Chiral Separation of Hexahydrocannabinolic Acid (HHCA) Isomers Have Differential Activity Against Jurkat T Cells

The use of phytocannabinoid compounds has exploded since the opening up of medicinal and recreational cannabis markets as well as the legalization of industrial hemp. Chemical derivatives of the naturally occurring phytocannabinoids have been explored as novel therapeutics to treat numerous diseases and medical conditions. Here, we describe a new chemically modified phytocannabinoid derivative, namely hexahydrocannabinolic acid (HHCA), produced from plant-derived tetrahydrocannabinolic acid (THCA). Catalytic hydrogenation of THCA affords HHCA as a diastereomeric mixture at the 9-position on the ring that was separated chromatographically into the isolated 9R and 9S isomers. We assessed their cytotoxic activity on Jurkat T cells and, while a mixture of both isomers of HHCA were found to be more active than THCA, the isolated 9S HHCA isomer was significantly more active than the 9R HHCA isomer. This finding offers not only new molecules to assess for drug discovery, but possibly new mechanisms of action for chemically modified phytocannabinoids.