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Cited by 228Smoking Behavior and CessationSubstance Abuse Treatment and OutcomesBehavioral Health and Interventions

Tobacco addiction

Open access
Hatsukami, Dorothy K, Stead, Lindsay F, Gupta, Prakash C·2008·The Lancet
DOI 10.1016/s0140-6736(08)60871-5PMC PMC4732578
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Abstract

Tobacco use is associated with 5 million deaths per year worldwide and is regarded as one of the leading causes of premature death. Comprehensive programmes for tobacco control can substantially reduce the frequency of tobacco use. An important component of a comprehensive programme is the provision of treatment for tobacco addiction. Treatment involves targeting several aspects of addiction including the underlying neurobiology and behavioural processes. Furthermore, building an infrastructure in health systems that encourages and helps with cessation, as well as expansion of the accessibility of treatments, is necessary. Although pharmacological and behavioural treatments are effective in improving cessation success, the rate of relapse to smoking remains high, emphasising the strong addictive nature of nicotine. The future of treatment resides in improvement in patient matching to treatment, combination or novel drugs, and viewing nicotine addiction as a chronic disorder that might need long-term treatment.

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AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes the diagnosis, pathophysiology, and treatment of tobacco/nicotine addiction, emphasizing that tobacco use causes 5 million deaths annually worldwide and that pharmacotherapies and counseling can improve cessation. It concludes that nicotine addiction should be treated as a chronic disorder, with future gains expected from better patient matching, combination or novel medications, and broader treatment delivery.

Key findings

  • Tobacco use is associated with 5 million deaths per year worldwide; there are about 1.2 billion smokers, half of whom will die of smoking-caused diseases, with projections of 10 million deaths per year by 2020.
  • Pharmacotherapies roughly double to triple quit rates: pooled ORs were NRT 1.8 (95% CI 1.7–1.9; 104 studies), bupropion 1.9 (1.7–2.2; 31 studies), varenicline 3.2 (2.4–4.3; 4 studies), nortriptyline 2.3 (1.6–3.4; 6 studies), and clonidine 1.9 (1.3–2.7; 6 studies); estimated abstinence with active therapy was about 17–22% across these classes.
  • In the general population, >70% of smokers want to quit and 45% make a quit attempt, but <5% succeed; physician advice can enhance cessation 3–5 fold above 5%, and brief advice yields a small but significant 2.5% absolute increase.
  • Combination nicotine patch plus ad libitum NRT improved efficacy over single NRT (7 studies, OR 1.4, 95% CI 1.1–1.8), while combining nicotine and non-nicotine therapies was not strongly supported; varenicline beat bupropion in pooled analysis (OR 1.7, 95% CI 1.3–2.2).

Methods

  • Narrative review; search focused on existing meta-analyses plus MEDLINE/PubMed for articles not covered, primarily medication treatments, using terms for smoking cessation, NRT, antidepressants, varenicline, bupropion, clonidine, nortriptyline, nicotine vaccine, and rimonabant.
  • Included studies were selected if considered to have sufficient sample size and rigorous methodology and to add to the manuscript; global prevalence data came from WHO and American Cancer Society databases.
  • Main analysis was qualitative synthesis of cited meta-analyses and trials, reporting pooled odds ratios and abstinence rates; no new primary data were collected.

Limitations

  • The paper states that global prevalence rates are not strictly comparable because samples may not be representative, time periods, smoking definitions, and age cutoffs differ; they are described as the best available data.
  • The paper states that most evidence-based treatments come from developed countries, though they may generalize to developing countries, and culturally sensitive interventions are underway.
  • Evident from the text: this is a narrative review, not a systematic review, with study selection based on author judgment of sample size and rigor; one author (Hatsukami) reports advising Pfizer on varenicline and receiving a grant from Nabi Biopharmaceuticals for nicotine vaccine trials.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(08)60871-5

Cites

147 of 150 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 129 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Abstract

    Among women, only about 10% of the global population lives in a country where the prevalence of smoking is greater than 24%.

    “In contrast, among women, only about 10% of the global population lives in a country where the prevalence is greater than 24%.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Abstract

    More men smoke compared to women.

