Endogenous Cannabinoids in Basal Ganglia and their Potential Participation in Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of California
Investigators Name
Piomelli, Daniele, PhD

Our lab studies the mechanisms of formation and inactivation of the endocannabinoids, brain marijuana-like substances that serve as central components of a signaling system involved in the control of cognition, emotion and pain. Physiological experiments show that anandamide (the best known of the endocannabinoids) may be as important in regulating brain functions as other better understood neurotransmitters such as dopamine and serotonin. Anandamide and other endocannabinoids are released from neurons by a unique mechanism: they are stored in the membrane of neurons in the form of phospholipid precursors, which are cleaved by enzymes stimulated by receptor activation. After release, the endocannabinoids activate a receptor protein on the surface of neighboring cells, and are rapidly eliminated to stop their biological actions. We are interested in understanding at the molecular and cellular level how the endocannabinoids are released and inactivated, and in determining what may be their physiological functions. A primary role of the endocannabinoid system may be to regulate movement by modulating the activity of the neurotransmitter dopamine. Our experiments suggest that dopamine triggers the release of anandamide, which in turn may act as a brake preventing excess dopamine activity. Thus a dysfunction of this neurotransmitter balance may participate in neurological and psychiatric disorders, and more specifically in Tourette Syndrome where there may be a hyperfunctionality of the dopamine system. We will explore this hypothesis by using two approaches. On the one hand, we will conduct animal studies to investigate in detail the interactions between dopamine and anandamide. On the other, we will determine whether anandamide levels are altered in patients with Tourette Syndrome. These studies may shed light on the neurochemical mechanisms underlying Tourette Syndrome, and may offer novel therapeutic possibilities for the treatment of this condition. Daniele Piomelli, Ph.D. University of California, Irvine, CA Award $39,983 THE OCHSMAN FAMILY FUND AWARD Tourette Association of America Inc. – Research Grant Award 1999-2000