Neurobiology of Nicotine Addiction: Implications for Smoking Cessation Treatment
Abstract
Nicotine sustains addictive tobacco use, which in turn causes much premature disability and death. The essence of drug addiction is loss of control of drug use. Molecular biology studies suggest that the alpha(4)beta(2) nicotinic acetylcholine receptor subtype is the main receptor mediating nicotine dependence. Nicotine acts on these brain nicotinic cholinergic receptors to facilitate neurotransmitter release (dopamine and others), producing pleasure, stimulation, and mood modulation. Neuroadaptation develops with repeated exposure to nicotine, resulting in tolerance to many of the effects of nicotine. When a smoker stops smoking, a nicotine withdrawal syndrome ensues, characterized by irritability, anxiety, increased eating, dysphoria, and hedonic dysregulation, among other symptoms. Smoking is also reinforced by conditioning, such that specific stimuli that are psychologically associated with smoking become cues for an urge to smoke. These include the taste and smell of tobacco, as well as particular moods, situations, and environmental cues. Pharmacotherapies to aid smoking cessation should ideally reduce nicotine withdrawal symptoms and block the reinforcing effects of nicotine obtained from smoking without causing excessive adverse effects. Further, given the important role of sensory effects of smoking and psychoactive effects of nicotine, counseling and behavioral therapies are important adjuncts to and substantially augment the benefits of pharmacotherapy.
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Receptor desensitization may be a major contributor to upregulation in chronic users of nicotine-containing products.
“It has been suggested that receptor desensitization may be a major contributor to the upregulation observed in chronic users of nicotine-containing products (Benowitz 2008).”
From Nicotine Withdrawal (2015) · cites this paper as Benowitz 2008
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- Authors
- Benowitz, N. L.
- Affiliations
- San Francisco General Hospital (US)
- Corresponding author
- Benowitz, Neal L.
- ORCID
- Benowitz, Neal L.
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 121
- Issue
- 4
- Pages
- S3-S10
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W2155128264
- Cited by
- 385
- References
- 50
- Citations by year
- 2026: 16 · 2025: 17 · 2024: 12 · 2023: 26 · 2022: 20 · 2021: 15 · 2020: 13 · 2019: 15 · 2018: 13 · 2017: 22 · 2016: 20 · 2015: 13 · 2014: 31 · 2013: 28 · 2012: 39
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- nicotine dependence, smoking cessation, α4β2 nicotinic acetylcholine receptor, dopamine release, neural adaptation, nicotine withdrawal symptoms, cue reactivity, pharmacotherapy, behavior therapy, counseling
- MeSH terms
- Smoking Prevention, Humans, Neurobiology, Nicotine, Receptors, Nicotinic, Smoking, Substance Withdrawal Syndrome, Smoking Cessation
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