In a nationwide cohort of patients with chronic pain, the use of medical cannabis was associated with a 64% risk increase of arrhythmias compared with no use. This poses a potential health concern and is vital knowledge for any physician prescribing medical cannabis. The use of medical cannabis was not associated with an elevated risk of ACS or HF.
As the stigma surrounding cannabis wanes and its potential medicinal value becomes more widely accepted, an increasing number of people are turning to the plant for both recreational and therapeutic purposes. However, despite its growing popularity, our understanding of how cannabis affects the human body is still limited. While a body of evidence points to the therapeutic potential of cannabis, it is important also to consider the potential risks associated with its use. A study by Holt et al. presented at the 43rd European Society of Cardiology Congress
Treatment with medical cannabis for chronic pain is in popular demand, and a rising number of countries allow physicians to prescribe medical cannabis for pain management. However, data on drug safety is scarce. Studies have shown a risk of cardiovascular side effects following the use of recreational cannabis warranting further investigations into the safety of prescribing medical cannabis.
last fall, for instance, suggested a possible link between cannabis use and an increased risk of cardiovascular events, bringing into question its safety.
About the Study
Holt and colleagues conducted an observational study to examine the potential risk of cardiovascular events in 4,562 patients with chronic pain who were prescribed medical cannabis (cannabinoid, cannabidiol, or dronabinol) compared to a control group who weren’t taking the medication. Specifically, they looked at the risk of new-onset arrhythmias (abnormal heart rhythms), acute coronary syndrome (ACS, a condition caused by the sudden, reduced blood flow to the heart), and heart failure. The researchers used the Danish national registers to follow the cohort, who, importantly, did not have a history of arrhythmias, ACS, heart failure, or medical cannabis use prior to the study period (2018 to 2021). Patients from the exposed cohort were matched to controls in age group, sex, and chronic pain diagnosis.
The study found that the risk of new-onset arrhythmias was higher in the group prescribed medical cannabis compared to the control group, with a risk ratio of 1.64 (95% CI: 1.04-2.23) – a 64% relative risk increase. The 180-day absolute risks were 0.71% (95% CI: 0.47%-0.94%) for exposed subjects vs. 0.43% (95% CI: 0.37%-0.49%) for controls, indicating an absolute risk increase of 0.28% with cannabis use. This 0.28% absolute risk increase translates to one case of arrhythmia for every 360 users. However, the risk of ACS or heart failure was not elevated in the group prescribed medical cannabis compared to the control group.
A cause for alarm?
Given the lack of human data on medical cannabis and potential cardiovascular risks, these findings are certainly noteworthy. However, upon closer examination, the limitations of the study suggest that there may not yet be cause for alarm.
One potential source of selection bias in this study is the difference in comorbidities between the exposed and control groups. Comorbidities refer to the presence of health conditions that an individual may be experiencing in addition to their “main” condition or the condition of interest within the study. In this study, the exposed group had more comorbidities, including hypertension, ischemic heart disease, chronic kidney disease, and diabetes mellitus, than the control group, which could potentially affect the results if the exposed group was more vulnerable to certain adverse events due to their overall health status. For example, in patients with hypertension, the heart muscle may enlarge (a condition known as cardiac hypertrophy), which can also involve the growth of fibrous tissue and a decrease in connectivity between cells. These changes can disrupt the normal electrical properties of the heart and increase the likelihood of arrhythmias.
Another source of selection bias in this study is the fact that the exposed group had higher exposure to other medications compared to the control group. Other medications taken by the exposed group may interact with medical cannabis, altering the effects of both on the body and impacting susceptibility to CV concerns. It is also possible that other medications, if metabolized by the same enzymes in the body as CBD, could potentially interfere with the absorption, distribution, metabolism, and elimination of both substances. Notably, a significantly higher percentage of the exposed group (42.2%) were also taking opioid medications compared to the control group (12.3%). CBD has been shown to inhibit CYP2D6, an enzyme involved in the metabolism of opioids such as oxycodone, which may lead to an increase in the serum concentrations of these medications. In 2019, research by Dashi et al. revealed a link between opioid overdose and the occurrence of ischemic events, heart failure, and arrhythmias in patients hospitalized due to opioid overdose. Additionally, a review by Behzadi, Joukar, and Beik suggests that opioids can themselves trigger arrhythmias, and higher doses of these medications may exacerbate this effect.
The Bottom Line
Holt et al. showed that medical cannabis use was associated with a small increase in the risk of arrhythmias, but the presence of major confounds in this study stymies any meaningful interpretation of these findings with respect to the effects of cannabis per se. Those with pre-existing cardiovascular conditions may want to proceed with caution in light of the possibility that medical cannabis negatively impacts CV health, but ultimately, more research is needed.
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