• FLORENCE PRIBADI Pharmacology, Faculty of Medicine, Universitas Ciputra Surabaya, Citraland CBD Boulevard, Made, Kec Sambikerep, Surabaya 60219, East Java, Indonesia
  • RAHAJOE IMAM SANTOSA Clinical Pathologist, Faculty of Medicine, Universitas Ciputra Surabaya, Citraland CBD Boulevard, Made, Kec Sambikerep, Surabaya 60219, East Java, Indonesia
  • ARIEF GUNAWAN DARMANTO Pharmacology, Faculty of Medicine, Universitas Ciputra Surabaya, Citraland CBD Boulevard, Made, Kec Sambikerep, Surabaya 60219, East Java, Indonesia




Nicotine, Cigarette, Tobacco, Cognitive-enhancing effects


Nicotine is a major chemical of tobacco that makes smokers having difficulties to stop consuming cigarette. That chemical is an alkaloid-based plant and known for one of the major compound of cigarette. Many researches showed the negative side of nicotine. In contrast, a recent study showed the benefits of nicotine. Some researches proved that nicotine has high possibility to improve the depressive behavior both in animal models and human subject. In addition, more research also proved that nicotine has cognitive-enhancing effects, which means it has the ability to improve the function of working memory, episodic memory, attention, and fine motor function. The current review deliberates about the good side and the diversity usage of nicotine, particularly in medicine, as novel therapeutics for neurodegenerative diseases.


Download data is not yet available.


