Delta9-tetrahydrocannabinol and 11-hydroxy-delta9-tetrahydrocannabinol: behavioral effects and tolerance development.

Abstract

The effects of intravenous injections of Δ9-tetrahydrocannabinol (Δ9-THC) and its hydroxylated metabolite, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC) were studied in pigeons, whose rates of key pecking were maintained by a variable-interval 3-minute schedule of food presentation. A dose of 0.03 mg/kg of either Δ9-THC or 11-OH-Δ9-THC produced an almost immediate decrease in the rate of key-peck responding, with the rate of responding returning to control levels within 30 to 45 minutes after injection. Doses of 0.1 to 0.3 mg/kg of either Δ9-THC or 11-OH-Δ9-THC completely eliminated responding immediately after injection with a gradual recovery of responding beginning within 60 to 90 minutes (0.1 mg/kg) or 195 to 240 minutes (0.3 mg/kg). The gradual recovery of responding took place over a 60- to 90-minute period for both doses of Δ9-THC and 11-OH-Δ9-THC. Finally, tolerance developed to successive daily injections of 0.3 mg/kg of either Δ9-THC or 11-OH-Δ9-THC over an 8- to 15-day period and a reciprocal cross-tolerance was demonstrated between Δ9-THC and 11-OH-Δ9-THC. On the basis of these effects on the schedule-controlled behavior of pigeons, Δ9-THC and 11-OH-Δ9-THC are indistinguishable.