Interactions between Δ9-tetrahydrocannabinol and cannabidiol as evaluated by drug discrimination procedures in rats and pigeons

Abstract

Animals (rats and pigeons) were trained to discriminate between the presence and absence of Δ 9-THC; the training doses were respectively: 0.56 mg/kg (pigeons) and 3.0 mg/kg (rats). Once the drug discrimination was mastered the pigeons were tested repeatedly after a single intramuscular (i.m.) injection of Δ 9-THC (0.56 mg/kg) at the following intervals 0.5, 1.5, 4.5 and 9 hr after the injection. These results were compared with data from a separate procedure, i.e. where the various intervals after injection were examined only once per injection and both procedures yielded essentially the same outcome. Thus, less than 50% appropriate responding to THC was observed at 0.5 and 9 hr after injection whereas greater than 90% responding to THC occurred at 1.5 and 4.5 hr. The two procedures have previously been compared in rats (Järbe Swedberg and Mechoulam 1981). The repeated tests procedure was then used to evaluate combinations of Δ 9-THC and cannabidiol in both species. Cannabidiol prolonged the cue effects of 1 mg/kg of Δ 9-THC (intraperitoneal route of administration) in rats but did not change the time-effect curve for Δ 9-THC in pigeons (dose range examined: 0.10–0.56 mg/kg); the challenge doses of cannabidiol were, respectively: 30.0 mg/kg (i.p.) and 17.5 mg/kg (i.m.). The rate of responding did not differ in tests with combinations of Δ 9-THC and cannabidiol as compared to Δ 9-THC given alone in pigeons. Subcutaneously administered 3-PPP a dopamine pre-synaptic blocker, did not induce responding appropriate for Δ 9-THC in rats.