    “It is clear that more men smoke compared to women.”
    Quote in the paperNot a substantial claim
  • Findingreasoning
    § Abstract

    The estimated abstinence rate with NRT is 18% (95% CI 17% to 19%) when applied to the median placebo quit rate of 11%.

    “For example, the median control group quit rate across all NRT trials is 11% and the estimated odds ratio is 1.8 (95% CI 1.7, 1.9), giving an estimated quit rate on active therapy of 18% (95% CI 17%, 19%)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [88] Tatley

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  • Findingcitation
    § Abstract

    No significant differences in cessation rates were observed between the recommended 300 mg dose and the 150 mg dose (OR 1.07, 95% CI 09.87, 1.32).

    “No significant differences in cessation rates were observed between the recommended 300 mg dose and the 150 mg dose (OR 1.07, 95% CI 09.87, 1.32;) (97).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Pierce, 2002, Impact of over-the-counter sales on effectiveness of pharmaceutical aids for smoking cessation, JAMA source

      Not checked in the free run.

  • Interpretationreasoning
    § Abstract

    Addiction to nicotine is a consequence of the speed and magnitude of nicotine delivery, the clearance of nicotine, its effect on the brain, the development of physical dependence, and the occurrence of associative learning.

    “The addiction to nicotine is a consequence of the speed and magnitude of nicotine delivery, the clearance of nicotine, its effect on the brain, the development of physical dependence, and the occurrence of associative learning where stimuli linked with smoking trigger tobacco use.”
    Quote in the paperSubstantial claim
  • May combine two claims. 39
  • Classified as probably not a substantial claim. 4

  • May combine two claims.

    Findingown data
    § Abstract

    About 45% of the global population lives in countries where the prevalence of smoking among males is greater than 45%, and about 92% of the global population lives where prevalence among men is more than 25%.

    “About 45% of the global population lives in countries where the prevalence of smoking among males is greater than 45%, and about 92% of the global population lives where prevalence among men is more than 25%.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Abstract

    Based on analyses of the World Health Organization and American Cancer Society database, Tables 1a and 1b show the distribution of prevalence of smoking among adult men and women in different countries of the world.

    “Based on the analyses of the World Health Organization and American Cancer Society database, Tables 1a and 1b show the distribution of prevalence of smoking among adult men and women in different countries of the world.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Despite their limitations, the WHO and American Cancer Society prevalence data are the best data available.

  • May combine two claims.

    Premisecitation
    § Abstract

    Higher alkalinity is associated with greater absorption in the non-ionized state, which crosses cell membranes more rapidly than ionized nicotine.

    “Higher alkalinity is associated with greater absorption in the non-ionized state, which crosses cell membranes more rapidly than ionized nicotine (13, 14).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] Piper, 2006, Assessing tobacco dependence: a guide to measure evaluation and selection, Nicotine Tob Res source

      Not checked in the free run.

    • cites [14] Baker, 2007, Time to first cigarette in the morning as an index of ability to quit smoking: implications for nicotine dependence, Nic Tob Research

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Abstract

    Nicotine is metabolized to cotinine primarily by C-oxidation via CYP2A6 metabolizing enzymes, and CYP2A6 activity varies significantly among individuals, which may affect smoking behaviors.

    “Nicotine is metabolized to cotinine primarily by C-oxidation via CYP2A6 metabolizing enzymes. Cotinine is further hydroxylated to trans 3-hydroxycotinine also via CYP2A6 enzymes. CYP2A6 activity varies significantly among individuals, which may affect smoking behaviors (16–21),”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [16] Benowitz, 1999, Nicotine addiction, Prim Care source

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    • cites [17] Zevin, 1998, Clinical pharmacology of nicotine, Clin Dermatol source

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    • cites [18] Henningfield, 1993, Nicotine delivery kinetics and abuse liability, J Consult Clin Psychol source

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    • cites [19] Hukkanen, 2005, Metabolism and disposition kinetics of nicotine, Pharmacol Rev source

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    • cites [20] Henningfield, 1996, Pharmalogical aspects of drug dependence: toward an integrated neurobehavioral approach

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    • cites [21] Paterson, 2000, Neuronal nicotinic receptors in the human brain, Prog Neurobiol source

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  • May combine two claims.

    Interpretationreasoning
    § Abstract

    The rate of relapse to smoking remains high, demonstrating the strong addictive nature of nicotine.

    “While current pharmacological and behavioral treatments are effective in improving cessation success, the rate of relapse to smoking remains high, demonstrating the strong addictive nature of nicotine.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning
    § Abstract

    The prevalence rates in Tables 1a and 1b are not strictly comparable because samples may not be representative, time periods may differ, definitions of smoking may differ, and age cutoffs may differ.

    “These prevalence rates are not strictly comparable: samples may not be representative of the population of the country, time period to which they refer may be different, the definition of smoking may be different (e.g. smoking of at least one cigarette a day for a specified time period vs. smoking of at least 100 cigarettes in lifetime) and even age cut offs may be different.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Abstract

    The 1988 Surgeon General report concluded that cigarettes and other forms of tobacco are addictive, nicotine is the drug that causes this addiction, and the pharmacological and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.

    “The 1988 Surgeon’s General report, The Health Consequences of Smoking: Nicotine Addiction (4), described three major conclusions: 1) cigarettes and other forms of tobacco are addictive, 2) nicotine is the drug that causes this addiction, and 3) the pharmacological and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and coc”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Henningfield, 1998, Tobacco-dependence medications: public health and regulatory issues, Food Drug Law J

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    Premisecitation
    § Abstract

    Treatment with nicotine patches has been examined with smokers who have cardiovascular disease and the medications have been found to be safe.

    “Treatment with nicotine patches has been examined with smokers who have cardiovascular disease and the medications have been found to be safe (154).”
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    • cites [154]

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    Premisecitation
    § Abstract

    The physician and other health care professionals can have a powerful impact in helping to facilitate cessation and can enhance cessation rates by 3 to 5 fold above 5%.

    “Although the majority of smokers will quit on their own (76), the physician and other health care professionals can have a powerful impact in helping to facilitate the cessation of tobacco products and can enhance cessation rates by 3 to 5 fold above 5% (72).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [72] 2002, Cigarette smoking among adults—United States, 2000, MMWR Morb Mortal Wkly Rep

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  • May combine two claims.

    Interpretationcitation
    § Abstract

    With chronic or even acute administration of nicotine, neural adaptations occur to attain homeostasis; some nAChR subtypes are upregulated, and receptors also become desensitized or inactivated, one potential mechanism leading to the development of tolerance.

    “With chronic or even acute administration of nicotine, neural adaptations occur to attain homeostasis resulting from the increased activity on the nAChR receptor sites and increased concentration of neurotransmitters. Although some nAChR subtypes are upregulated by chronic nicotine treatment, that is, their numbers increase, receptors also become desensitized or inactivated, one potential mechan”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [13] Piper, 2006, Assessing tobacco dependence: a guide to measure evaluation and selection, Nicotine Tob Res source

      Not checked in the free run.

    • cites [36] Hughes, 1990, Effect of dose on nicotine's reinforcing, withdrawal-suppression and self-reported effects, J Pharmacol Exp Ther

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    • cites [37] Hughes, 1992, The nicotine withdrawal syndrome: a brief review and update, Int J Smoking Cessation

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  • May combine two claims.

    Premisecitation
    § Abstract

    Among tobacco users, withdrawal symptoms, with the exception of weight, peak during the first week of abstinence and then gradually decrease to baseline levels by two to four weeks; more recent studies have found withdrawal to be persistent and elevated for several months after quitting.

    “Among tobacco users, withdrawal symptoms, with the exception of weight, peaks during the first week of abstinence and then gradually decreases to baseline levels by two to four weeks (38–40); although more recent studies have found withdrawal to be persistent and elevated for several months after quitting (41, 42).”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [38] Gilbert, 2002, Mood disturbance fails to resolve across 31 days of cigarette abstinence in women, J Consult Clin Psychol source

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    • cites [39] Piasecki, 2002, Have we lost our way? The need for dynamic formulations of smoking relapse proneness, Addiction source

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    • cites [40] Hughes, 1990, Effects of abstinence from tobacco: a critical review

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    • cites [41] Piasecki, 2003, Smoking withdrawal dynamics: I. Abstinence distress in lapsers and abstainers, J Abnorm Psychol source

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    • cites [42] Piasecki, 2000, Smoking withdrawal dynamics in unaided quitters, J Abnorm Psychol source

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  • May combine two claims.

