This retrospective study examined the association between CUD and adverse cardiovascular outcomes among patients visiting the ED. Although cannabis is often perceived as relatively harmless [6], our findings before and after propensity matching suggest that patients with CUD may have a higher risk of mortality and MI compared to controls. However, stroke incidence did not differ significantly between the groups. Additionally, when comparing CUD to ARD, the CUD cohort demonstrated higher rates of stroke and MI after matching, though overall mortality remained higher in the ARD group.

The relationship between CUD and all-cause mortality remains controversial in the literature. Sun Y et al. reported an elevated risk ratio for CVD mortality among cannabis users but did not find a significant increase in overall mortality. Interestingly, early initiation of cannabis use (before age 18) was associated with a higher risk of CVD mortality, suggesting that duration of exposure may be a critical factor [7]. Vallée A similarly found increased CVD mortality in females but no difference in all-cause mortality for either sex [8]. Conversely, studies by Vozoris NT et al., Calabria B et al., and the Institute of Medicine concluded that cannabis use was not associated with an increase in overall mortality [9-11]. These discrepancies likely stem from differences in study populations, patterns of cannabis use, and unmeasured confounding variables, highlighting the need for further investigation into the long-term effects of CUD.

These findings regarding stroke incidence in patients with CUD contrast with some of the existing literature. Although this analysis did not find a statistically significant difference in stroke risk among patients with CUD, a large meta-analysis of over three million individuals reported a small increase in the odds of stroke (OR 1.17, 95% CI 1.10-1.25), with a mean stroke onset age of just 26.2 years [5]. This early age of onset is consistent with other reports [12], raising concerns about early cardiovascular compromise in younger users. Some studies also suggest a temporal relationship between recent cannabis use and stroke onset [12]. Notably, San Luis CV et al. reported a decreased risk of stroke among cannabis users [13], while Desai R et al. found that geriatric patients with both CUD and peripheral vascular disease had a significantly increased stroke risk compared to controls [14]. These divergent findings emphasize the complexity of the cannabis-stroke relationship and the possible influence of age, comorbidities, and timing of exposure.

This study demonstrated that cannabis use may increase MI risk. We found that post-propensity-matched patients with CUD had significantly higher MI rates compared to controls. This aligns with findings from Desai R et al., who reported elevated MI risk among cannabis users (OR 1.08, 95% CI 1.04-1.12) [14], and with other studies indicating an increased risk of acute MI within one hour of cannabis use [15]. However, some reports have failed to find a significant association between cannabis use and cardiovascular outcomes after adjusting for sociodemographic and behavioral factors [16]. Importantly, frequent cannabis use following MI was associated with increased mortality in a study by Mukamal KJ et al., suggesting that cannabis may worsen outcomes in patients with pre-existing heart disease [17]. The heterogeneity in findings across studies may be attributed to variations in study design, sample size, and the potency or form of the drug.

When comparing CUD and ARD, this study found that patients with CUD had significantly higher rates of MI and stroke. While alcohol use is well known to increase cardiovascular risks, especially at high doses, there is also conflicting evidence suggesting a dose-dependent protective effect of moderate alcohol consumption on ischemic heart disease [18]. Alcohol has also been linked to dysrhythmias and cardiomyopathy, both of which can elevate stroke risk [19]. This study did not assess consumption patterns for either substance, which may explain the divergence from prior findings on alcohol’s nuanced cardiovascular impact. Nevertheless, growing literature suggests that cannabis may also exhibit dose-dependent cardiovascular effects, similar to alcohol.

A recent 2024 study from Amsterdam highlighted the role of consumption methods in determining cardiovascular risk. Smoking cannabis was found to elevate MI risk, particularly in younger adults, likely due to combustion-related toxins such as carbon monoxide [20]. In contrast, alternative forms of intake (such as edibles or vaping) may pose fewer cardiovascular risks. This finding reinforces the need to evaluate not only cannabis use but also the mode and frequency of consumption when assessing cardiovascular outcomes.

Limitations

This study has several limitations that must be acknowledged. As a retrospective study, our analysis cannot establish causation between cannabis use and adverse cardiovascular events. The observational nature of the study limits our ability to draw definitive conclusions about causality. While we utilized propensity score matching to control for confounding variables, there may still be unmeasured confounders that could bias our results, even in a well-matched cohort. For instance, lifestyle factors, socioeconomic status, and genetic predispositions, which were not accounted for, might influence both cannabis use and cardiovascular outcomes. Additionally, due to the privacy policies of the TriNetX database, we were unable to evaluate site clustering or specific hospital distributions. This restriction may limit the generalizability of our findings, as the impact of cannabis use on cardiovascular events could vary by location and healthcare setting.

The study relies on ICD codes to identify CUD, which may not capture the full extent of use, including dosage, frequency, and method of consumption (e.g., smoking, ingestion, vaping). Some patients who use cannabis but were not identified as having a disorder may therefore have been missed. These factors may provide additional context for understanding the nuanced effects of cannabis on cardiovascular health; however, this information is not available within the database. In addition, using nicotine dependence as a covariate may miss some individuals who smoke cigarettes. Moreover, although the TriNetX platform integrates data from various HCOs, there is potential for incomplete data, particularly regarding mortality events occurring outside affiliated HCOs. Although 94% of HCOs in the network are linked to US death registries, there remains a small risk of missed death events. There is also significant variability in the composition of cannabis products, including differences in the concentrations of tetrahydrocannabinol and cannabidiol, which could have differing effects on cardiovascular health. This heterogeneity was not available for capture in our study. Additionally, our study utilized historical data from 2005 to 2022, during which time the legal status of and societal attitudes toward cannabis changed significantly [8]. These changes may have affected patterns of use and reporting accuracy over time.