People who smoke cannabis more than once a month have an increased risk of heart disease and heart attack, a new study has found – but the same study has also identified a mechanism and a molecule that may counteract the risk.

While links between weed and poor heart health have already been identified, the latest research sheds more light on the mechanisms behind the relationship, as well as analyzing data from a huge sample: half a million individuals.

In further tests on mice, the study also found that tetrahydrocannabinol (THC), weed's psychoactive component, leads to both inflammation in the endothelial cells that line the insides of blood vessels, as well as atherosclerosis (artery hardening or thickening).

"Marijuana has a significantly adverse effect on the cardiovascular system," says biologist Mark Chandy, from 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."

The human part of the study involved records of 500,000 participants in the UK Biobank project. Around 11,000 of those individuals smoked weed more than once a month, and they were significantly more likely to suffer a heart attack.

What's more, cannabis users were more likely than non-cannabis users to have their first heart attack before the age of 50. These premature heart attacks can go on to increase the risk of future heart attacks and other cardiovascular problems.

While it's not enough to show direct causation, the study controlled for other factors like age, body mass index and sex. It's enough to identify cannabis use as a risk factor for cardiovascular disease.

Wanting to look further into this relationship, the researchers found that the number of inflammatory molecules in the blood of volunteers rose significantly in the three hours after smoking a cannabis cigarette. That inflammation can lead to heart attacks.

Additional tests showed THC promoting inflammation in human endothelial cells grown in the lab, and lab mice developing significantly larger atherosclerosis plaques if they were injected with THC. It all adds up to a pretty comprehensive association.

THC creates its effects by binding to a receptor called CB1 in the human brain. The researchers went on to use machine learning models to look for CB1 antagonists: molecules that could limit this binding when the receptor becomes overactive.

They were successful in their search, identifying genistein – a naturally occurring molecule in soybean – that in mice seems to block the harmful effects of THC (inflammation and atherosclerosis) while keeping the ones that are beneficial for medical use (including dulling pain and stimulating appetite).

Side effects in patients such as increased anxiety and mood disorders have prevented scientists from using CB1 antagonists in the past, but the early signs are that these problems might not appear with genistein.

"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," says 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."

The next step is to run human clinical trials to see if genistein can indeed reduce the risk of heart disease in weed smokers. Future studies could also look at CBD (cannabidiol), another cannabinoid in cannabis that doesn't have the psychoactive effects of THC.

THC remains a controlled substance in the United States, which means it's strictly regulated for medical research use. With that in mind, the researchers admit that the long-term health effects of regular weed smoking are largely unclear.

Legalization of cannabis continues to expand in the US, and the researchers say that it could be decades before the long-term effects of this on cardiovascular health will be seen. In the meantime, further study is going to be invaluable.

"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," says radiologist Joseph Wu from Stanford University.

The research has been published in Cell.