Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence.

Abstract

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.

• Authors: Evangelia Liakoni, Kathryn C Edwards, Gideon St Helen, Natalie Nardone, Delia A Dempsey, Rachel F Tyndale, Neal L Benowitz
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 105 Issue 3 Pg. 641-651 (03 2019) ISSN: 1532-6535 [Electronic] United States
• PMID: 30242831 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 American Society for Clinical Pharmacology and Therapeutics.

Chemical References

• Nicotine

Topics

• Adult
• Cigarette Smoking (metabolism)
• Female
• Humans
• Male
• Middle Aged
• Nicotine (administration & dosage, metabolism)
• Saliva (drug effects, metabolism)
• Smoking Cessation
• Substance Withdrawal Syndrome (diagnosis, metabolism)
• Tobacco Use Disorder (diagnosis, metabolism)
• Young Adult