Evaluation of the hypothermic action of tetrahydrocannabinols in mice and squirrel monkeys.

The hypothermic action of Δ9-tetrahydrocannabinol (Δ9-THC), 11-hydroxy-Δ8- tetrahydrocannabinol (11-OH-Δ8-THC) and the synthetic tetrahydrocannabinol, 1-hydroxy 3-(1,2-dimethylheptyl) - 6,6,9-rimethyl - 7,8,9,10 - tetrahydro - 6 -dibenzopyran (DMHP), have been studied in the mouse and squirrel monkey. In the mouse the magnitude of the hypothermic response to Δ9-THC has been shown to decrease as ambient temperature is increased from 20 to 35°C. Acute toxicity increases as ambient temperature is raised or lowered from 20°C. In studies carried out at 20°C, where toxicity is minimal and hypothermia to Δ9-THC is nearly maximal, a dose-response relationship has been shown for the hypothermic response to intravenous Δ9-THC, 11-OH-Δ8- THC and DMHP in the mouse. Maximal hypothermia recorded was 12.77 ± 0.60°C (Δ9-THC, 32 mg/kg), > 12.45°C (DMHP, 2 mg/kg) and 6.20 ± 0.35°C (11-OH-Δ8- THC, 32 mg/kg). Hypothermic responses of comparable magnitude but slower onset were recorded in the monkey after intravenous administration of Δ9-THC or DMHP at an ambient temperature of 24°C. The importance of ambient temperature control during studies of the action of tetrahydrocannabinols on other systems is discussed.