Comparative pharmacology of Delta9-tetrahydrocannabinol and its metabolite, 11-OH-Delta9-tetrahydrocannabinol.

ABSTRACT

A comparison of the psychologic and physiologic effects of intravenously administered Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-Delta(9)-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-Delta(9)-THC (1 mg) to all subjects. In contrast, the peak psychologic "high" was delayed 10-20 min after the i.v. administration of Delta(9)-THC (1 mg). There was some individual variation in response among subjects. Psychologic effects correlated well with plasma levels of unchanged [(3)H]11-OH-Delta(9)-THC. About 75% of the administered radioactive dose was excreted in urine (25%) and feces (50%) after [(3)H]11-OH-Delta(9)-THC administration. The disposition, excretion, and metabolism of [(3)H]11-OH-Delta(9)-THC appear to be similar to that previously reported after [(14)C]Delta(9)-THC administration. These findings, in conjunction with the marked psychologic high seen after 11-OH-Delta(9)-THC, suggest that in man, Delta(9)-THC, the active constituent in marihuana, is converted to 11-OH-Delta(9)-THC, which is in part responsible for the psychologic effects.