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