1. Malczewska Jasko?a K, Jasiewicz B, Mrowczynska L. Nicotine alkaloids as antioxidant and potential protective agents against in vitro oxidative haemolysis. Chem Biol Interact 2016;243:62–71.
2. Davis RA, Stiles MF, deBethizy JD, Reynolds JH. Dietary nicotine: a source of urinary cotinine. Food Chem Toxicol 1991;29:821–7.
3. International Agency for Research on Cancer (IARC), World Health Organization. Tobacco smoke and involuntary smoking IARC Monographs on the evaluation of carcinogenic risks to humans Vol. 83. Lyon: IARCPress; 2004. Available from: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Tobacco-Smoke-And-Involuntary-Smoking-2004 [Last accessed on 10 Feb 2020]
4. International Agency for Research on Cancer (IARC), World Health Organization. Drinking coffee, mate, and very hot beverages IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 116. Lyon: IARCPress; 2018. Available from: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Drinking-Coffee-Mate-And-Very-Hot-Beverages-2018 [Last accessed on 10 Feb 2020]
5. International Agency for Research on Cancer (IARC) World Health Organization. DDT, lindane, and 2,4-D IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 113. Lyon: IARCPress; 2018. Available from: https://monographs.iarc.fr/wp-content/uploads/2018/07/mono113.pdf [Last accessed on 10 Feb 2020]
6. World Health Organization. A guide for tobacco users to quit. Geneva: World Health Organization; 2014. Available from: https://www.who.int/tobacco/publications/smoking_cessation/9789241506939/en/ [Last accessed on 10 Feb 2020]
7. Cogliano VJ, Baan R, Straif K, Grosse Y, Lauby Secretan B, El Ghissassi F, et al. Preventable exposures associated with human cancers. J Natl Cancer Inst 2011;103:1827–39.
8. Aubin HJ, Farley A, Lycett D, Lahmek P, Aveyard P. Weight gain in smokers after quitting cigarettes: meta-analysis. Br Med J 2012;345:4439.
9. Audrain Mcgovern J, Benowitz NL. Cigarette smoking, nicotine, and body weight. Clin Pharmacol Ther 2011;90:164–8.
10. Bush T, Lovejoy JC, Deprey M, Carpenter KM. The effect of tobacco cessation on weight gain, obesity and diabetes risk. Obesity 2016;24:1834–41.
11. Kryfti M, Dimakou K, Toumbis M, Daniil Z, Hatzoglou C, Gourgoulianis KI. Effects of smoking cessation on serum leptin and adiponectin levels. Tob Induc Dis 2015;13:30.
12. Bunneu PE, Hansen M, LeSage M. Effects of isolated tobacco alkaloids and tobacco products on deprivation induced food intake and meal patterns in rats. Pharmacol Biochem Behav 2018;165:45–55.
13. Hu Y, Zong G, Liu G, Wang M, Rosner B, Pan A, et al. Smoking cessation, weight change, type 2 diabetes, and mortality. N Engl J Med 2018;379:623–32.
14. Liu R, Gao Z, Wang H, Tang X, Gao L, Song Y, et al. Association of baseline smoking status with long-term prognosis in patients who underwent percutaneous coronary intervention: large single-center data. J Interv Cardiol 2019. https://doi.org/10.1155/2019/3503876
15. Kufner A, Nolte CH, Galinovic I, Brunecker P, Kufner GM, Endres M, et al. Smoking-thrombolysis paradox: recanalization and reperfusion rates after intravenous tissue plasminogen activator in smokers with ischemic stroke. Stroke 2013;44:407–13.
16. Gupta T, Kolte D, Khera S, Harikrishnan P, Mujib M, Aronow WS, et al. Smoker’s paradox in patients with st-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. J Am Hear Assoc 2016;5:1–10.
17. Venkatason P, Salleh NM, Zubairi Y, Hafidz I, Ahmad WAW, Han SK, et al. The bizzare phenomenon of smokers’ paradox in the immediate outcome post acute myocardial infarction: an insight into the Malaysian national cardiovascular database-acute coronary syndrome (NCVD-ACS) registry year 2006–2013. Springerplus 2016;5:534.
18. Aune E, Røislien J, Mathisen M, Thelle DS, Otterstad JE. The “smoker’s paradox” in patients with acute coronary syndrome: a systematic review. BMC Med 2011;9:97.
19. Bell TM, Bayt DR, Zarzaur BL. “Smoker’s paradox” in patients treated for severe injuries: lower risk of mortality after trauma observed in current smokers. Nicotine Tob Res 2015;17:1499–504.
20. Aaseth J, Dusek P, Roos MP. Prevention of progression in Parkinson’s disease. BioMetals 2018;31:737–47.
21. Barreto GE, Iarkov A, Moran VE. Beneficial effects of nicotine, cotinine and its metabolites as potential agents for Parkinson’s disease. Front Aging Neurosci 2015;6:340.
22. Budzianowski J. [Tobacco--once a medicinal plant. does it contain substances with medicinal properties?]. Przegl Lek 2013;70:865–8.
23. Getachew B, Csoka AB, Aschner M, Tizabi Y. Nicotine protects against manganese and iron-induced toxicity in SH-SY5Y cells: implication for Parkinson’s disease. Neurochem Int 2019;124:19–24.
24. Tizabi Y, Getachew B. Nicotinic receptor intervention in parkinson’s disease: future directions. Clin Pharmacol Transl Med 2017;1:14–9.
25. Lewis RS, Nicholson JS. Aspects of the evolution of Nicotiana tabacum L. and the status of the United States nicotiana germplasm collection. Genet Resour Crop Evol 2007;54:727–40.
26. Djajadi D. Tobacco diversity in Indonesia. J Biol Res 2015;20:27–32.
27. Commission Secretariat VII Indonesian House of people’s. Kunjungan spesifik komisi VII DPR RI ke Provinsi Jawa Timur pengelolaan limbah di perusahaan rokok PT. HM Sampoerna; 2018. Available from: http://www.dpr.go.id/dokakd/dokumen/K7-12-2639ccef7ca140a729a6aa350afbf03c.pdf [Last accessed on 10 Feb 2020]
28. Tobacco Control Support Center. Fakta tembakau dan permasalahannya di Indonesia. Kemenkes. Jakarta: Tobacco Control and Support Center-IAKMI; 2014. Available from: http://www.tcsc-indonesia.org/wp-content/uploads/2016/06/Buku-Fakta-Tembakau-2014__Web-Version.pdf [Last accessed on 10 Feb 2020]
29. Kosen S, Thabrany H, Kusumawardani N, Martini S. Review of evidence series: health and economic costs of tobacco in Indonesia. Kementerian Kesehatan Republik Indonesia. Jakarta: Lembaga Penerbit Badan Penelitian dan Pengembangan Kesehatan (LPB); 2017. Available from: https://www.litbang.kemkes.go.id/review-of-evidence-series-health-and-economic-costs-of-tobacco-in-indonesia [Last accessed on 10 Feb 2020]
30. Hamdani T. Cukai rokok naik, pengusaha prediksi penjualan di 2020 anjlok. Detik Finance; 2019. Available from: https://finance.detik.com/industri/d-4731454/cukai-rokok-naik-pengusaha-prediksi-penjualan-di-2020-anjlok [Last accessed on 10 Feb 2020].
31. Qolbi N. Laba bersih mayoritas emiten rokok meningkat tapi penjualan turun, begini rekomendasi. Kontan.co.id; 2019. Available from: https://investasi.kontan. co.id/news/laba-bersih-mayoritas-emiten-rokok-meningkat-tapi-penjualan-turun-begini-rekomendasi?page=all [Last accessed on 10 Feb 2020]
32. Indonesian Directorate General of Customs and Excise. Dialog interaktif di udara, bea cukai Ambon sosialisasikan pengenaan cukai cairan rokok elektrik (vape). Indonesian Directorate General of Customs and Excise; 2018. Available from: https://www.beacukai.go.id/berita/dialog-interaktif-di-udara-bea-cukai-ambon-sosialisasikan-pengenaan-cukai-cairan-rokok-elektrik-vape-.html [Last accessed on 10 Feb 2020]
33. Philip Moris International. Delivering a smoke-free future | PMI-Philip Morris International. Philip Moris International (PMI); 2019. Available from: https://www.pmi.com/our-transformation/ delivering-a-smoke-free-future [Last accessed on 10 Feb 2020].
34. Geiss O, Kotzias D. Tobacco, cigarettes and cigarette smoke an overview. European Commission Directorate General Joint Research Centre. Luxembourg: European Commission Directorate-General Joint Research Centre Institute for Health and Consumer Protection; 2007. Available from: https://ec.europa.eu/jrc/en/publication/eur-scientific-and-technical-research-reports/tobacco-cigarettes-and-cigarette-smoke-overview [Last accessed on 10 Feb 2020]
35. Butler T. Power in smoke: the language of tobacco and authority in caroline England. Studies Philol 2009;106:100–18.
36. Smith EA, Malone RE. “Everywhere the soldier will be”: wartime tobacco promotion in the us military. Am J Public Health 2009;99:1595–602.
37. Hanafin J, Clancy L. History of tobacco production and use. Prog Respir Res 2015;42:1–18.
38. Routh HB, Bhowmik KR, Parish JL, Parish LC. Historical aspects of tobacco use and smoking. Clin Dermatol 1998;16:539–44.
39. Laccourreye O, Werner A, Laccourreye H, Bonfils P. Tobacco and otorhinolaryngology: Epic and disaster. Eur Ann Otorhinolaryngol Head Neck Dis 2014;131:183–8.
40. Charlton A. Medicinal uses of tobacco in history. JRSM 2004;97:292–6.
41. Hajdu SI, Vadmal MS. The use of tobacco. Ann Clin Lab Sci Spring 2010;40:178–81.
42. Fusetto R, O’Hair RA. Nicotine as an insecticide in Australia: a short history. Chemistry 2015;38:18–21.
43. Wu J. Understanding of nicotinic acetylcholine receptors. Acta Pharmacol Sin 2009;30:653–5.
44. Gotti C, Clementi F. Neuronal nicotinic receptors: from structure to pathology. Prog Neurobiol 2004;74:363–96.
45. Bertrand D, Lee CHL, Flood D, Marger F, Donnelly Roberts D. Therapeutic potential of ?7 nicotinic acetylcholine receptors. Pharmacol Rev 2015;67:1025–73.
46. Yamada Nomoto K, Yoshino O, Akiyama I, Ushijima A, Ono Y, Shima T, et al. Alpha-7 nicotinic acetylcholine receptor (nAChR) agonist inhibits the development of endometriosis by regulating inflammation. Am J Reprod Immunol 2016;76:491–8.
47. Nott A, Levin ED. Dorsal hippocampal ?7 and ?4?2 nicotinic receptors and memory. Brain Res 2006;1081:72–8.
48. Levin E, Bradley A, Addy N, Sigurani N. Hippocampal ?7 and ?4?2 nicotinic receptors and working memory. Neuroscience 2002;109:757–65.
49. Levin ED. Nicotinic receptor subtypes and cognitive function. J Neurobiol 2002;53:633–40.
50. Valentine G, Sofuoglu M. Cognitive effects of nicotine: recent progress. Curr Neuropharmacol 2018;16:403–14.
51. Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E, et al. Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial. Neurology 2012;78:91–101.
52. Levin ED. Complex relationships of nicotinic receptor actions and cognitive functions. Biochem Pharmacol 2013;86:1145–52.
53. Salmanzadeh H, Ahmadi Soleimani SM, Pachenari N, Azadi M, Halliwell RF, Rubino T, et al. Adolescent drug exposure: a review of evidence for the development of persistent changes in brain function. Brain Res Bull 2020;156:105–17.
54. Gandelman JA, Newhouse P, Taylor WD. Nicotine and networks: potential for enhancement of mood and cognition in late-life depression. Neurosci Biobehav Rev 2018;84:289–98.
55. Zurkovsky L, Taylor WD, Newhouse PA. Cognition as a therapeutic target in late-life depression: potential for nicotinic therapeutics. Biochem Pharmacol 2013;86:1133–44.
56. Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry 2013;202:329–35.
57. Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, et al. Transdermal nicotine for the treatment of mood and cognitive symptoms in nonsmokers with late-life depression. J Clin Psychiatry 2018;79:18m12137.
58. Taylor WD, Steffens DC, McQuoid DR, Payne ME, Lee SH, Lai TJ, et al. Smaller orbital frontal cortex volumes associated with functional disability in depressed elders. Biol Psychiatry 2003;53:144–9.
59. Burke J, McQuoid DR, Payne ME, Steffens DC, Krishnan RR, Taylor WD. Amygdala volume in late-life depression: relationship with age of onset. Am J Geriatr Psychiatry 2011;19:771–6.
60. Zhao Z, Taylor WD, Styner M, Steffens DC, Krishnan KRR, MacFall JR. Hippocampus shape analysis and late-life depression. PLoS One 2008;3:e1837.
61. Taylor WD, MacFall JR, Payne ME, McQuoid DR, Steffens DC, Provenzale JM, et al. Greater MRI lesion volumes in elderly depressed subjects than in control subjects. Psychiatry Res Neuroimaging 2005;139:1–7.
62. MacFall JR, Taylor WD, Rex DE, Pieper S, Payne ME, McQuoid DR, et al. Lobar distribution of lesion volumes in late-life depression: the biomedical informatics research network (BIRN). Neuropsychopharmacology 2006;31:1500–7.
63. Salin Pascual RJ, Rosas M, Jimenez Genchi A, Rivera Meza BL, Delgado Parra V. Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression. J Clin Psychiatry 1996;57:387–9.
64. Newhouse P. Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol 2004;4:36–46.
65. Jansari AS, Froggatt D, Edginton T, Dawkins L. Investigating the impact of nicotine on executive functions using a novel virtual reality assessment. Addiction 2013;108:977–84.
66. Butters MA, Becker JT, Nebes RD, Zmuda MD, Mulsant BH, Pollock BG, et al. Changes in cognitive functioning following treatment of late-life depression. Am J Psychiatry 2000;157:1949–54.
67. Revathikumar P, Bergqvist F, Gopalakrishnan S, Korotkova M, Jakobsson P, Lampa J, et al. Immunomodulatory effects of nicotine on interleukin 1? activated human astrocytes and the role of cyclooxygenase 2 in the underlying mechanism. J Neuroinflammation 2016;13:256.
68. Noshita T, Murayama N, Nakamura S. Effect of nicotine on neuronal dysfunction induced by intracerebroventricular infusion of amyloid-? peptide in rats. Eur Rev Med Pharmacol Sci 2015;19:334–43.
69. Murphy MP, LeVine H. Alzheimer’s disease and the amyloid-? peptide. J Alzheimer’s Dis 2010;19:311–23.
70. Lombardo S, Maskos U. Role of the nicotinic acetylcholine receptor in Alzheimer’s disease pathology and treatment. Neuropharmacology 2015;96:255–62.
71. Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 2015;3:136.
72. Benson FE, Nierkens V, Willemsen MC, Stronks K. Smoking cessation behavioural therapy in disadvantaged neighbourhoods: an explorative analysis of recruitment channels. Subst Abuse Treat Prev Policy 2015;10:28.
73. Cherry KE, Blanchard B, Walker EJ, Smitherman EA, Lyon BA. Knowledge of memory aging across the lifespan. J Genet Psychol 2014;175:547–53.
74. Jia J, Peng J, Li Z, Wu Y, Wu Q, Tu W, et al. Cannabinoid CB2 receptor mediates nicotine-induced anti-inflammation in n9 microglial cells exposed to ? amyloid via protein kinase C. Mediators Inflamm 2016;8:1-10.
75. Xue M, Zhu L, Zhang J, Qiu J, Du G, Qiao Z, et al. Low dose nicotine attenuates A? neurotoxicity through activation early growth response gene 1 pathway. PLoS One 2015; 10:e0120267.
76. Ng YP, Or TCT, Ip NY. Plant alkaloids as drug leads for Alzheimer’s disease. Neurochem Int 2015;89:260–70.
77. Hritcu L, Stefan M, Brandsch R, Mihasan M. Enhanced behavioral response by decreasing brain oxidative stress to 6-hydroxy-l-nicotine in Alzheimer’s disease rat model. Neurosci Lett 2015;591:41–7.



How to Cite

PRIBADI, F., R. I. SANTOSA, and A. G. DARMANTO. “A REVIEW ON NICOTINE FOR HEALTH: INSIGHT FOR ‘PRO-HEALTH’ NICOTINE USAGE”. International Journal of Current Pharmaceutical Research, vol. 12, no. 4, July 2020, pp. 13-18, doi:10.22159/ijcpr.2020v12i4.39081.



Review Article(s)