Involvement of endogenous cannabinoids in the pharmacological effects of cannabinoids

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Pharmacological interaction in mice between cannabinoids and endogenous cannabinoids was studied and the following reaults were obtained.1)Tolerance developed in the cataleptogenic effect of anandamide but not in the hypothermic effect of the endogenous cannabinoid.1)A significant cross-tolerance was not developed in the cataleptogenic effect of tetrahvdrocannabinol and anandamide.1)A significant cross-tolerance was developed in the hypothermic effect of anandamide in tetrahydrocannabinol-tolerant mice, but not in mice pretreated with cannabidol and cannabinol1)Anandamide attenuated the hypothermic effects of tetrahydrocannabinol and its active metabolites, 11-hydroxy-tetrahvdrocannabinol and 11-oxo-tetrahydrocannabinol1)2-Arachidonoylglycerol also attenuated the hypothermic effect of 11-hydroxy-tetrahydrocannabinolThese results indicate that anandamide and 2-arachidonoylglycerol interact with certain cannabinoids in their pharmacological effects.