{{Short description|Chronic disease}} {{Infobox medical condition (new) | name = Nicotine dependence | synonyms = Nicotine addiction; tobacco dependence; tobacco use disorder; cigarette dependence | image = Tobacco dependence 1.webm | alt = Video with visual medical explanation of nicotine dependence and its health effects | caption = Video of medical explanation of nicotine dependence and its health effects | pronounce = | field = | symptoms = | complications = [[Health effects of tobacco]] | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = 10-year shorter lifespan{{#tag:ref|Current smokers are estimated to die an average of 10 years earlier than non-smokers.<ref name="premature death"/>|group=notes}} | prevalence = 1.2 billion tobacco users globally (2022)<ref name="WHOreport2024"/> | deaths = 8 million per year (2023)<ref name=":0" /> }} '''Nicotine dependence'''{{#tag:ref|'''Nicotine dependence'''<ref name="D'Souza2011"/> is also variously known as '''cigarette dependence''',{{sfn|Stratton|2018|p=Dependence and Abuse Liability, 256}} '''tobacco dependence''',<ref name=PiperMcCarthy2006/> or '''tobacco use disorder'''.<ref name=AkermanBrunette2015/>|group=notes}} is a state of [[substance dependence]] on [[nicotine]].<ref name="D'Souza2011"/> It is a [[Chronic condition|chronic]], relapsing disease characterized by a [[Compulsive behavior|compulsive]] craving to use the drug despite social consequences, loss of control over drug intake, and the emergence of [[withdrawal symptoms]].<ref name="FalconeLee2015">{{cite book|last1=Falcone|first1=Mary|title=Translational Neuropsychopharmacology|last2=Lee|first2=Bridgin|last3=Lerman|first3=Caryn|last4=Blendy|first4=Julie A.|year=2015|isbn=978-3-319-33911-5|series=Current Topics in Behavioral Neurosciences|volume=28|pages=121–150|chapter=Translational Research on Nicotine Dependence|doi=10.1007/7854_2015_5005|issn=1866-3370|pmc=3579204|pmid=26873019}}</ref> [[Drug tolerance|Tolerance]] is another component of drug dependence.<ref name=SG1988/> Nicotine dependence develops over time as an individual continues to use nicotine.<ref name=SG1988/> While [[Cigarette|cigarettes]] are the most commonly used [[tobacco product]], all forms of tobacco use—including [[smokeless tobacco]] and [[e-cigarette]] use—can cause dependence.<ref name=":0">{{Cite web |date=2024-07-31 |title=Tobacco |url=https://www.who.int/news-room/fact-sheets/detail/tobacco |access-date=2024-10-04 |website=www.who.int |language=en}}</ref><ref>{{Cite journal |last1=Jankowski |first1=Mateusz |last2=Krzystanek |first2=Marek |last3=Zejda |first3=Jan Eugeniusz |last4=Majek |first4=Paulina |last5=Lubanski |first5=Jakub |last6=Lawson |first6=Joshua Allan |last7=Brozek |first7=Grzegorz |date=2019-06-27 |title=E-Cigarettes are More Addictive than Traditional Cigarettes-A Study in Highly Educated Young People |journal=International Journal of Environmental Research and Public Health |volume=16 |issue=13 |page=2279 |doi=10.3390/ijerph16132279 |issn=1660-4601 |pmc=6651627 |pmid=31252671 |doi-access=free}}</ref> Nicotine dependence is a serious [[public health]] problem because it leads to continued tobacco use and the [[Health effects of tobacco|associated negative health effects]]. Tobacco use is one of the leading [[preventable causes of death]] worldwide, causing more than 8 million deaths per year and killing half of its users who do not quit.<ref name=":0" /><ref>{{Cite journal |last1=Doll |first1=Richard |last2=Peto |first2=Richard |last3=Boreham |first3=Jillian |last4=Sutherland |first4=Isabelle |date=2004-06-22 |title=Mortality in relation to smoking: 50 years' observations on male British doctors |journal=BMJ |volume=328 |issue=7455 |page=1519 |doi=10.1136/bmj.38142.554479.ae |pmid=15213107 |issn=0959-8138|pmc=437139 }}</ref> Current smokers are estimated to die an average of 10 years earlier than non-smokers.<ref name="premature death">{{Cite journal |last1=Banks |first1=Emily |last2=Joshy |first2=Grace |last3=Weber |first3=Marianne F |last4=Liu |first4=Bette |last5=Grenfell |first5=Robert |last6=Egger |first6=Sam |last7=Paige |first7=Ellie |last8=Lopez |first8=Alan D |last9=Sitas |first9=Freddy |last10=Beral |first10=Valerie |date=2015-02-24 |title=Tobacco smoking and all-cause mortality in a large Australian cohort study: findings from a mature epidemic with current low smoking prevalence |journal=BMC Medicine |volume=13 |issue=1 |page=38 |doi=10.1186/s12916-015-0281-z |doi-access=free |pmid=25857449 |issn=1741-7015|pmc=4339244 }}</ref>
According to the [[World Health Organization]], "Greater nicotine dependence has been shown to be associated with lower motivation to quit, difficulty in trying to quit, and failure to quit, as well as with smoking the first cigarette earlier in the day and smoking more cigarettes per day."<ref>{{Cite web|title=WHO {{!}} Gender, women, and the tobacco epidemic|url=https://www.who.int/tobacco/publications/gender/women_tob_epidemic/en/|archive-url=https://web.archive.org/web/20140604233633/http://www.who.int/tobacco/publications/gender/women_tob_epidemic/en/|archive-date=June 4, 2014|access-date=2021-04-17|website=WHO}}</ref> The WHO estimates that there were 1.24 billion tobacco users globally {{As of|2022|alt=in 2022}}, with the number projected to decline to 1.20 billion in 2025.