In vivo metabolism of the n-butyl-homologues of δ⁹-tetrahydrocannabinol and δ⁸-tetrahydrocannabinol by the mouse

Abstract

1. n-Butyl-homologues of δ⁸-tetrahydrocannabinol (δ⁸-THC) and δ⁹-THC were synthesized from 5-butyl-1,3-dihydroxybenzene and (1S)-cis-verbenol, and the δ⁹-isomer was shown to have the same g.l.c.-mass spectral characteristics as the natural product.

2. Metabolism of these cannabinoids was studied in mice following i.p. injection. Metabolites were extracted from the livers, separated from endogenous lipids by chromatography on Sephadex LH-20 and examined by g.l.c.-mass spectrometry.

3. Thirteen metabolites were identified fmm both n-butyl-δ⁸-THC and n-butyl-δ⁹-THC.

4. Major metabolic routes were hydroxylations in the 2′, 3′, 8 and 11 positions and oxidation of the resulting 11-hydroxy-metabolites to carboxylic acids.

5. Metabolism was very similar to that of the pentyl homologues, the major constituents of cannabis, but with the production of a greater proportion of acidic metabolites at the expense of alcohols.