A robust new study led by researchers from Stanford University has found a strong association between increased risk of heart attack and regular marijuana use. The study indicates THC can trigger inflammation in blood vessel cells and the researchers call for medical marijuana users to be aware of potential cardiovascular risks.
Published in the journal Cell, the new study first analyzed data from around 500,000 people, looking at the relationship between marijuana use and heart attack. After controlling for age, gender and body weight, the data showed those subjects who smoked marijuana more than once a month were much more likely to have a heart attack before the age of 50 compared to non-users.
The next step was to investigate how marijuana could be increasing a person’s risk of heart attack. Focusing particularly on THC, the researchers discovered the cannabinoid did promote inflammation in human endothelial cells grown in the lab. Inflammation of endothelial cells – the cells that line the inside of blood vessels and the heart – is a key indicator of heart disease.
“Marijuana has a significantly adverse effect on the cardiovascular system,” said co-lead author on the new study, Mark Chandy. “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.”
The final part of the research was an investigation to find molecules that could block the pro-inflammatory properties of THC without interrupting the psychoactive effects of the drug. The main action of THC is binding to CB1 receptors, so the researchers used machine-learning to screen a massive volume of molecules known to bind to CB1 and block the effects of THC.
One molecule that stood out was a naturally occurring substance called genistein. Found in soybeans, genistein does not effectively cross the blood-brain barrier so the researchers hypothesized it could possibly block the inflammatory effects of THC on endothelial cells while maintaining the psychoactive effects of THC on the brain. Subsequent mouse studies verified the hypothesis, showing genistein reducing endothelial dysfunction in THC-treated mice without disrupting the drug’s effects on the animal’s central nervous system.
“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,” added Chandy. “So genistein is potentially a safer drug than previous CB1 antagonists. It is already used as a nutritional supplement, and 99 percent of it stays outside the brain, so it shouldn’t cause these particular adverse side effects.”
According to the researchers, a more thorough clinical trial is needed to explore the effects of genistein on marijuana users and cardiovascular risk. The researchers also indicate CBD, another key cannabinoid in marijuana, may also have anti-inflammatory effects that could counter the potential cardiovascular effect of THC.
Prior research looking at the negative psychiatric effects of marijuana have suggested increased volumes of THC in modern strains of cannabis could lead to higher rates of adverse mental health issues. CBD, on the other hand, is a known anti-psychotic agent so it may be crucial to balance levels of these two cannabinoids in strains of medical marijuana.
Joesph Wu, senior author on the new study, said it is important medical and recreational marijuana users are aware of the potential adverse cardiovascular effects of the drug. And moving forward it will be crucial to develop ways to mitigate these adverse effects.
“There’s a growing public perception that marijuana is harmless or even beneficial,” said Wu. “Marijuana clearly has important medicinal uses, but recreational users should think carefully about excessive use.”
The new study was published in the journal Cell.
Source: Stanford Medicine
