Chemical characterisation of oxidative degradation products of Δ9-THC

Abstract

The chemical analysis of a sample of Δ9-THC, which had been stored in an ethanol/propylene glycol solution for 5 years, resulted in the isolation of several hydroxylated Δ9-THC derivatives, the main of which were trans-cannabitriol monoethyl ether (4) and trans-propanediol ethers 7 and 8. cis-Cannabitriol monoethyl ether (5) and the oxidised derivatives 3 and 6 were detected in lesser amounts. The structure elucidation of the unprecedented cannabinoids 3, 5, 7 and 8 was achieved mainly by NMR techniques. Full NMR assignment of compounds 4 and 6 were also made. The detection of cannabitriol (6) and the corresponding solvent-adduct analogues (compounds 4–8) was in agreement with the decomposition mechanisms previously proposed for Δ9-THC. The isolation of the endoperoxide 3 represents indirect evidence of the existence of unstable precursors that were suspected to be intermediates in the non-enzymatic oxidation pathway of Δ9-THC. Both isomers of cannabitriol monoethyl ether exhibited weak affinity at either CB1 (Ki=2.25, 6.30 μM) or CB2 cannabinoid receptors (Ki=1.97, 3.13 μM), the trans isomer always being more potent than the cis isomer.