Treatment of nicotine addiction: present therapeutic options and pipeline developments
Open accessAbstract
Tobacco use is a global pandemic that poses a substantial and costly health burden. There are some treatment options are available, but currently marketed smoking-cessation drugs lack high levels of efficacy, particularly in real-life settings. Consequently, there is a compelling need for more effective pharmacotherapies to aid smokers in maintaining long-term abstinence. Advances in the understanding of the mechanisms involved in nicotine dependence have recently been translated into new medications and vaccines that interfere with nicotine signaling, many of which are currently at an advanced stage of development. In the present article we review current and emerging pharmacotherapies for tobacco dependence, focusing on the mechanistic rationale for their potential anti-addiction efficacy, major findings in preclinical and clinical studies, and future research directions.
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Varenicline is thought to be effective through partial agonism of α4β2 nAChRs.
“Varenicline has been touted as being effective through its partial agonism of α4β2 nAChRs.”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [239]
Partial agonism of α4β2 nAChRs is thought to decrease withdrawal and cravings.
“This effect is thought to decrease withdrawal and cravings [239].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [239]
Exposure to nicotine conjugated to immunogenic proteins leads to production of IgGs, some targeted against nicotine.
“Exposure to nicotine conjugated to immunogenic proteins (e.g. cholera toxin b, a virus-like particle, and Pseudomonas exotoxin A) leads to production of IgGs, some of which will be targeted against nicotine [239, 246].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [239]
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A novel and efficient nicotine vaccine using nano-lipoplex as a delivery vehicle
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Achieving appropriate regulations for electronic cigarettes
Saitta, D., Ferro, G. A., & Polosa, R. (2014) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622314521271 · Cited by 46 · see citing works
“nicotine replacement therapy (NRT), bupropion and varenicline] are accessible to those determined to quit [Polosa and Benowitz, 2011], but they lack high levels of efficacy in real-life settings [Casella et al.”
Caponnetto, P., Campagna, D., Ahluwalia, J. S., Russell, C., Maglia, M. G., Riela, P. M., Longo, F., Busà, B., & Polosa, R. (2023) · BMC Medicine · doi:10.1186/s12916-023-02919-2 · Cited by 45 · see citing works
“It is expected to help with the cessation of nicotine vaping in light of its mechanism of action that attenuates nicotine withdrawal symptoms and craving [36, 37].”
BackgroundAlasmari, F. F., Alexander, L. E. C., Hammad, A. M., Bojanowski, C. M., Moshensky, A., & Sari, Y. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00885 · Cited by 44 · see citing works
Lack of Substantial Post-Cessation Weight Increase in Electronic Cigarettes Users
Russo, C., Cibella, F., Mondati, E. G. M., Caponnetto, P., Frazzetto, E., Caruso, M., Caci, G., & Polosa, R. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15040581 · Cited by 42 · see citing works
“For those willing to quit, a combination of pharmacotherapy and intensive behavioural intervention for smoking cessation can support quit attempts and can double or triple quit rates [5,6].”
BackgroundHandling relapse in smoking cessation: strategies and recommendations
Caponnetto, P., Keller, E., Bruno, C. M., & Polosa, R. (2012) · Internal and Emergency Medicine · doi:10.1007/s11739-012-0864-z · Cited by 43 · see citing works
“notion that depressive symptoms significantly lower the smoking cessation, success rates [19, 22] account for the positive effect on quitting success of the antidepressant bupropion.”
BackgroundBaker, T. E., Lespérance, P., Tucholka, A., Potvin, S., Larcher, K. M.-H., Zhang, Y., Jutras‐Aswad, D., & Conrod, P. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.01.015 · Cited by 40 · see citing works
Nicotine vaccines to treat tobacco dependence
Goniewicz, M. L., & Delijewski, M. (2012) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.22060 · Cited by 40 · see citing works
“There are also additional treatments like monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, nicotine receptor antagonists, opioid receptor antagonists, bromocriptine, anti-anxiety drugs, and others under investigation, like inhibitors of the isoforms of the cytochrome P-450 and cannabinoid-1 recep…”
BackgroundEffects of the Nanoparticle-Based Vaccine, SEL-068, on Nicotine Discrimination in Squirrel Monkeys
Desai, R. I., & Bergman, J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.64 · Cited by 40 · see citing works
“Unfortunately, these treatment approaches are characterized by low rates of success and disappointingly high rates of relapse in individuals who want to quit (Polosa and Benowitz, 2011).”
