Marihuana-like activity of new synthetic tetrahydrocannabinols.

11-Methy-delta8-, 9-nor-delta8, and 9-nor-delta9-tetrahydrocannabinol (THC), newly synthesized cannabinoids which are not 11-hydroxyated in vivo, were tested for cannabinoid activity. Delta8-, delta9-THC and each synthetic analog produced static ataxia in unanesthetized dogs, hypotension and bradycardia in anesthetized dogs, and decreased spontaneous activity in mice. All synthetic analogs tested produced a greater degree of tolerance to the behavioral effect in dogs than did delta8-THC. 11-Methyl-delta8-THC was more effective than delta8-THC in decreasing spontaneous activity in mice, but was less active in producing the behavioral and cardiovascular effects in dogs. 9-nor-delta9-THC was less active than delta9-TCH, but 9-nor-delta8-THC was as active as delta8-THC in all observations. These results suggest that the 11-hydroxy metabolites of delta8- and delta 9-THC are not solely responsible for the biological activity of tetrahydrocannabinol.