The results point towards the hypothesis that increased CB1R levels could be a confounding effect of antipsychotic medication in schizophrenia that is circumveneted by high fat feeding.
In this study, although the result indicates that CNR1 and CNR2 variations are unlikely to influence schizophrenia susceptibility in a Korean population, the findings would provide meaningful information for further genetic studies.
Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB(1)R binding compared with the control group.
In either case, greater CB1R receptor availability may contribute to the increased susceptibility of schizophrenia subjects to the deleterious effects of cannabis use.
The most well established finding is the down-regulation of cannabinoid CB1 receptors (CB1R) after chronic and recent cannabis exposure, but it remains uncertain whether this effect is present in cannabis users with schizophrenia.
The hippocampi of schizophrenia-like brains that were treated with the cannabinoid receptor-1 inverse antagonist AM251 expressed H3K9ac at the level observed in normal brains.
However, further studies are necessary to unravel the relationship between mutations in the CNR1 gene and the genetic susceptibility for the manifestation of certain subtypes or schizophrenia i.e. the predominance of negative or positive symptoms or as predictors of the clinical course.
Indeed, in several brain regions implicated in the putative neural circuitry of SZ (e.g., hippocampus, frontal cortex, cerebellum), cannabinoid receptor type 1 (CB1Rs) and glutamate N-methyl-D-aspartate receptors (NMDARs) have direct and indirect interactions.
Finally, there is also evidence that some genetic alterations of the CNR1 gene can act as a protectant factor against schizophrenia or can induce a better pharmacological response to atypical antipsychotics.
Our hypothesis that an association with the (AAT)n-repeat marker of CNR1 would not be found with the more general type of schizophrenia was also confirmed.
Therefore, the endocannabinoid system could represent a therapeutic target for schizophrenia as a regulator of glutamate and GABA release via the CB1 receptor (CB1R).
Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia.
The results demonstrate no association between CNR1 genotypes and schizophrenic disorders (P = 0.409), with these negative findings suggesting that, for Chinese populations, the (AAT)n triplet repeat in the promoter region of the CNR1 gene is not directly involved in the pathogenesis of schizophrenic disorders.
The relative mRNA amounts encoding for A2A, D2, and CB1 receptors were similar in brains of drug-free, antipsychotic-treated subjects with schizophrenia and controls.
The present review surveys what is currently known about the interactions of CB1Rs with dopamine, serotonin, and glutamate systems, because all three of those neurotransmitters are well-established in the pathophysiology of schizophrenia and psychosis.
Seven out of the 32 tSNPs within PPARA (rs4253765, rs4263776, rs6007662, rs1800206, rs4253763, rs6008197 and rs4253655) and 3 out of 12 tSNPs within CNR1 (rs1049353, rs7766029 and rs806366) were nominally associated with SZ (uncorrected p<0.05).