Is the highest density of CB1 receptors in paranoid schizophrenia a correlate of endocannabinoid system functioning?

Increased binding of type 1 cannabinoid (CB1) receptor ligands in the dorsolateral prefrontal cortex and other areas has been shown in post-mortem studies, although there are some inconsistent results. The study by Dalton et al. employed a more rigorous control for potentially confounding variables and investigated whether the density of CB1 receptors and their mRNA expression were different in subtypes of schizophrenia patients. They observed an increased density of CB1 receptors in paranoid schizophrenia as compared with nonparanoid schizophrenia patients and controls. This finding strengthens the evidence for the involvement of endocannabinoids in schizophrenia. However, it is difficult to reconcile with previous observations of increased levels of anandamide in the cerebrospinal fluid in paranoid schizophrenia, since CB1 receptor agonists were shown to induce the downregulation of these receptors. The precise role of the endocannabinoid system in the pathophysiology of schizophrenia remains far from understood.