With increasing evidence that cannabis use is associated with adverse cardiovascular effects, questions are undoubtedly being asked about the safety of the drug for medical uses. Rod Tucker investigates.
Cannabis was one of the first plants cultivated by man, and its first use can be traced to ancient China where evidence suggests it was used for medical purposes from around 2,700 BC and for textiles and other uses as early as 4,000 BC.
Although the plant contains hundreds of compounds, the two most well studied are tetrahydrocannabinol (THC) and cannabidiol (CBD). In the late 1980s and early 1990s, the site of action for cannabis was identified with the discovery of two major cannabinoid receptors, CB1 and CB2, and their endogenous ligands, which form part of the endocannabinoid system.
While THC is the main psychoactive compound in cannabis that produces the euphoric ‘high’ sensation, over the last decade it has become increasingly clear that it is CBD that has a number of therapeutic benefits. Recognition of this fact has given rise to the terms ‘medical cannabis’ or ‘medical marijuana’.
Cannabis benefits and adverse effects
In a 2021 meta-analysis published in the BMJ, researchers concluded that there was moderate- to high-certainty evidence that medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning and sleep quality in patients with both chronic, non-cancer pain and cancer-related pain.
Although medical cannabis use is associated with some adverse effects such as cognitive impairment, vomiting, drowsiness and impaired attention, there has been little attention paid to any potential adverse cardiovascular (CV) sequelae. One likely explanation is that there remains some uncertainty over the magnitude of these effects and therefore whether such risks should be highlighted.
In fact, in a statement on the use of cannabis and its CV effects, the American Heart Association (AHA) states that ‘overall, evidence is still inconclusive for cannabis use and adverse cardiovascular outcomes’ and it called for carefully designed prospective studies to examine this issue in more detail.
Since the publication of the AHA statement, more evidence has come to light, which suggests that the use of cannabis has several adverse effect on the CV system.
For several states in the US and many other countries such as Canada, use of recreational cannabis has been legalised although this has had some unintended consequences, such as an increase cannabis and alcohol poly use, in addition to adverse cardiovascular effects.
In a recent abstract in the Journal of the Society for Cardiovascular Angiography and Interventions, researchers found that cannabis users were at a more than three times greater risk of developing peripheral artery disease than non-users (Odds ratio, OR = 3.68, p<0.001). Fortunately, however, there was no increased risk for any subsequent intervention or mortality from their peripheral ischaemia.
Despite this, a further abstract revealed that cannabis users were at a statistically significant higher risk of having a myocardial infarction (OR = 3.33, p < 0.001) and an increased likelihood of requiring a percutaneous coronary intervention during hospitalisation (OR = 1.76, p <0.001). Furthermore, users were also at a markedly increased risk of all-cause mortality during hospitalisation (OR = 14.77, p < 0.001).
Cannabis use also increases the risk of arrhythmias and in particular, atrial fibrillation (AF) as well as myocardial injury in those without pre-existing cardiovascular disease. While these studies are concerning, a 2020 systematic review on the cardiac effects of cannabis use concluded that while there is an increased risk of cardiac dysrhythmia, which can be life-threatening, this is rare.
A more recent meta-analysis of observational studies published in 2023 in the journal Toxicology Reports, indicated that cannabis use does increase the risk of an acute myocardial infarction, stroke and any adverse cardiovascular event. Nevertheless, while the pooled odds ratio estimates for each event were non-significant there was also a high degree of heterogeneity among studies.
THC vs CBD
With a clear body of evidence implicating the development of adverse CV outcomes among cannabis users, a limitation of the data is that it is derived from self-reported, recreational use. Furthermore, the focus of research has been on the adverse cardiovascular effects of THC, whereas medical cannabis is predominately based on CBD.
So, is there evidence that CBD-based medical cannabis is harmful to the heart? While there is currently a paucity of data on the CV effects of medicinal cannabis, the available information is somewhat reassuring.
One review highlighted the anti-inflammatory and anti-oxidant effects of CBD and suggested that it appears to have positive effect on the CV system. Further evidence to support the beneficial impact of CBD on the CV system comes from studies in patients with hypertension.
For instance, a study of medicinal cannabis use in older hypertensives published in the European Journal of Internal Medicine, found that after only three-months use of mainly cannabis oil, there was a signification drop in blood pressure. Interestingly, the researchers were unable to detect any adverse changes to participant’s ECGs and no new sustained arrhythmias developed, even though the median daily intake of THC and CBD was roughly the same (21 mg). Similar blood pressure reducing effects were seen in a recent randomised, placebo-controlled, cross-over trial in hypertensive patients using an oral CBD product.
Additionally, repeated CBD dosing has been shown to reduce arterial stiffness and improve endothelial function, revealing a potentially valuable role for those with vascular diseases. Whilst studies to date are largely positive and do not suggest harmful effects on the heart, a recent analysis by Danish researchers sounded a note of caution. Using a national registry, the team examined the potential adverse cardiac effects of CBD when used for the management of chronic pain. Their findings revealed a 64% increased risk of arrhythmias among CBD users compared to non-users.
While it has become recognised that the recreational use of cannabis is associated with deleterious effects on the cardiovascular system, this seems to be less likely with medical cannabis. Nonetheless, research to more clearly delineate the cardiovascular risks associated with medicinal cannabis use is urgently required. In the meantime, clinicians need to remain wary, because the jury is still out on whether or not medical cannabis and the cardiovascular system represents a dangerous combination.