Grant: Project Grant

Functional connections between nerve cells (called synapses) are essential to establish the architecture of the nervous system. The modification of synapses is thought to be one of the mechanisms by which learning and memory occur. It has been known for decades that cannabis consumption has a profound influence on learning and memory and that maternal marijuana smoking during perinatal period causes cognitive and social deficits that last in the adulthood of the offspring. For the moment, we do not know if these effects are mediated by the classic CB1 and CB2 cannabinoid receptors or by other receptors such as the GPR55. Altogether, these observations led us to investigate a novel function for cannabinoids (like cannabidiol (CBD)) or other GPR55 ligands in regulating the formation and the maintenance of synapses. We have shown that GPR55 stimulation increases the synapse number and blockade of this receptor decreases it. Therefore, the main objective of this project is to identify the contribution and the mechanisms by which GPR55, and its ligands modulate the synapse number. The identification of a fundamental molecular mechanism regulating the connections between nerve cells will provide important insight into normal brain function and learning process. Furthermore, it will probably permit the discovery of new pharmacological targets and the development of innovative therapeutic strategies aiming at treating congenital or neurodegenerative diseases. This project is timely because Canadians are among the highest consumers of cannabis in the World and its consumption might be on the rise when it will be legalized in 2018. Moreover, the GPR55 system is the target of several compounds in the pipelines of pharmaceutical companies (Sativex(THC+CBD), Epidiolex, and GWP42003(CBD)). Thus, the results obtained from the proposed experiments will potentially explain some of the side effects produced by these drugs.