TY - JOUR T1 - TETRAHYDROCANNABINOL METABOLISM IN MAN JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 461 LP - 468 VL - 1 IS - 1 AU - LOUIS LEMBERGER Y1 - 1973/01/01 UR - http://dmd.aspetjournals.org/content/1/1/461.abstract N2 - 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 ER -