No study to-date has systematically investigated the impact of CNR1 on quantitative phenotypic features in schizophrenia and inter-relationships with marijuana misuse.
Our findings demonstrate that CB1 gene disruption dramatically alters the behavioural effects of the NMDA antagonist phencyclidine, suggesting that the CB1 receptor is involved in schizophrenia.
There is also tantalizing evidence from postmortem, neurochemical, and genetic studies suggesting CB1 receptor dysfunction (endogenous hypothesis) in schizophrenia that warrants further investigation.
Recently, an (AAT)n triplet repeat polymorphism within the cannabinoid receptor gene CNR1 has been found to be associated with both schizophrenia and substance dependence, and to modulate the P300 potential.
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.
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 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.
The findings that reduced GAD(67) mRNA expression can induce lower CB1R mRNA expression support the hypothesis that lower cortical levels of CB1Rs in schizophrenia may partially compensate for deficient GAD(67)-mediated GABA synthesis by reducing endogenous cannabinoid suppression of GABA release.
To gain insight into this factor, we assessed the postnatal developmental trajectory of CB1R expression in the methylazoxymethanol (MAM) model of schizophrenia.
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.
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.