The DOI matches its Crossref record; 146 of the 149 references it cites were found in a registry or an index, and 3 are not checked yet; none of the 129 sources its claims cite is checked for support yet.
Tobacco addiction
Open accessAbstract
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.
Checked 2026-10-10 · 3 references not checked yet
Overview
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.
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Claims the paper makes
91 Not checked yet · 16 Own interpretation · 4 Own result · 2 No basis given · 1 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, among women, only about 10% of the global population lives in a country where the prevalence is greater than 24%.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is clear that more men smoke compared to women.”
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“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%)”
What the sources say
- Not checked yetcites [88] Tatley
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
What the sources say
- Not checked yetcites [97] Pierce, 2002, Impact of over-the-counter sales on effectiveness of pharmaceutical aids for smoking cessation, JAMA source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diagnosis based on these criteria is also limited because of its unidimensional and categorical nature, rather than reflecting the potentially multidimensional and continuous aspects of addiction.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the shorter term (i.e., over the next thirty years), the main determinant of significantly reducing the accelerated increase of tobacco-related morbidity and mortality would be if smokers were able to quit smoking (3).”
What the sources say
- Not checked yetcites [3] Mackay, 2006
hedgeddirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Of the various types of nAChRs that exist in the central nervous system (CNS), members of the so-called bungarotoxin-insensitive subtypes, which are composed of alpha and beta subunits and includes the ubiquitous α4β2-containing subtype, have been extensively implicated in the behavioral effects of nicotine, including its dependence-related effects such as nicotine self-administration and neurotra”
What the sources say
- Not checked yetcites [25] Mansvelder, 2000, Long-term potentiation of excitatory inputs to brain reward areas by nicotine, Neuron source
- Not checked yetcites [26] Boyadjieva, 1997, The secretory response of hypothalamic beta-endorphin neurons to acute and chronic nicotine treatments and following nicotine withdrawal, Life Sci source
- Not checked yetcites [27] Wonnacott, 2005, Nicotine: from molecular mechanisms to behaviour, Curr Opin Pharmacol source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“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.”
What the sources say
- Not checked yetcites [72] 2002, Cigarette smoking among adults—United States, 2000, MMWR Morb Mortal Wkly Rep
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Nicotine administration also increases the extracellular noradrenaline in various parts of the brain (32–35);”
What the sources say
- Not checked yetcites [32] Fu, 2001, Norepinephrine secretion in the hypothalamic paraventricular nucleus of rats during unlimited access to self-administered nicotine: an in vivo microdialysis study, J Neurosci source
- Not checked yetcites [33] Pidoplichko, 1997, Nicotine activates and desensitizes midbrain dopamine neurons, Nature source
- Not checked yetcites [34] Benwell, 1995, Desensitization of the nicotine-induced mesolimbic dopamine responses during constant infusion with nicotine, Br J Pharmacol source
- Not checked yetcites [35] Hughes, 2007, Effects of abstinence from tobacco: valid symptoms and time course, Nicotine Tob Res source
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 39
- Probably not a substantial claim. 4
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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%.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Despite their limitations, the WHO and American Cancer Society prevalence data are the best data available.
None of the sources cited for this claim have been checked yet.
In the paper
“Higher alkalinity is associated with greater absorption in the non-ionized state, which crosses cell membranes more rapidly than ionized nicotine (13, 14).”
What the sources say
- Not checked yetcites [13] Piper, 2006, Assessing tobacco dependence: a guide to measure evaluation and selection, Nicotine Tob Res source
- Not checked yetcites [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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“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),”
What the sources say
- Not checked yetcites [16] Benowitz, 1999, Nicotine addiction, Prim Care source
- Not checked yetcites [17] Zevin, 1998, Clinical pharmacology of nicotine, Clin Dermatol source
- Not checked yetcites [18] Henningfield, 1993, Nicotine delivery kinetics and abuse liability, J Consult Clin Psychol source
- Not checked yetcites [19] Hukkanen, 2005, Metabolism and disposition kinetics of nicotine, Pharmacol Rev source
- Not checked yetcites [20] Henningfield, 1996, Pharmalogical aspects of drug dependence: toward an integrated neurobehavioral approach
- Not checked yetcites [21] Paterson, 2000, Neuronal nicotinic receptors in the human brain, Prog Neurobiol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“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”
What the sources say
- Not checked yetcites [4] Henningfield, 1998, Tobacco-dependence medications: public health and regulatory issues, Food Drug Law J
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Treatment with nicotine patches has been examined with smokers who have cardiovascular disease and the medications have been found to be safe (154).”
What the sources say
- Not checked yetcites [154]
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“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).”
