Changes of CB1 cannabinoid receptor expression following Selective Serotonin Reuptake Inhibitors (SSRI) and First Generation Antipsychotics (FGA) in depression and bipolar disorder

The human endogenous cannabinoid system is an apparently involved in the pathophysiology of psychiatric disorders. In schizophrenia (SZ), endocannabinoids and their receptors are significantly altered. Increased radioligand binding to cannabinoid receptors 1 (CB1-R) was found in SZ, both in dorsolateral prefrontal cortex and the anterior cingulate cortex (ACC). We analyzed the expression of the CB1-R in ACC at the protein level using immunohistochemistry. In a quantitative post-mortem study, 60 patients suffering SZ, bipolar disorder (BD), major depression (MDD) and controls were included. Numerical densities of neurons and glial cells immunopositive for CB1-R were evaluated. No evidence of an increased or decreased density of CB1-R immunopositive cells in SZ or BD was found. In MDD, we could demonstrate a significantly decreased CB1-R expression on glial cells, indicating that the human endogenous cannabinoid system might be involved in mood disorders. Further, in MDD the intake of SSRI reduced the numerical density of CB1-R-immunoreactive-neurons (p=.005), while in BD first generation antipsychotics reduced the numerical density of CB1-R-immunoreactive-glial cells (p=.04) Therefore, it must be assumed that different medications do have an impact on the expression of CB1-R. Discrepancies between the results obtained on human brain CB1-R in various investigations hitherto might be attributed to different methodological approaches and require further studies for clarification.