    Interpretationcitation
    § Abstract

    In addition to the physiological basis for addiction, behavioral or learning factors sustain addiction; environmental stimuli become associated with the positive reinforcing effects of nicotine and withdrawal symptoms, and through associative learning these stimuli control behavior and evoke craving or drug seeking.

    “In addition to the physiological basis for addiction, there are behavioral or learning factors that sustain addiction. Stimuli in the environment become associated with the positive reinforcing effects of nicotine and withdrawal symptoms. Over time and through associative learning, these stimuli begin to control behavior, such that when a tobacco user is exposed to these stimuli, they evoke cra”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Abstract

    Co-morbid psychiatric disorders may predispose a smoker to begin or persist in smoking; a population survey found that 41% of individuals with mental illness smoked cigarettes, and those with past-month illness were estimated to consume over 40% of the cigarettes smoked by the sample.

    “Furthermore, co-morbid psychiatric disorders may predispose a smoker to begin or persist in smoking. A population survey found that 41% of individuals with mental illness smoked cigarettes. Those with past-month illness were estimated to consume over 40% of the cigarettes smoked by the sample (64).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Breslau, 1991, Nicotine dependence, major depression, and anxiety in young adults, Arch Gen Psychiatry source

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  • May combine two claims.

    Premisecitation
    § Abstract

    Symptoms of greater intensity, positive slope and variability predict relapse to smoking, and symptoms of craving and negative affect are the most likely to be associated with relapse.

    “Symptoms of greater intensity, positive slope and variability have been observed to predict relapse to smoking (45, 46) and symptoms of craving and negative affect were the most likely to be associated with relapse (47, 48).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [45] Piasecki, 1998, Profiles in discouragement: two studies of variability in the time course of smoking withdrawal symptoms, J Abnorm Psychol source

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    • cites [46] McCarthy, 2006, Life before and after quitting smoking: an electronic diary study, J Abnorm Psychol source

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    • cites [47] Brandon, 1990, Postcessation cigarette use: the process of relapse, Addict Behav source

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  • May combine two claims.

    Premisecitation
    § Abstract

    Upon abstinence from nicotine, the smoker experiences withdrawal symptoms including negative affect such as irritability, frustration or anger, anxiety, dysphoric or depressed mood, restlessness, difficulty concentrating, insomnia, decreased heart rate, and increased appetite.

    “Because the body develops a homeostatic response, upon abstinence from the drug, the smoker experiences withdrawal symptoms. These withdrawal symptoms include negative affect such as irritability, frustration or anger, anxiety, dysphoric or depressed mood, restlessness, difficulty concentrating, insomnia, decreased heart rate, and increased appetite (5).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] 1988

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  • May combine two claims.

    Premisecitation
    § Abstract

    In the U.S., more than 70% of smokers want to quit each year and 45% make a quit attempt, but less than 5% in the general population are successful.

    “In the U.S., although more than 70% of smokers want to quit each year and 45% make a quit attempt, less than 5% in the general population are successful (74).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [74] Fiore, 1990, Methods used to quit smoking in the United States. Do cessation programs help?, JAMA source

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  • May combine two claims.

    Interpretationcitation
    § Abstract

    To date, results suggest no evidence to strongly support combining a nicotine and non-nicotine therapy, but combination of nicotine patch with an ad libitum form of NRT may confer some benefit.

    “To date, the results suggest that there is no evidence to strongly support combining a nicotine and non-nicotine therapy, however, the combination of nicotine patch with an ad libitum form of NRT may confer some benefit (73).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] Taylor, 2005

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  • May combine two claims.

    Premisecitation
    § Abstract

    One study found a combination of bupropion and nicotine patch to be more efficacious than patch only, but not bupropion alone.

