Profound hypothermia in mammals treated with tetrahydrocannabinols, morphine, or chlorpromazine

The tetrahydrocannabinols are among the most potent hypothermic agents known. A comparison of the hypothermic action of delta9-tetrahydrocannabinol (delta9-THC) with chlorpromazine (CPZ) and morphine shows the following order of hypothermic potency: CPZ greater than delta9-THC greater than morphine. A marked depression of oxygen consumption is produced by delta9-THC both in vivo and in the isolated perfused liver preparation. Simultaneous measurement of core temperature and tail temperature after delta9-THC shows that tail temperature is decreased more by delta9-THC than it is in animals that attain comparable core hypothermia without drug treatment. From these results, it is concluded that delta9-THC-induced hypothermia results primarily from decreased heat production and not from increased heat loss. Therefore, the processes involved in the hypothermic response to delta9-THC appear to differ from those that mediate CPZ- or morphine-induced hypothermia. A hypothesis is discussed in which the hypothermic action of delta9-THC is related to inhibition of membrane ATPase.