Grant: Project Grant

L-DOPA remains the most effective drug therapy for Parkinson's patients. Yet it is known that longterm use or use of high doses of L-DOPA lead to the development an important undesirable side effect known as L-DOPA induced dyskinesia (LID). In this application, we propose to test whether L-DOPA response can be increased and LID can be improved with combining L-DOPA with Cannabinoid compounds. It is known that the Cannabinoid system can modulate the dopamine system (which is affected in Parkinson's disease) and we have preliminary results showing that compounds acting on the cannabinoid system can enhance L-DOPA response in an animal model. In this project, we propose to systematically test multiple compounds (including THC, CBD) that act on the cannabinoid system and assess their effects on two L-DOPA responses. Our preliminary results show that some cannabinoid compounds increase L-DOPA response. One of our test compounds is already in human clinical trials and further confirmation of our results in pre-clinical animal models of Parkinson's would make this compound be a good candidate for test in human Parkinson's patients since it is already undergoing clinical trials. In summery, our study will investigate the effect of multiple compounds modulating the cannabinoid system in order to identify novel potential drugs that would improve L-DOPA responses or improve LID.