{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:24:54Z","timestamp":1786969494918,"version":"build-2736575974"},"reference-count":224,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Tobacco use remains one of the leading preventable causes of morbidity and mortality worldwide, contributing to more than 7 million deaths annually and imposing a substantial economic burden on healthcare systems and global productivity. The addictive properties of tobacco are primarily mediated by nicotine, which exerts its effects through neuronal nicotinic acetylcholine receptors (nAChRs) within brain reward circuits. Among these receptor subtypes, \u03b14\u03b22-containing nAChRs play a central role in nicotine dependence by regulating dopaminergic signaling associated with reinforcement, craving, withdrawal, and relapse. Repeated nicotine exposure induces neuroadaptive changes in receptor expression and neural circuitry, contributing to the chronic and relapsing nature of addiction. Advances in addiction neuroscience and receptor pharmacology have enhanced the understanding of nicotine-mediated signaling and facilitated the development of evidence-based smoking cessation therapies. Current treatment approaches include nicotine replacement therapies, antidepressant-based interventions, and partial nAChR agonists such as varenicline and cytisine. Emerging strategies encompass subtype-selective ligands, allosteric modulators, immunotherapeutics, neuromodulation techniques, and digital health technologies aimed at improving cessation outcomes. This review summarizes the neuropharmacological mechanisms underlying nicotine addiction and critically examines current and emerging therapeutic strategies, highlighting their mechanisms of action, clinical efficacy, limitations, and future potential for tobacco cessation.<\/jats:p>","DOI":"10.3390\/biology15161412","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:00:05Z","timestamp":1786964405000},"page":"1412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuropharmacology of Nicotine Addiction and Therapeutic Strategies for Smoking Cessation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-4171","authenticated-orcid":false,"given":"Ahmed A.","family":"Hefny","sequence":"first","affiliation":[{"name":"ArGan\u2019sLab, Department of Chemistry and Biochemistry, Faculty of Science, Wilfrid Laurier University, Waterloo, ON N2L 3C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul C.","family":"Karuturi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Science, Waterloo University, Waterloo, ON N2L 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0854-6449","authenticated-orcid":false,"given":"Subha","family":"Kalyaanamoorthy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Waterloo University, Waterloo, ON N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-8251","authenticated-orcid":false,"given":"Praveen P. N.","family":"Rao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Science, Waterloo University, Waterloo, ON N2L 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8689-943X","authenticated-orcid":false,"given":"Aravindhan","family":"Ganesan","sequence":"additional","affiliation":[{"name":"ArGan\u2019sLab, Department of Chemistry and Biochemistry, Faculty of Science, Wilfrid Laurier University, Waterloo, ON N2L 3C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021). 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