Chapter 18 - Future perspectives: Cannabinoid CB2 receptor ligands and their therapeutic potential in mental diseases

Abstract

The ubiquitous cannabinoid receptors (CBRs) and elements of the endocannabinoid system are major targets of investigation for their impact in neurological and mental disorders. Yet, little attention had been paid to the neuronal and functional expression of cannabinoid type-2 receptors (CB2Rs) in the brain and therefore their role in neuropsychiatric disorders has been much less well characterized. Our studies provided the first evidence for neuronal brain effects of the CB2R and its possible role in neuropsychiatric disorders. We have identified novel human and rodent cannabinoid type-1 (CB1) and CB2 receptor isoforms with differential tissue expression patterns. So, just as for CB1R gene variants, our findings also indicate increased risk of schizophrenia, depression, drug abuse, and eating and autism spectrum disorders in low CB2R function. The nature of the interaction between CB1Rs and CB2Rs has not been well studied and characterized; nonetheless emerging evidence suggests that CB1 and CB2 receptors may work independently and/or cooperatively in different neuronal populations to regulate diverse physiological and biological functions in mental and neurological disorders. Therefore, studying CBR genomic structure, and its polymorphic nature, subtype specificity and their variants, and associated regulatory elements that confer vulnerabilities to a number of mental disturbances, may provide deeper insight into the underlining mechanisms. Thus, understanding gene variants of components of the endocannabinoid system may provide novel targets for the effects of cannabinoids in health and disease.