To summarize, although chronic treatment of PC-3 and DU-145 cells with the agonists WIN-55,212-2 and GW-405833 did produce CBR downregulation as expected for action at canonical CBRs, prolonged exposure with the antagonists/inverse agonists AM-251 and rimonabant unexpectedly also resulted in receptor downregulation, adding additional support that CBRs expressed in prostate cancer cells are indeed non-canonical. The gene discussed is CNR1; the disease is prostate cancer.