GPCR (G protein-coupled receptors) are cell surface receptors that can detect molecules on the cellular membranes and activate cellular responses . The GPCR activation is mediated through bound agonists. Estimated 34% of approved drugs target the GPCR complex in various target organs. The GPCR complex, is implicated in a variety of physiological processes, not limited to but including, regulation of immune system activity and inflammation, autonomic nervous system transmission, homeostasis modulation, and implicated in growth and metastasis of certain types of tumors . The CB1 and CB2 receptor are class A serpentine G protein-coupled receptor (GPCR) that signals primarily through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi and the ERK1/2 (extracellular signal-regulated kinases 1/2) pathways . Although they are not limited to these specific pathways, they are the most common pathways. Over 100 GPCR's have been expressed at the mRNA level within pancreatic adenocarcinoma tumors . Several GPCRs GPRC5A, F2R and F2RL1 are expressed in multiple PDAC cell types while other GPCRs are expressed in a specific setting within microenvironments of the cell . Although the research of targeting GPCRs in pancreatic cancers are relatively new , increased the relevance of targeting this complex using agonists and antagonists of GPCR becomes pertinent.