入手容易な材料によるカンナビジオールからΔ⁹-およびΔ⁸-テトラヒドロカンナビノールへの変換過程

抄録

 Cannabidiol (CBD), an uncontrolled cannabinoid in marijuana, is readily converted to the controlled Δ⁹- and Δ⁸-THCs under acidic conditions. In this study, we monitored the time-course conversion of CBD into the two THCs using easily available acids and solvents by gas chromatography-mass spectrometry. Placing CBD (3.3 mg/mL) in 4.2 mM sulfuric acid-glacial acetic acid solution at room temperature resulted in the production of Δ⁹-Tetrahydrocannabinol (Δ⁹-THC) after 3 hours, followed by Δ⁸-THC after 96 hours. The conversion continued, and their relative abundance was Δ⁹-THC>CBD>Δ⁸-THC after 192 hours. Elevating the sulfuric acid concentration to 42 mM promoted the conversion to where CBD depleted in 3 hours, Δ⁹-THC production peaked (and started to decline) at 12 hours, and Δ⁸-THC became the major constituent at 100 hours. Replacing sulfuric acid with muriatic acid showed the similar time-course conversion. The THCs/CBD ratio varies under acidic conditions; this ratio can be used as an indicator for identifying the product lots of liquid drugs containing THCs converted from CBD. Ethanol, alternative solvent to glacial acetic acid, kept CBD unchanged with 42 mM sulfuric acid for 192 hours at room temperature, but conversion into Δ⁹-THC was observed after 6 hours when heated at 70℃. Without an acid catalyst, CBD was stable under heating cycles from 60℃ to 130℃ in an electric vaporizer. Thus, the unintentional production of THCs seems unlikely only by heating a commercial CBD product. The CBD-to-THCs conversion also yielded several by-products. Among them, possible Δ⁸-iso-THC was detected under all 12 combination conditions (two catalytic acids and six solvents) investigated in this study. Additionally, the use of alcohol solvents produced alcohol adducts of the THCs. Detection of by-products therefore can provide more solid information for identifying the product lots and estimating the condition of CBD conversion.