Many organic reactions rely on CO 2 sources to generate important structural units and valuable chemicals. In this study, we compared the effects of cannabidiol (CBD) and cannabidiolic acid (CBDA) on the supercritical CO 2 (scCO 2 )-induced de/carboxylation reaction. The results showed that CBD was directly carboxylated in the ortho -position to form CBDA with up to 62% conversion. Meanwhile, CBDA decarboxylation occurred on hemp plant material via varying composition. Mechanistic studies revealed that CBD carboxylation was influenced not only by the physical properties of scCO 2 , but also by the vegetable matrix.