Development of tolerance and cross-tolerance to the cataleptogenic effects of Δ8-tetrahydrocannabinol and 11-hydroxy-Δ8-tetrahydrocannabinol in mice

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Tolerance developed to the cataleptogenic effects of delta 8-tetrahydrocannabinol (delta 8-THC) and 11-hydroxy-delta 8-THC on daily administration (5 mg/kg per day i.v.) of these substances in mice. Reciprocal cross-tolerance was also demonstrated between both cannabinoids. The ED50S (mg/kg i.v.) for delta 8-THC and 11-hydroxy-delta 8-THC were 13.0 (10.2-16.5) and 5.3 (3.4-8.2), respectively, in delta 8-THC-tolerant mice (7 days' treatment) while the corresponding ED50S were 20.8 (17.6-24.5) and 11.7 (8.5-15.7), respectively, in 11-hydroxy-delta 8-THC-tolerant mice. These values were much higher than those in the vehicle-treated mice [delta 8-THC, 4.1 (2.8-5.9); 11-hydroxy-delta 8-THC, 0.98 (0.53-1.81)].

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