Nicotine metabolism and addiction among adolescent smokers


Correspondence to: Mark L. Rubinstein, University of California, San Francisco, 3333 California Street, Suite 245, San Francisco, CA 94118, USA. E-mail:



The purpose of this study was to determine the association between the nicotine metabolic rate and smoking behavior, including addiction, in adolescent smokers.


Baseline data from a prospective study of adolescent smoking behaviors and nicotine metabolism.


The setting was an out-patient university hospital in San Francisco.


Adolescent smokers (n = 164) aged 13–17 years old.


Participants completed self-report measures of smoking behavior and nicotine dependence (modified Fagerström Tolerance Questionnaire: mFTQ). The nicotine metabolite ratio (NMR), a phenotypic marker of the rate of nicotine metabolism, was calculated using the ratio of concentrations of deuterium-labeled 3′-hydroxycotinine to cotinine-d4.


Participants reported smoking a mean of 2.86 cigarettes per day (CPD) [median = 1.78, standard deviation (SD) = 3.35] for 1.37 years (median = 1.0, SD = 1.36). Results from multivariate analyses accounting for age, race/ethnicity, gender and duration of smoking indicated that slower metabolizers smoked more CPD than faster metabolizers (the NMR was inversely related to CPD; P = 0.02). Slower metabolizers also showed greater dependence on the mFTQ (NMR was negatively associated with the mFTQ; P = 0.02).


In adolescence, slower clearance of nicotine may be associated with greater levels of addiction, perhaps mediated by a greater number of cigarettes smoked.