What the sources say
- Not checked yetcites [72] 2002, Cigarette smoking among adults—United States, 2000, MMWR Morb Mortal Wkly Rep
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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”
What the sources say
- Not checked yetcites [13] Piper, 2006, Assessing tobacco dependence: a guide to measure evaluation and selection, Nicotine Tob Res source
- Not checked yetcites [36] Hughes, 1990, Effect of dose on nicotine's reinforcing, withdrawal-suppression and self-reported effects, J Pharmacol Exp Ther
- Not checked yetcites [37] Hughes, 1992, The nicotine withdrawal syndrome: a brief review and update, Int J Smoking Cessation
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
What the sources say
- Not checked yetcites [38] Gilbert, 2002, Mood disturbance fails to resolve across 31 days of cigarette abstinence in women, J Consult Clin Psychol source
- Not checked yetcites [39] Piasecki, 2002, Have we lost our way? The need for dynamic formulations of smoking relapse proneness, Addiction source
- Not checked yetcites [40] Hughes, 1990, Effects of abstinence from tobacco: a critical review
- Not checked yetcites [41] Piasecki, 2003, Smoking withdrawal dynamics: I. Abstinence distress in lapsers and abstainers, J Abnorm Psychol source
- Not checked yetcites [42] Piasecki, 2000, Smoking withdrawal dynamics in unaided quitters, J Abnorm Psychol source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
What the sources say
- Not checked yetcites [64] Breslau, 1991, Nicotine dependence, major depression, and anxiety in young adults, Arch Gen Psychiatry source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
What the sources say
- Not checked yetcites [45] Piasecki, 1998, Profiles in discouragement: two studies of variability in the time course of smoking withdrawal symptoms, J Abnorm Psychol source
- Not checked yetcites [46] McCarthy, 2006, Life before and after quitting smoking: an electronic diary study, J Abnorm Psychol source
- Not checked yetcites [47] Brandon, 1990, Postcessation cigarette use: the process of relapse, Addict Behav source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
What the sources say
- Not checked yetcites [5] 1988
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
What the sources say
- Not checked yetcites [74] Fiore, 1990, Methods used to quit smoking in the United States. Do cessation programs help?, JAMA source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
What the sources say
- Not checked yetcites [73] Taylor, 2005
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“One study found a combination of bupropion and nicotine patch to be more efficacious that patch only, but not bupropion alone (101).”
What the sources say
- Not checked yetcites [101] Hall, 2002, Psychological intervention and antidepressant treatment in smoking cessation, Arch Gen Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Clonidine, which is α2 adrenergic autoreceptor agonist, decreases noradrenergic activity and firing in the locus ceruleus.”
What the sources say
- Not checked yetcites [96] Hughes, 2003, A meta-analysis of the efficacy of over-the-counter nicotine replacement, Tob Control source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“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).”
What the sources say
- Not checked yetcites [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
- Not checked yetcites [104] Jorenby, 1999, A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation, N Engl J Med source
- Not checked yetcites [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
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Although bupropion produced significantly higher cessation rates than nicotine patch in one trial (101), this has not been replicated.”
What the sources say
- Not checked yetcites [101] Hall, 2002, Psychological intervention and antidepressant treatment in smoking cessation, Arch Gen Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“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).”
What the sources say
- Not checked yetcites [113] Prochazka, 2004, A randomized trial of nortriptyline combined with transdermal nicotine for smoking cessation, Arch Intern Med source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“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)”
What the sources say
- Not checked yetcites [119] Tonstad, 2006, Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial, JAMA source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nortriptyline is a reuptake inhibitor, primarily of noradrenaline but also serotonin.”
What the sources say
- Not checked yetcites [96] Hughes, 2003, A meta-analysis of the efficacy of over-the-counter nicotine replacement, Tob Control source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
What the sources say
- Not checked yetcites [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
- Not checked yetcites [104] Jorenby, 1999, A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation, N Engl J Med source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
What the sources say
- Not checked yetcites [98] Stead, 2002, Effectiveness of over-the-counter nicotine replacement therapy, JAMA source
- Not checked yetcites [99] Franzon, 2002, Effectiveness of over-the-counter nicotine replacement therapy, JAMA source
- Not checked yetcites [100] Fryer, 1999, Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine, J Pharmacol Exp Ther source
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The major side effect for varenicline was nausea; about 30% of participants experienced this symptom.”
What the sources say
- Not checked yetcites [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
- Not checked yetcites [104] Jorenby, 1999, A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation, N Engl J Med source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
What the sources say
- Not checked yetcites [139]
- Not checked yetcites [140]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
What the sources say
- Not checked yetcites [73] Taylor, 2005
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
What the sources say
- Not checked yetcites [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.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The CB1 antagonist reduces the nicotine-induced increase in dopamine turnover in the nucleus acumens and nicotine self-administration in animals (137)”
What the sources say
- Not checked yetcites [137] Hughes, 2004, Shape of the relapse curve and long-term abstinence among untreated smokers, Addiction source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“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).”