BackgroundNicotine’ actions on energy balance: Friend or foe?
Seoane‐Collazo, P., Diéguez, C., Nogueiras, R., Rahmouni, K., Fernández‐Real, J. M., & López, M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107693 · Cited by 39 · see citing works
“In terms of drug dependence, nicotine-addiction is present in a higher number of people than for any other drug (Polosa & Benowitz, 2011).”
Novel Anti-Nicotine Vaccine Using a Trimeric Coiled-Coil Hapten Carrier
Miller, K. D., Roque, R., & Clegg, C. H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114366 · Cited by 35 · see citing works
“To date, most hapten carriers are derived from microbial sources like keyhole limpet hemocyanin (KLH), tetanus toxoid, diphtheria toxoid, and pseudomonas exotoxin A [8, 9, 11, 13], although they may be limited in important ways.”
BackgroundAn efficient early phase 2 procedure to screen medications for efficacy in smoking cessation
Perkins, K. A., & Lerman, C. E. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3364-6 · Cited by 34 · see citing works
“Dozens of drugs have been tested for efficacy in smoking cessation over the last 20 years, but few of these have shown success (Benowitz and Peng 2000; Foulds et al. 2006; Harmey et al. 2012; Hughes et al. 2004; Schnoll and Lerman 2006; Polosa and Benowitz 2011).”
BackgroundBelief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers
Gu, X., Lohrenz, T. M., Salas, R., Baldwin, P. R., Soltani, A., Kirk, U., Cinciripini, P. M., & Montague, P. R. (2016) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2016.00126 · Cited by 34 · see citing works
“Other exclusion criteria include: (1) left handedness; (2) claustrophobia; (3) DSM-IV Axis I or II diagnosis (36), exclusive of nicotine dependence; (4) pregnancy; (5) contraindications to MRI: pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants; (6) active me…”
BackgroundArnold, M. M., Loughlin, S. E., Belluzzi, J. D., & Leslie, F. M. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.05.035 · Cited by 33 · see citing works
Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal
Turner, J. R., Wilkinson, D. S., Poole, R. L., Gould, T. J., Carlson, G. C., & Blendy, J. A. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.105 · Cited by 29 · see citing works
Smoking cessation: present status and future perspectives
Caponnetto, P., Russo, C., & Polosa, R. (2012) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2012.02.005 · Cited by 28 · see citing works
Rouabhia, M., Alanazi, H., Park, H. J., & Gonçalves, R. B. (2018) · Journal of Oral Implantology · doi:10.1563/aaid-joi-d-18-00009 · Cited by 29 · see citing works
Yohn, N. L., Turner, J. R., & Blendy, J. A. (2014) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.211706 · Cited by 28 · see citing works
“In addition, maintenance of smoking cessation is at best modest, with 80% of smokers relapsing within the first year of quitting (Polosa and Benowitz, 2011).”
BackgroundMelis, M., & Pistis, M. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.03.009 · Cited by 26 · see citing works
Pharmacologic Characterization of a Nicotine-Discriminative Stimulus in Rhesus Monkeys
Cunningham, C. S., Javors, M. A., & McMahon, L. R. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.193078 · Cited by 26 · see citing works
“Many different non-nicotinic compounds are either in use as smoking cessation aids or are being considered for that indication (Buchhalter et al., 2008; Polosa and Benowitz, 2011), and many of these have discriminative stimulus effects on their own.”
