Pharmacological potency of R- and S-3'-hydroxy-delta 9-tetrahydrocannabinol: additional structural requirement for cannabinoid activity.

The pharmacological potency of R- and S-3'-hydroxy-delta 9-tetrahydrocannabinol (THC) was compared to that of delta 9-THC as well as R/S-3'-OH-delta 9-THC. The S-isomer was found to be considerably more potent than the R-isomer in producing hypoactivity in mice, static-ataxia in dogs, and in generalization testing in rats trained to discriminate delta 9-THC from vehicle. S-3'-OH-delta 9-THC was more active than delta 9-THC in these tests which means that delta 9-THC may be either activated or inactivated in vivo depending upon which metabolite is formed. The difference in potency of these isomers suggests that the conformation of the side chain is critical for behavioral activity. The R and S isomers were found to be equally active in producing hypothermia in mice which is in contrast to the behavioral effects.