What the sources say
- Not checked yetcites [130] Godtfredsen, 2005, Effect of smoking reduction on lung cancer risk, JAMA source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
What the sources say
- Not checked yetcites [146]
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, it is clear that effective treatments are available and promising new treatments are being developed.”
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
What the sources say
- Not checked yetcites [61] Lasser, 2000, Smoking and mental illness, JAMA source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
What the sources say
- Not checked yetcites [150]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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)”
What the sources say
- Not checked yetcites [147]
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is important to keep in mind that nicotine or tobacco addiction should be treated as a chronic disorder.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“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).”
What the sources say
- Not checked yetcites [149]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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%.”
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?
In the citing paper
“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]
In the citing paper
“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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Abstract
“95% CI 09.87, 1.32”
§ Abstract
“OR 1.07”
Citations
Cites
The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire
HEATHERTON, T. F., KOZLOWSKI, L. T., FRECKER, R. C., & FAGERSTROM, K. (1991) · British Journal of Addiction · doi:10.1111/j.1360-0443.1991.tb01879.x · Cited by 10,738
Nicotine replacement therapy for smoking cessation
Stead, L. F., Perera, R., Bullen, C., Mant, D., Hartmann‐Boyce, J., Cahill, K., & Lancaster, T. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000146.pub4 · Cited by 2,564
Self-citationSmoking and Mental Illness: A Population-Based Prevalence Study
Lasser, K., Boyd, J. W., Woolhandler, S., Himmelstein, D. U., McCormick, D., & Bor, D. H. (2000) · JAMA · doi:10.1001/jama.284.20.2606 · Cited by 2,508
Fagerström, K.-O. (1978) · Addictive Behaviors · doi:10.1016/0306-4603(78)90024-2 · Cited by 2,221
Physician advice for smoking cessation
Stead, L. F., Buitrago, D., Preciado, N., Sanchez, G., Hartmann-Boyce, J., & Lancaster, T. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000165.pub4 · Cited by 1,955
Self-citationCigarette smoking among adults — United States, 1988
Bachman, J. G., Johnston, L. D., & O’Malley, P. M. (1992) · Patient Education and Counseling · doi:10.1016/0738-3991(92)90149-d · Cited by 1,705
Measuring nicotine dependence: A review of the Fagerstrom Tolerance Questionnaire
Fagerstrom, K. O., & Schneider, N. G. (1989) · Journal of Behavioral Medicine · doi:10.1007/bf00846549 · Cited by 1,598
A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation
Jorenby, D. E., Leischow, S. J., Nides, M. A., Rennard, S. I., Johnston, J. A., Hughes, A. R., Smith, S. S., Muramoto, M. L., Daughton, D. M., Doan, K., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199903043400903 · Cited by 1,585
Metabolism and Disposition Kinetics of Nicotine
Hukkanen, J., Jacob, P., & Benowitz, N. L. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.3 · Cited by 1,583
Research works printed but not linked: 5
- Hughes, 1992, The nicotine withdrawal syndrome: a brief review and update, Int J Smoking Cessation, 1, 21
- Hughes, 1990, Effects of abstinence from tobacco: a critical review, 317
- 2001, Tobacco use prevention and control, Am J Prev Med, 20, 1
- 2000, Introducing the guide to community preventive services, Am J Prev Med, 18, 1
- 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
Hazardous Compounds in Tobacco Smoke
Talhout, R., Schulz, T., Florek, E., van Benthem, J., Wester, P., & Opperhuizen, A. (2011) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph8020613 · Cited by 834
Lopez‐Quintero, C., Cobos, J. P. D. L., Hasin, D. S., Okuda, M., Wang, S., Grant, B. F., & Blanco, C. (2010) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2010.11.004 · Cited by 733
Smokeless tobacco and cigarette smoking: chemical mechanisms and cancer prevention
Hecht, S. S., & Hatsukami, D. K. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-021-00423-4 · Cited by 300
Self-citationNicotine activates the chemosensory cation channel TRPA1
Talavera, K., Gees, M., Karashima, Y., Meseguer, V., Vanoirbeek, J. A., Damann, N., Everaerts, W., Benoit, M., Janssens, A., Vennekens, R., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2379 · Cited by 256
The Global Research Neglect of Unassisted Smoking Cessation: Causes and Consequences
Chapman, S. F., & MacKenzie, R. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000216 · Cited by 237
Metadata
- 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
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 371
- Issue
- 9629
- Pages
- 2027-2038
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- 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
- green
- www.ncbi.nlm.nih.gov
- 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 › Public Health, Environmental and Occupational Health › 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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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