Skip to main navigation menu Skip to main content Skip to site footer
FrancoAngeli Journals

Saggi, Studi e Ricerche

No. 72 (2025)

La citisina nel trattamento del disturbo da uso di tabacco: un trattamento efficace e sicuro per il controllo del craving

DOI
https://doi.org/10.3280/mis72-2025oa21255
Submitted
ottobre 10, 2025
Published
2026-01-30

Abstract

Tobacco smoking is a leading cause of morbidity and mortality worldwide, and chronic use is recognized as a pathology in its own right: tobacco use disorder.

The most effective approach to quitting smoking combines behavioral support with pharmacological therapy. Medications aim to control withdrawal symptoms but, above all, reduce craving, which remains the hallmark of addiction.

Addiction develops over years, during which the brain's neurological mechanisms change, altering the response to stimuli and modifying memory pathways.

As with other addictions (opiates or alcohol), pharmacological treatment must allow for a sufficiently long period of time to restore balance to the altered circuits.

Cytisine represents a highly attractive therapeutic option with a well-established history in Eastern European countries. Cytisine acts as a partial agonist of α4β2 nicotinic acetylcholine receptors. This means that: It binds to these receptors in the brain with a very high affinity, weakly stimulating them, producing sufficient amounts of dopamine to alleviate withdrawal symptoms and craving. At the same time, it blocks the binding of nicotine derived from smoking, reducing or eliminating the sensation of pleasure and gratification the smoker derives from smoking. 

To date, prescribing behavior follows patterns that cannot be shared given the chronicity of the disease: it is essential to change the treatment approach and evaluate the effectiveness of treatment based on more appropriate parameters, such as the reduction of craving and the disappearance/reduction of withdrawal symptoms.

