Hexahydrocannabinol (HHC) and Δ9-tetrahydrocannabinol (Δ9-THC) driven activation of cannabinoid receptor 1 results in biased intracellular signaling
Cannabis plant extracts include many compounds in addition to Δ9-THC and CBD. Further, β-arrestin initiates internalization of the receptor and, at the same time, facilitates activation of signaling pathways such as ERK1/2 or JNK319,20. The resulting mixture of ∆8-THC and MeOH was used for the reduction without further purification. G protein activation induced by CB1R stimulation To test whether HHC induces signaling via CB1R, we first measured the G protein activation in the transfected cells. Overall, the results indicate that the (9R)-HHC epimer stimulates GRK3-CB1R and β-arrestin2-CB1R interactions more effectively than Δ9-THC or the (9S)-HHC epimer.