    “One study found a combination of bupropion and nicotine patch to be more efficacious that patch only, but not bupropion alone (101).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Hall, 2002, Psychological intervention and antidepressant treatment in smoking cessation, Arch Gen Psychiatry source

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    Premisecitation
    § Abstract

    Clonidine is an α2 adrenergic autoreceptor agonist that decreases noradrenergic activity and firing in the locus ceruleus.

    “Clonidine, which is α2 adrenergic autoreceptor agonist, decreases noradrenergic activity and firing in the locus ceruleus.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Hughes, 2003, A meta-analysis of the efficacy of over-the-counter nicotine replacement, Tob Control source

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  • May combine two claims.

    Premisecitation
    § Abstract

    Of three trials comparing varenicline to bupropion, two had significant effects on long-term abstinence and the pooled OR showed a significant effect for varenicline (OR 1.7, 95% CI 1.3 to 2.2).

    “Of the three trials comparing varenicline to bupropion, two had significant effects on long term abstinence and the pooled OR showed a significant effect for varenicline (OR 1.7, 95% CI 1.3, 2.2).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [103] Wagena, 2005, Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease, Arch Intern Med source

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    • cites [104] Jorenby, 1999, A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation, N Engl J Med source

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    • cites [105] Jorenby, 2006, Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial, JAMA source

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  • May combine two claims.

    Premisecitation
    § Abstract

    Bupropion produced significantly higher cessation rates than nicotine patch in one trial, but this has not been replicated.

    “Although bupropion produced significantly higher cessation rates than nicotine patch in one trial (101), this has not been replicated.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [101] Hall, 2002, Psychological intervention and antidepressant treatment in smoking cessation, Arch Gen Psychiatry source

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    Premisecitation
    § Abstract

    One year continued use of nortriptyline appears to improve continuous abstinence rates over the course of a year compared to 8 weeks of nortriptyline (plus 8 week nicotine patch therapy in both conditions); however, no differences were observed in point prevalence abstinence at one year.

    “In a study by Hall and colleagues, one year continued use of nortriptyline appears to improve continuous abstinence rates over the course of a year compared to 8 weeks of nortriptyline (plus 8 week nicotine patch therapy in both conditions); however, no differences were observed in point prevalence abstinence at one year (113).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [113] Prochazka, 2004, A randomized trial of nortriptyline combined with transdermal nicotine for smoking cessation, Arch Intern Med source

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    Premisecitation
    § Abstract

    Varenicline has shown some efficacy as a relapse prevention agent; continuous abstinence rates from weeks 13 to 24 and 13 to 52 were significantly higher for varenicline compared to placebo, but the effect was relatively modest (OR at 52 weeks 1.3, 95% CI 1.1 to 1.7).

    “The continuous abstinence rates from weeks 13 to 24 and weeks 13 to 52 were significantly higher for varenicline compared to placebo but the effect was relatively modest (OR at 52 weeks 1.3; 95% CI 1.1, 1.7)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [119] Tonstad, 2006, Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial, JAMA source

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    Premisecitation
    § Abstract

    Nortriptyline is a reuptake inhibitor primarily of noradrenaline but also serotonin.

    “Nortriptyline is a reuptake inhibitor, primarily of noradrenaline but also serotonin.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Hughes, 2003, A meta-analysis of the efficacy of over-the-counter nicotine replacement, Tob Control source

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  • May combine two claims.

    Premisecitation
    § Abstract

    Varenicline is a potent α4 β2 partial agonist that provides tobacco withdrawal relief by its agonist action and blocks the reinforcing effects of nicotine by its antagonist action.

    “This drug is varenicline, a potent α4 β2 partial agonist, which provides tobacco withdrawal relief by its agonist action and blocks the reinforcing effects of nicotine by its antagonist action (103, 104).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [103] Wagena, 2005, Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease, Arch Intern Med source

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    • cites [104] Jorenby, 1999, A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation, N Engl J Med source

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  • May combine two claims.

    Premisecitation
    § Abstract

    Three trials directly comparing bupropion and nortriptyline showed no significant differences, and the pooled odds ratio, though favouring bupropion, was non-significant (OR 1.4, 95% CI 0.9 to 2.3).

    “Three trials have directly compared bupropion and nortriptyline (98–100). None showed significant differences and the pooled odds ratio, though favouring bupropion, was non significant (OR 1.4, 95% CI 0.9, 2.3).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [98] Stead, 2002, Effectiveness of over-the-counter nicotine replacement therapy, JAMA source

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    • cites [99] Franzon, 2002, Effectiveness of over-the-counter nicotine replacement therapy, JAMA source

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    • cites [100] Fryer, 1999, Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine, J Pharmacol Exp Ther source

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    Premisecitation
    § Abstract

    The major side effect for varenicline was nausea; about 30% of participants experienced this symptom.

    “The major side effect for varenicline was nausea; about 30% of participants experienced this symptom.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [103] Wagena, 2005, Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease, Arch Intern Med source

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    • cites [104] Jorenby, 1999, A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation, N Engl J Med source

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    Premisecitation
    § Abstract

    In a pooled analysis of three large double-blind, placebo-controlled trials, significant end-of-treatment effects were observed for 20 mg CB1 antagonist vs placebo (22.0% vs 15.0%, p=0.0003) and significantly reduced weight gain among non-obese abstainers (0.8 kg vs 2.5 kg, p<0.0003).

    “In a pooled analysis, significant end-of-treatment effects were observed for 20 mg CB1 antagonist vs. placebo (22.0% vs. 15.0%, p=0.0003) and a significantly reduced weight gain among the non-obese abstainers (0.8 kg vs. 2.5 kg, p < 0.0003; 139).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [139]

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    • cites [140]

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  • May combine two claims.

    Interpretationcitation
    § Abstract

    A combination of medications that includes nicotine patch and ad libitum nicotine replacement may improve efficacy over a single NRT in helping heavily dependent smokers quit smoking; however, a combination of nicotine and non-nicotine therapies may not enhance treatment effect.

    “To date, a combination of medications that includes nicotine patch and ad libitum nicotine replacement may improve efficacy over a single NRT in helping heavily dependent smokers quit smoking; however, a combination of nicotine and non-nicotine therapies may not enhance treatment effect.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] Taylor, 2005

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  • May combine two claims.

    Premisecitation
    § Abstract

    In one published human study, the nicotine vaccine was safe and well tolerated, and the highest dose (200 μg) led to significantly higher 4-week continuous abstinence rates than the other vaccine doses and placebo.

    “One published study (136) showed that the vaccine was safe and well tolerated and, although not intended as a treatment study, the highest dose of the vaccine (200 μg) led to significantly higher 4-week continuous abstinence rates than the other vaccine doses and placebo.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [136] Cinciripini PM, Aubin H-J, Dale LC, Niaura R, Anthenelli RM, Stratus Group. Pooled analysis of three short-term, randomised, double-blind, placebo controlled trials with Rimonabant 20 mg/day in smoking cessation. 8th annual conference of the Society on Research on Nicotine and Tobacco Europe; Sept 23–26, 2006; Kusadasi, Turkey.

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    Premisecitation
    § Abstract

    The CB1 antagonist rimonabant reduces nicotine-induced increase in dopamine turnover in the nucleus acumens and nicotine self-administration in animals.

    “The CB1 antagonist reduces the nicotine-induced increase in dopamine turnover in the nucleus acumens and nicotine self-administration in animals (137)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [137] Hughes, 2004, Shape of the relapse curve and long-term abstinence among untreated smokers, Addiction source

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  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning
    § Abstract

    Genotyping smokers at this point is premature.

    “Pharmacogenetics for tobacco addiction is an evolving and relatively new area and therefore, genotyping smokers at this point is premature; however, this area of research is likely to provide valuable data on a potential method for matching patients to treatment.”
    Quote in the paperNot a substantial claim

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    Premisecitation
    § Abstract

    Reducers did experience risk reduction in lung cancer risk compared to continuous smokers, but only by 25% (HR 0.7, 95% CI 0.5 to 1.0).