<ref name="WHOreport2024">{{Cite book |last=World Health Organization |author-link=World Health Organization |date=2024-01-16 |title=WHO global report on trends in prevalence of tobacco use 2000–2030 |url=https://iris.who.int/bitstream/handle/10665/375711/9789240088283-eng.pdf?sequence=1 |access-date=2024-10-04 |page=19 |publisher=World Health Organization |format=PDF |isbn=978-92-4-008828-3}}</ref> Of the 34 million smokers in the United States in 2018, 74.6% smoked every day, indicating the potential for some level of nicotine dependence.<ref>{{Cite journal|last=Creamer|first=MeLisa R.|date=2019|title=Tobacco Product Use and Cessation Indicators Among Adults — United States, 2018|journal=MMWR. Morbidity and Mortality Weekly Report|language=en-us|volume=68|issue=45|pages=1013–1019|doi=10.15585/mmwr.mm6845a2|pmid=31725711|pmc=6855510|issn=0149-2195|doi-access=free}}</ref> There is an increased incidence of nicotine dependence in individuals with [[psychiatric disorders]], such as [[anxiety disorders]] and [[substance use disorders]].<ref name="MoylanJacka2012" /><ref>{{Cite journal |last1=Airagnes |first1=Guillaume |last2=Sánchez-Rico |first2=Marina |last3=Deguilhem |first3=Amélia |last4=Blanco |first4=Carlos |last5=Olfson |first5=Mark |last6=Ouazana Vedrines |first6=Charles |last7=Lemogne |first7=Cédric |last8=Limosin |first8=Frédéric |last9=Hoertel |first9=Nicolas |date=2024-09-11 |title=Nicotine dependence and incident psychiatric disorders: prospective evidence from US national study |url=https://www.nature.com/articles/s41380-024-02748-6 |journal=Molecular Psychiatry |volume=30 |issue=3 |language=en |pages=1080–1088 |doi=10.1038/s41380-024-02748-6 |pmid=39261672 |issn=1476-5578|url-access=subscription }}</ref>
Various methods exist for measuring nicotine dependence.<ref name="PiperMcCarthy2006" /> Common assessment scales for cigarette smokers include the [[Fagerström Test for Nicotine Dependence]], the ''[[Diagnostic and Statistical Manual of Mental Disorders]]'' criteria, the Cigarette Dependence Scale, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives.<ref name="PiperMcCarthy2006" />
[[Nicotine]] is a [[parasympathomimetic]] [[stimulant]]<ref name=BeebeMyers2012/> that binds to [[Nicotinic acetylcholine receptor|nicotinic acetylcholine receptors]] in the brain.<ref name=Bullen2014/> [[Neuroplasticity]] within the brain's [[reward system]], including an increase in the number of nicotine receptors, occurs as a result of long-term nicotine use and leads to nicotine dependence.<ref name="D'Souza2011"/> In contrast, the effect of nicotine on human brain structure (e.g., [[gray matter]] and [[white matter]]) is less clear.<ref name=Hamp2019>{{cite journal | vauthors = Hampton WH, Hanik I, Olson IR | title = [Substance Abuse and White Matter: Findings, Limitations, and Future of Diffusion Tensor Imaging Research] | language = en | journal = Drug and Alcohol Dependence | volume = 197 | issue = 4 | pages = 288–298 | year = 2019 | pmid = 30875650 | pmc = 6440853 | doi = 10.1016/j.drugalcdep.2019.02.005 | quote = Heavy nicotine use in the form of smoking tobacco has been linked to neuropathy (Brody, 2006), often manifesting as prefrontal gray matter atrophy (Gallinat et al., 2006; Zhang et al., 2011). Conversely, consumption of nicotine via smoking has been associated with higher white matter volume (Gazdzinski et al., 2005; Yu et al., 2011). Studies examining nicotine use via DTI have found similarly conflicting results. In chronic nicotine users, heavy consumption has been associated with lower FA (Lin et al., 2013) and higher FA (Paul et al., 2008), as well has both lower RD (Wang et al., 2017) and higher RD (Lin et al., 2013). The results of studies examining non-chronic, regular nicotine use are similarly split. Regular nicotine use has been associated with lower FA (Huang et al., 2013; Liao et al., 2011; Zhang et al., 2011) and higher FA (Hudkins et al., 2012; Wang et al., 2017). These seemingly conflicting nicotine results may be partly accounted for by the developmental stage in which it is consumed, with higher FA more commonly observed in younger nicotine users (Hudkins et al., 2012; Jacobsen et al., 2007). Alternatively, it maybe that the association between nicotine use and higher FA in adolescents is temporary, eventually leading to microstructural declines with chronic use. Future longitudinal studies could formally address this theory.}}</ref> Genetic risk factors contribute to the development of dependence.<ref name=Saccone2010/> For instance, [[Genetic marker|genetic markers]] for specific types of nicotinic receptors (the α5–α3–β4 nicotinic receptors) have been linked to an increased risk of dependence.<ref name=Saccone2010/> Evidence-based treatments—including medications such as [[nicotine replacement therapy]], [[bupropion]], [[varenicline]], or [[cytisine]], and [[Behaviour therapy|behavioral counseling]]—can double or triple a smoker's chances of successfully [[Quitting smoking|quitting]].<ref name=Fiore2008/>
== Definition == [[File:Anyone Can Become Addicted to Drugs.webm|right|thumb|A [[National Institute on Drug Abuse]] video entitled ''Anyone Can Become Addicted to Drugs''.<ref>{{cite web|url=https://www.drugabuse.gov/related-topics/addiction-science|title=Anyone Can Become Addicted to Drugs|publisher=[[National Institute on Drug Abuse]]|date=July 2015}}</ref>|alt=A National Institute on Drug Abuse video explaining that anyone can become addicted to drugs.]]
