Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation. Academic Article uri icon

Overview

abstract

  • Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ9-THC. In mice, genistein blocked Δ9-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 Δ9-THC-induced atherosclerosis.

publication date

  • April 29, 2022

Research

keywords

  • Cannabis
  • Cardiovascular Diseases
  • Hallucinogens

Identity

PubMed Central ID

  • PMC9400797

Scopus Document Identifier

  • 85129930623

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2022.04.005

PubMed ID

  • 35489334

Additional Document Info

volume

  • 185

issue

  • 10