References

  1. American Psychiatric Association, DSM-5 Task Force (2013). Diagnostic and statistical manual of mental disorders: DSM-5™ (5th ed.). American Psychiatric Publishing, Inc. Doi: 10.1176/appi.books.9780890425596.
  2. Amram D.L., Zagà V., Vegliach A. (2022). Una review narrativa sulle complesse proprietà di rinforzo della nicotina. Tabaccologia, XX(4): 8-26.
  3. Benowitz N.L. (2009). Pharmacology of Nicotine: Addiction, Smoking-Induced Disease, and Therapeutics. Annu Rev Pharmacol Toxicol., 49: 57-71. Doi: 10.1146/annurev.pharmtox.48.113006.094742.
  4. Boido C.C., Tasso B., Boido V., Sparatore F. (2003). Cytisine derivatives as ligands for neuronal nicotine receptors and with various pharmacological activities. Farmaco, Mar, 58(3): 265-77. doi: 10.1016/S0014-827X(03)00017-X. PMID: 12620422.
  5. Bondi L., Lucantoni A. Aumentare l’efficacia dei trattamenti del tabagismo con la costituzione di una rete integrata di interventi. Edizioni Cultura Salute | Editore Perugia, accesso eseguito il giorno agosto 20, 2025.
  6. Cardonna F. et al. (2006). Polimorfismi del gene CYP2A6 e dipendenza dal fumo in un gruppo di soggetti della Sicilia Occidentale. -- https://iris.unipa.it/handle/10447/6456.
  7. Castaldelli-Maia J.M., Martins S.S., Walker N. (2018). The effectiveness of Cytisine versus Nicotine Replacement Treatment for smoking cessation in the Russian Federation. Int J Drug Policy, Aug, 58: 121-125. Doi: 10.1016/j.drugpo.2018.05.012. Epub 2018 Jun 18. PMID: 29929154.
  8. Etter J.F. (2006). Cytisine for smoking cessation: a literature review and a meta-analysis. Arch Intern Med., Aug 14-28, 166(15): 1553-9. Doi: 10.1001/archinte.166.15.1553. PMID: 16908787.
  9. European Network for Smoking and Tobacco Prevention. ENSP (2016). Guidelines for treating tobacco dependence the comprehensive guide to the implementation of treatments and strategies to treat tobacco dependence. https://elearning-ensp.eu/assets/English%2520version.pdf.
  10. Ferger B., Spratt C., Teismann P., Seitz G., Kuschinsky K. (1998). Effects of cytisine on hydroxyl radicals in vitro and MPTP-induced dopamine depletion in vivo. Eur J Pharmacol., Nov 6, 360(2-3): 155-63. Doi: 10.1016/s0014-2999(98)00696-7. PMID: 9851582.
  11. Giulietti F., Filipponi A., Rosettani G., Giordano P., Iacoacci C., Spannella F., Sarzani R. (2020). Pharmacological Approach to Smoking Cessation: An Updated Review for Daily Clinical Practice. High Blood Press Cardiovasc Prev., Oct, 27(5): 349-362. Doi: 10.1007/s40292-020-00396-9. Epub 2020 Jun 23. PMID: 32578165; PMCID: PMC7309212.
  12. Gotti C., Clementi F. (2021). Cytisine and cytisine derivatives. More than smoking cessation aids. Pharmacol Res., Aug, 170, 105700. Doi: 10.1016/j.phrs.2021.105700. Epub 2021 Jun 2. PMID: 34087351.
  13. Igari M., Alexander J.C., Ji Y., Qi X., Papke R.L., Bruijnzeel A.W. (2014). Varenicline and cytisine diminish the dysphoric-like state associated with spontaneous nicotine withdrawal in rats. Neuropsychopharmacology, Jan, 39(2): 455-65. Doi: 10.1038/npp.2013.216. Epub 2013 Aug 21. PMID: 23966067; PMCID: PMC3870769.
  14. Jeong S.H., Newcombe D., Sheridan J., Tingle M. (2015). Pharmacokinetics of cytisine, an α4β2 nicotinic receptor partial agonist, in healthy smokers following a single dose. Drug Test Anal., Jun, 7(6): 475-82. Doi: 10.1002/dta.1707. Epub 2014 Sep 17. PMID: 25231024.
  15. Jeong S.H., Sheridan J., Bullen C., Newcombe D., Walker N., Tingle M. (2019). Ascending single dose pharmacokinetics of cytisine in healthy adult smokers. Xenobiotica, Nov, 49(11): 1332-1337. Doi: 10.1080/00498254.2018.1557760. Epub 2019 Jun 19. PMID: 30526213.
  16. Leaviss J., Sullivan W., Ren S., Everson-Hock E., Stevenson M., Stevens J.W., Strong M., Cantrell A. (2014). What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation. Health Technol Assess., May, 18(33): 1-120. Doi: 10.3310/hta18330. PMID: 24831822; PMCID: PMC4780997.
  17. Linea guida per il trattamento della dipendenza da tabacco e da nicotina. guidelines_2020_italian_forprint.pdf.
  18. Loukola A. et al. (2014). Genetics and smoking. Curr Addict Reports, March 1, 1(1): 75-82. Doi: 10.1007/s40429-013-0006-3.
  19. Mitchell R.G. (1951). Laburnum poisoning in children; report on ten cases. Lancet, Jul 14, 2(6672): 57-8. Doi: 10.1016/s0140-6736(51)91315-3. PMID: 14842114.
