Neurobiology of Nicotine Addiction: Implications for Smoking Cessation Treatment

  • Neal L. Benowitz
    Requests for reprints should be addressed to Neal L. Benowitz, MD, Division of Clinical Pharmacology and Experimental Therapeutics, University of California-San Francisco, Box 1220, San Francisco, California 94143-1220.
    Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, San Francisco, California, USA; and Departments of Medicine, Psychiatry, and Biopharmaceutical Sciences, University of California–San Francisco, San Francisco, California, USA
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      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 α4β2 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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