Collaborating scientists in Taiwan and the U.S. have identified a compound in soybeans that may help to prevent some of the adverse cardiovascular effects of both recreational and medical marijuana use. The researchers, at National Taiwan University in Taipei, Stanford Cardiovascular Institute, and Stanford University, report the results of their laboratory studies in a poster presentation at the American Heart Association’s Basic Cardiovascular Sciences 2019 Scientific Sessions. The abstract (#497, Poster session 2) is titled “Studying Cardiovascular Effects Of Marijuana On Healthy Individuals using Human Derived Induced Pluripotent Stem Cells.”
Marijuana is the most widely used illicit drug in the world, and its legal status is increasingly being relaxed for recreational use. However, studies have linked marijuana smoking with an increased risk of heart attack and stroke. “Epidemiological studies indicate that marijuana increases the risk of coronary artery disease (CAD),” wrote the research team, headed by Tzu-Tan “Thomas” Wei, PhD, who is assistant professor of pharmacology in the College of Medicine at National Taiwan University.
Three synthetic cannabis drugs are also now approved by FDA for treating chemotherapy-induced nausea and vomiting, but such drugs also have side effects. Medical cannabis therapies containing delta-9-tetrahydrocannabinol (THC)—the main psychoactive component of marijuana—are associated with cardiovascular effects, including changes to heart rate and blood pressure. “These medications are prescribed to reduce the nausea and vomiting induced by chemotherapy and to increase appetite in certain people with acquired immune deficiency syndrome,” said Wei.
The effects of THC are linked with the chemical binding to one of two cannabinoid receptors (CB1 and CB2). Drugs that block the CB1 receptor have shown therapeutic potential but have not been without their own issues. “Previously, a drug that blocked CB1 was approved in Europe for the treatment of obesity, but it had to be withdrawn because of severe psychiatric side effects,” Wei added. And as the researchers stated, “Therefore, developing new CB1 antagonists are an unmet and growing clinical need with marijuana use on the rise.”
For their reported study, the investigators first generated human induced pluripotent stem cell-derived endothelial cells (HiPSC-ECs) from five healthy individuals. Endothelial cells are a cell type that lines the internal surfaces of blood vessels. Tests showed that exposing the cells to THC induced inflammation and oxidative stress, which are known to affect the inner linings of blood vessels and are associated with the development of heart disease. When the researchers used genetic techniques to knock down the CB1 gene or prevent expression of the CB1 receptor the adverse effects of THC were reduced. They also demonstrated that the soybean-derived antioxidant, an isoflavone designated JW-1, could similarly block the CB1 receptor in endothelial, with similar effects. “Here we found compound JW-1, an isoflavone abundantly presenting in soybeans, partially docked into the CB1 receptor and inhibited CB1 activity, suggesting that compound JW-1 was a novel CB1 antagonist, they wrote. “Knockdown of CB1 receptor with siRNA, abrogation of receptor expression with CRISPR, and compound JW-1 treatment could rescue the effect of delta9-THC.”
Further experiments using a laboratory technique known as wire myography to examine the response of mouse arteries to THC also showed that treatment using JW-1 blocked THC’s negative effects on the function of the inner vessel lining. “Discovering a new way to protect blood vessels without psychiatric side effects would be clinically important with the rapid growth of cannabis use worldwide,” Wei commented.
The researchers are now testing cells derived from regular marijuana users and those who smoke both cigarettes and marijuana. They are also investigating the impact of THC along with the other main component of marijuana, cannabidiol. “Meanwhile, if you have heart disease, talk to your doctor before you use marijuana or one of the synthetic THC-containing medications,” Wei advised. “Marijuana may cause more severe effects on the cardiovascular system in those with pre-existing heart disease.”