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Levine A, Huang Y, Drisaldi B, Griffin EA, Pollak DD, Xu S, etal. (November 2011). "Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine". Science Translational Medicine. 3 (107): 107ra109. doi: 10.1126/scitranslmed.3003062. PMC 4042673. PMID 22049069. Nicotine and cigarette smoke both induce the expression of liver enzymes (e.g., certain cytochrome P450 proteins) which metabolize drugs, leading to the potential for alterations in drug metabolism. [75] Pod mod electronic cigarettes use nicotine in the form of a protonated nicotine, rather than free-base nicotine found in earlier generations. [159] Preparation [ edit ]

a b Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". The American Journal of Drug and Alcohol Abuse. 40 (6): 428–37. doi: 10.3109/00952990.2014.933840. PMID 25083822. S2CID 19157711. The knowledge of ΔFosB induction in chronic drug exposure provides a novel method for the evaluation of substance addiction profiles (i.e. how addictive they are). Xiong et al. used this premise to evaluate the potential addictive profile of propofol (119). Propofol is a general anaesthetic, however its abuse for recreational purpose has been documented (120). Using control drugs implicated in both ΔFosB induction and addiction (ethanol and nicotine),... European Food Safety Authority (7 May 2009). "Potential risks for public health due to the presence of nicotine in wild mushrooms". EFSA Journal. 7 (5): 286r. doi: 10.2903/j.efsa.2009.286r. Nicotine was often compared to caffeine in advertisements in the 1980s by the tobacco industry, and later in the 2010s by the electronic cigarettes industry, in an effort to reduce the stigmatization and the public perception of the risks associated with nicotine use. [194] Research [ edit ] Central nervous system [ edit ]

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Barua RS, Rigotti NA, Benowitz NL, Cummings KM, Jazayeri MA, Morris PB, etal. (December 2018). "2018 ACC Expert Consensus Decision Pathway on Tobacco Cessation Treatment: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents". Journal of the American College of Cardiology. 72 (25): 3332–3365. doi: 10.1016/j.jacc.2018.10.027. PMID 30527452.

Nicotine has been used as an insecticide since at least the 1960s, in the form of tobacco extracts [17] [48] [49] (although other components of tobacco also seem to have pesticide effects). [50] Nicotine pesticides have not been commercially available in the US since 2014, [51] and homemade pesticides are banned on organic crops [52] and caution is recommended for small gardeners. [53] Nicotine pesticides have been banned in the EU since 2009. [54] Foods are imported from countries in which nicotine pesticides are allowed, such as China, but foods may not exceed maximum nicotine levels. [54] [55] Neonicotinoids, such as imidacloprid, which are derived from and structurally similar to nicotine, are widely used as agricultural and veterinary pesticides as of 2016. [56] [48] Performance [ edit ] Sanner T, Grimsrud TK (31 August 2015). "Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment - A Review". Frontiers in Oncology. 5: 196. doi: 10.3389/fonc.2015.00196. PMC 4553893. PMID 26380225. Gause GF (1941). "Chapter V: Analysis of various biological processes by the study of the differential action of optical isomers". In Luyet, B. J. (ed.). Optical Activity and Living Matter. A series of monographs on general physiology. Vol.2. Normandy, Missouri: Biodynamica. Kothari AN, Mi Z, Zapf M, Kuo PC (2014). "Novel clinical therapeutics targeting the epithelial to mesenchymal transition". Clinical and Translational Medicine. 3: 35. doi: 10.1186/s40169-014-0035-0. PMC 4198571. PMID 25343018. a b c D'Souza MS, Markou A (July 2011). "Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments". Addiction Science & Clinical Practice. 6 (1): 4–16. PMC 3188825. PMID 22003417. Withdrawal symptoms upon cessation of nicotine intake: Chronic nicotine use induces neuroadaptations in the brain's reward system that result in the development of nicotine dependence. Thus, nicotine-dependent smokers must continue nicotine intake to avoid distressing somatic and affective withdrawal symptoms. Newly abstinent smokers experience symptoms such as depressed mood, anxiety, irritability, difficulty concentrating, craving, bradycardia, insomnia, gastrointestinal discomfort, and weight gain (Shiffman and Jarvik, 1976; Hughes et al., 1991). Experimental animals, such as rats and mice, exhibit a nicotine withdrawal syndrome that, like the human syndrome, includes both somatic signs and a negative affective state (Watkins et al., 2000; Malin et al., 2006). The somatic signs of nicotine withdrawal include rearing, jumping, shakes, abdominal constrictions, chewing, scratching, and facial tremors. The negative affective state of nicotine withdrawal is characterized by decreased responsiveness to previously rewarding stimuli, a state called anhedonia.

