Editing Nicotine (section)

{{Short description|Chemical stimulant produced by some plants}}
{{About|the chemical|other uses|Nicotine (disambiguation)}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Use dmy dates|date=January 2024}}
{{Infobox drug
| Verifiedfields = 
| imageL = Nicotine molecule ball from xtal.png
| imageR = Nicotine molecule spacefill from xtal.png
| image_classR = bg-transparent
| caption = 
| image2 = 
| tradename = Nicorette, others
| Drugs.com = {{drugs.com|monograph|nicotine}}
| pregnancy_AU = D
| pregnancy_US = D
| legal_AU = S7
| legal_AU_comment = 
| legal_CA = Unscheduled
| legal_CA_comment = 
| legal_BR = Unscheduled
| legal_DE = Unscheduled
| legal_DE_comment = 
| legal_NZ = Unscheduled
| legal_NZ_comment = 
| legal_UK = GSL
| legal_UK_comment = <ref>{{cite web |title=The Medicines (Products Other Than Veterinary Drugs) (General Sale List) Amendment Order 2001 |url=https://www.legislation.gov.uk/uksi/2001/2068/note/made?view=plain |website=legislation.gov.uk |access-date=2 August 2022}}</ref>
| legal_US = OTC
| legal_US_comment = and [[prescription drug|prescription]]
<ref name="PubChem Nicotine">{{cite encyclopedia | title=Nicotine | url=https://pubchem.ncbi.nlm.nih.gov/compound/nicotine | series=PubChem Compound Database | publisher=United States National Library of Medicine&nbsp;– National Center for Biotechnology Information | access-date={{CURRENTDMY}} | date=16 February 2019}}</ref>
| legal_UN = Unscheduled
| legal_UN_comment = 
| legal_EU = 
| legal_status = In general legal for all uses for tobacco and nicotine products as electronic cigarettes, OTC for nicotine gums and lozenges.
| dependency_liability = [[Physical dependence|Physical]]: Low–moderate<ref>{{cite book |doi=10.1007/978-3-319-13482-6_4 |chapter=Nicotine Withdrawal |title=The Neuropharmacology of Nicotine Dependence |series=Current Topics in Behavioral Neurosciences |date=2015 | vauthors = McLaughlin I, Dani JA, De Biasi M |volume=24 |pages=99–123 |pmid=25638335 |pmc=4542051 |isbn=978-3-319-13481-9 }}</ref> [[Psychological dependence|Psychological]]: High<ref name=Dependence-withdrawal/><ref>{{cite journal | vauthors = Cosci F, Pistelli F, Lazzarini N, Carrozzi L | title = Nicotine dependence and psychological distress: outcomes and clinical implications in smoking cessation | journal = Psychology Research and Behavior Management | volume = 4 | pages = 119–128 | date = 2011 | pmid = 22114542 | pmc = 3218785 | doi = 10.2147/prbm.s14243 | doi-access = free }}</ref>
| addiction_liability = Very high<ref>{{cite book | vauthors = Hollinger MA |title=Introduction to Pharmacology | edition = Third |url=https://books.google.com/books?id=qfrLBQAAQBAJ&pg=PA222|date=19 October 2007|publisher=CRC Press|location=Abingdon|isbn=978-1-4200-4742-4|pages=222–223}}</ref>
| routes_of_administration = [[Inhalation]]; [[Insufflation (medicine)|insufflation]]; [[Oral route|oral]] – buccal, sublingual, and ingestion; [[transdermal]]; [[suppository|rectal]]
| class = [[Stimulant]]; [[Nootropic]]; [[Euphoriant]]
<!--Pharmacokinetic data-->| bioavailability = 
| protein_bound = <5%
| metabolism = Primarily [[hepatic]]: [[CYP2A6]], [[CYP2B6]], [[FMO3]], others
| elimination_half-life = 1–2 hours; 20 hours active metabolite
| metabolites = [[Cotinine]]
| excretion = [[Renal]], [[urine pH]]-dependent;<ref name="inchem">{{cite web | url=http://www.inchem.org/documents/pims/chemical/nicotine.htm | vauthors = Landoni JH | title=Nicotine (PIM) | website=INCHEM | publisher=International Programme on Chemical Safety | access-date=29 January 2019}}</ref><br /> {{nowrap|10–20%}} (gum), 30% (inhaled); {{nowrap|10–30%}} (intranasal)
