D8-THC binds to cannabinoid receptors CB1 and CB2 in mammals. These receptors are the primary receptors in the endocannabinoid system, and their activation by endogenous and exogenous substances is responsible for the effects mediated by the endocannabinoid system.

The endogenous ligands of the cannabinoid receptors are termed endocannabinoids. They are N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG).