When a 5 mg/kg i.v. dose of Δ8-tetrahydrocannabinol (Δ8-THC) and 11-hydroxy-Δ8-tetrahydrocannabinol (11-OH-Δ8-THC) was administered daily to mice, tolerance to their hypothermic effects developed quickly. Cross-tolerance to the hypothermic effect also developed between Δ8-THC and 11-OH-Δ8-THC. Tolerance development was dose-dependent and dose-effect experiments indicated that the magnitude of the tolerance developed to 11-OH-Δ8-THC was greater than that to Δ8-THC. Both cannabinoids were cross-tolerant to chlorpromazine in the hypothermic effect, but not to morphine, pentobarbital and reserpine under the conditions used. The present results suggest that 11-OH-Δ8-THC has some role in the development of tolerance to the hypothermic effect of Δ8-THC in mice.
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