Nicotine dependence is defined as a neurobiological adaptation to repeated drug exposure that is manifested by highly controlled or compulsive use, the development of tolerance, experiencing withdrawal symptoms upon cessation including cravings, and an inability to quit despite harmful effects.<ref name="SG1988" /> Nicotine dependence has also been conceptualized as a chronic, relapsing disease.<ref name="Fiore2008" /> A 1988 [[Surgeon General of the United States|Surgeon General]] report states, "Tolerance" is another aspect of drug addiction [dependence] whereby a given dose of a drug produces less effect or increasing doses are required to achieve a specified intensity of response. Physical dependence on the drug can also occur, and is characterized by a withdrawal syndrome that usually accompanies drug abstinence. After cessation of drug use, there is a strong tendency to relapse."<ref name=SG1988>{{cite book|last1=U.S. Department of Health and Human Services|title=The health consequences of smoking: Nicotine addiction: A report of the Surgeon General|date=1988|publisher=U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Health Promotion and Education, Office on Smoking and Health. DHHS Publication No. (CDC) 88-8406|url=https://profiles.nlm.nih.gov/ps/access/NNBBZD.pdf|archive-url=https://web.archive.org/web/20110611114241/http://profiles.nlm.nih.gov/ps/access/NNBBZD.pdf|archive-date=June 11, 2011}}</ref>
Nicotine dependence leads to heavy smoking and causes severe [[withdrawal symptom]]s and relapse back to smoking.<ref name=SG1988/> Nicotine dependence develops over time as a person continues to use [[nicotine]].<ref name=SG1988/> Teenagers do not have to be daily or long-term smokers to show [[nicotine withdrawal|withdrawal symptoms]].<ref name=CamengaKlein2016>{{cite journal|last1=Camenga|first1=Deepa R.|last2=Klein|first2=Jonathan D.|title=Tobacco Use Disorders|journal=Child and Adolescent Psychiatric Clinics of North America|volume=25|issue=3|year=2016|pages=445–460|issn=1056-4993|doi=10.1016/j.chc.2016.02.003|pmc=4920978|pmid=27338966}}</ref> Relapse should not frustrate the nicotine user from trying to quit again.<ref name=Fiore2008>{{cite book|last1=Fiore|first1=MC|last2=Jaen|first2=CR|last3=Baker|first3=TB|display-authors=etal|title=Treating tobacco use and dependence: 2008 update|date=2008|publisher=U.S. Department of Health and Human Services, U.S. Public Health Service|location=Rockville, MD|url=http://bphc.hrsa.gov/buckets/treatingtobacco.pdf|access-date=2016-09-02|archive-url=https://web.archive.org/web/20160327225607/http://bphc.hrsa.gov/buckets/treatingtobacco.pdf|archive-date=2016-03-27}}</ref> A 2015 review found "Avoiding withdrawal symptoms is one of the causes of continued smoking or relapses during attempts at cessation, and the severity and duration of nicotine withdrawal symptoms predict relapse."<ref name=PistilloClementi2015>{{cite journal|last1=Pistillo|first1=Francesco|last2=Clementi|first2=Francesco|last3=Zoli|first3=Michele|last4=Gotti|first4=Cecilia|title=Nicotinic, glutamatergic and dopaminergic synaptic transmission and plasticity in the mesocorticolimbic system: Focus on nicotine effects|journal=Progress in Neurobiology|volume=124|year=2015|pages=1–27|issn=0301-0082|doi=10.1016/j.pneurobio.2014.10.002|pmid=25447802|s2cid=207407218}}</ref> Symptoms of nicotine dependence include irritability, anger, impatience, and problems in concentrating.<ref name=Shaik2016>{{cite journal|last1=Shaik|first1=Sabiha Shaheen|title=Tobacco Use Cessation and Prevention – A Review|journal=Journal of Clinical and Diagnostic Research|volume=10|issue=5|pages=ZE13-7|year=2016|issn=2249-782X|doi=10.7860/JCDR/2016/19321.7803|pmc=4948554|pmid=27437378}}</ref>
== Diagnosis == There are different ways of measuring nicotine dependence.<ref name=PiperMcCarthy2006/> The five common [[substance dependence|dependence]] assessment scales are the [[Fagerström Test for Nicotine Dependence]], the ''[[Diagnostic and Statistical Manual of Mental Disorders]]'', the Cigarette Dependence Scale, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives.<ref name=PiperMcCarthy2006/>
The Fagerström Test for Nicotine Dependence focuses on measuring physical dependence which is defined "as a state produced by chronic drug administration, which is revealed by the occurrence of signs of physiological dysfunction when the drug is withdrawn; further, this dysfunction can be reversed by the administration of drug".<ref name=PiperMcCarthy2006>{{cite journal|last1=Piper|first1=Megan|last2=McCarthy|first2=Danielle|last3=Baker|first3=Timothy|title=Assessing tobacco dependence: A guide to measure evaluation and selection|journal=Nicotine & Tobacco Research|volume=8|issue=3|year=2006|pages=339–351|issn=1462-2203|doi=10.1080/14622200600672765|pmid=16801292|s2cid=22437505}}</ref> The long use of Fagerström Test for Nicotine Dependence is supported by the existence of significant preexisting research, and its conciseness.<ref name=PiperMcCarthy2006/>
The 4th edition of the [[American Psychiatric Association]] [[Diagnostic and Statistical Manual of Mental Disorders#DSM-IV (1994)|Diagnostic and Statistical Manual of Mental Disorder (DSM-IV)]] had a nicotine dependence diagnosis which was defined as "...a cluster of cognitive, behavioral, and physiological symptoms..."<ref name=PiperMcCarthy2006/> In the updated ''[[DSM-5]]'' there is no nicotine dependence diagnosis, but rather Tobacco Use Disorder, which is defined as, "A problematic pattern of tobacco use leading to clinically significant impairment or distress, as manifested by at least 2 of the following [11 symptoms], occurring within a 12-month period."<ref name=APA2013>{{cite book|author=American Psychiatric Association|title=Diagnostic and Statistical Manual of Mental Disorders (DSM-5®)|url=https://books.google.com/books?id=-JivBAAAQBAJ|date=22 May 2013|publisher=American Psychiatric Pub|isbn=978-0-89042-557-2|page=571}}</ref>