<!--Identifiers-->| IUPAC_name = 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
| image = File:Nikotin - Nicotine.svg
| image_class = skin-invert-image
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 54-11-5
| ATC_prefix = N07
| ATC_suffix = BA01
| ATC_supplemental = {{ATCvet|P53|AX13}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 18723
| PubChem = 89594
| IUPHAR_ligand = 2585
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00184
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 80863
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6M3C89ZY6R
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03365
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 3
| PDB_ligand = NCT
<!--Chemical data-->| C = 10
| H = 14
| N = 2
| chirality = [[Chiral]]
| smiles = c1ncccc1[C@@H]2CCCN2C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H14N2/c1-12-7-3-5-10(12)9-4-2-6-11-8-9/h2,4,6,8,10H,3,5,7H2,1H3/t10-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = SNICXCGAKADSCV-JTQLQIEISA-N
| density = 1.01
| melting_point = -79
| boiling_point = 247
}}
{{tobacco}}
'''Nicotine''' is a [[natural product|naturally produced]] [[alkaloid]] in the [[nightshade]] family of plants (most predominantly in [[tobacco]] and ''[[Duboisia hopwoodii]]'')<ref name="FagerströmReview">{{cite journal | vauthors = Fagerström K |title=Nicotine: Pharmacology, Toxicity and Therapeutic use |journal=Journal of Smoking Cessation |date=December 2014 |volume=9 |issue=2 |pages=53–59 |doi=10.1017/jsc.2014.27 |doi-access=free }}</ref> and is widely used [[recreational drug use|recreationally]] as a [[stimulant]] and [[anxiolytic]]. As a [[pharmaceutical drug]], it is used for [[smoking cessation]] to relieve [[drug withdrawal|withdrawal symptoms]].<ref name=SajjaRahman2016>{{cite journal | vauthors = Sajja RK, Rahman S, Cucullo L | title = Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 36 | issue = 3 | pages = 539–554 | date = March 2016 | pmid = 26661236 | pmc = 4794105 | doi = 10.1177/0271678X15616978 }}</ref><ref name="PubChem Nicotine" /><ref name="IUPHAR nicotine clinical data">{{cite web |title=Nicotine: Clinical data |url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=clinical&ligandId=2585 |website=IUPHAR/BPS Guide to Pharmacology |publisher=International Union of Basic and Clinical Pharmacology |quote=Used as an aid to smoking cessation and for the relief of nicotine withdrawal symptoms.}}</ref><ref name=Abou-Donia2015>{{cite book |vauthors = Abou-Donia M |title=Mammalian Toxicology |url=https://books.google.com/books?id=3mGRBgAAQBAJ&pg=PA587 |date=5 February 2015 |publisher=John Wiley & Sons |isbn=978-1-118-68285-2 |pages=587–}}</ref> Nicotine acts as a [[receptor agonist]] at most [[nicotinic acetylcholine receptor]]s (nAChRs),<ref name=IUPHAR/><ref name=MalenkaNicotine/><ref name="Kishioka_2014">{{cite journal | vauthors = Kishioka S, Kiguchi N, Kobayashi Y, Saika F | title = Nicotine effects and the endogenous opioid system | journal = Journal of Pharmacological Sciences | volume = 125 | issue = 2 | pages = 117–124 | date = 2014 | pmid = 24882143 | doi = 10.1254/jphs.14R03CP | doi-access = free }}</ref> except at two [[nicotinic receptor subunits]] ([[nAChRα9]] and [[nAChRα10]]) where it acts as a [[receptor antagonist]].<ref name=IUPHAR/>