BackgroundThe Importance of Conditioned Stimuli in Cigarette and E-Cigarette Craving Reduction by E-Cigarettes
Heel, M. V., Gucht, D. V., Vanbrabant, K., & Baeyens, F. (2017) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph14020193 · Cited by 26 · see citing works
Modeling drug exposure in rodents using e-cigarettes and other electronic nicotine delivery systems
Miliano, C., Scott, E. R., Murdaugh, L. B., Gnatowski, E. R., Faunce, C. L., Anderson, M. S., Reyes, M. M., Gregus, A. M., & Buczynski, M. W. (2019) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2019.108458 · Cited by 25 · see citing works
Simone, A. D., Ruda, G. F., Albani, C., Tarozzo, G., Bandiera, T., Piomelli, D., Cavalli, A., & Bottegoni, G. (2014) · Chemical Communications · doi:10.1039/c4cc00967c · Cited by 25 · see citing works
Respiratory infections and pneumonia: potential benefits of switching from smoking to vaping
Campagna, D., Amaradio, M. D., Sands, M. F., & Polosa, R. (2016) · Pneumonia · doi:10.1186/s41479-016-0001-2 · Cited by 25 · see citing works
“Pharmacotherapy combined with behavioural smoking cessation support may double or triple quit rates [8], but efficacy rates, obtained in the context of rigorous randomised controlled trials, are not replicated in real-life, with disappointingly low cessation rates of about 4–5 % [9–11].”
BackgroundCounseling patients with asthma and allergy about electronic cigarettes: an evidence-based approach
Polosa, R., Campagna, D., & Sands, M. F. (2015) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2015.10.012 · Cited by 24 · see citing works
Newland, N., Lowe, F., Camacho, O. M., McEwan, M., Gale, N., Ebajemito, J. K., Hardie, G., Murphy, J., & Proctor, C. (2019) · Internal and Emergency Medicine · doi:10.1007/s11739-019-02090-8 · Cited by 23 · see citing works
“Although known for its psychoactive properties [11], nicotine is not a carcinogen [12] and does not contribute to smoking-related diseases [1].”
BackgroundYou, S., Li, X., Xiong, J., Zhu, X., Zhangsun, D., Zhu, X., & Luo, S. (2019) · Marine Drugs · doi:10.3390/md17090490 · Cited by 22 · see citing works
“The concentration of GABA had no significant increase in VTA after nicotine addiction, it was the same as previous studies [34].”
BackgroundResultInfluentialMorjaria, J. B., Campagna, D., Caci, G., O’Leary, R., & Polosa, R. (2022) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2023.2167716 · Cited by 22 · see citing works
“wal symptoms in combination with cessation counseling for best results [126,127].”
BackgroundCaponnetto, P., Polosa, R., Auditore, R., Minutolo, G., Signorelli, M. S., Maglia, M. G., Alamo, A., Palermo, F., & Aguglia, E. (2014) · Trials · doi:10.1186/1745-6215-15-88 · Cited by 22 · see citing works
“Moreover, the prescribing information for bupropion and varenicline, two important first-line medications for nicotine dependence, carry a black-box warning highlighting an increased risk of psychiatric symptoms and suicidal ideation in patients reporting any history of psychiatric illness [5].”
BackgroundKumar, M., Keady, J. V., Aryal, S. P., Hessing, M. C., Richards, C. I., & Turner, J. R. (2023) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2023.08.019 · Cited by 17 · see citing works
Suppression of Nicotine-Induced Pathophysiology by an Adenovirus Hexon-Based Antinicotine Vaccine
Rosenberg, J. B., De, B. P., Hicks, M. J., Janda, K. D., Kaminsky, S. M., Worgall, S., & Crystal, R. G. (2013) · Human Gene Therapy · doi:10.1089/hum.2012.245 · Cited by 21 · see citing works
“Pharmaceutical treatments, such as various nicotine delivery strategies, bupropion (Zyban), varenicline (Chantix), nortriptyline, and clonidine have been marketed to alleviate the symptoms of nicotine withdrawal (Nides, 2008; Polosa and Benowitz, 2011).”
InfluentialNicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice
Higa, K. K., Grim, A., Kamenski, M. E., van Enkhuizen, J., Zhou, X., Li, K., Naviaux, J. C., Wang, L., Naviaux, R. K., Geyer, M. A., et al. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4572-2 · Cited by 20 · see citing works
“Since the success of quitting attempts can be increased by two-or threefold with the aid of counseling and medications, it is imperative to better understand and develop more accessible treatments to aid smoking cessation (Fiore et al. 2008; Polosa and Benowitz 2011; Ashare and Schmidt 2014).”
Caponnetto, P., Caruso, M., Maglia, M. G., Emma, R., Saitta, D., Busà, B., Polosa, R., Prosperini, U., Pennisi, A., Benfatto, F., et al. (2020) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2020.100518 · Cited by 19 · see citing works
“But while smoking cessation may be the most desirable final outcome from a health point of view [4], many smokers are unable or unwilling to quit.”
BackgroundZhao, Z., Hu, Y. Y., Harmon, T. M., Pentel, P. R., Ehrich, M. F., & Zhang, C. (2018) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2018.04.016 · Cited by 18 · see citing works
Ahmadi‐Soleimani, S. M., Amiry, G. Y., Khordad, E., Masoudi, M., & Beheshti, F. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122100 · Cited by 17 · see citing works
Guy, E. G., Fisher, D. C., Higgins, G. A., & Fletcher, P. J. (2014) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000092 · Cited by 17 · see citing works
“Pharmaceutical interventions, such as nicotine replacement therapy, varenicline and bupropion, have shown some efficacy in abating tobacco use, but quit rates still remain low, remaining around the 20% range (George and O’Malley, 2004; Polosa and Benowitz, 2011).”
BackgroundInfluentiall-tetrahydropalmatine reduces nicotine self-administration and reinstatement in rats
Faison, S. L., Schindler, C. W., Goldberg, S. R., & Wang, J. B. (2016) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-016-0093-6 · Cited by 17 · see citing works
“A variety of treatments are currently on the market to treat nicotine addiction including bupropion, varenicline, and nicotine replacement therapy [2, 22].”
BackgroundLoSchiavo, C. E., Acuna, N., & Halkitis, P. N. (2020) · Annals of Behavioral Medicine · doi:10.1093/abm/kaaa052 · Cited by 17 · see citing works
Bellanca, C. M., Augello, E., Benedetto, G. D., Burgaletto, C., Cantone, A. F., Cantarella, G., Bernardini, R., Polosa, R., & the DiaSmokeFree Working Group (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1406860 · Cited by 17 · see citing works
“Approved fi rst-line medications for smoking cessation include various forms of nicotine-replacement therapy (NRT), bupropion, and varenicline (Polosa and Benowitz, 2011).”
BackgroundEvidence-based treatments for smoking cessation
Chaney, S. E., & Sheriff, S. (2012) · The Nurse Practitioner · doi:10.1097/01.npr.0000412892.27557.e8 · Cited by 15 · see citing works
Nicotine‐induced molecular alterations are modulated by GABAB receptor activity
Varani, A. P., Pedrón, V. T., Aon, A. J., Höcht, C., Acosta, G. B., Bettler, B., & Balerio, G. N. (2017) · Addiction Biology · doi:10.1111/adb.12506 · Cited by 16 · see citing works
“NIC stimulates nAChRs located on dopaminergic, glutamatergic and GABAergic neurons of the VTA, causing the release of DA in the Acb that is responsible for the NIC-induced rewarding properties (Paterson 2009; De Biasi & Dani 2011; Polosa & Benowitz 2011).”
