Metabolism of Δ1‐tetrahydrocannabinol by the isolated perfused dog lung. Comparison with in vitro liver metabolism

The metabolism of (—)-Δ1-tetrahydrocannabinol (Δ1-THC) has been studied in the isolated perfused dog lung. After intravascular administration of [3H]-Δ1-THC there was an overall biotransformation of 12%. Two major metabolites were isolated and identified as 3“-hydroxy-Δ1-THC and 4”-hydroxy-Δ1-THC. 7-Hydroxy-Δ1-THC was also present together with small amounts of 6α-hydroxy-Δ1-THC and 6β-hydroxy-Δ1-THC. An in vitro experiment using a dog liver microsomal preparation was also carried out and showed that the major metabolites were 6β-hydroxy-Δ1-THC and 6α-hydroxy-Δ1-THC. 7-Hydroxy-Δ1-THC and 1,2-epoxy-hexahydrocannabinol were also isolated together with small amounts of 3“-hydroxy-Δ1-THC and 4”-hydroxy-Δ1-THC. The side-chain hydroxylated compounds are hitherto undescribed metabolites of Δ1-THC.