Chemical characterisation of oxidative degradation products of Δ9-THC

Abstract The chemical analysis of a sample of Δ 9 -THC, which had been stored in an ethanol/propylene glycol solution for 5 years, resulted in the isolation of several hydroxylated Δ 9 -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 Δ 9 -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 Δ 9 -THC. Both isomers of cannabitriol monoethyl ether exhibited weak affinity at either CB 1 ( K i =2.25, 6.30 μM) or CB 2 cannabinoid receptors ( K i =1.97, 3.13 μM), the trans isomer always being more potent than the cis isomer.