Pharmacological Activities in the Mouse of Δ9 -Tetrahydrocannabinol Metabolites Oxidized at the 8-Position

Abstract

The pharmacological effects of Δ9-tetrahydrocannabinol (THC) metabolites, 8α-hydroxy-Δ9-THC (8α-OH-Δ9-THC), 8β-OH-Δ9-THC and 8-oxo-Δ9-THC, were examined in the mouse. Cataleptogenic, hypothermic and pentobarbital-induced sleep-prolonging effects were produced by intravenous injection of the metabolites and compared with those of Δ9-THC. In all the pharmacological indices, Δ9-THC and 8-oxo-Δ9-THC had the highest and the lowest activity, respectively. The activity of 8α-OH-Δ9-THC was less potent in catalepsy and more potent in hypothermia than that of 8β-OH-Δ9-THC, while they were equipotent in barbiturate synergism. These results suggest that oxidation at the 8-position is one of the detoxication pathways of Δ9-THC, and also indicate the complexity of cannabinoid action in the central nervous system. © 1985, The Pharmaceutical Society of Japan. All rights reserved.