Selected Grantee Publications

Cannabinoid Receptor 1 Antagonist Genistein Attenuates Marijuana-Induced Vascular Inflammation

Wei et al., Cell. 2022.

https://www.doi.org/10.1016/j.cell.2022.04.005

Marijuana use is increasing and is associated with increased risk of cardiovascular disease (CVD); however, the link between marijuana and CVD remains largely unknown. Investigators demonstrated that a psychoactive component of marijuana, Δ⁹-tetrahydrocannabinol (Δ⁹‑THC), activates cannabinoid receptor 1 (CB1), causing vascular inflammation, oxidative stress, endothelial dysfunction, and atherosclerosis. This in silico virtual screening study suggested that genistein, a soybean isoflavone, would be a putative CB1 antagonist. Their validation study showed that in male mice, genistein blocked Δ⁹-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. This study for the first time revealed that genistein is a CB1 antagonist that attenuates Δ⁹-THC-induced atherosclerosis while preserving clinically useful effects. Supported by ORIP (S10OD030452) and others.