RT Journal Article
SR Electronic
T1 TETRAHYDROCANNABINOL METABOLISM IN MAN
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 461
OP 468
VO 1
IS 1
A1 LOUIS LEMBERGER
YR 1973
UL http://dmd.aspetjournals.org/content/1/1/461.abstract
AB In man the pharmacologic effects elicited afterΔ 9-THC administration appear to correlate with the plasma levels of metabolites of Δ9-THC. 11-OH-Δ9-THC produces pharmacologic effects in man similar to those seen after Δ9-THC administration. This suggests that Δ9-THC is converted in vivo to 11-OH-Δ9-THC and that the latter is the active compound responsible for the effects of marihuana and hashish. The observation that the subjective effects of 11-OH-Δ9-THC administered iv are almost immediate in onset, whereas the effects of the same dose of Δ9-THC administered in a like fashion showed a delayed onset, lends additional support for this hypothesis. The quantitative and qualitative similarity of the excretory and metabolic patterns for Δ9-THC and 11-OH-Δ9-THC in man further support this hypothesis (table 5). In one subject who served as his own control (a typical cross-over experiment), the pharmacologic effects produced by 11-OH-Δ9-THC were comparable to those seen after Δ9-THC administration. In a second subject, 11-OH-Δ9-THC appeared to be twice as potent as Δ9-THC. It thus appears that in man these compounds vary from being almost equipotent to twice as active, differing only in their onset and duration of action. In a third subject, Δ9-THC produced only minimal effects. It appears as if the responses to a fixed 1-mg dose were correlated to the patients’ weights. These results are consistent with the effects in mice (16), where 11-OH-Δ9-THC has been reported to be about two times more potent than Δ9-THC. In summary, these studies provide direct evidence that after the administration of marihuana or hashish, the Δ9-THC is rapidly converted in man (presumably by microsomal hydroxylating enzymes) to 11-OH-Δ9-THC, which is responsible for the majority of the pharmacologic effects. Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics