The Metabolism of Deuterium-Labelled Analogues of Δ¹-, Δ ⁶-, and Δ ⁷- Tetrahydrocannabinol and the Use of Deuterium Labelling

Abstract

The in vivo and in vitro metabolism of Δ ¹-tetrahydrocannabinol (Δ ¹-THC,I), the main psychoactive principle of Cannabis sativa L., has been extensively studied in several species and to date some forty to fifty metabolites have been identified (1–4). Fewer studies have been made with the isomeric A⁶-THC (II), but from reported work it would appear that similar metabolic routes are involved (5, 6). The metabolism of the inactive Δ ⁷-THC (III) does not seem to have been reported. The major biotransformation pathways of Δ ¹- and Δ ⁶-THC involve allylic and aliphatic hydroxylations, oxidation to acids and ketones, ß-oxidation of the pentyl side-chain, epoxide formation and hydrolysis, reduction of the double bond and conjugation with glucuronic acid. Metabolites containing up to three metabolically introduced groups have been reported. Many of these metabolites are present in only very small amounts (1–10 ng/g of tissue) and thus their isolation in quantities sufficient for the recording of NMR or IR spectra is difficult. GC-MS although having the sensitivity to record spectra of such small amounts of material, does not always yield sufficient information for full structure elucidation.