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Cannabis Linked to Heart Disease, But a Soybean Compound May Mitigate Risk, Study Finds

By Alexander Beadle

Published: May 05, 2022   
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Frequent cannabis users are more likely to have a premature heart attack – a heart attack before the age of 50 – than non-users, according to new research from scientists at Stanford University. 

The study, published in the journal Cell, also showed that THC causes inflammation and oxidative stress in the endothelial cells that line the interior of blood vessels. This inflammation is a hallmark of atherosclerosis, the term given to the thickening of blood vessel walls due to the build-up of fatty plaques, which can lead to heart attack.

The researchers also found that this inflammation and atherosclerosis could be mitigated by genistein, a small molecule that is found naturally in soy and fava beans. Unlike other cannabinoid receptor type 1 (CB1) antagonists, genistein’s poor penetration across the blood-brain barrier means that the compound is able to address the inflammation of endothelial cells without causing adverse psychiatric side effects.

The Stanford researchers hope to soon conduct clinical trials looking at whether genistein might reduce the risk of cardiovascular disease in cannabis consumers.

Frequent cannabis smokers are more likely to suffer premature heart attacks

The Stanford researchers first examined genetic and medical data from around 500,000 individuals aged 40 to 69, taken from the UK Biobank database. Around 35,000 people in the database reported smoking cannabis, and of these around 11,000 reported smoking more than once per month.

After controlling for other demographic factors, such as age, body mass index, and sex, the researchers found that the more frequent cannabis smokers were significantly more likely than their peers to have had a heart attack. Frequent users were also more likely than non-users to have had a premature heart attack.

“There’s a growing public perception that marijuana is harmless or even beneficial,” senior study author Joseph Wu, a professor of cardiovascular medicine and of radiology and the director of the Stanford Cardiovascular Institute, said in a statement.

“Marijuana clearly has important medicinal uses, but recreational users should think carefully about excessive use.”

The researchers also performed a number of additional experiments to assess the relationship between THC and blood vessel inflammation. They saw increased levels of proinflammatory cytokines in human endothelial cells exposed to THC, lasting for up to 10 days after the initial exposure. Blood samples taken from volunteer recreational cannabis users also showed significant levels of inflammatory molecules.

Finally, laboratory mice specially bred to have high cholesterol levels were also seen to develop much larger atherosclerosis plaques when injected with THC levels equivalent a human smoking once per day.

“Marijuana has a significantly adverse effect on the cardiovascular system,” said lead study author Mark Chandy, an instructor of medicine at Stanford University.

“As more states legalize marijuana use, I expect we will begin to see a rise in heart attacks and strokes in the coming years. Our studies of human cells and mice clearly outline how THC exposure initiates a damaging molecular cascade in the blood vessels. It’s not a benign drug.”

Soybean compound could address blood vessel inflammation

Activation of the CB1 receptor is known to promote inflammation and oxidative stress and has been highlighted as a possible contributor to cardiovascular disease. The development of CB1 receptor antagonists to block these effects could be significant in reducing this cardiovascular disease risk, but the significant psychiatric side effects associated with current CB1 antagonist drugs have seen them fall out of favor.

In the hopes of identifying other possible CB1 antagonists with more tolerable side effects, the Stanford University researchers used machine-learning techniques to screen a large database of protein structures and identify compounds similar in structure to known CB1 antagonist drugs.

They found that genistein, an existing dietary supplement that is naturally found in soybeans, was capable of binding to CB1, but has poor penetration across the blood-brain barrier. This means that the soybean compound could potentially block the harmful inflammatory effects of THC while leaving the psychoactive effects of THC on the brain unchanged.

“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,” Chandy said. “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.”

When repeating the endothelial cell studies to include the use of genistein, they found that the cells recovered from THC-induced inflammation in just 4-6 days when the genistein and THC were co-applied, and in 6-8 days when the genistein was given after the initial THC exposure.

“As more states legalize the recreational use of marijuana, users need to be aware that it could have cardiovascular side effects,” said Wu. “But genistein works quite well to mitigate marijuana-induced damage of the endothelial vessels without blocking the effects marijuana has on the central nervous system, and it could be a way for medical marijuana users to protect themselves from a cardiovascular standpoint.”

Cannabis and heart health

While scientists agree that more research is still needed to properly characterize the effects of THC and wider cannabis products on the cardiovascular system, early research would appear to suggest that cannabis should be used with caution by those with heart conditions.

A study published last year in the Canadian Medical Association Journal found that young people who use cannabis are at a greater risk of heart attack than their sober peers. Habitual cannabis use has also been linked to greater aortic stiffness, which can be a risk factor for cardiovascular disease.

A scientific statement released by the American Heart Association in 2020 concluded that cannabis use does not seem to confer any particular benefits to heart health. Additionally, the statement highlighted a number of studies suggesting that cannabis use may be linked to an increased risk of heart attacks, atrial fibrillation, and heart failure.

“We do acknowledge the limited scope of evidence defining the cardiovascular safety of marijuana at present,” Muthiah Vaduganathan, a cardiologist at Brigham and Women's Hospital, Massachusetts, told Analytical Cannabis in 2020. “However, based on what we know, we believe there is sufficient evidence to give us pause.”

“We believe broader-scale clinical research is needed to better understand the safety of marijuana, especially on cardiovascular health,” he added.


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