Nicotine constitutes approximately 0.6–3.0% of the dry weight of tobacco.<ref>{{cite web|url=http://dccps.nci.nih.gov/tcrb/monographs/9/m9_3.PDF |archive-url=https://ghostarchive.org/archive/20221009/http://dccps.nci.nih.gov/tcrb/monographs/9/m9_3.PDF |archive-date=2022-10-09 |url-status=live |title=Smoking and Tobacco Control Monograph No.&nbsp;9 |access-date=19 December 2012}}</ref> Nicotine is also present at [[Parts-per notation|ppb]] concentrations in edible plants in the family [[Solanaceae]], including [[potato]]es, [[tomato]]es, and [[eggplant]]s,<ref name=SiegmundLeitner1999/> though sources disagree on whether this has any biological significance to human consumers.<ref name=SiegmundLeitner1999/> It functions as an [[plant defense against herbivory|antiherbivore toxin]]; consequently, nicotine was widely used as an [[insecticide]] in the past,<ref>{{cite book |vauthors = Rodgman A, Perfetti TA |title=The chemical components of tobacco and tobacco smoke |place=Boca Raton, FL |publisher=CRC Press |year=2009 |lccn=2008018913 |isbn=978-1-4200-7883-1}}{{page needed|date=December 2013}}</ref><ref name=Ujvary>{{cite book |vauthors = Ujváry I |contribution=Nicotine and Other Insecticidal Alkaloids |veditors = Yamamoto I, Casida J |title=Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor |pages=29–69 |publisher=Springer-Verlag |location=Tokyo |year=1999}}</ref> and [[neonicotinoid]]s (structurally similar to nicotine), such as [[imidacloprid]], are some of the most effective and widely used insecticides.

Nicotine is highly [[addictive]].<ref name="pmid23494236">{{cite journal |vauthors=Perkins KA, Karelitz JL |title=Reinforcement enhancing effects of nicotine via smoking |journal=[[Psychopharmacology]] |volume=228 |issue=3 |pages=479–486 |date=August 2013 |pmid=23494236 |pmc=3707934 |doi=10.1007/s00213-013-3054-4 |url= |issn=}}</ref><ref name=Grana2014/><ref name=Siqueira2016/> Slow-release forms (gums and patches, when used correctly) can be less addictive and help in quitting.<ref name="pmid17640334">{{cite journal |vauthors=Etter JF |title=Addiction to the nicotine gum in never smokers |journal=[[BMC Public Health]] |volume=7 |issue= |page=159 |date=July 2007 |pmid=17640334 |pmc=1939993 |doi=10.1186/1471-2458-7-159 |url= |issn= |doi-access=free }}</ref><ref>{{cite journal | vauthors = Olausson P, Jentsch JD, Taylor JR | title = Nicotine enhances responding with conditioned reinforcement | journal = Psychopharmacology | volume = 171 | issue = 2 | pages = 173–178 | date = January 2004 | pmid = 13680077 | doi = 10.1007/s00213-003-1575-y | s2cid = 11855403 }}</ref><ref name="assets.publishing.service.gov.uk">{{cite web | work = Public Health England. | title = Evidence Review of E-Cigarettes and Heated Tobacco Products | date = 2018 | url = https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/684963/Evidence_review_of_e-cigarettes_and_heated_tobacco_products_2018.pdf }}</ref><ref>{{cite web|url=http://www.healthnz.co.nz/Addiction_TobNic.htm|title = Tobacco more addictive than Nicotine|archive-url=https://web.archive.org/web/20230420062215/http://www.healthnz.co.nz/Addiction_TobNic.htm|archive-date=2023-04-20}}</ref> Animal research suggests that [[monoamine oxidase inhibitors]] present in tobacco smoke may enhance nicotine's addictive properties.<ref name="RCP" /><ref name="SmithMAO">{{cite journal | vauthors = Smith TT, Rupprecht LE, Cwalina SN, Onimus MJ, Murphy SE, Donny EC, Sved AF | title = Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine | journal = Neuropsychopharmacology | volume = 41 | issue = 9 | pages = 2335–2343 | date = August 2016 | pmid = 26955970 | pmc = 4946064 | doi = 10.1038/npp.2016.36 }}</ref> An average [[cigarette]] yields about 2&nbsp;mg of absorbed nicotine.<ref name=MayerNewLethalDose2013/>
