Clinicians should warn patients about the potential of cannabis to harm cardiovascular health – depending on how much they use, and how much stock should be placed in observational studies – while another expert has suggested the avoidance of cannabis altogether.
The link between cannabinoids and cardiovascular disease, which used to be limited to evidence from pre-clinical studies, case reports and case series, is now evident in epidemiological studies, a Stanford University team reported in their recent paper in Nature Reviews Cardiology.
A large-scale US study from 2024 relied on survey data from more than 430 000 respondents and found the 4% of respondents who reported using cannabis daily had a 49% increased risk for myocardial infarction and a twofold increased risk for stroke. The added risk from cannabis was similar among those who also smoked tobacco and those who never used tobacco.
The effect was also dose dependent. Among weekly users, cannabis was associated with a 3% increased likelihood of heart attack and a 5% increased risk for stroke.
Heart attack and stroke
The latest findings echo another Stanford University study from 2022, which analysed UK Biobank data from 500 000 participants aged 40, and found those who reported smoking cannabis were significantly more likely to have a heart attack than non-users (53% vs 45%).
Several studies have found an association between arrhythmia, especially atrial fibrillation, and cannabis use. A study published last year in the European Heart Journal showed the risk for new onset arrhythmia in the first 180 days was 0.8% among more than 5 000 patients who had filled a cannabis prescription vs 0.4% for control participants, matched according to age, sex and the use of other pain medications.
Although cannabis contains 100t cannabinoids, research from cell culture and mouse models suggest tetrahydrocannabinol (THC) can cause inflammation and oxidative stress inside the vasculature, said Mark Chandy, MD, PhD, a cardiologist scientist and assistant professor at Western University in London, Ontario, Canada.
He is a co-author on the Stanford study as well as the Nature Reviews Cardiology paper, reports Medscape.
THC binds to the CB1 receptor, found in the brain, but also in the myocardium, vascular endothelial, and smooth muscle cells. The CB1 receptor promotes atherosclerotic changes, Chandy said, adding that mouse models have found that cannabis increases atherosclerotic plaques.
Scientists also theorise that cannabis might have a prothrombotic effect, increasing the risk for heart attacks and strokes.
When it comes to arrhythmia, the activation of CB1 and CB2 receptors can also lead to enzyme inhibition that could ultimately affect the heart’s electrical conduction system.
Disturbing the heart’s electrical conduction
Chip Lavie, MD, medical director at the John Ochsner Heart and Vascular Institute in New Orleans, said that “vasospasm and constriction of blood vessels combined with high platelet aggregation” is the most probable mechanism for the association between cannabis and cardiovascular disease.
However, studies also show that cannabis can increase the heart rate. “Many studies show the benefits of a low resting heart rate,” he said.
Considering the evidence, he recommends patients avoid cannabis. If that is not possible, patients should reduce their cannabis use and consume edible cannabis or oils, rather than smoking.
Although there isn’t enough evidence to show that consuming cannabis by edibles or oils is safer for the heart, burning cannabis adds toxins.
Chandy suggested cardiologists inform patients who use cannabis about the potential long-term cardiovascular side effects. “I would advise them not to use cannabis. At least, they should be able to make an informed decision about it and know the potential consequences.”
“Despite the emerging association between cardiovascular disease and cannabis use, there isn’t super strong evidence of causal effects,” said Anders Holt, MD, a cardiologist at Copenhagen University Hospital, Denmark, who led the study that found higher rates of arrythmia among medical cannabis users.
Mouse models frequently don’t translate to human physiology, he said.
Weighing the evidence
As long-term randomised controlled trials studying cannabis and the heart are not feasible or ethical, evidence comes from observational studies, which are prone to confounders.
For example, those who consume cannabis recreationally may be more likely to engage in other activities, like alcohol consumption or high-caloric diets, which can have an impact on cardiovascular results.
Much of the evidence linking cannabis use with coronary artery disease is based on studies of participants being asked about recent cannabis use. Patients may misremember previous use, focus only on their use in the last week, or hide their cannabis use from doctors.
Holt’s study was less prone to recall bias, as it relied on medical prescriptions, rather than self-reported data. Still, there could be important differences between patients who fill medical cannabis prescriptions and those who don’t.
The big picture, however, is that it may not matter whether the association between cannabis and an increased cardiovascular disease risk “is due to the lifestyle, or the selection of these patients, or the active components”, suggested Holt. “We know that people who use cannabis are at an elevated risk, so maybe they should be getting a more vigilant approach.”
Talking to patients
Holt said it would be reasonable “to bring up emerging evidence questioning whether medical cannabis is entirely safe for the heart” when talking to patients about lifestyle changes that they can make to reduce their risk for cardiovascular complications.
Despite the increased risk for arrhythmia, Holt said his study doesn’t imply that medical cannabis shouldn’t be used for chronic pain, however.
For one, the overall absolute risk for arrhythmia remains low. For another, treating pain allows patients to engage in activities that are good for their overall health, and cannabis could be safer than alternatives.
“There is very good evidence that non-steroidal anti-inflammatory drugs (NSAIDs), anti-epileptic drugs, and opioids are not ideal for the heart either.”
In addition to discussing why patients use cannabis, Chandy suggested cardiologists discuss with patients how much cannabis they consume and the route of administration. “One of the good things about legalisation is that we now have labels to indicate approximately how much THC is inside,” he added.
Chandy is especially concerned about synthetic cannabinoids, created in labs to bind more tightly to the CB1 receptor and create more intense psychedelic effects.
“The data is more limited on the synthetic cannabis but given that it’s binding so tightly to the CB1 receptor, I would expect that it would cause more cardiovascular disease.”
He also worries that the effects of cannabis will become more pronounced in the coming decades as research shows more young people are using cannabis. “Just as with cigarettes, it’s not just how much, but how long you’re exposed to it.”
Study details
The relationship between cannabis and cardiovascular disease: clearing the haze
Mark Chandy, Nerea Jimenez-Tellez & Joseph Wu.
Published in Nature Reviews Cardiology on 23 January 2025
Abstract
Cannabis has been consumed for centuries, but global regulatory changes over the past three decades have increased the availability and consumption of cannabis. Cannabinoids are touted to have therapeutic potential for many diseases and could be a replacement for opioids for analgesia and sedation. However, cannabinoids can cause substantial adverse cardiovascular events that would mitigate any potential benefit. The endocannabinoid system regulates mood, satiety and memory, and modulates the cardiovascular system. The link between cannabinoids and cardiovascular disease, which used to be limited to evidence from preclinical studies, case reports and case series, is now evident in epidemiological studies. Cannabinoids adversely affect the cardiovascular system, causing myocardial infarction, cerebrovascular accidents, arrhythmia and heart failure. The effects of novel cannabinoids are unknown, and synthetic cannabinoids have the potential to cause even more substantial harm than traditional cannabinoids. Therefore, with the increasing availability and use of cannabis, the acute and chronic effects of this drug are becoming apparent.
Medscape article – Cannabis Is Interfering With the Heart (Open access)
See more from MedicalBrief archives:
Frequent cannabis use bumps up heart attack risk – US study
Large study finds marijuana smokers at high risk of heart attacks
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