Action of delta-9-tetrahydrocannabinol. An approach to the active metabolite hypothesis.

The active metabolite hypothesis, that delta-9-tetrahydrocannabinol (THC) must be converted to its 11-hydroxy metabolite before it becomes active, was tested in a study of subjects chosen as rapid and slow hydroxylators of drugs on the basis of antipyrine and phenylbutazone plasma disappearance rates. Although the sample of subjects showed the customary wide variations in effects experienced after an intravenously administered dose of THC, it was impossible to correlate either the speed of onset, total intensity, or duration of these effects with speed of hydroxylation of drugs. Although 11-hydroxy-THC has unquestioned activity indistinguishable from THC itself, it need not necessarily be solely responsible for the pharmacologic activity of THC.