Systems pharmacology of the endocannabinoid system

In this thesis, a system pharmacology approach, integrating metabolomics, pharmacology and chemical biology, was applied to understand and modulate the endocannabinoid system across different model systems (cells, zebrafish, mice and humans). The endocannabinoid system (ECS) and its function in the brain was discovered after identifying THC: the active ingredient of cannabis (marijuana) plant. It is perhaps the most important physiological signalling system involved in establishing and maintaining human health. In disease conditions the ECS system is dysregulated and becomes either highly active or less active. Due to the widespread effects throughout the body, targeting ECS system is believed to hold promise as a treatment target in the field of medicine. In this thesis, the functional role of the ECS was studied in healthy and diseased conditions. In addition, the ECS was modulated using enzyme inhibitors to gain a better understanding in different signalling pathways. Furthermore, to understand the drug pharmacology and whether such new compound inhibitors may modify disease biochemistry; this includes the study of target engagement, downstream effects and the off-target effects inhibitors. Overall, we are convinced that by applying system pharmacology approach to study ECS can lead to develop novel therapeutic biomarkers to treat metabolic or neurological diseases.