Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):183-9. doi: 10.2174/157015911795017191.
Several studies have suggested that the endocannabinoid system plays significant roles in the vulnerability to psychiatric disorders including drug abuse. To examine the possible association of the CNR1 and CNR2 genes, which encode cannabinoid receptors CB1 and CB2, with methamphetamine dependence, we investigated three single nucleotide polymorphisms (SNPs) (rs806379, rs1535255, rs2023239) in intron 2 of the CNR1 gene and a nonsynonymous SNP, Q63R, in the CNR2 gene. The study samples consisted of 223 patients with methamphetamine dependence and 292 age- and sex- matched controls. There were no significant differences between the patients and controls in genotypic or allelic distribution of any SNP of the CNR1 and CNR2 genes. We also analyzed the clinical features of methamphetamine dependence. Rs806379 of the CNR1 gene showed a significant association with the phenotype of latency of psychosis after the first consumption of methamphetamine. Patients with the T allele or T-positive genotypes (T/T or A/T) may develop a rapid onset of psychosis after methamphetamine abuse. The present study suggests a possibility that genetic variants of the CNR1 gene may produce a liability to the complication of psychotic state after abuse of methamphetamine; however, our findings need to be confirmed by future replications.
几项研究表明，内源性大麻素系统在易患精神疾病（包括药物滥用）方面发挥着重要作用。为了研究编码大麻素受体 CB1 和 CB2 的 CNR1 和 CNR2 基因的可能相关性，我们研究了 CNR1 基因内含子 2 中的三个单核苷酸多态性（SNP）（rs806379、rs1535255、rs2023239）和 CNR2 基因中的一个非同义 SNP（Q63R）。研究样本包括 223 名甲基苯丙胺依赖患者和 292 名年龄和性别匹配的对照。CNR1 和 CNR2 基因的任何 SNP 的基因型或等位基因分布在患者和对照组之间均无显著差异。我们还分析了甲基苯丙胺依赖的临床特征。CNR1 基因的 rs806379 与首次使用甲基苯丙胺后精神病潜伏期的表型有显著关联。携带 T 等位基因或 T 阳性基因型（T/T 或 A/T）的患者可能在滥用甲基苯丙胺后迅速出现精神病。本研究提示，CNR1 基因的遗传变异可能导致滥用甲基苯丙胺后出现精神病状态的并发症；然而，我们的发现需要未来的复制研究来证实。
