Moreover, based on evidence from the most recent studies (e.g., CB2 and TRPV1 agonists have anti-proliferative, pro-apoptotic, and anti-invasive effects in the most frequent primary cancer affecting bone, namely, osteosarcoma), the EC/EV system could also be a very promising therapeutic target in primary bone tumor and in chemotherapy-induced osteoporosis. Here, CNR2 is linked to osteosarcoma.