The Cigarette Dependence Scale was developed "to index dependence outcomes and not dependence mechanisms".<ref name=PiperMcCarthy2006/> The Nicotine Dependence Syndrome Scale, "a 19-item self-report measure, was developed as a multidimensional scale to assess nicotine dependence".<ref name=PiperMcCarthy2006/> The Wisconsin Inventory of Smoking Dependence Motives "is a 68-item measure developed to assess dependence as a motivational state".<ref name=PiperMcCarthy2006/>
== Mechanisms == Traditional cigarettes are the most common delivery device for nicotine.<ref>{{Cite web|title=Exploring The Prevalence Of Smoking In The UK {{!}} News {{!}} Vaping Guides {{!}} IndeJuice (UK)|url=https://indejuice.com/uk/vape-guides/news/exploring-the-prevalence-of-smoking-in-the-uk|access-date=2021-05-08|website=indejuice.com|language=en}}</ref> However, [[electronic cigarette]]s are becoming more popular.<ref name=Payne2016>{{cite journal|last1=Payne|first1=JD|last2=Orellana-Barrios|first2=M|last3=Medrano-Juarez|first3=R|last4=Buscemi|first4=D|last5=Nugent|first5=K|title=Electronic cigarettes in the media.|journal=Proc (Bayl Univ Med Cent).|volume=29|issue=3|pages=280–3|year=2016|pmc=4900769|pmid=27365871|doi=10.1080/08998280.2016.11929436}}</ref> Nicotine can also be delivered via other tobacco products such as chewing tobacco, snus, pipe tobacco, hookah, all of which can produce nicotine dependence.<ref>{{Cite web|last=Publishing|first=Harvard Health|title=Breaking free from nicotine dependence|url=https://www.health.harvard.edu/newsletter_article/breaking-free-from-nicotine-dependence|access-date=2021-05-08|website=Harvard Health}}</ref>
=== Biomolecular === [[File:Dopamine.svg|thumb|170 px|Dopamine]] Pre-existing cognitive and mood disorders may influence the development and maintenance of nicotine dependence.<ref name=BessonForget2016>{{cite journal|last1=Besson|first1=Morgane|last2=Forget|first2=Benoît|title=Cognitive Dysfunction, Affective States, and Vulnerability to Nicotine Addiction: A Multifactorial Perspective|journal=Frontiers in Psychiatry|volume=7|page=160|year=2016|issn=1664-0640|doi=10.3389/fpsyt.2016.00160|pmc=5030478|pmid=27708591|doi-access=free}}{{CC-notice|cc=by4|url=http://journal.frontiersin.org/article/10.3389/fpsyt.2016.00160/full|author(s)=Morgane Besson and Benoît Forget}}</ref> Nicotine is a [[parasympathomimetic]] [[stimulant]]<ref name=BeebeMyers2012>{{cite book|author1=Richard Beebe|author2=Jeff Myers|title=Professional Paramedic, Volume I: Foundations of Paramedic Care|url=https://books.google.com/books?id=bS8KAAAAQBAJ&pg=PA640|date=19 July 2012|publisher=Cengage Learning|isbn=978-1-133-71465-1|pages=640–}}</ref> that binds to and activates [[nicotinic acetylcholine receptor]]s in the brain,<ref name=Bullen2014/> which subsequently causes the release of [[dopamine]] and other [[neurotransmitter]]s, such as [[norepinephrine]], [[acetylcholine]], [[serotonin]], [[gamma-aminobutyric acid]], [[glutamate]], [[endorphin]]s,<ref name=BMJ2014>{{cite journal|title=Republished: Nicotine and health|journal=BMJ|volume=349|issue=nov26 9|year=2014|article-number=2014.7.0264rep|issn=1756-1833|doi=10.1136/bmj.2014.7.0264rep|pmid=25428425|s2cid=45426626|last1=Drug Therapeutics |first1=Bulletin }}</ref> and several [[neuropeptide]]s.<ref name=RahmanReitz2005>{{cite book|author1=Atta-ur- Rahman|author2=Allen B. Reitz|title=Frontiers in Medicinal Chemistry|url=https://books.google.com/books?id=tCyDoIHToBQC&pg=PA279|date=1 January 2005|publisher=Bentham Science Publishers|isbn=978-1-60805-205-9|pages=279–}}</ref> Repeated exposure to nicotine can cause an increase in the number of nicotinic receptors, which is believed to be a result of receptor [[Desensitization (medicine)|desensitization]] and subsequent receptor [[upregulation]].<ref name=BMJ2014/> This upregulation or increase in the number of nicotinic receptors significantly alters the functioning of the brain [[reward system]].<ref name=Martin-Soelch2013/> With constant use of nicotine, [[drug tolerance|tolerance]] occurs at least partially as a result of the development of new nicotinic acetylcholine receptors in the brain.<ref name=BMJ2014/> After several months of nicotine abstinence, the number of receptors go back to normal.<ref name=Bullen2014>{{cite journal|last1=Bullen|first1=Christopher|title=Electronic Cigarettes for Smoking Cessation|journal=Current Cardiology Reports|volume=16|page=538|issue=11|year=2014|issn=1523-3782|doi=10.1007/s11886-014-0538-8|pmid=25303892|s2cid=2550483|url=http://qmro.qmul.ac.uk/xmlui/handle/123456789/16169|url-access=subscription}}</ref> Nicotine also stimulates nicotinic acetylcholine receptors in the [[adrenal medulla]], resulting in increased levels of adrenaline and [[beta-endorphin]].<ref name=BMJ2014/> Nicotine alters neural responses of the [[amygdala]]. <ref>{{cite journal|last1=Mihov|first1=Yoan|last2=Hurlemann|first2=Rene|author2-link=Rene Hurlemann|location=[[University of Bonn]]|date=July 2012|url=https://eric.ed.gov/?id=EJ976154|title=Altered Amygdala Function in Nicotine Addiction: Insights from Human Neuroimaging Studies|journal=[[Neuropsychologia]]|volume=50|issue=8|publisher=[[Education Resources Information Center]], [[Institute of Education Sciences]] - [[United States Department of Education]]|DOI= 10.1016/j.neuropsychologia.2012.04.028|PMID=22575084}}</ref> Its physiological effects stem from the stimulation of nicotinic acetylcholine receptors, which are located throughout the [[central nervous system|central]] and [[peripheral nervous system]]s.<ref name=SGUS2014>{{cite book |url=https://stacks.cdc.gov/view/cdc/21569/Share|title=The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General |chapter=Nicotine |year=2014|pages=107–138|publisher=[[Surgeon General of the United States]]|pmid=24455788 |author=Lushniak, Boris D. |author2=Samet, Jonathan M. |author3=Pechacek, Terry F. |author4=Norman, Leslie A. |author5=Taylor, Peter A.}}</ref> Chronic nicotinic acetylcholine receptor activation from repeated nicotine exposure can induce strong effects on the brain, including changes in the brain's physiology, that result from the stimulation of regions of the brain associated with reward, pleasure, and anxiety.<ref name=Rowell2015>{{cite journal|last1=Rowell|first1=Temperance R|last2=Tarran|first2=Robert|title=Will Chronic E-Cigarette Use Cause Lung Disease?|journal=American Journal of Physiology. Lung Cellular and Molecular Physiology|volume=309|issue=12|year=2015|pages=L1398–L1409|issn=1040-0605|doi=10.1152/ajplung.00272.2015|pmid=26408554|pmc=4683316}}</ref> These complex effects of nicotine on the brain are still not well understood.<ref name=Rowell2015/>