BackgroundSpruell, T., Colavita, G., Donegan, T., Egawhary, M., Hurley, M., Aveyard, P. N., Johnstone, E. C., Murphy, M. F. G., & Munafo, M. R. (2011) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntr246 · Cited by 15 · see citing works
Caring for the smoking asthmatic patient
Polosa, R., Caponnetto, P., & Sands, M. F. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.04.015 · Cited by 15 · see citing works
Cohen, G. A., Bellanca, C. M., Bernardini, R., Rose, J. E., & Polosa, R. (2024) · iScience · doi:10.1016/j.isci.2024.111090 · Cited by 15 · see citing works
Effectiveness of Electronic Aids for Smoking Cessation
Meier, E. M., Tackett, A. P., & Wagener, T. L. (2013) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-013-0343-8 · Cited by 14 · see citing works
“Similar reductions in cigarette smoking were seen in a sample of smokers diagnosed with schizophrenia, a population with high rates of smoking, for which traditional medications (ie, Bupropion and Varenicline) come with strong warnings for use due to their potential negative side effects (eg, psychiatric symptoms and…”
Exenatide once weekly for smoking cessation
Yammine, L., Kosten, T. R., Cinciripini, P. M., Green, C. E., Meininger, J. C., Minnix, J. A., & Newton, T. F. (2018) · Medicine · doi:10.1097/md.0000000000009567 · Cited by 14 · see citing works
“developing improved therapeutic approaches to assist smoking cessation.([2,3]) One innovative approach is based on animal studies showing that glucagon-like peptide-1 (GLP-1) receptor agonists attenuate rewards induced by alcohol,([4,5]) cocaine,([6,7]) amphetamine,([6,8]) and most relevant here, nicotine.”
BackgroundBraverman, E. R., Dennen, C. A., Gold, M. S., Bowirrat, A., Gupta, A., Baron, D. A., Roy, A., Smith, D. E., Cadet, J. L., & Blum, K. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19095480 · Cited by 13 · see citing works
Fletcher, P. J., Li, Z., Silenieks, L. B., MacMillan, C., DeLannoy, I., & Higgins, G. A. (2018) · Addiction Biology · doi:10.1111/adb.12602 · Cited by 12 · see citing works
“Given that multiple factors and mechanisms contribute to nicotine dependence, drug-combination therapy may increase this success rate (Wu et al. 2006; Polosa & Benowitz 2011).”
BackgroundFraleigh, N. L., Boudreau, J., Bhardwaj, N., Eng, N. F., Murad, Y. M., Lafrenie, R. M., Acevedo, R., Oliva, R., Díaz‐Mitoma, F., & Le, H. (2016) · Heliyon · doi:10.1016/j.heliyon.2016.e00147 · Cited by 12 · see citing works
“It is believed that a vaccine capable of generating antibodies with higher affinity and titers against nicotine could help achieve higher abstinence rates and facilitate smoking cessation [4, 6, 7, 8, 9, 10].”
Hardie, G., Gale, N., McEwan, M., Milleri, S., Ziviani, L., Proctor, C., & Murphy, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-19167-8 · Cited by 12 · see citing works
Formulation of Nanovaccines toward an Extended Immunity against Nicotine
Hu, Y. Y., Zhao, Z., Ehrich, M. F., & Zhang, C. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c07049 · Cited by 11 · see citing works
Quintanilla, M. E., Morales, P., Ezquer, F. E., Ezquer, M., Herrera‐Marschitz, M., & Israel, Y. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.617418 · Cited by 11 · see citing works
Shen, X. Y., Orson, F. M., & Kosten, T. R. (2011) · F1000 Medicine Reports · doi:10.3410/m3-20 · Cited by 10 · see citing works
“As a result, three pharmaceutical companies have moved nicotine vaccines forward to human studies [29].”
BackgroundAhmadi‐Soleimani, S. M., Ghasemi, S., Rahmani, M. A., Gharaei, M., Bezanaj, M. M., & Beheshti, F. (2024) · Scientific Reports · doi:10.1038/s41598-024-61932-4 · Cited by 10 · see citing works
“Studies on human populations have revealed that nicotine-alcohol interaction further complicates the post-quit behavioral outcomes, therefore, finding therapeutic or ameliorative strategies are of paramount significance 61–63 .”
