How THC works: Explaining ligand affinity for, and partial agonism of, cannabinoid receptor 1

Abstract Interaction with cannabinoid receptor 1 (CB1) partially determines the bioactivity of the phytocannabinoids. Consequently, there has also been significant effort directed toward preparing synthetic cannabinoids with either enhanced agonistic or antagonistic activity against this receptor. The design process of these molecules, and the identification of off-target effects at this receptor for molecules designed to target other proteins, would be aided by a reliable computational tool that can accurately predict binding. Furthermore, although the mechanism of CB1 agonism is understood,