Changes in 5-HT receptor binding induced by tetrahydrocannabinol metabolites in bovine cerebral cortex

Effects of four cannabinoids, Delta(8)-tetrahydrocannabinol (Delta(8)-THC), 11-hydroxy-Delta(8)-THC (11-OH-Delta(8)-THC), 11-oxo-Delta(8)-THC, and Delta(8)-THC-11-oic acid, on the bindings of [H-3]5-HT and [H-3]ketanserin to bovine synaptic membrane were examined by ligand binding assay. Both 11-OH-Delta(8)-THC and 11-oxo-Delta(8)-THC, which are psychopharmacologically active metabolites, significantly decreased the specific [H-3]5-HT binding to the membrane. Scatchard analyses indicated that 11-OH-Delta(8)-THC caused significant increase in the KD value with changes in Bmax, whereas 11-oxo-Delta(8)-THC caused significant increase only in the KD value. On the other hand, Delta(8)-THC-11-oic acid, an inactive metabolite, did not alter specific [H-3]5-HT binding. The results also indicated that all cannabinoids did not alter the specific [H-3]ketanserin binding. The present study reveals that the pharmacological activity of THC may be partially mediated through the active metabolites of THC on serotonergic receptors.