When these receptors are not occupied by nicotine, they are believed to produce withdrawal symptoms.<ref name=Benowitz2010>{{cite journal|last1=Benowitz|first1=NL|title=Nicotine addiction.|journal=The New England Journal of Medicine|date=17 June 2010|volume=362|issue=24|pages=2295–303|doi=10.1056/NEJMra0809890|pmc=2928221|pmid=20554984}}</ref> These symptoms can include cravings for nicotine, anger, irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger, weight gain, and difficulty concentrating.<ref name=Martin2016>{{cite web|url=https://www.medlineplus.gov/ency/article/000953.htm|website=Medline Plus|title=Nicotine and Tobacco |date=7 June 2016}}</ref>
[[Neuroplasticity]] within the brain's reward system occurs as a result of long-term nicotine use, leading to nicotine dependence.<ref name="D'Souza2011">{{cite journal|vauthors=D'Souza MS, Markou A |title=Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments|journal=Addict Sci Clin Pract|volume=6|issue=1|pages=4–16|year=2011|pmc=3188825|pmid=22003417}}</ref> There are genetic risk factors for developing dependence.<ref name=Saccone2010/> For instance, genetic markers for a specific type of nicotinic receptor (the α5-α3-β4 nicotine receptors) have been linked to increased risk for dependence.<ref name=Saccone2010>{{cite journal|last1=Saccone|first1=NL|last2=Culverhouse|first2=RC|last3=Schwantes-An|first3=TH|last4=Cannon|first4=DS|last5=Chen|first5=X|last6=Cichon|first6=S|last7=Giegling|first7=I|last8=Han|first8=S|last9=Han|first9=Y|last10=Keskitalo-Vuokko|first10=K|last11=Kong|first11=X|last12=Landi|first12=MT|last13=Ma|first13=JZ|last14=Short|first14=SE|last15=Stephens|first15=SH|last16=Stevens|first16=VL|last17=Sun|first17=L|last18=Wang|first18=Y|last19=Wenzlaff|first19=AS|last20=Aggen|first20=SH|last21=Breslau|first21=N|last22=Broderick|first22=P|last23=Chatterjee|first23=N|last24=Chen|first24=J|last25=Heath|first25=AC|last26=Heliövaara|first26=M|last27=Hoft|first27=NR|last28=Hunter|first28=DJ|last29=Jensen|first29=MK|last30=Martin|first30=NG|last31=Montgomery|first31=GW|last32=Niu|first32=T|last33=Payne|first33=TJ|last34=Peltonen|first34=L|last35=Pergadia|first35=ML|last36=Rice|first36=JP|last37=Sherva|first37=R|last38=Spitz|first38=MR|last39=Sun|first39=J|last40=Wang|first40=JC|last41=Weiss|first41=RB|last42=Wheeler|first42=W|last43=Witt|first43=SH|last44=Yang|first44=BZ|last45=Caporaso|first45=NE|last46=Ehringer|first46=MA|last47=Eisen|first47=T|last48=Gapstur|first48=SM|last49=Gelernter|first49=J|last50=Houlston|first50=R|author-link50=Richard Houlston|last51=Kaprio|first51=J|last52=Kendler|first52=KS|last53=Kraft|first53=P|last54=Leppert|first54=MF|last55=Li|first55=MD|last56=Madden|first56=PA|last57=Nöthen|first57=MM|last58=Pillai|first58=S|last59=Rietschel|first59=M|last60=Rujescu|first60=D|last61=Schwartz|first61=A|last62=Amos|first62=CI|last63=Bierut|first63=LJ|title=Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.|journal=[[PLOS Genetics]]|date=5 August 2010|volume=6|issue=8|article-number=e1001053|doi=10.1371/journal.pgen.1001053|pmc=2916847|pmid=20700436 |doi-access=free }}{{open access}}</ref><ref>{{cite journal|last1=Ware|first1=JJ|last2=van den Bree|first2=MB|last3=Munafò|first3=MR|title=Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis.|journal=Nicotine & Tobacco Research|date=2011|volume=13|issue=12|pages=1167–75|doi=10.1093/ntr/ntr118|pmc=3223575|pmid=22071378}}</ref> The most well-known hereditary influence related to nicotine dependence is a mutation at rs16969968 in the nicotinic acetylcholine receptor ''[[CHRNA5]]'', resulting in an amino acid alteration from aspartic acid to asparagine.<ref name=YuMcClellan2016>{{cite journal|last1=Yu|first1=Cassie|last2=McClellan|first2=Jon|title=Genetics of Substance Use Disorders|journal=Child and Adolescent Psychiatric Clinics of North America|volume=25|issue=3|year=2016|pages=377–385|issn=1056-4993|doi=10.1016/j.chc.2016.02.002|pmid=27338962}}</ref> The [[single-nucleotide polymorphism]]s (SNPs) rs6474413 and rs10958726 in ''CHRNB3'' are highly correlated with nicotine dependence.<ref name=WenYang2016/> Many other known variants within the ''CHRNB3–CHRNA6'' nicotinic acetylcholine receptors are also correlated with nicotine dependence in certain ethnic groups.<ref name=WenYang2016>{{cite journal|last1=Wen|first1=L|last2=Yang|first2=Z|last3=Cui|first3=W|last4=Li|first4=M D|title=Crucial roles of the CHRNB3–CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research|journal=Translational Psychiatry|volume=6|issue=6|year=2016|pages=e843|issn=2158-3188|doi=10.1038/tp.2016.103|pmid=27327258|pmc=4931601}}</ref> There is a relationship between ''CHRNA5''-''CHRNA3''-''CHRNB4'' nicotinic acetylcholine receptors and complete smoking cessation.<ref name=ChenHorton2016/> Increasing evidence indicates that the genetic variant ''CHRNA5'' predicts the response to smoking cessation medicine.<ref name=ChenHorton2016>{{cite journal|last1=Chen|first1=Li-Shiun|last2=Horton|first2=Amy|last3=Bierut|first3=Laura|title=Pathways to precision medicine in smoking cessation treatments|journal=Neuroscience Letters|volume=669|pages=83–92|year=2018|issn=0304-3940|doi=10.1016/j.neulet.2016.05.033|pmid=27208830|pmc=5115988}}</ref>