The estimated lower dose limit for fatal outcomes is 500–1,000&nbsp;mg of ingested nicotine for an adult (6.5–13&nbsp;mg/kg).<ref name="RCP">{{cite web |author1=Royal College of Physicians |title=Nicotine without smoke: Tobacco harm reduction |work=RCP London |url=https://www.rcplondon.ac.uk/projects/outputs/nicotine-without-smoke-tobacco-harm-reduction |access-date=16 September 2020 |date=28 April 2016}}</ref><ref name=MayerNewLethalDose2013/> Nicotine addiction involves drug-reinforced behavior, compulsive use, and relapse following abstinence.<ref name="Caponnetto2012">{{cite journal | vauthors = Caponnetto P, Campagna D, Papale G, Russo C, Polosa R | title = The emerging phenomenon of electronic cigarettes | journal = Expert Review of Respiratory Medicine | volume = 6 | issue = 1 | pages = 63–74 | date = February 2012 | pmid = 22283580 | doi = 10.1586/ers.11.92 | s2cid = 207223131 }}</ref> Nicotine [[drug dependence|dependence]] involves [[Drug tolerance|tolerance]], [[Reverse tolerance|sensitization]],<ref name=JainMukherjee2008>{{cite journal | vauthors = Jain R, Mukherjee K, Balhara YP | title = The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review | journal = Yonsei Medical Journal | volume = 49 | issue = 2 | pages = 175–188 | date = April 2008 | pmid = 18452252 | pmc = 2615322 | doi = 10.3349/ymj.2008.49.2.175 }}</ref> [[physical dependence]], and [[psychological dependence]],<ref>{{cite journal | vauthors = Miyasato K | title = [Psychiatric and psychological features of nicotine dependence] | journal = Nihon Rinsho. Japanese Journal of Clinical Medicine | volume = 71 | issue = 3 | pages = 477–481 | date = March 2013 | pmid = 23631239 }}</ref> which can cause distress.<ref name=Parrott2015/><ref name=psych_addiction>{{cite journal | vauthors = Parrott AC | title = Nicotine psychobiology: how chronic-dose prospective studies can illuminate some of the theoretical issues from acute-dose research | journal = Psychopharmacology | volume = 184 | issue = 3–4 | pages = 567–576 | date = March 2006 | pmid = 16463194 | doi = 10.1007/s00213-005-0294-y | s2cid = 11356233 | url = http://psy.swansea.ac.uk/staff/parrott/Parrott2006NicotineReviewArticleInPsychopharmacology.pdf }}</ref> [[Nicotine withdrawal]] symptoms include [[Depression (mood)|depression]], stress, anxiety, [[irritability]], difficulty concentrating, and sleep disturbances.<ref name=Dependence-withdrawal/> Mild nicotine withdrawal symptoms are measurable in unrestricted smokers, who experience normal moods only as their blood nicotine levels peak, with each cigarette.<ref name=Parrott2003/> On quitting, withdrawal symptoms worsen sharply, then gradually improve to a normal state.<ref name=Parrott2003/>

Nicotine use as a tool for [[quitting smoking]] has a good safety history.<ref name="Schraufnage2014">{{cite journal |vauthors=Schraufnagel DE, Blasi F, Drummond MB, Lam DC, Latif E, Rosen MJ, Sansores R, Van Zyl-Smit R |date=September 2014 |title=Electronic cigarettes. A position statement of the forum of international respiratory societies |journal=American Journal of Respiratory and Critical Care Medicine |volume=190 |issue=6 |pages=611–618 |doi=10.1164/rccm.201407-1198PP |pmid=25006874 |s2cid=43763340|url=https://figshare.com/articles/journal_contribution/10758143 }}</ref> Animal studies suggest that nicotine may adversely affect cognitive development in adolescence, but the relevance of these findings to human brain development is disputed.