Comparative Pharmacology of Δ<sup>9</sup>-Tetrahydrocannabinol and its Metabolite, 11-OH-Δ<sup>9</sup>-Tetrahydrocannabinol

Louis Lemberger; Robert Martz; Bruce Rodda; Robert Forney; Howard Rowe

doi:10.1172/JCI107431

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

Louis Lemberger, Robert Martz, Bruce Rodda, Robert Forney, and Howard Rowe

Published October 1, 1973 - More info

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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.