As laws and public attitudes about cannabis use shift and evolve, researchers are seeking to better understand the long-term public health implications of more widespread use. Elucidating how cannabis and its constituents work inside the body and identifying risk factors for adverse effects can provide guidance for both healthcare providers and consumers to make informed decisions. Researchers at Stanford Medicine have now identified links between cannabis use and heart disease, and found that THC induces inflammation in human endothelial cells and worsens atherosclerosis in mice. Additionally, the researchers discovered that a compound found in soybeans could help mitigate some adverse effects without blocking the drug’s psychoactive effects.
The researchers took several approaches to explore the link between cannabis use and cardiovascular health. The team analyzed data from the UK Biobank, a database including genetic and medical information from about 500,000 people, and found a correlation between frequent cannabis smoking and heart attack risk. Nearly 35,000 participants in the database reported smoking cannabis, and about 11,000 of those participants smoked cannabis more than once per month. The researchers discovered that the higher frequency smokers were significantly more likely than others in the study to have a had heart attack, controlling for other factors including age, body mass index and sex. The team also found that the frequent smokers were more likely than nonusers to have had their first heart attack before the age of 50.
Testing the effects of THC on human cells and animal models in the lab, the researchers observed that human endothelial cells showed inflammation and hallmarks of atherosclerosis when exposed to THC, and laboratory mice bred to have high cholesterol and fed a high-fat diet developed significantly larger atherosclerosis plaques when injected with THC levels comparable to smoking one marijuana cigarette a day, compared to those that did not receive THC. Additionally, when volunteers smoked a marijuana cigarette, the levels of inflammatory cytokines in their blood increased significantly over the three hours after smoking. According to the researchers, these effects are due to binding of THC to CB1 receptors in the heart and vasculature system.
The team explored the potential of using a CB1 antagonist to counteract the effects of this interaction with THC. The researchers used machine-learning techniques to screen a large database of protein structures and identify molecules structurally similar to previously identified CB1 antagonists, that would not penetrate the brain and cause potential psychiatric side effects. This search led the team to genistein, a naturally-occuring compound in soy and fava beans, which could block THC’s inflammatory and atherosclerotic properties without affecting its psychoactive properties due to poor brain penetration. When genistein was added to human endothelial cells treated with THC and given to mice injected with THC, it prevented the adverse cardiovascular effects but did not interfere with its psychoactive effects. This research was published in Cell.
“We didn’t see any blocking of the normal painkilling or sedating effects of THC in the mice that contribute to marijuana’s potentially useful medicinal properties,” said co-lead author Mark Chandy. “So genistein is potentially a safer drug than previous CB1 antagonists. It is already used as a nutritional supplement, and 99% of it stays outside the brain, so it shouldn’t cause these particular adverse side effects.”
The researchers hope to conduct clinical trials in the future to learn whether genistein can reduce the risk of cardiovascular disease in cannabis users. They also plan to extend their research to include CBD in addition to THC.