Potent α Glucosidase Inhibition by a Non Psychoactive CBG/CBD Rich Cannabis Extract

Cannabinoids from Cannabis sativa have attracted increasing attention as potential adjuncts for diabetes management due to their ability to inhibit carbohydrate-digesting enzymes. This study aimed to investigate the α-glucosidase inhibitory activity of purified cannabinoids and chemotyped cannabis extracts to identify potent non-psychoactive candidates. Purified delta‑9‑tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) were first evaluated in vitro. Among these compounds, THC exhibited the strongest inhibitory activity (IC₅₀ = 90.19±3.14 μg/mL), followed by CBD (IC₅₀ = 331.54±7.45 μg/mL) and CBN (IC₅₀ = 536.65 ± 9.85 μg/mL). For comparison, the reference drug acarbose showed an IC₅₀ value of (484.10± 4.26 μg/mL) under the same assay conditions. Because the psychoactive nature and regulatory restrictions of THC limit its direct application, several cannabis chemotype extracts with distinct cannabinoid profiles were subsequently examined. Among the crude extracts, the THC-rich chemotype (Black Dragon) showed the strongest inhibition (IC₅₀ = 271.77 ± 6.98 μg/mL). Notably, a hybrid chemotype designated CBG-F1, characterized by a balanced CBG:CBD ratio of approximately 1:1.3, demonstrated markedly stronger activity (IC₅₀ = 111.51±8.42 μg/mL), approaching the potency of purified THC despite containing no major psychoactive cannabinoids. Enzyme kinetic analysis using Lineweaver–Burk plots revealed that CBG-F1 acts as a non-competitive inhibitor of α-glucosidase, reducing catalytic activity without affecting substrate binding affinity. These findings highlight the potential of CBG/CBD-rich cannabis chemotypes as promising non-psychoactive sources of α-glucosidase inhibitors and support their further development as functional ingredients for supportive antidiabetic applications.