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Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence
Author(s) -
Liakoni Evangelia,
Edwards Kathryn C.,
St. Helen Gideon,
Nardone Natalie,
Dempsey Delia A.,
Tyndale Rachel F.,
Benowitz Neal L.
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1238
Subject(s) - nicotine , abstinence , cotinine , cyp2a6 , smoking cessation , craving , medicine , cigarette smoking , nicotine withdrawal , metabolite , saliva , anesthesia , pharmacology , physiology , psychiatry , metabolism , addiction , pathology , cytochrome p450 , cyp1a2
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. CYP 2A6 normal ( n = 82) and reduced ( n = 42) genotype predicted plasma nicotine concentrations but not withdrawal symptoms.