A repeated test procedure to assess onset and duration of the cue properties of (-) delta 9-THC, (-) delta 8-THC-DMH and (+) delta 8-THC.

Rats were trained in a two-lever operant box in drug discrimination procedure to respond differentially to the effects induced by 3 mg/kg of (-) delta 9-tetrahydrocannabinol (delta 9-THC) and the drug vehicle. Tests with (-) delta 9-THC and the dimethyl-heptyl (DMH) homologue of (-) delta 8-THC indicated that (-) delta 8-THC-DMH was more potent but had a slower onset of action than (-) delta 9-THC. Two ways of testing the onset and duration of action were compared. In one procedure (separate tests) the time course of the drug action was established by testing each time interval on separate days with a new injection each test day, whereas in the other procedure (repeated tests) all intervals were evaluated after a single injection. The results were similar for both procedures. The median time intervals for the decay of the (-) delta 9-THC stimulus were 122 and 127 min for the separate and repeated tests procedures respectively. The median time intervals for the onset of action of the (-) delta 9-THC-like effects of (-) delta 8-THC-DMH were 65 and 62 min for the separate and repeated tests procedures respectively. The median time intervals for the decay of (-) delta 8-THC-DMH (0.30 and 0.56 mg/kg) was between 8 and 24h after injection. Furthermore, a stereoselective action is indicated, as (+) delta 8-THC (5.6 and 10 mg/kg) did not substitute for (-) delta 9-THC.