THCA synthase is the enzyme responsible for converting cannabigerolic acid (CBGA) into tetrahydrocannabinolic acid (THCA), the precursor to psychoactive THC. This flavin-dependent oxidocyclase catalyzes a complex stereospecific cyclization reaction that forms THCA's characteristic tricyclic structure. The enzyme shows remarkable substrate specificity, preferentially converting CBGA while showing minimal activity toward other cannabinoid precursors.
THCA synthase is expressed primarily in glandular trichome secretory cells during flowering, with expression levels and enzyme activity varying significantly between populations. High-THC varieties produce abundant, highly active THCA synthase, while CBD-dominant varieties possess mutations in the THCA synthase gene that render it non-functional, shunting cannabinoid biosynthesis toward CBDA instead. The enzyme's catalytic mechanism involves oxidative cyclization coupled with molecular oxygen reduction, producing THCA and hydrogen peroxide as products. Understanding THCA synthase function explains why some landrace populations produce predominantly THC (functional enzyme) while others maintain balanced ratios (intermediate enzyme activity) or produce mainly CBD (non-functional THCA synthase with functional CBDA synthase). Regional variation in THCA synthase activity reflects millennia of selection—for psychoactive effects in drug cultivars, for fiber in hemp, or for balanced profiles in traditional medicinal populations.
