Constitutive activity at the cannabinoid CB ₁ receptor and behavioral responses

The cannabinoid receptor type 1, found mainly on cells of the central and peripheral nervous system, is a major component of the endogenous cannabinoid system. Constitutive and endogenous activity at cannabinoid receptor type 1 regulates a diverse subset of biological processes including appetite, mood, motor function, learning and memory, and pain. The complexity of cannabinoid receptor type 1 activity is not limited to the constitutive activity of the receptor: promiscuity of ligands associated with and the capability of this receptor to instigate G protein sequestration also complicates the activity of cannabinoid receptor type 1. The therapeutic use of cannabinoid receptor type 1 agonists is still a heavily debated topic, making research on the mechanisms underlying the potential benefits and risks of cannabinoid use more vital than ever. Elucidation of these mechanisms and the quest for agonists and antagonists with greater specificity will allow a greater control of the side effects and risks involved in utilizing cannabinoids as therapeutic agents. In this chapter, we review a small subset of techniques used in the pharmacological application of and the behavioral effects of molecules acting at the paradoxical cannabinoid receptor type 1.