An Overview on Computational Methods Targeting the Endocannabinoid System

Humanity’s interaction with Cannabis spans 12,000 years, playing diverse roles in cultures worldwide. Chemical elucidation of Cannabis, particularly key phytocannabinoids like cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), unfolded in the last century. Over 550 secondary metabolites, including terpenes and flavonoids, contribute to its chemical diversity. Initial notions of psychoactive effects being nonreceptor-mediated were dispelled with the discovery of stereospecific receptors, notably CB1 and CB2, explaining Cannabis’ action. CB1, abundant in the central nervous system, and CB2, found in peripheral tissues, are crucial for psychoactivity and diverse physiological effects. Endocannabinoids like anandamide and 2-arachidonoylglycerol serve as natural ligands. The endocannabinoid system orchestrates complex regulatory signals and reactions, influencing cognition, immunity, and more. This understanding opens therapeutic avenues, addressing conditions like pain, anxiety, and mood disorders. Computer-aided drug design with a focus on the FAAH (fatty acid amide hydrolase) enzyme, the CB1 and CB2 receptors, and their ligands employs several combined computational techniques for the potential development of new drugs that act on the endocannabinoid system, that can be used in several somatic dysregulations and complex diseases to for which there is still no efficient treatment.