=== Psychosocial === In addition to the specific neurological changes in nicotinic receptors, there are other changes that occur as dependence develops.{{Citation needed|date=October 2018}} Through various conditioning mechanisms ([[operant conditioning|operant]] and [[classical conditioning|cue/classical]]), smoking comes to be associated with different mood and cognitive states as well as external contexts and cues.<ref name=Martin-Soelch2013>{{cite journal|last1=Martin-Soelch|first1=Chantal|title=Neuroadaptive Changes Associated with Smoking: Structural and Functional Neural Changes in Nicotine Dependence|journal=Brain Sciences|volume=3|issue=1|year=2013|pages=159–176|issn=2076-3425|doi=10.3390/brainsci3010159|pmc=4061825|pmid=24961312|doi-access=free}}</ref>
== Treatment == There are treatments for nicotine dependence, although the majority of the evidence focuses on treatments for cigarette smokers rather than people who use other forms of tobacco (e.g., [[chewing tobacco|chew]], [[snus]], [[pipe tobacco|pipes]], [[hookah]], e-cigarettes).{{Citation needed|date=September 2016}} [[Evidence-based medicine]] can double or triple a smoker's chances of quitting successfully.<ref name=Fiore2008/> Mental health conditions, especially Major depressive disorder, may also impact the success of attempts to quit smoking.<ref>Kaprio, J., Kinnunen, T. H., Korhonen, T., Latvala, A., Ranjit, A., Depressive symptoms predict smoking cessation in a 20-year longitudinal study of adult twins, Addictive Behaviors, 2020 https://doi.org/10.1016/j.addbeh.2020.106427 </ref>
=== Medication === There are eight major evidence-based medications for treating nicotine dependence: [[bupropion]], [[cytisine]] (not approved for use in some countries, including the US), [[nicotine gum]], [[nicotine inhaler]], [[nicotine lozenge|nicotine lozenge/mini-lozenge]], [[nicotine nasal spray]], [[nicotine patch]], and [[varenicline]].<ref name=Hartmann-Boyce2013/> These medications have been shown to significantly improve long-term (i.e., 6-months post-quit day) abstinence rates, especially when used in combination with psychosocial treatment.<ref name=Fiore2008/> The [[nicotine replacement therapy|nicotine replacement treatments]] (i.e., patch, lozenge, gum) are dosed based on how dependent a smoker is—people who smoke more cigarettes or who smoke earlier in the morning use higher doses of nicotine replacement treatments.{{Citation needed|date=October 2018}} There is no consensus for remedies for tobacco use disorder among pregnant smokers who also use [[alcohol (drug)|alcohol]] and stimulants.<ref name=AkermanBrunette2015>{{cite journal|last1=Akerman|first1=Sarah C.|last2=Brunette|first2=Mary F.|last3=Green|first3=Alan I.|last4=Goodman|first4=Daisy J.|last5=Blunt|first5=Heather B.|last6=Heil|first6=Sarah H.|title=Treating Tobacco Use Disorder in Pregnant Women in Medication-Assisted Treatment for an Opioid Use Disorder: A Systematic Review|journal=Journal of Substance Abuse Treatment|volume=52|year=2015|pages=40–47|issn=0740-5472|doi=10.1016/j.jsat.2014.12.002|pmc=4382443|pmid=25592332}}</ref>
====Vaccine==== [[TA-NIC]] is a proprietary [[vaccine]] in development similar to [[TA-CD]] but being used to create human anti-nicotine [[antibody|antibodies]] in a person to destroy [[nicotine]] in the human body so that it is no longer effective.<ref>{{Cite web |url=http://www.celticpharma.com/theportfolio/ta-nic.html |title=CelticPharma: TA-NIC Nicotine Dependence. |access-date=2009-10-27 |archive-url=https://web.archive.org/web/20091206100218/http://www.celticpharma.com/theportfolio/ta-nic.html |archive-date=2009-12-06 }}</ref>
=== Psychosocial === Psychosocial interventions delivered in-person (individually or in a group) or over the phone (including mobile phone interventions) have been shown to effectively treat nicotine dependence.<ref name=Hartmann-Boyce2013>{{cite journal|last1=Hartmann-Boyce|first1=J|last2=Stead|first2=LF|last3=Cahill|first3=K|last4=Lancaster|first4=T|title=Efficacy of interventions to combat tobacco addiction: Cochrane update of 2012 reviews.|journal=Addiction|date=October 2013|volume=108|issue=10|pages=1711–21|pmid=23834141|doi=10.1111/add.12291}}</ref> These interventions focus on providing support for quitting and helping with smokers with problem-solving and developing healthy responses for coping with cravings, negative moods, and other situations that typically lead to relapse.{{Citation needed|date=October 2018}} The combination of pharmacotherapy and psychosocial interventions has been shown to be especially effective.<ref name=Fiore2008/>
=== Emerging Medical Treatment === A non-invasive, brain-based therapy called rTMS (repetitive transcranial magnetic stimulation) gained FDA approval in 2020 for treating nicotine addiction and aiding the quitting process.<ref>Jordan, T., Apostol, M. R., Nomi, J., & Petersen, N, Unraveling neural complexity: Exploring brain entropy to yield mechanistic insight in neuromodulation therapies for tobacco use disorder, Imaging Neuroscience, 2024, https://doi-org.libaccess.sjlibrary.org/10.1162/imag_a_00061</ref> Studies have found patients who undergo rTMS have reduced cigarette cravings and number of cigarettes smoked, as well as greater long term success with cessation.<ref>Barnea-Ygael, N., Bystritsky, T., Casuto, L., Deutsch, F., Duffy, W., Feifel, D., George, M. S., Iosifescu, D. V., Li, X., Lipkinsky Grosz, M., Martinez, D., Morales, O., Moshe, H., Nunes, E. V., Roth, Y., Stein, A., Toder, D., Tendler, A., Winston, J., Ward, H., Wirecki, T., Vapnik, A. Zangen, A., Repetitive transcranial magnetic stimulation for smoking cessation: A pivotal multicenter double‐blind randomized controlled trial, World Psychiatry, 2021, https://doi.org/10.1002/wps.20905</ref> While this therapy is relevantly new for treating nicotine additions, it has a longer history as a therapeutic treatment for Major depressive disorder, Obsessive-compulsive disorder, and migraines. Side effects of this therapy are relatively mild because of the noninvasive nature of the treatment.
