Cannabinoid control of motor function at the basal ganglia

Classic and novel data strengthen the idea of a prominent role for the endocannabinoid signaling system in the control of movement. This finding is supported by three-fold evidence: (1) the abundance of the cannabinoid CB1 receptor subtype, but also of CB2 and vanilloid VR1 receptors, as well as of endocannabinoids in the basal ganglia and the cerebellum, the areas that control movement; (2) the demonstration of a powerful action, mostly of an inhibitory nature, of plant-derived, synthetic, and endogenous cannabinoids on motor activity, exerted by modulating the activity of various classic neurotransmitters; and (3) the occurrence of marked changes in endocannabinoid transmission in the basal ganglia of humans affected by several motor disorders, an event corroborated in animal models of these neurological diseases. This three-fold evidence has provided support to the idea that cannabinoid-based compounds, which act at key steps of the endocannabinoid transmission [receptors, transporter, fatty acid amide hydrolase (FAAH)], might be of interest because of their potential ability to alleviate motor symptoms and/or provide neuroprotection in a variety of neurological pathologies directly affecting basal ganglia structures, such as Parkinson's disease and Huntington's chorea, or indirectly, such as multiple sclerosis and Alzheimer's disease. The present chapter will review the knowledge on this issue, trying to establish future lines for research into the therapeutic potential of the endocannabinoid system in motor disorders.