Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 105, Issue 3, Pages 641-651Publisher
WILEY
DOI: 10.1002/cpt.1238
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Funding
- National Institute on Drug Abuse [R01 DA031193, P30 DA012393, U01 020830]
- National Center for Research Resources [S10 RR026437]
- Bangerter-Rhyner Foundation
- Canada Research Chairs program (Canada Research Chair in Pharmacogenomics)
- Canadian Institutes of Health Research grant [FDN-154294]
- Campbell Family Mental Health Research Institute of Centre for Addiction and Mental Health
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This study investigated the influence of the rate of nicotine metabolism, as indicated by the nicotine metabolite ratio (NMR), on tobacco dependence. We stratified 136 smokers on the basis of saliva NMR as fast (n = 65) and slow (n = 71) metabolizers. Two loading cigarettes were smoked after overnight, and a reward cigarette was smoked after 6 hours of daytime, abstinence. Blood nicotine concentrations, expired carbon monoxide, withdrawal/craving, and reward questionnaires were collected before/after smoking and during daytime abstinence. Compared with slow metabolizers, fast metabolizers had a shorter nicotine elimination half-life (P < 0.001), lower plasma nicotine concentrations (P < 0.001), and higher withdrawal/craving scores (P < 0.05) for most times during daytime abstinence, indicating that fast metabolizers are likely smoking more to relieve withdrawal symptoms (negative reinforcement). Reward/satisfaction scores were similar in fast and slow metabolizers, suggesting that faster nicotine metabolism, assessed by NMR, is not associated with greater positive reinforcement. CYP2A6 normal (n = 82) and reduced (n = 42) genotype predicted plasma nicotine concentrations but not withdrawal symptoms.
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