Neurobiology of Nicotine Addiction: Implications for Smoking Cessation Treatment NealL. Benowitz, MD Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service …

CHARACTERISTICS OF ADDICTION. Distinct definitions or criteria for drug dependence or addiction have been put forth by different health organizations or authorities. In the present article, the terms”dependence” and “addiction”are used interchangeably. These terms are considered equivalent because they describe similar neurochemical and psychological processes that sustain drug use. Furthermore, both terms indicate loss of control over drug-taking behavior—the principal characteristic of drug addiction. Thus, once a person is addicted to a drug, it is difficult to stop using it even when there are compelling reasons to do so. Drug dependence has been defined by the World HealthOrganization (WHO) as”abehavioral pattern in which the use of a given psychoactive drug is givena sharply higher priority over other behaviors which once had a significantly higher value.” In other words, the drug has come to control behavior to an extent that is considered detrimental to the individual or society. EVIDENCE THAT NICOTINE IS ADDICTING. There are many lines of evidence for tobacco addiction and the role of nicotine in sustaining tobacco addiction. The first and most basic line of evidence for tobacco addiction is that most smokers state they would like to quit smoking but are unable to do so easily. Studies indicate that, on average, smokers require 4 or more quit attempts before they are successful in achieving abstinence. Further, in approximately 97% ofsmokers, unaided quit attempts are unsuccessful for achieving long-term abstinence. Data for patients with medical diseases are even more compelling. Although the risk of smoking after myocardial infarction should be a powerful motivation to quit, 50%of people quit smoking afteraheart attack despite these known risks. Similar data are noted in patients with lung 15 and laryngeal cancer. NEUROBIOLOGY OF NICOTINE ADDICTION. Nicotinic Acetylcholine Receptors. When a person inhales smoke from a cigarette, nicotine is distilled from the tobacco and carried in the smoke particles into the lungs, where it is absorbed rapidly into the pulmonary venous circulation. It then enters the arterial circulation and moves quickly to the brain. Nicotine diffuses readily into brain tissue, where it binds to nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels. When a cholinergic agonist binds to the outside of the channel, the channel opens, allowing the entry of…

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