PMID: 6113937May 1, 1981Paper

Metabolic disposition of delta 8-tetrahydrocannabinol and its active metabolites, 11-hydroxy-delta 8-tetrahydrocannabinol and 11-oxo-delta 8-tetrahydrocannabinol, in mice

Drug Metabolism and Disposition : the Biological Fate of Chemicals
K WatanabeH Yoshimura

Abstract

Metabolic disposition of delta 8-tetrahydrocannabinol (delta 8-THC), 11-hydroxy-delta 8-THC (11-OH-delta 8-THC), and 11-oxo-delta 8-THC was studied in mouse blood, liver, and brain. After administration of these cannabinoids at a dose of 10 mg/kg iv, the concentration in blood declined biphasically. The biological half-lives of the slower phases were 32, 12, and 6 min, respectively, for delta 8-THC, 11-OH-delta 8-THC, and 11-oxo-delta 8-THC. 11-OH- and 11-oxo-delta 8-THC were also eliminated faster from brain than is delta 8-THC. The peak levels of 11-OH- and 11-oxo-delta 8-THC in brain were, however, higher (10.64 and 4.25 microgram/g, respectively) than that of delta 8-THC (3.48 microgram/g) at 0.5 min after the iv injection (10 mg/kg). These results indicate that 11-OH- and 11-oxo-delta 8-THC are distributed more readily from blood to brain in mice than is delta 8-THC, and explain the greater pharmacological activity of these metabolites, as reported previously. It was also interesting to note that a much higher level of 11-OH-delta 8-THC (3.27 microgram/g) was found in brain than in liver(0.74 microgram/g) and blood (0.29 microgram/ml) at 15 min after the injection of 11-oxo-delta 8-THC (10 microgram/kg, iv). In this case t...Continue Reading

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