Cross-tolerance to the hypothermic effect of delta 8-tetrahydrocannabinol 11-hydroxy-delta 8-tetrahydrocannabinol and chlorpromazine in the mouse.

When a 5 mg/kg i.v. dose of delta 8-tetrahydrocannabinol (delta 8-THC) and 11-hydroxy-delta 8-tetrahydrocannabinol (11-OH-delta 8-THC) was administered daily to mice, tolerance to their hypothermic effects developed quickly. Cross-tolerance to the hypothermic effect also developed between delta 8-THC and 11-OH-delta 8-THC. Tolerance development was dose-dependent and dose-effect experiments indicated that the magnitude of the tolerance developed to 11-OH-delta 8-THC was greater than that to delta 8-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-delta 8-THC has some role in the development of tolerance to the hypothermic effect of delta 8-THC in mice.