Our analysis of 2019 National Inpatient Sample data revealed that CUD is an independent risk factor for MACCE in hospitalized patients without a history of tobacco use disorder (TUD). Older patients with CVD risk and CUD had a MACCE incidence of almost 20% higher than the non-CUD group.

Recreational cannabis use has been implicated with arrhythmias, stroke [4,5,7,8], and heart failure [5]. Auer et al. [9] and Mittleman et al. [10] reported cannabis and concomitant tobacco use as risk factors for subclinical atherosclerosis. In contrast, our study found higher rates of MACCE (AMI, dysrhythmia, cardiac arrest, and stroke) in cannabis users even after excluding cases with tobacco use disorder. This raises doubts about the presumption that cardiovascular effects related to cannabis could be influenced by tobacco use disorder. The main reason behind these presumptions is cannabis and tobacco co-use. Studies have shown that cannabis users have an increased risk of using cigarettes and other tobacco-related products [11]. However, cannabis is equally potent in causing cardiovascular effects in the absence of smoking. Although the active ingredients (tetrahydrocannabinol vs. nicotine) in cannabis and tobacco are different, both of these produce a copious amount of chemicals when smoked, and these chemicals are predominantly identical. Furthermore, due to a different mode of smoking when compared to tobacco, cannabis chemicals are usually retained for a longer time in the body [12].

Stroke from cannabis use can be attributed to the procoagulant effect of its metabolite, delta-9-tetrahydrocannabinol, on platelets [13]. Its effect on short-term cerebral vasoconstriction is also a possible mechanism of stroke, especially in older individuals with increased CVD risk secondary to preexisting atherosclerosis [14]. Cannabis arteritis has already been described, given its deleterious effects on peripheral arteries, as something similar to Buerger’s disease, which is associated with tobacco smoking [15]. The Multicentric Study of Atherosclerosis, involving 1485 adult participants of age >65, similar to our study population, concluded that supraventricular tachycardia, premature atrial contractions, and non-sustained ventricular tachycardias were more frequently reported in regular cannabis users compared to never users [16]. The cardiovascular effects of cannabis use are not just acute, i.e., cannabis arteritis, cannabis-induced vasospasms, and platelet aggregation, but cannabis use is also hypothesized to be involved in atherosclerosis progression due to the abundance of CB1 and CB2 receptors (cannabinoid receptors) in the pulmonary and cardiovascular systems [17].

Conversely, Reis et al. [18] reported that 84% of adults (n = 5113 adults) had a history of using cannabis. The cumulative lifetime and recent cannabis use did not show an association with the incidence of CVD, stroke or TIA, coronary heart disease, or cardiac mortality. However, a comprehensive review conducted by Ravi et al. [19], involving 13 studies, concluded varied findings regarding the potential link between cannabis use and cardiovascular risk elements and outcomes like myocardial infarction and stroke. This is understandable because parallel randomized controlled trials would question ethicality, so all we can do is generate hypotheses based on observational studies. Using a nationally sampled database with enough samples, our study is unique in this sense. Notably, Chen et al. [20] introduced a novel dimension by investigating the genetic liability of CUD, revealing an association with an elevated risk of stroke, atrial fibrillation, heart failure, and pulmonary embolism, but the connection with coronary artery disease, myocardial infarction, and deep venous thrombosis remained weak. However, in our population-based analysis, patients with adverse cardiovascular and cerebrovascular events were almost twice as likely to be hypertensive and 30% more likely to be suffering from hyperlipidemia. Additionally, CUD patients were more likely to be male and of black origin. However, this population-based cross-sectional study pooling data from 2008–2017 concluded that legalization of cannabis was not associated with use disorder among blacks [21]. The mechanism of the increased rate of stroke in our study among a CUD cohort (5.2% vs. 4.8%, p = 0.002) who do not smoke tobacco remains to be established; however, it could be secondary to higher risk of hypertensive emergencies in older patients and arrhythmias [22,23].

Although we have substantial evidence to infer that CUD could be an independent risk factor for MACCE in older patients, including those who don’t use tobacco, the interpretation of this NIS database analysis should be conducted cautiously. It is essential to consider other factors that might influence the relationship between CUD and adverse cardiovascular outcomes. For instance, individuals with CUD may engage in other lifestyle habits or behaviors that could contribute to cardiovascular risk, since cannabis use is associated with increased substance abuse [11]. Also, the interaction between cannabis use and other pre-existing health conditions should be considered. It is important to acknowledge that a few of the patients might have had multiple hospitalizations during the period analyzed. Additionally, patients with CUD who were not hospitalized might not be a part of our study. Further research, especially prospective cohort studies and randomized control trials (RCTs), is imperative to establish a causal association between CUD and MACCE and elucidate the mechanistic effects of cannabis on the cardiovascular system. Additionally, basic science research focusing on various metabolic pathways is essential to understand the complete pathophysiology and long-term effects. Careful use of cannabis, both for recreational and medicinal purposes, is essential, especially in vulnerable age groups like the older population, and the CVD risk must be weighed against the benefits for use of cannabis in this age group. Furthermore, sustained research and data acquisition efforts would help clinicians and patients to make informed choices.