In this study, we reported the following: (1) GPR55 activation by O-1602 induced monocyte adhesion to endothelial cells via Mac-1 expression; (2) Mac-1 expression is regulated by binding of the transcription factors AP-1 and NF-κB to the nt −750 to −503 promoter region of Mac-1 in monocytes, (3) signaling cascades of GPR55 activation to Mac-1 gene expression are Gq/Ca2+/CaMKK and PI-3K, and (4) blockage of GPR55 protected against atherosclerosis progression along with improved lipid profiles, as shown in Figure 12. Here, CAMKK2 is linked to atherosclerosis.