    “However, reducers did experience risk reduction in lung cancer risk compared to continuous smokers, but only by 25% (HR 0.7, 95% CI 0.5, 1.0) (130).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [130] Godtfredsen, 2005, Effect of smoking reduction on lung cancer risk, JAMA source

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    Premisecitation
    § Abstract

    Smokers who possess the Asp40 variant of the OPRM1 gene tend to be more likely to be abstinent and more likely to respond to transdermal nicotine during but not after treatment than smokers who are homozygous for Asp40.

    “Smokers who possess the Asp40 variant of the OPRM1 gene, which has been associated with increased binding affinity of beta-endorphins in one study (143) but not others (144, 145), tend to be more likely to be abstinent and more likely to respond to transdermal nicotine during but not after treatment than smokers who are homozygous for Asp40 (146).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [146]

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Abstract

    Using medications to reduce smoking among those smokers not interested in quitting does not deter cessation attempts and may in fact facilitate them; however, cessation should remain the primary end goal.

    “Using medications to reduce smoking among those smokers not interested in quitting does not deter cessation attempts and may in fact facilitate them; however, cessation should remain the primary end goal.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation
    § Conclusion

    Effective treatments are available and promising new treatments are being developed.

    “However, it is clear that effective treatments are available and promising new treatments are being developed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Abstract

    Smokers who possessed a variant of P450-CYP2B6, which may be associated with slower metabolism of nicotine, experienced a higher relapse rate compared to smokers without this variant; bupropion mitigated this effect, but only in women.

    “smokers who possessed a variant of a gene, P450-CYP2B6, which may be associated with a slower metabolism of nicotine, experienced a higher relapse rate compared to smokers without this variant. Bupropion was found to mitigate this effect, but only in women (61).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [61] Lasser, 2000, Smoking and mental illness, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Conclusion

    Among smokers who quit without treatment, the percent who achieve abstinence for at least one week is 25-51% and at least three months is 10-20%; by six months, only 3-5% have achieved prolonged abstinence.

    “Among smokers who quit without treatment, the percent who can achieve abstinence for at least one week is 25–51% and at least three months is 10–20%. By six months, only 3–5% have achieved prolonged abstinence (150).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [150]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Abstract

    A recent study demonstrated an opposite effect in which smokers homozygous for Asp40 showed greater abstinence with the nicotine versus placebo patch and those smokers with the variant showed no differences between the patches.

    “A recent study, however, demonstrated an opposite effect in which smokers homozygous for Asp40 showed greater abstinence with the nicotine versus placebo patch and those smokers with the variant showed no differences between the patches (147)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [147]

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Abstract

    Continuing smokers on medications for a prolonged period of time in smokers who are trying to maintain abstinence may be beneficial, but there is no evidence to suggest that all smokers should be given long term treatment.

    “Continuing smokers on medications for a prolonged period of time in smokers who are trying to maintain abstinence may be beneficial, but there is no evidence to suggest that all smokers should be given long term treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationnone given
    § Conclusion

    Nicotine or tobacco addiction should be treated as a chronic disorder.

    “It is important to keep in mind that nicotine or tobacco addiction should be treated as a chronic disorder.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Abstract

    Smokers with both DRD2 A1 allele and dopamine beta-hydroxylase (DBH) A allele responded significantly better to transdermal nicotine than placebo, and smokers with the other genotypes did not.

    “Other studies have found that smokers with both DRD2 A1 allele, which is associated with reduced number of DRD2 receptors in the corpus striatum (148), and dopamine beta-hydroxylase (DBH) A allele responded significantly better to transdermal nicotine than placebo and smokers with the other genotypes did not (149).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [149]

      Not checked in the free run.

42 of 42

  • The paper relies on this without support.

    Comprehensive tobacco control programs can significantly reduce the prevalence of tobacco use.

    “Comprehensive tobacco control programs can significantly reduce the prevalence of tobacco use.”

  • The paper relies on this without support.

    Most evidence-based treatments have been from studies conducted in developed countries.

    “Although smoking is a global problem and the burden of tobacco-related death and disease has been shouldered by developing countries, most of the evidenced-based treatments have been from studies conducted in developed countries.”

  • The paper relies on this without support.

    These evidence-based treatments may be generalized to developing countries.

    “Nonetheless, these treatments may be generalized to developing countries and efforts are underway to develop culturally sensitive interventions that are based on the principles of these evidence-based treatments.”

