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Pediatrics. 2008 Sep;122(3):e643-7. doi: 10.1542/peds.2007-3679.

Rate of nicotine metabolism and withdrawal symptoms in adolescent light smokers.

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University of California, Division of Adolescent Medicine, 3333 California St, Suite 245, San Francisco, CA 94118, USA.



The rate of nicotine metabolism may contribute to vulnerability in adolescents' transition from smoking initiation to addiction. The objectives of this study were to examine the associations between the rate of nicotine metabolism and cigarette consumption, addiction, and withdrawal symptoms in a sample of adolescent light smokers.


Twenty adolescent smokers between 13 and 17 years old, who smoked between 1 and 6 cigarettes daily for >/=6 months, were recruited from several San Francisco Bay area schools and pediatric clinics from 2006 to 2007.


Participants underwent 24 hours of supervised tobacco abstinence. Serum was collected at baseline and at 24 hours for measurement of the nicotine metabolites cotinine and 3'-hydroxycotinine. Participants also completed self-report measures, which included smoking behavior, nicotine dependence, and withdrawal scales at baseline and 24 hours after baseline. The ratio of serum 3'-hydroxycotinine/cotinine (the nicotine metabolite ratio), a measure of the rate of nicotine metabolism, was computed by using measurements from the 24-hour serum samples.


Participants were divided into 2 groups: faster metabolizers (3'-hydroxycotinine/cotinine ratio >/= 0.5; n = 5) and slower metabolizers (3'-hydroxycotinine/cotinine ratio < 0.5; n = 15). Faster metabolizers reported greater withdrawal symptoms after 24 hours of abstinence compared with slower metabolizers even after adjusting for the number of cigarettes smoked per day. The metabolite ratio was significantly correlated with self-described level of addiction.


This is the first study to report a significant relationship between the rate of nicotine metabolism and withdrawal symptoms and self-reported addiction in adolescent light smokers. Given the association between withdrawal symptoms and nicotine addiction, adolescent smokers who are faster metabolizers of nicotine may be at greater risk for becoming addicted to nicotine compared with slower metabolizers.

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