Cannabinoid Receptor 1 Gene Association With Nicotine Dependence

Abstract

Context The endogenous cannabinoid system has been implicated in drug addiction in animal models. The cannabinoid receptor 1 (CNR1) gene is 1 of the 2 receptors expressed in the brain. It has been reported to be associated with alcoholism and multiple drug abuse and dependence. Objective To test the hypothesis that the CNR1 gene is associated with nicotine dependence. Design Genotype-phenotype association study. Ten single-nucleotide polymorphisms were genotyped in the CNR1 gene in 2 independent samples. For the first sample (n=688), a 3-group case-control design was used to test allele association with smoking initiation and nicotine dependence. For the second sample (n = 961), association was assessed with scores from the Fagerström Test for Nicotine Dependence (FTND). Settings Population samples selected from the Mid-Atlantic Twin Registry. Participants White patients aged 18 to 65 years who met the criteria of inclusion. Main Outcome Measures Fagerström Tolerance Questionnaire and FTND scores. Results Significant single-marker and haplotype associations were found in both samples, and the associations were female specific. Haplotype 1-1-2 of markers rs2023239-rs12720071-rs806368 was associated with nicotine dependence and FTND score in the 2 samples (P<.001 and P = .009, respectively). Conclusion Variants and haplotypes in the CNR1 gene may alter the risk for nicotine dependence, and the associations are likely sex specific.

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

“…Several studies have demonstrated nicotine-induced alterations in brain CB 1 receptor expression and function (Gerard et al, 2010;Marco et al, 2007;Werling et al, 2009). Screening of two independent clinical populations revealed that CB 1 gene variants are associated with nicotine dependence (Chen et al, 2008) and the CB 1 receptor antagonist Rimonabant (SR141716A) prolonged abstinence rates in smokers expressing motivation to quit . SR141716A and the related CB 1 antagonist AM251 reduce nicotine selfadministration (SA) by rats (Cohen et al, 2002(Cohen et al, , 2005Forget et al, 2009;Shoaib, 2008), attenuate nicotine-induced increases in nucleus accumbens (NAc) dopamine (DA) (Cheer et al, 2007;Cohen et al, 2002;Grieder et al, 2012), and reduce reinstatement of nicotine-seeking behavior in animal models of relapse (Forget et al, 2009).…”

CNR1 Gene is Associated with High Neuroticism and Low Agreeableness and Interacts with Recent Negative Life Events to Predict Current Depressive Symptoms

“…This genetic region has been linked to schizophrenia (Levinson et al, 2000;Leroy et al, 2001), but this has not been replicated, although recently the CNR1 gene has been associated with specific symptoms or with non-responder status for antipsychotic drugs rather than with schizophrenia as a disorder (Chavarria-Siles et al, 2008;Hamdani et al, 2008). There are more convincing results on the association of the CNR1 gene and substance abuse disorders (Zhang et al, 2004;Zuo et al, 2007;Chen et al, 2008), although there is a negative replication study (Herman et al, 2006). Regarding depression, two studies with significantly smaller sample sizes failed to find any association with depression using the (AAT) n polymorphism (Barrero et al, 2005;Tsai et al, 2001), although the former found that a significant association emerged when only the depressed patients with Parkinson's disease were considered (Barrero et al, 2005).…”

Association of the DRD2 TaqIA, 5-HT1B A-161T, and CNR1 1359 G/A Polymorphisms with Alcohol Dependence

“…There is increasing evidence from pharmacologic and neurochemical studies that the endogenous cannabinoid system is involved in addiction to substance abuse. Of the two known cannabinoid receptors, the receptor which is mainly responsible for neurophysiological and behavioral responses related to addictive behavior is CNR1 35 . The association of three polymorphisms in CNR1 (rs1049353, rs806379, and AAT repeat) with substance dependence has been reported in the literature.…”