The cannabimimetic activity of the two enantiomers of 11-hydroxy-delta-8-tetrahydrocannabinol (11-OH-delta-8-THC) was evaluated in pigeons trained to discriminate between the presence and absence of (-)-delta-9-tetrahydrocannabinol [(-)-delta-9-THC]. (-)-11-OH-Delta-8-THC exhibited cannabimimetic activity with a potency (ED50, 0.17 mg/kg) similar to that of delta-9-THC. The duration of action for (-)-11-OH-delta-8-THC was shorter than that observed for delta-9-THC. No cannabimimetic activity was seen after administrations of (+)-11-OH-delta-8-THC, indicating enantiomeric selectivity for the discriminable effects. A dose-related decrease in response rate occurred with (-)-11-OH-delta-8-THC, but not with (+)-11-OH-delta-8-THC; the latter compound produced an increase in responding at 3 mg/kg. Open-field behavior in Mongolian gerbils indicated marked suppression of rearing (vertical activity) after treatments with (-)-delta-9-THC and (-)-11-OH-delta-8-THC; this did not occur after (+)-11-OH-delta-8-THC. The results support the notion of cannabimimetic enantiospecificity.
Animals Behavior, Animal