Brain levels of delta1-tetrahydrocannabinol and its metabolites in mice tolerant to the hypothermic effect of delta1-tetrahydrocannabinol.

Repeated voluntary consumption of cannabis in milk (approximately 8 mg per day for 15 days) produced in mice tolerance to the hypothermic effect of tritiated Delta(1)-tetrahydrocannabinol ([(3)H]-Delta(1)-THC; 2 mg/kg i.v.) but not to the effect of [(3)H]-Delta(1)-THC on immobility index. The development of tolerance was not accompanied by any detectable change in levels of radioactivity in the brain assigned to Delta(1)-THC or its metabolites. It was concluded that changes in metabolism or distribution of Delta(1)-THC are not responsible for tolerance at least to the hypothermic effect of Delta(1)-THC in mice.