Novel Type 1 Cannabinoid Receptor Allosteric Modulators

The type 1 cannabinoid receptor (CB1R) is present at high levels throughout the brain and other parts of the body. CB1R is activated by the body's own cannabinoids (anandamide and 2-arachidonoylglycerol), synthetic cannabinoids, and cannabinoids from marijuana (e.g. THC and cannabidiol). CB1R is considered a potential target for the regulation of appetite and the treatment of addiction, pain, spasticity in multiple sclerosis, Parkinson's disease, Huntington's disease, epilepsy, post-traumatic stress disorder, and anxiety. Despite its potential as a therapeutic target, we are still learning how the many naturally occurring and synthetic cannabinoids that exist affect CB1R and how CB1R in turn produces distinct effects in the body. To this end, new compounds known as allosteric modulators are being developed that can increase or decrease CB1R's response to the body's cannabinoids, but lack intrinsic activity and will not, therefore, produce the intoxicating effects associated with other cannabinoids. The goals of my research are: (1) to develop allosteric modulators of CB1R that alter the body's response to its own cannabinoids, (2) test those modulators in animal models, and (3) to apply the knowledge gained from goals 1 and 2 to specific disease states where cannabinoids might be therapeutically beneficial. This research project will provide insight into the mechanisms of CB1R activity, important considerations for the use of cannabinoids as a medicine, and lead to the development of new drug compounds.