== Epidemiology == First-time nicotine users develop a dependence about 32% of the time.<ref name=MacDonald2016>{{cite journal|last1=MacDonald|first1=K|last2=Pappa|first2=K|title=WHY NOT POT?: A Review of the Brain-based Risks of Cannabis|journal=Innov Clin Neurosci|volume=13|issue=3–4|date=April 2016|pages=13–22|pmid=27354924|pmc=4911936}}</ref> There are approximately 976 million smokers in the world.<ref name=Ng2014>{{cite journal|last1=Ng|first1=M|last2=Freeman|first2=MK|last3=Fleming|first3=TD|last4=Robinson|first4=M|last5=Dwyer-Lindgren|first5=L|last6=Thomson|first6=B|last7=Wollum|first7=A|last8=Sanman|first8=E|last9=Wulf|first9=S|last10=Lopez|first10=AD|last11=Murray|first11=CJ|last12=Gakidou|first12=E|title=Smoking prevalence and cigarette consumption in 187 countries, 1980-2012.|journal=JAMA|date=8 January 2014|volume=311|issue=2|pages=183–92|pmid=24399557|doi=10.1001/jama.2013.284692|doi-access=free}}</ref> Estimates are that half of smokers (and one-third of former smokers) are dependent based on DSM criteria, regardless of age, gender or country of origin, but this could be higher if different definitions of dependence were used.<ref name=Hughes06Prev>{{cite journal|last1=Hughes|first1=JR|last2=Helzer|first2=JE|last3=Lindberg|first3=SA|title=Prevalence of DSM/ICD-defined nicotine dependence.|journal=Drug and Alcohol Dependence|date=8 November 2006|volume=85|issue=2|pages=91–102|pmid=16704909|doi=10.1016/j.drugalcdep.2006.04.004}}</ref> Recent data suggest that, in the United States, the rates of daily smoking and the number of cigarettes smoked per day are declining, suggesting a reduction in population-wide dependence among current smokers.<ref name=MMWR14>{{cite journal|publisher=Centers for Disease Control and Prevention|title=Current Cigarette Smoking Among Adults — United States, 2005–2013|journal=Morbidity and Mortality Weekly Report|date=2014|issue=63|pages=1108–1112|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6347a4.htm}}</ref> However, there are different groups of people who are more likely to smoke than the average population, such as those with low education or low socio-economic status and those with mental illness.<ref name=MMWR14/> There is also evidence that among smokers, some subgroups may be more dependent than other groups.{{Citation needed|date=October 2018}} Men smoke at higher rates than do women and score higher on dependence indices; however, women may be less likely to be successful in [[smoking cessation|quitting]], suggesting that women may be more dependent by that criterion.<ref name=MMWR14/><ref>{{cite journal|last1=Weinberger|first1=AH|last2=Pilver|first2=CE|last3=Mazure|first3=CM|last4=McKee|first4=SA|title=Stability of smoking status in the US population: a longitudinal investigation.|journal=Addiction|date=September 2014|volume=109|issue=9|pages=1541–53|pmc=4127136|pmid=24916157|doi=10.1111/add.12647}}</ref> There is an increased frequency of nicotine dependence in people with anxiety disorders.<ref name="MoylanJacka2012">{{cite journal |last1=Moylan |first1=Steven |last2=Jacka |first2=Felice N |author-link2=Felice Jacka |last3=Pasco |first3=Julie A |last4=Berk |first4=Michael |year=2012 |title=Cigarette smoking, nicotine dependence and anxiety disorders: a systematic review of population-based, epidemiological studies |journal=BMC Medicine |volume=10 |issue=1 |page=123 |doi=10.1186/1741-7015-10-123 |issn=1741-7015 |pmc=3523047 |pmid=23083451 |doi-access=free}}</ref> 6% of smokers who want to quit smoking each year are successful at quitting.<ref name=Rachid2016>{{cite journal|last1=Rachid|first1=Fady|title=Neurostimulation techniques in the treatment of nicotine dependence: A review|journal=The American Journal on Addictions|volume=25|issue=6|year=2016|pages=436–451|issn=1055-0496|doi=10.1111/ajad.12405|pmid=27442267}}</ref> Nicotine withdrawal is the main factor hindering smoking cessation.<ref name=Wadgave2016>{{cite journal|last1=Wadgave|first1=U|last2=Nagesh |first2=L|title=Nicotine Replacement Therapy: An Overview.|journal=International Journal of Health Sciences|volume=10|pages=425–435|issue=3|year=2016|pmc=5003586|pmid=27610066|doi=10.12816/0048737}}</ref> A 2010 [[World Health Organization]] report states, "Greater nicotine dependence has been shown to be associated with lower motivation to quit, difficulty in trying to quit, and failure to quit, as well as with smoking the first cigarette earlier in the day and smoking more cigarettes per day."<ref name=WHO2010>{{cite web|url=https://www.who.int/tobacco/publications/gender/en_tfi_gender_women_addiction_nicotine.pdf|archive-url=https://web.archive.org/web/20131030205723/http://www.who.int/tobacco/publications/gender/en_tfi_gender_women_addiction_nicotine.pdf|archive-date=October 30, 2013|title=Gender, women, and the tobacco epidemic|publisher=World Health Organization|year=2010}}</ref> E-cigarettes may result in starting nicotine dependence again.<ref name=DeVitoKrishnan-Sarin2017/> Greater nicotine dependence may result from dual use of traditional cigarettes and e-cigarettes.<ref name=DeVitoKrishnan-Sarin2017>{{cite journal|last1=DeVito|first1=Elise E.|last2=Krishnan-Sarin|first2=Suchitra|title=E-cigarettes: Impact of E-Liquid Components and Device Characteristics on Nicotine Exposure|journal=Current Neuropharmacology|volume=15|issue=4|pages=438–459|year=2017|issn=1570-159X|doi=10.2174/1570159X15666171016164430|pmc=6018193|pmid=29046158}}</ref> Like tobacco companies did in the last century, there is a possibility that e-cigarettes could result in a new form of dependency on nicotine across the world.<ref name=Schraufnagel2015>{{cite journal|last1=Schraufnagel|first1=Dean E.|title=Electronic Cigarettes: Vulnerability of Youth|journal=Pediatric Allergy, Immunology, and Pulmonology|volume=28|issue=1|year=2015|pages=2–6|issn=2151-321X|doi=10.1089/ped.2015.0490|pmc=4359356|pmid=25830075}}</ref>