  20. Ofori S., Lu C., Olasupo O.O., Dennis B.B., Fairbairn N., Devereaux P.J., Mbuagbaw L. (2023). Cytisine for smoking cessation: A systematic review and meta-analysis. Drug Alcohol Depend., Oct 1, 251, 110936. Doi: 10.1016/j.drugalcdep.2023.110936. Epub 2023 Aug 25. PMID: 37678096.
  21. Pasman J.A. et al. Genetic Risk for Smoking: Disentangling Interplay Between Genes and Socioeconomic Status. Behavior Genetics. Doi: 10.1007/s10519-021-10094-4.
  22. Prochaska J.J. (2024). Manuali MSD Edizione Professionisti, luglio -- https://www.msdmanuals.com/it/professionale/argomenti-speciali/usodi-tabacco/fumo-e-altri-usi-del-tabacco.
  23. Puljevic´ C., Stjepanovic´ D., Meciar I., Kang H., Chan G., Morphett K., Bendotti H., Kunwar G., Gartner C. (2024). Systematic review and meta-analyses of cytisine to support tobacco cessation. Addiction, Oct, 119(10): 1713-1725. Doi: 10.1111/add.16592. Epub 2024 Jul 4. PMID: 38965792.
  24. Rungruanghiranya S., Tulatamakit S., Chittawatanarat K., Preedapornpakorn K., Wongphan T., Sutanthavibul N., Preechawong S., Petborom P. (2024). Efficacy and safety of cytisine versus nortriptyline for smoking cessation: A multicentre, randomized, double-blinded and placebo-controlled trial. Respirology, Oct, 29(10): 880-887. Doi: 10.1111/resp.14787. Epub 2024 Jul 14. PMID: 39004954.
  25. Sharma G., Vijayaraghavan S. (2008). Nicotinic Receptors: Role in Addiction and Other Disorders of the Brain. Subst Abuse, Nov 11, 1: 81-95.
  26. Società Italiana di Tabaccologia (SITAB) (2018). Linee guida per il trattamento della dipendenza da tabacco. https://www.tabaccologia.it/filedirectory/PDF/guide lines 2018_onlin e.pdf.
  27. S´wia˛tkowski W., Budzyn´ska B., Macia˛g M., S´wia˛ tkowska A., Tylz˙anowski P., Rahnama-Hezavah M., Stachurski P., Chałas R. (2023). Nicotine and Cytisine Embryotoxicity in the Experimental Zebrafish Model. Int J Mol Sci., Jul 28, 24(15), 12094. Doi: 10.3390/ijms241512094. PMID: 37569468; PMCID: PMC10419251.
  28. Tiwari R.K., Sharma V., Pandey R.K., Shukla S.S. (2020). Nicotine Addiction: Neurobiology and Mechanism. Journal of Pharmacopuncture, 23(1): 1-7. Doi: 10.3831/KPI.2020.23.001.
  29. Tobacco and Genetics Consortium (2010). Genome-wide meta-analyses identify multiple loci associated with smoking behaviour. Nat Genet, May, 42(5): 441-7. Doi: 10.1038/ng.571. Epub 2010 Apr 25.
  30. Torazzi A., Tedesco E., Ceccato S., Santin L., Campagnari S., Losso L., Toldo S., Casari R., Arzenton E., Marini P., Chiamulera C., Lugoboni F. (2024). Safety and efficacy of CyTisine for smoking cessation in a hOSPital context (CITOSP): study protocol for a prospective observational study. Front Public Health, Sep 30, 12, 1350176. Doi: 10.3389/fpubh.2024.1350176. PMID: 39403432; PMCID: PMC11471529.
  31. Tutka P., Vinnikov D., Courtney R.J., Benowitz N.L. (2019). Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation. Addiction, Nov., 114(11): 1951-1969. doi: 10.1111/add.14721. Epub 2019 Jul 19. PMID: 31240783.
  32. Walker N., Howe C., Glover M., McRobbie H., Barnes J., Nosa V., Parag V., Bassett B., Bullen C. (2014). Cytisine versus nicotine for smoking cessation. N Engl J Med., Dec 18, 371(25): 2353-62. Doi: 10.1056/NEJMoa1407764. PMID: 25517706.
  33. Walker N., Bullen C., Barnes J., McRobbie H., Tutka P., Raw M., Etter J.F., Siddiqi K., Courtney R.J., Castaldelli-Maia J.M., Selby P., Sheridan J., Rigotti N.A. (2016). Getting cytisine licensed for use world-wide: a call to action. Addiction, Nov, 111(11): 1895-1898. Doi: 10.1111/add.13464. Epub 2016 Jul 17. PMID: 27426482.
  34. Walker N., Smith B., Barnes J., Verbiest M., Parag V., Pokhrel S., Wharakura M.K., Lees T., Cubillos Gutierrez H., Jones B., Bullen C. (2021). Cytisine versus varenicline for smoking cessation in New Zealand indigenous Ma¯ori: a randomized controlled trial. Addiction, Oct, 116(10): 2847-2858. Doi: 10.1111/add.15489. Epub 2021 May 4. PMID: 33761149; PMCID: PMC8519028.
  35. West R., Zatonski W., Cedzynska M., Lewandowska D., Pazik J., Aveyard P., Stapleton J. (2011). Placebo-controlled trial of cytisine for smoking cessation. N Engl J Med., Sep 29, 365(13): 1193-200. Doi: 10.1056/NEJMoa1102035. PMID: 21991893.
  36. WHO - toolkit for delivering 5A’s and 5R’s brief tobacco intervention in primary care - 2014 - Toolkit for delivering the 5A’s and 5R’s brief tobacco interventions in primary care.