012 were analyzed. Data on past-year alcohol use, tobacco use, and demographics were collected at baseline. Self-reported smoking abstinence and current alcohol use data were collected at 1 and 7 months posttreatment. Chi-square and multivariate logistic regression analyses were conducted. RESULTS: At 1 month, adjusted odds of continued smoking were 1.54 times greater (95% confidence interval [CI] = 1.05% to 2.23%) for moderate drinkers and 2.59 times greater (95% CI = 1.33% to 4.28%) for heavy drinkers than nondrinkers. At 7 months, adjusted odds of continued smoking were not greater for moderate drinkers than nondrinkers, and were 2.32 times greater (95% CI = 1.35% to 3.96%) among heavy alcohol drinkers than nondrinkers. At 1 month, adjusted odds of smoking cessation were 2.33 times greater (95% CI = 1.04% to 3.09%) for alcohol users assigned to nicotine replacement therapy than for those not assigned to nicotine replacement therapy. This relationship was not observed at 7 months. CONCLUSIONS: Moderate and heavy drinking might impact smoking cessation efforts. Recent moderate drinking may be associated with short-term continued smoking and heavy drinking associated with relapse in the short and long term. IMPLICATIONS: This study suggests that moderate drinking may influence the process to quit smoking. Further study is needed to better understand the implications of moderate drinking for smoking cessation. Providing information alone may not be effective in helping people abstain from drinking during smoking cessation, especially if moderate drinkers do not perceive their behavior as reducing their chance for a successful quit attempt. Tailoring smoking cessation interventions to include strategies to reduce moderate-to-heavy alcohol consumption may improve smoking cessation outcomes among alcohol users attempting to quit smoking.

Reprint of: Prevention and Treatment of Tobacco Use: JACC Health Promotion Series.

Tobacco use is the leading preventable cause of death worldwide and is a major risk factor for cardiovascular disease (CVD). Both prevention of smoking initiation among youth and smoking cessation among established smokers are key for reducing smoking prevalence and the associated negative health consequences. Proven tobacco cessation treatment includes pharmacotherapy and behavioral support, which are most effective when provided together. First-line medications (varenicline, bupropion, and nicotine replacement) are effective and safe for patients with CVD. Clinicians who care for patients with CVD should give as high a priority to treating tobacco use as to managing other CVD risk factors. Broader tobacco control efforts to raise tobacco taxes, adopt smoke-free laws, conduct mass media campaigns, and restrict tobacco marketing enhance clinicians' actions working with individual smokers.

[Interventions for smoking cessation in 2018]. / Les outils du sevrage tabagique en 2018.

Smoking cessation treatments have been proved effective to stop smoking. For pharmacological treatments, nicotine replacement therapies (NRT) as well as bupropion allow to increase 6 month-abstinence rates by more than 80% in comparison with placebo while varenicline prescription doubles success rates in the same conditions. These results mean that for 10 smokers who quit with placebo, 18 are expected to quit with NRT or bupropion and 28 are expected to quit with varenicline. Varenicline is 50% more effective than nicotine patch and 70% more effective than nicotine gum. Nevertheless, a combination including NRT patch and oral nicotine forms is as effective as varenicline, thus leading to encourage the prescription of a combination NRT when NRT are chosen. For these three pharmacological treatments, cardiovascular as well as neuropsychiatric tolerance were not found statistically different from placebo in randomized controlled trials. Yet, bupropion prescription leads to an increasing risk of seizure (1/1000 to 1/1500). For behavioral treatment, motivational interviewing as well as cognitive behavior therapies are been proven to be effective to stop smoking but few smokers have access to this treatment. Smoking cessation mobile application and smartphone application seem to be promising in terms of effectiveness and might be useful to reach more smokers.

Comparing the New York State Smokers' Quitline Reach, Services Offered, and Quit Outcomes to 44 Other State Quitlines, 2010 to 2015.

PURPOSE: To summarize the reach, services offered, and cessation outcomes of the New York Quitline and compare with other state quitlines. DESIGN: Descriptive study. SETTING: Forty-five US states. PARTICIPANTS: State-sponsored tobacco cessation quitlines in 45 US states that provided complete data to the Centers for Disease Control and Prevention's National Quitline Data Warehouse (NQDW) for 24 quarters over 6 years (2010-Q1 through 2015-Q4). INTERVENTION: Telephone quitlines that offer tobacco use cessation services, including counseling, self-help materials, and nicotine replacement therapy (NRT), to smokers at no cost to them. MEASURES: Percentage of adult tobacco users in the state who received counseling and/or free NRT from state quitlines (reach), services offered by state quitlines, and cessation outcomes among quitline clients 7 months after using quitline services. ANALYSIS: Reach, services offered, and cessation outcomes for the New York Quitline were compared with similar measures for the other 44 state quitlines with complete NQDW data for all quarters from 2010 through 2015. RESULTS: New York's average annual quitline reach from 2010 through 2015 was 3.0% per year compared to 1.1% per year for the other 44 states examined. CONCLUSION: Although the New York Quitline was open fewer hours per week and offered fewer counseling sessions and a smaller amount of free NRT than most of the other 44 state quitlines, the New York Quitline had similar quit rates to most of those state quitlines.