CNS Effects of CB2 Cannabinoid Receptors

Cannabinoids, endocannabinoids and marijuana use activates two well characterized cannabinoid receptors (CBRs), CB1-Rs and CB2-Rs. The expression of CB1-Rs in the brain and periphery has been well studied, but CB2-Rs have received much less attention than CB1-Rs. CB2-Rs were previously thought to be predominantly expressed in immune cells in the periphery and were traditionally referred to as peripheral CB-Rs. We and others have now demonstrated the presence of CB2-Rs in neuronal, glial and endothelial cells in the brain, and this warrants a re-evaluation of the central nervous system (CNS) effects of CB2-Rs. However, many features of CB2-R gene structure, variants and regulation remain poorly characterized compared to the CB1-R. To further improve understanding of the role of CB2-Rs in the brain, we hypothesized that genetic variants of CB2-R (CNR2) gene might be associated with depression in a human population and that alteration in CNR2 gene expression may be involved in the effects of abused substances in rodents. In this review we show that our data and those of others reveal that CB2-Rs are expressed in neurons in the brain and play a role in depression and substance abuse beyond neuro-immuno-cannabinoid activity.