COMPETITIVE-INHIBITION OF DELTA-8-TETRAHYDROCANNABINOL AND ITS ACTIVEMETABOLITES FOR CANNABINOID RECEPTOR-BINDING

In vitro binding characteristics of Delta(8)-tetrahydrocannabinol (Del ta(8)-THC) and its metabolites, 11-hydroxy-Delta-(THC)-T-8(11-OH-Delta (8)-THC) and 11-oxo-Delta(8)-THC, as well as an inactive metabolite, D elta(8)-THC-11-oic acid, as a cannabinoid receptor site from bovine co rtex were examined using the specific agonist [H-3]CP-55940, 11-OH-Del ta(8)-THC and 11-oxo-Delta(8)-THC strongly inhibited the specific bind ing of [H-3]CP-55940. The K-i values of 11-OH-Delta(8)-THC and 11-oxo- Delta(8)-THC for the specific binding of [H-3]CP-55940 were 52 and 143 nm, respectively, whereas that of Delta(8)-THC-11-oic acid was 917 nm . Scatchard plot analyses indicated that 11-OH-Delta(8)-THC and 11-oxo -Delta(8)-THC caused a significant increase in the apparent K-D value without changing the apparent B-max. These results reveal that active metabolites of Delta(8)-THC also competitively bind to the cannabinoid receptor as agonists.