Dissecting the cannabinergic control of behavior: The where matters

The endocannabinoid system is the target of the main psychoactive component of the plant Cannabis sativa, the Δ(9)-tetrahydrocannabinol (THC). This system is composed by the cannabinoid receptors, the endogenous ligands, and the enzymes involved in their metabolic processes, which works both centrally and peripherally to regulate a plethora of physiological functions. This review aims at explaining how the site-specific actions of the endocannabinoid system impact on memory and feeding behavior through the cannabinoid receptors 1 (CB1 R). Centrally, CB1 R is widely distributed in many brain regions, different cell types (e.g. neuronal or glial cells) and intracellular compartments (e.g. mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB1 R according to their cell-type localization (e.g. glutamatergic or GABAergic neurons). Thus, understanding the cellular and subcellular function of CB1 R will provide new insights and aid the design of new compounds in cannabinoid-based medicine. Also watch the Video Abstract.