  • The paper relies on this without support.

    The use of medicinal nicotine leads to the reduction in withdrawal symptoms.

    “The use of medicinal nicotine leads to the reduction in withdrawal symptoms.”

  • The paper relies on this without support.

    Despite their limitations, the WHO and American Cancer Society prevalence data are the best data available.

    “Despite limitations, they are the best data available.”

  • The paper relies on this without support.

    Quit rates in the absence of pharmacotherapy depend on motivation, level of dependence, amount of behavioural support, definition of abstinence, and period of follow-up.

    “The quit rates that can be expected in the absence of pharmacotherapy will depend on the motivation and level of dependence of the smokers and the amount of behavioural support provided, as well as the definition of abstinence and period of follow-up.”

  • The paper relies on this without support.

    The absolute cessation rate with currently available pharmacotherapies remains around 20%.

    “Although currently available pharmacotherapies have been shown to improve success rates, the absolute cessation rate remains relatively low—around 20%.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Smokers develop withdrawal symptoms when they abstain from nicotine.

    “Because the body develops a homeostatic response to nicotine, smokers have withdrawal symptoms on abstinence from the drug [1].”

    From Nicotine withdrawal and agitation in ventilated critically ill patients (2010) · cites this paper as [1]

  • The proportion of smokers observed in the cohort (31%) reflects the proportion of smokers usually reported in the general population.

    “the 31% of smokers we observed in our cohort study, among them a majority of male gender, reflects the proportion of smokers that are usually reported in the general population [1].”

    From Nicotine withdrawal and agitation in ventilated critically ill patients (2010) · cites this paper as [1]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Bupropion confidence interval has a lower bound above its upper bound

    Minor

    The stated 95% confidence interval runs from 9.87 to 1.32, placing its lower bound above its upper bound. It also cannot contain the reported odds ratio of 1.07.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Hughes, 1992, The nicotine withdrawal syndrome: a brief review and update, Int J Smoking Cessation, 1, 21
  2. Hughes, 1990, Effects of abstinence from tobacco: a critical review, 317
  3. 2001, Tobacco use prevention and control, Am J Prev Med, 20, 1
  4. 2000, Introducing the guide to community preventive services, Am J Prev Med, 18, 1
  5. Cinciripini PM, Aubin H-J, Dale LC, Niaura R, Anthenelli RM, Stratus Group. Pooled analysis of three short-term, randomised, double-blind, placebo controlled trials with Rimonabant 20 mg/day in smoking cessation. 8th annual conference of the Society on Research on Nicotine and Tobacco Europe; Sept 23–26, 2006; Kusadasi, Turkey.

Cited by

Sorted by citations

Related

Authors
Hatsukami, D. K., Stead, L. F., & Gupta, P. C.
Affiliations
  • University of Minnesota (US)
  • University of Oxford (GB)
  • Healis Sekhsaria Institute For Public Health (IN)
Corresponding author
Hatsukami, Dorothy K
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2008-06
Volume
371
Issue
9629
Pages
2027-2038
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(08)60871-5
PMC
PMC4732578
OpenAlex
W2470020720
Semantic Scholar
d5cb96d003a188279f60a1faa3c6e6bb2aa6ea54
Cited by
227
References
144
Citations by year
2026: 4 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 9 · 2020: 9 · 2019: 14 · 2018: 6 · 2017: 10 · 2016: 12 · 2015: 10 · 2014: 13 · 2013: 17 · 2012: 17
FWCI
2.45
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Cancer Society
  • National Institutes of Health (5p50da013333-10)
  • National Institute on Drug Abuse (P50- DA013333)
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Social Sciences › Psychology › Applied Psychology › Behavioral Health and Interventions
Keywords
tobacco dependence, nicotine dependence, smoking cessation, tobacco control, pharmacotherapy, behavioral interventions, relapse, neurobiology of addiction, treatment accessibility, patient matching
MeSH terms
Counseling, Female, Humans, Male, Nicotine, Physician's Role, Smoking, Tobacco Use Disorder, Prevalence, Smoking Cessation, Nicotinic Agonists

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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