title: Cannabinoid receptor 1 (CNR1) gene variant moderates neural index of cognitive disruption during nicotine withdrawal.
abstract: Nicotine withdrawal-related disruption of cognitive control may contribute to the reinforcement of tobacco use. Identification of gene variants that predict this withdrawal phenotype may lead to tailored pharmacotherapy for smoking cessation. Variation on the cannabinoid receptor 1 gene (CNR1) has been related to nicotine dependence, and CNR1 antagonists may increase attention and memory functioning. We targeted CNR1 variants as moderators of a validated neural marker of nicotine withdrawal-related cognitive disruption. CNR1 polymorphisms comprising the 'TAG' haplotype (rs806379, rs1535255 and rs2023239) were tested independently, as no participants in this sample possessed this haplotype. Nicotine withdrawal-related cognitive disruption was indexed as increased resting electroencephalogram (EEG) alpha-1 power density across 17 electrodes. Seventy-three Caucasian Non-Hispanic smokers (≥15 cigarettes per day) visited the laboratory on two occasions following overnight smoking/nicotine deprivation. Either two nicotine or two placebo cigarettes were smoked prior to collecting EEG data at each session. Analyses showed that rs806379 moderated the effects of nicotine deprivation increasing slow wave EEG (P = 0.004). Smokers homozygous for the major allele exhibited greater nicotine withdrawal-related cognitive disruption. The current findings suggest potential efficacy of cannabinoid receptor antagonism as a pharmacotherapy approach for smoking cessation among individuals who exhibit greater nicotine withdrawal-related cognitive disruption.
authors.affiliation: Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USA. david.evans@moffitt.org.|Departments of Oncologic Sciences & Psychology, University of South Florida, Tampa, FL, USA. david.evans@moffitt.org.
authors.forename: D E
authors.initials: DE
authors.lastname: Evans
authors.affiliation: Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USA.|Departments of Oncologic Sciences & Psychology, University of South Florida, Tampa, FL, USA.|Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Sutton
authors.affiliation: Department of Psychology, Colorado State University, Fort Collins, CO, USA.
authors.forename: K G
authors.initials: KG
authors.lastname: Jentink
authors.affiliation: Department of Biostatistics, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USA.|Departments of Oncologic Sciences & Psychology, University of South Florida, Tampa, FL, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USA.|Departments of Oncologic Sciences & Psychology, University of South Florida, Tampa, FL, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Drobes
mesh_terms: D000328:Adult; D002186:Cannabinoids / Q000235:genetics / Q000378:metabolism; D003071:Cognition / Q000187:drug effects* / Q000502:physiology*; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000235:genetics / Q000523:psychology; D016540:Smoking Cessation / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C571130:CNR1 protein, human; D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D009538:Nicotine
keywords: Alpha-1; CNR1; EEG; ERP; cannabinoid; cognitive control; genetics; nicotine withdrawal; smoking