Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.
Wei, Tzu-Tang , Chandy, Mark , Nishiga, Masataka , Zhang, Angela , Kumar, Kaavya Krishna , Thomas, Dilip , Manhas, Amit , Rhee, Siyeon , Justesen, Johanne Marie , Chen, Ian Y , Wo, Hung-Ta , Khanamiri, Saereh , Yang, Johnson Y , Seidl, Frederick J , Burns, Noah Z , Liu, Chun , Sayed, Nazish , Shie, Jiun-Jie , Yeh, Chih-Fan , Yang, Kai-Chien , Lau, Edward , Lynch, Kara L , Rivas, Manuel , Kobilka, Brian K , Wu, Joseph C
Publication Details
- Journal: Cell
- Volume: 185 (10 )
- Pages: 1676-1693.e23
- Published: May 2022
- Type: Journal Article
Abstract
Epidemiological studies reveal that marijuana increases the risk of
cardiovascular disease (CVD); however, little is known about the mechanism. Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Delta(9)-THC-induced inflammation and oxidative stress via NF-kappaB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Delta(9)-THC. In mice, genistein blocked Delta(9)-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Delta(9)-THC-induced atherosclerosis.
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Added: January 15, 2026 | Updated: January 15, 2026