== Concerns == [[File:Smoking, Nicotine and Addiction - The Cold Hard Facts - The Real Cost.webm|thumb|right|Nicotine use and addiction.|alt=Nicotine use and addiction.]] Nicotine dependence results in substantial mortality, morbidity, and socio-economic impacts.<ref name=Rachid2016/> Nicotine dependence is a serious [[public health]] concern due to it being one of the leading causes of avoidable deaths worldwide.<ref name=Rachid2016/> The [[medical community]] is concerned that e-cigarettes may escalate global nicotine dependence, particularly among adolescents who are attracted to many of the flavored e-cigarettes.<ref name=Palazzolo2013>{{cite journal|title=Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review.|first1=Dominic L.|last1=Palazzolo|journal=Frontiers in Public Health|volume=1|issue=56|page=56|date=November 2013|doi=10.3389/fpubh.2013.00056|pmc=3859972|pmid=24350225|doi-access=free}}</ref> There is strong evidence that vaping induces symptoms of dependence in users.{{sfn|Stratton|2018|p=Chapter 8-52}} Many organizations such the World Health Organization, [[American Lung Association]], and [[Australian Medical Association]] do not approve of vaping for quitting smoking in youth, making reference to concerns about their safety and the potential that experimenting with vaping may result in nicotine dependence and later tobacco use.<ref name=YoongStockings2018>{{cite journal|last1=Yoong|first1=Sze Lin|last2=Stockings|first2=Emily|last3=Chai|first3=Li Kheng|last4=Tzelepis|first4=Flora|last5=Wiggers|first5=John|last6=Oldmeadow|first6=Christopher|last7=Paul|first7=Christine|last8=Peruga|first8=Armando|last9=Kingsland|first9=Melanie|last10=Attia|first10=John|last11=Wolfenden|first11=Luke|title=Prevalence of electronic nicotine delivery systems (ENDS) use among youth globally: a systematic review and meta-analysis of country level data|journal=Australian and New Zealand Journal of Public Health|volume=42|issue=3|pages=303–308|year=2018|issn=1326-0200|doi=10.1111/1753-6405.12777|pmid=29528527|doi-access=free|hdl=1959.3/457642|hdl-access=free}}</ref> {{clear}}
== See also == *[[Nicotine poisoning]] *[[Nicotine withdrawal]]
== Notes == {{reflist|group=notes}}
== Bibliography == *{{cite book|last1=Stratton|first1=Kathleen|last2=Kwan|first2=Leslie Y.|last3=Eaton|first3=David L.|url=https://www.nap.edu/resource/24952/012318ecigaretteHighlights.pdf|title=Public Health Consequences of E-Cigarettes|publisher=[[National Academies of Sciences, Engineering, and Medicine]]|pages=1–774|date=January 2018|doi=10.17226/24952|pmid=29894118|ref={{harvid|Stratton|2018}}|isbn=978-0-309-46834-3}}
== References == {{reflist}}
==External links== {{Commons category}} *[http://cde.drugabuse.gov/instrument/d7c0b0f5-b865-e4de-e040-bb89ad43202b Fagerstrom Test of Nicotine Dependence (Heatherton et al., 1991)] *[http://www.livingwellseontario.ca/livingwell/assets/File/Webinars/Heaviness%20of%20Smoking%20Scale.pdf Heaviness of Smoking Index (Heatherton et al., 1989)] {{Webarchive|url=https://web.archive.org/web/20170202010417/http://www.livingwellseontario.ca/livingwell/assets/File/Webinars/Heaviness%20of%20Smoking%20Scale.pdf |date=2017-02-02 }} *[http://dsm.psychiatryonline.org/doi/book/10.1176/appi.books.9780890425596 Diagnostic and Statistical Manual of Mental Disorders V (DSM-V)] *[http://growyourwellness.com/sites/default/files/attachments/2014/07/KawakamiArticle_TDSquestionnaire.pdf Tobacco Dependence Screener (Kawakami et al., 1999)] {{Webarchive|url=https://web.archive.org/web/20160927183545/http://growyourwellness.com/sites/default/files/attachments/2014/07/KawakamiArticle_TDSquestionnaire.pdf |date=2016-09-27 }} *[https://web.archive.org/web/20160821101829/http://ntr.oxfordjournals.org/content/6/2/327.full.pdf+html Nicotine Dependence Syndrome Scale (NDSS; Shiffman, Waters & Hickcox, 2004)] *[http://www.nature.com/npp/journal/v28/n2/full/1300030a.html Cigarette Dependence Scale (Etter et al., 2003)] *[http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.546.8124&rep=rep1&type=pdf Wisconsin Inventory of Smoking Dependence Motives (Piper et al., 2004)]
{{Dependence treatment}} {{Addiction}} {{Psychoactive substance use}} {{Cigarettes}} {{Medical resources | ICD10 = {{ICD10|F|17||f|17}}.2 | ICD9 = {{ICD9|305}}.1 | OMIM = 188890 | SNOMED CT = 56294008 | ICD10CM = {{ICD10CM|F17.2}} }} {{Authority control}}
{{DEFAULTSORT:Nicotine Dependence}} [[Category:Substance dependence]] [[Category:Health effects of tobacco]] [[Category:Smoking]] [[Category:Disorders due to use of nicotine]] [[Category:Nicotine|dependence]]