<ref name="2016 SGR">{{cite web |title=E-Cigarette Use Among Youth and Young Adults. 2016 Surgeon General's report.lts |url=https://e-cigarettes.surgeongeneral.gov/documents/2016_SGR_Full_Report_508.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://e-cigarettes.surgeongeneral.gov/documents/2016_SGR_Full_Report_508.pdf |archive-date=2022-10-09 |url-status=live |website=surgeongeneral.gov}}</ref><ref name="RCP" /> At low amounts, it has a mild [[analgesic]] effect.<ref name=Schraufnagel2015>{{cite journal | vauthors = Schraufnagel DE | title = Electronic Cigarettes: Vulnerability of Youth | journal = Pediatric Allergy, Immunology, and Pulmonology | volume = 28 | issue = 1 | pages = 2–6 | date = March 2015 | pmid = 25830075 | pmc = 4359356 | doi = 10.1089/ped.2015.0490 }}</ref> According to the [[International Agency for Research on Cancer]], "nicotine is not generally considered to be a carcinogen".<ref>[[International Agency for Research on Cancer|IARC]] Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal Habits and Indoor Combustions. Lyon (FR): International Agency for Research on Cancer; 2012. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No.&nbsp;100E.) [https://www.ncbi.nlm.nih.gov/books/NBK304395/ TOBACCO SMOKING].</ref><ref name=IARCCancerStatement/>
The [[Surgeon General of the United States]] indicates that evidence is inadequate to infer the presence or absence of a causal relationship between exposure to nicotine and risk for cancer.<ref name=SGUS2014/> Nicotine has been shown to produce birth defects in humans and is considered a [[teratogen]].<ref name=Kohlmeier2015>{{cite journal | vauthors = Kohlmeier KA | title = Nicotine during pregnancy: changes induced in neurotransmission, which could heighten proclivity to addict and induce maladaptive control of attention | journal = Journal of Developmental Origins of Health and Disease | volume = 6 | issue = 3 | pages = 169–181 | date = June 2015 | pmid = 25385318 | doi = 10.1017/S2040174414000531 | s2cid = 29298949 }}</ref><ref name="TOXNET Nicotine entry">{{cite web | title=Nicotine | url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@DOCNO+1107 | work=United States National Library of Medicine&nbsp;– Toxicology Data Network | publisher=Hazardous Substances Data Bank |date=20 August 2009}}</ref> The [[median lethal dose]] of nicotine in humans is unknown.<ref name="ECHA nicotine monograph"/> High doses are known to cause [[nicotine poisoning]], organ failure, and death through paralysis of respiratory muscles,<ref name=SGUS2014/><ref name="Effah2022">{{cite journal | vauthors = Effah F, Taiwo B, Baines D, Bailey A, Marczylo T | title = Pulmonary effects of e-liquid flavors: a systematic review | journal = Journal of Toxicology and Environmental Health Part B: Critical Reviews | volume = 25 | issue = 7 | pages = 343–371 | date = October 2022 | pmid = 36154615 | pmc = 9590402 | doi = 10.1080/10937404.2022.2124563 | bibcode = 2022JTEHB..25..343E }}</ref> though serious or fatal overdoses are rare.<ref name="Lavoie">{{cite journal | vauthors = Lavoie FW, Harris TM | title = Fatal nicotine ingestion | journal = The Journal of Emergency Medicine | volume = 9 | issue = 3 | pages = 133–136 | year = 1991 | pmid = 2050970 | doi = 10.1016/0736-4679(91)90318-a }}</ref>

{{TOC limit|3}}