Cannabidiol Cyclization to Tetrahydrocannabinol in Consumer CBD Products

The 2018 Agricultural Improvement Act distinguished “marijuana” from “hemp”, with the latter defined as the plant Cannabis sativa L. and its derivatives which contain less than 0.3% Δ9-THC ((-)-trans-Δ9-tetrahydrocannabinol) by dry mass. Consequently, Americans are purchasing an unprecedented quantity of hemp-derived cannabinoid formulations, many of questionable quality. Most hemp-derived cannabidiol (CBD) products, even those marketed as “THC-free”, contain some amount of Δ9-THC. The unintended consumption of Δ9-THC carries a plethora of risks including adverse health effects, legal consequences, and possible loss of employment. As such, a detailed mechanistic understanding of THC’s appearance in CBD products is necessitated.
Contaminant Δ9-THC could be an artifact of inadequate CBD purification or improper product handling and storage conditions that induce CBD transformation to THC. Traditionally, the isomerization of CBD to THC is catalyzed by strong Lewis and protic acids, proceeding quickly in organic solvent; however, CBD is also known to convert to THC when subjected to elevated temperatures. THC impurities have also been formed in laboratory-synthesized CBD stored under a humid, CO2-saturated atmosphere. Presumably, this atmosphere enables the formation of carbonic acid, which then acts as catalyst for the cyclization into THC. Heat-induced decarboxylation of tetrahydrocannabinolic acid (THCA, another precursor to THC) may likewise prove to be a source of THC.
Here, we summarize the current mechanistic understanding regarding the appearance of THC in CBD oils and present our evaluation of commercial CBD formulations exposed to CO2 directly and by contact with aqueous solution. HPLC-DAD quantification data of CBD and THC before and after (i.) heating at 60 ◦C and (ii.) sparging with CO2 will be presented. Gas-phase computational thermochemical data will also be presented.