BackgroundGrebenstein, P. E., Harp, J. L., & Rowland, N. E. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.07.012 · Cited by 9 · see citing works
“Moreover, varenicline has several negative side effects such as headaches, gastrointestinal complaints, and psychiatric disturbances (Freedman 2007; Kohen and Kremen 2007; Kuehn 2008; Polosa and Benowitz 2011; Purvis et al. 2009) that might limit its acceptance.”
BackgroundThe Persistent Challenge of Developing Addiction PharmacotherapiesPreprint
Swinford-Jackson, S. E., O’Brien, C. P., Kenny, P. J., Vanderschuren, L. J. M. J., Unterwald, E. M., & Pierce, R. C. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a040311 · Cited by 10 · see citing works
“Nicotine gum, nicotine lozenges, patches, nasal sprays, and inhalers are all popular forms of nicotine replacement therapy and are effective in maintaining abstinence from tobacco use (Polosa and Benowitz 2011).”
BackgroundKrysiński, A., Russo, C., Campagna, D., Pino, A. D., John, S., Belsey, J., Caponnetto, P., Vudu, L., Lim, C. W., Ciaula, A. D., et al. (2023) · Internal and Emergency Medicine · doi:10.1007/s11739-023-03467-6 · Cited by 8 · see citing works
“…cigarette consumption has significantly decreased, but this trend has not been observed in those with diabetes [9–11], justifying an urgent need to target this vulnerable population with effective smoking cessation interventions, including counseling and nicotine-containing preparations [5, 12–15].”
BackgroundCocaine and Nicotine Research Illustrates a Range of Hypocretin Mechanisms in Addiction
Baimel, C., Borgland, S. L., & Corrigall, W. A. (2012) · Vitamins and hormones · doi:10.1016/b978-0-12-394623-2.00016-0 · Cited by 8 · see citing works
“…consist of a variety of nicotine replacement therapies, the antidepressant bupropion (ZybanÒ), the nicotinic ligand varenicline (ChantixÒ; ChampixÒ), and several second-line pharmacotherapies, medications which are effective but for which that effectiveness is limited (Polosa and Benowitz, 2011).”
BackgroundKučerová, J., Amchová, P., Siska, F., & Tizabi, Y. (2021) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2021.1907714 · Cited by 8 · see citing works
Krysiński, A., Russo, C., John, S., Belsey, J., Campagna, D., Caponnetto, P., Vudu, L., Lim, C. W., Purrello, F., Mauro, M. D., et al. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-045396 · Cited by 8 · see citing works
“12 15 Unfortunately, there is no convincing demonstration of effective cessation interventions in patients with diabetes 16 and, in general, most smokers are reluctant to seek formal treat-ment for stopping smoking with the vast majority making attempts to quit without assistance.”
RetractedCaraci, F., & Drago, F. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.05.003 · Cited by 7 · see citing works
“…if applied to nicotine addiction, should imply that tobacco dependence must be treated and monitored over time with current drugs for smoking cessation which are only modestly effective in real-life compared to results obtained in RCT (Raupach and van Schayck, 2011; Polosa and Benowitz, 2011).”
InfluentialElectronic cigarettes: Emerging trends and research hotspots
Zhang, Q., Fan, X., Yue, Y., & Zheng, R. (2020) · Tobacco Induced Diseases · doi:10.18332/tid/118719 · Cited by 7 · see citing works
Advancing Addiction Treatment: What Can We Learn from Animal Studies?
Wu, P. H., & Schulz, K. M. (2012) · ILAR Journal · doi:10.1093/ilar.53.1.4 · Cited by 7 · see citing works
“Clinical practice suggests that nicotine replacement therapy (bupropion, varenicline, and other nicotinic receptor partial agonists) and second-line medications such as nortriptyline and clonidine can ease craving (Fiore and Jaen 2008; Polosa and Benowitz 2011).”
