Anti-CNR1 (aa 320-334) polyclonal antibody

Objective: The endocannabinoid system contributes to the regulation of emotions, stress, memory, and cognition. It has been reported that endocannabinoids cause GABAergic inhibition and dopaminergic increase in the mesolimbic and nigrostriatal systems, thus playing a part in the neurobiology of schizophrenia. In this study, we investigate cannabinoid receptor 1 (CNR1) gene polymorphisms in schizophrenia patients. Methods: CNR1 gene polymorphisms were studied in 66 schizophrenia patients and 65 healthy controls. To obtain genomic DNA, proteinase K digestion and the salt-chloroform method were used. Clinical Global Impression severity scale (CGI-S) and Positive and Negative Syndrome Scale (PANSS) were administered to evaluate the severity of schizophrenia symptoms. CNR1 gene polymorphism was determined by using polymerase chain reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and Single Strand Conformation Polymorphism (SSCP) methods for the Rs6454674, Rs806368, and Rs1049353 sites. Results: There was no difference in CNR1 gene polymorphisms between schizophrenia patients and control groups (Rs6454674 T/G; p=0.973, Rs806368 T/C; p=0.349, Rs1049353 A/G; p=1.00). However, CGI-S, PANSS total, PANSS positive, PANSS negative and PANSS general psychopathology scores were significantly lower in schizophrenia patients with RS6454674 polymorphism than in those not showing polymorphism. Conclusion: Our results suggest that CNR1 gene polymorphisms may be associated with clinical symptoms and disease severity in schizophrenia patients.

Background: Cannabis is a commonly used drug and studies have shown that a significant portion of the variation in cannabis use disorders (CUDs) is heritable. Five genes known to play a role in the endocannabinoid system and CUDs were examined in a community sample of young adult Mexican Americans (MAs): CNR1, MGLL, FAAH, DAGLA, and DAGLB. Methods: Gene-based tests were run to test for association between each gene and two DSM-5 cannabis phenotypes. Subsequent linear regressions were run in PLINK using an additive model to determine which single nucleotide polymorphisms (SNPs) were driving the association. Results: FAAH was significantly associated with DSM-5 cannabis use disorder group count (DSM-5 CUD) using a gene-based test (p = 0.0035). This association survived Bonferroni correction for multiple testing at p < 0.004. Post hoc analyses suggested this association was driven by two common (minor allele frequency >5%) SNPs in moderate linkage disequilibrium, rs324420 and rs4141964, at p = 0.0014 and p = 0.0023, respectively. In both cases the minor allele increased risk for DSM-5 CUD. Conclusions: Genetic variation in FAAH was associated with DSM-5 CUD in MAs. This association was primarily driven by the missense SNP rs324420. In vitro work has provided evidence that the risk allele generates an enzyme with decreased expression and cellular stability. Although this SNP has been previously associated with substance use in the literature, this is the first association in a young adult MA sample. (C) 2016 Elsevier Ireland Ltd. All rights reserved.