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Clinical Pharmacology of Nicotine: Implications for Understanding, Presenting and Treating Tobacco Addiction

December 8, 2008: The Role of Nicotine Addiction in Tobacco Use

Neal L. Benowitz, M.D., Professor of Medicine, University of California, San Francisco

Key messages:

  • Genetic studies of tobacco dependence are important because they can help understand the brain mechanisms of nicotine addiction, guide the development of smoking cessation interventions and help to personalize smoking cessation therapy.
  • Twin studies indicate that smoking prevalence shows a high degree of heritability (50%) as does the level of dependence, cigarette consumption and specific withdrawal symptoms.
  • A strong link has been found between genetic variation in nicotinic receptor genes and the risk of lung cancer. This may reflect the association between nicotine addiction and lung cancer and/or that carcinogenic nicotine-derived nitrosamines may stimulate tumor growth through Nicotinic Acetylcholine Receptors.
  • In a study looking at nicotine metabolism as a determinant of dependence vulnerability and disease risks, Tyndale found that genetically slow metabolizers smoke fewer cigarettes per day and were able to quit more easily. Pregnancy is associated with very fast metabolism of nicotine. This has implications for their ability to quit.
  • The ratio of the nicotine metabolites 3'-hydroxcotinine to cotinine, measured in plasma, saliva or urine, is a biomarker of the rate of nicotine metabolism. Smokers with high ratios (faster metabolizers) have lower smoking cessation rates compared with smokers with low ratios when treated with nicotine patches. With bupropion treatment quitting rates are similar for fast and slow metabolizers. These findings indicate that pharmacotherapy may be able to be individualized based on the smoker's rate of metabolism as fast metabolism predicts a higher level of dependence and therefore a need for more intensive pharmacotherapy.
  • Cotinine screening is the best way to determine tobacco smoke exposure, and a 2006 study of exposure in urban hospital patients found that over 50% of the patients were either active smokers or were heavily exposed to secondhand smoke. If routine cotinine tests were performed and results entered on all patients' medical charts, health care providers would recognize the high prevalence of tobacco smoke exposure—particularly among low income populations—and this would perhaps lead to an increase in smoking cessation interventions.
  • Dr. Benowitz concluded his remarks by proposing a tobacco regulation strategy that might prevent nicotine addiction in youth. Regulation of the nicotine content of cigarettes and the use of a nicotine reduction strategy to prevent or reduce the level of nicotine addiction appears to be safe and feasible.

Following Dr. Benowitz's presentation, there was an opportunity for ICSH members to provide comments or ask questions.

Dr. Matthew McKenna introduced the final speaker.

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