BackgroundKangiser, M. M., Dwoskin, L. P., Zheng, G., Crooks, P. A., & Stairs, D. J. (2017) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000340 · Cited by 6 · see citing works
“Although varenicline has a low abuse liability, its actions as a partial agonist at α4β2 and as a full agonist at α7 nAChRs on dopaminergic, glutamatergic, and GABAergic neurons in the ventral tegmental area lead to DA release in the nucleus accumbens (Polosa and Benowitz, 2011).”
BackgroundThe Role of Halogen Bonding in Crystal Structures of 3-Halogeno Cytisine Derivatives
Przybył, A. K., & Kubicki, M. (2012) · Journal of Chemical Crystallography · doi:10.1007/s10870-012-0300-2 · Cited by 6 · see citing works
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Choi, H. D., & Shin, W. G. (2016) · Journal of Health Psychology · doi:10.1177/1359105316648479 · Cited by 5 · see citing works
Bellanca, C. M., Polosa, S. P., Augello, E., Benedetto, G. D., Burgaletto, C., Cantone, A. F., Gaudio, G., Nunnari, G., Campagna, D., Nailes, J. M., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1606150 · Cited by 4 · see citing works
“Medications for smoking cessation include various forms of nicotine replacement therapy (NRT), bupropion, varenicline, and cytisine (Polosa and Benowitz, 2011; Cohen et al., 2024) that have been shown to improve quit rates in the general population of smokers.”
Inhaling Risk: Smoking Impact on Male and Female Reproductive Health
Mishra, A., Khan, S. A., Jadhav, K., & Mehrotra, N. (2025) · Biosciences Biotechnology Research Asia · doi:10.13005/bbra/3338 · Cited by 4 · see citing works
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“Gene polymorphisms in nicotinic acetylcholine receptor subunits have been strongly linked to smoking or nicotine dependence (Kalamida et al., 2007; Polosa and Benowitz, 2011).”
BackgroundRusso, C., Caponnetto, P., Cibella, F., Maglia, M. G., Alamo, A., Campagna, D., Frittitta, L., Mauro, M. D., Leotta, C., Mondati, E. G. M., et al. (2021) · Internal and Emergency Medicine · doi:10.1007/s11739-021-02684-1 · Cited by 4 · see citing works
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“), Bupropion and Varenicline] and second-line medications (including nortriptyline and clonidine) [47].”
BackgroundThe effect of CNQX on self-administration: present in nicotine, absent in methamphetamine model
Hrickova, M., Amchová, P., & Kučerová, J. (2024) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2023.1305412 · Cited by 3 · see citing works
Kwong, W., & White, C. A. (2013) · BMC Nephrology · doi:10.1186/1471-2369-14-248 · Cited by 2 · see citing works
“Over the past 20 years, a variety of different options both pharmacologic and non-pharmacologic – have been proposed to facilitate the process of smoking cessation [1].”
BackgroundDevelopment of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery
Wang, H. (2017) · Queensland University of Technology · doi:10.5204/thesis.eprints.108006 · Cited by 3 · see citing works
- Authors
- Polosa, R., & Benowitz, N. L.
- Affiliations
- University of Catania (IT)
- San Francisco General Hospital (US)
- Corresponding author
- Polosa, Riccardo
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 32
- Issue
- 5
- Pages
- 281-289
- ISSN
- 0165-6147 (ISSN-L)
- PMC
- PMC5564372
- OpenAlex
- W2057469494
- Cited by
- 135
- References
- 68
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 11 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 9 · 2014: 13 · 2013: 14 · 2012: 20
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Merck
- National Institute on Drug Abuse (R01DA002277, R37DA002277)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- nicotine dependence, tobacco dependence, smoking cessation, pharmacotherapy, drug development pipeline
- MeSH terms
- Smoking Prevention, Humans, Nicotine, Smoking, Tobacco Use Disorder, Vaccines, Drug Design, Smoking Cessation
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.
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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