In this study we report data suggesting the presence of a non-CB1, non-CB2 cannabinoid site in the cerebellum of CB1(-/-) mice. We have carried out [S-35]GTPgammaS binding experiments in striata, hippocampi, and cerebella of CB1(-/-) and CB1(+/+) mice with Delta(9)-THC, WIN55,212-2, HU-210, SR141716A, and SR144528. In CB1(-/-) mice Delta(9)-THC and HU-210 did not stimulate [S-35]GTPgammaS binding. However, WIN55,212-2 was able to stimulate [S-35]GTPgammaS binding in cerebella of CB1(-/-) mice. The maximal effect of this stimulation was 31% that of wild type animals. This effect was reversible neither by CB1 nor CB2 receptor antagonists. Similar results were obtained with the endogenous cannabinoid, anandamide. However, adenylyl cyclase was not inhibited by WIN55,212-2 or anandamide in the CB1(-/-) animals. In striata and hippocampi of CB1(-/-) mice no [S-35]GTPgammaS stimulation curve could be obtained with WIN55,212. Our findings suggest that there is a nonCB1 non-CB2 receptor present in the cerebellum of CB1(-/-) mice. (C) 2002 Elsevier Science (USA).