Comparative Pharmacology of Δ9-Tetrahydrocannabinol and its Metabolite, 11-OH-Δ9-Tetrahydrocannabinol

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Abstract
A comparison of the psychologic and physiologic effects of intravenously administered Δ9-tetrahydrocannabinol (Δ9-THC) and 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC) was carried out in nine casual marihuana smokers. A marked tachycardia and psychologic “high” occurred within 3-5 min after the i.v. administration of 11-OH-Δ9-THC (1 mg) to all subjects. In contrast, the peak psychologic “high” was delayed 10-20 min after the i.v. administration of Δ9-THC (1 mg). There was some individual variation in response among subjects. Psychologic effects correlated well with plasma levels of unchanged [3H]11-OH-Δ9-THC. About 75% of the administered radioactive dose was excreted in urine (25%) and feces (50%) after [3H]11-OH-Δ9-THC administration. The disposition, excretion, and metabolism of [3H]11-OH-Δ9-THC appear to be similar to that previously reported after [14C]Δ9-THC administration. These findings, in conjunction with the marked psychologic high seen after 11-OH-Δ9-THC, suggest that in man, Δ9-THC, the active constituent in marihuana, is converted to 11-OH-Δ9-THC, which is in part responsible for the psychologic effects.