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Kishioka S, Kiguchi N, Kobayashi Y, Saika F (2014). "Nicotine effects and the endogenous opioid system". Journal of Pharmacological Sciences. 125 (2): 117–24. doi: 10.1254/jphs.14R03CP. PMID 24882143.

Royal College of Physicians. "Nicotine Without Smoke -- Tobacco Harm Reduction". p.125 . Retrieved 30 September 2020. Use of nicotine alone, in the doses used by smokers, represents little if any hazard to the user. a b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 9: Autonomic Nervous System". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nded.). New York: McGraw-Hill Medical. p.234. ISBN 9780071481274. Nicotine... is a natural alkaloid of the tobacco plant. Lobeline is a natural alkaloid of Indian tobacco. Both drugs are agonists are nicotinic cholinergic receptors... Sajja RK, Rahman S, Cucullo L (March 2016). "Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress". Journal of Cerebral Blood Flow and Metabolism. 36 (3): 539–54. doi: 10.1177/0271678X15616978. PMC 4794105. PMID 26661236. Dugas EN, Sylvestre MP, O'Loughlin EK, Brunet J, Kakinami L, Constantin E, O'Loughlin J (February 2017). "Nicotine dependence and sleep quality in young adults". Addictive Behaviors. 65: 154–160. doi: 10.1016/j.addbeh.2016.10.020. PMID 27816041.The primary therapeutic use of nicotine is treating nicotine dependence to eliminate smoking and the damage it does to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, inhalers, or nasal sprays to wean them off their dependence. A 2018 Cochrane Collaboration review found high-quality evidence that all current forms of nicotine replacement therapy (gum, patch, lozenges, inhaler, and nasal spray) therapies increase the chances of successfully quitting smoking by 50–60%, regardless of setting. [45] Lavoie FW, Harris TM (1991). "Fatal nicotine ingestion". The Journal of Emergency Medicine. 9 (3): 133–136. doi: 10.1016/0736-4679(91)90318-a. PMID 2050970. Xiu X, Puskar NL, Shanata JA, Lester HA, Dougherty DA (March 2009). "Nicotine binding to brain receptors requires a strong cation-pi interaction". Nature. 458 (7237): 534–7. Bibcode: 2009Natur.458..534X. doi: 10.1038/nature07768. PMC 2755585. PMID 19252481.

See also: Nicotine replacement therapy A 21 mg patch applied to the left arm. The Cochrane Collaboration finds that nicotine replacement therapy increases a quitter's chance of success by 50–60%, regardless of setting. [45] a b c Pictet A, Rotschy A (1904). "Synthese des Nicotins"[Synthesis of nicotine]. Berichte der Deutschen Chemischen Gesellschaft (in German). 37 (2): 1225–1235. doi: 10.1002/cber.19040370206. Nicotine also activates the sympathetic nervous system, [140] acting via splanchnic nerves to the adrenal medulla, stimulating the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream. a b c d e f g Parrott AC (April 2003). "Cigarette-derived nicotine is not a medicine". The World Journal of Biological Psychiatry. 4 (2): 49–55. doi: 10.3109/15622970309167951. PMID 12692774. S2CID 26903942. The nicotine content of popular American-brand cigarettes has increased over time, and one study found that there was an average increase of 1.78% per year between the years of 1998 and 2005. [186]Zhang S. "E-Cigs Are Going Tobacco-Free With Synthetic Nicotine". Wired. ISSN 1059-1028 . Retrieved 11 October 2022. a b Stolerman IP, Jarvis MJ (January 1995). "The scientific case that nicotine is addictive". Psychopharmacology. 117 (1): 2–10, discussion 14–20. doi: 10.1007/BF02245088. PMID 7724697. S2CID 8731555. The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that comprise nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from niacin (nicotinic acid) while the pyrrolidine is derived from N-methyl-Δ 1-pyrrollidium cation. [163] [164] Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for niacin and the tropane pathway for N-methyl-Δ 1-pyrrollidium cation. a b c d Landoni JH. "Nicotine (PIM)". INCHEM. International Programme on Chemical Safety . Retrieved 29 January 2019.