title: Nicotine Dependence, Nicotine Metabolism, and the Extent of Compensation in Response to Reduced Nicotine Content Cigarettes.
abstract: BACKGROUND
  The Food and Drug Administration has the authority to regulate tobacco product constituents, including nicotine, to promote public health. Reducing the nicotine content in cigarettes may lead to lower levels of addiction. Smokers however may compensate by smoking more cigarettes and/or smoking more intensely. The objective of this study was to test whether individual differences in the level of nicotine dependence (as measured by the Fagerstrom Test of Cigarette Dependence [FTCD]) and/or the rate of nicotine metabolism influence smoking behavior and exposure to tobacco toxicants when smokers are switched to reduced nicotine content cigarettes (RNC).
  
  
  METHODS
  Data from 51 participants from a previously published clinical trial of RNC were analyzed. Nicotine content of cigarettes was progressively reduced over 6 months and measures of smoking behavior, as well as nicotine metabolites and tobacco smoke toxicant exposure, CYP2A6 and nicotinic CHRNA5-A3-B4 (rs1051730) genotype were measured.
  
  
  RESULTS
  Higher baseline FTCD predicted smoking more cigarettes per day (CPD), higher cotinine and smoke toxicant levels while smoking RNC throughout the study, with no interaction by RNC level. Time to first cigarette (TFC) was associated with differences in compensation. TFC within 10 min was associated with a greater increase in CPD compared to TFC greater than 10 min. Neither rate of nicotine metabolism, nor CYP2A6 or nicotinic receptor genotype, had an effect on the outcome variables of interest.
  
  
  CONCLUSIONS
  FTCD is associated with overall exposure to nicotine and other constituents of tobacco smoke, while a short TFC is associated with an increased compensatory response after switching to RNC.
authors.affiliation: Center for Tobacco Control Research and Education, School of Medicine, University of California, San Francisco, CA;
authors.forename: Frank C
authors.initials: FC
authors.lastname: Bandiera
authors.affiliation: Center for Tobacco Control Research and Education, School of Medicine, University of California, San Francisco, CA;
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Ross
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada;
authors.forename: Seyedehtaraneh
authors.initials: S
authors.lastname: Taghavi
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA;
authors.forename: Kevin
authors.initials: K
authors.lastname: Delucchi
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada;
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.affiliation: Center for Tobacco Control Research and Education, School of Medicine, University of California, San Francisco, CA; Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, Departments of Medicine, Bioengineering and Therapeutic Sciences and the Center for Tobacco Control Research and Education, University of California, San Francisco, CA neal.benowitz@ucsf.edu.
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D000328:Adult; D003367:Cotinine / Q000097:blood; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009538:Nicotine / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics; D012907:Smoking / Q000378:metabolism*; D000074606:Smoking Prevention; D062789:Tobacco Products / Q000706:statistics & numerical data*; D014029:Tobacco Use Disorder / Q000378:metabolism* / Q000517:prevention & control*; D014481:United States
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine