title: Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.
abstract: The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Faulkner
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Dara G
authors.initials: DG
authors.lastname: Ghahremani
authors.affiliation: Department of Pharmacology &Toxicology, Campbell Family Mental Health Research Institute, Centre for Addiction &Mental Health (CAMH), University of Toronto, 1 King's College Circle, Toronto, ON, Canada.|Department of Psychiatry, Campbell Family Mental Health Research Institute, Centre for Addiction &Mental Health (CAMH), University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Chelsea M
authors.initials: CM
authors.lastname: Cox
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Ari S
authors.initials: AS
authors.lastname: Kazanjian
authors.affiliation: UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Paterson
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Shahrdad
authors.identifier: http://orcid.org/0000-0002-2425-1096
authors.initials: S
authors.lastname: Lotfipour
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Gerhard S
authors.initials: GS
authors.lastname: Hellemann
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Petersen
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: Vigil
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, CA, USA.
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects*; D001288:Attention / Q000187:drug effects*; D003258:Consumer Behavior; D003367:Cotinine / Q000031:analogs & derivatives / Q000097:blood; D066249:Craving / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D009538:Nicotine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012907:Smoking / Q000523:psychology*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D055815:Young Adult
chemical_list: C001381:hydroxycotinine; D009538:Nicotine; D003367:Cotinine