This study observed a relative increase in AF-related hospitalizations, anxiety, and chronic obstructive pulmonary disease (COPD) rates among the propensity matched CUD + subgroup compared to CUD- group even in absence of concomitant TUD in young, hospitalized men. After adjusting for demographic factors and comorbidities, the odds of AF-related hospitalization were 27% higher in the CUD + cohort compared to the CUD-cohort, though this difference was not statistically significant.

The mechanisms linking CUD to AF may involve direct toxic effects on the myocardium and autonomic nervous system, causing arrhythmogenic effects. Theoretically, THC stimulation increases the content of catecholamines and adrenaline in cardiac tissue, which may promote arrhythmias. Moreover, it is evident that cannabis increased action potential and decreased the rapid delayed rectifier potassium currents, the slow delayed rectifier potassium currents, and the transient outward rectifier potassium currents, which promote arrhythmias[10,11]. The CUD + group also had higher anxiety and stress, possibly contributing to arrhythmogenic triggers. Of note, the prevalence of co-diagnosed CUD and AF has risen substantially in recent years, which is concerning given the ongoing expansion of cannabis legalization[12]. In addition, a recent scientific statement from the American Heart Association suggests potential cardiovascular side effects of CUD by stimulating CB1R, causing sympathetic activation, myocyte hypertrophy, reduced mobility, and chronic endothelial dysfunction, leading to direct effects such as cardiomyopathy, acute myocardial infarction, and arrhythmias[13].

Importantly, this study highlights CUD as a potential contributor to racial and socio-economic disparities in AF outcomes[14]. The higher burden of CUD and related AF admissions in blacks warrants greater attention, as this could compound their underlying thromboembolic risk due to prothrombotic milieu, hyperactivation of adrenergic drive, and can potentiate conversion from paroxysmal to persistent AF[12]. Considering the younger age group of CUD + patients and the progression from paroxysmal to permanent AF with a low burden of hypertension, hyperlipidemia, diabetes, obesity, and alcohol use disorder, progressing from paroxysmal to persistent AF can escalate subsequent cardioembolic complications in higher-risk groups. Southern region hospitals reported a higher rate of AF admission among the CUD + cohort compared to the CUD-cohort, highlighting potential geographical factors contributing to variations in the cannabis-cardiovascular risk relationship. Regional differences could be due to existing differences in state-wise cannabis policies and decriminalization laws. Furthermore, it is important to consider the potential impact of different cannabis strains and potency levels, as these factors can vary across regions. Additionally, variations in healthcare access and quality between different regions may have influenced the rates of AF admission among individuals with CUD. Efforts to reduce the burden of CUD and AF among Black individuals should focus on addressing the root causes of these disparities, including socioeconomic disadvantage, limited access to healthcare, and exposure to environmental stressors[8]. Interventions that promote health equity, such as community-based education programs and policies that reduce barriers to healthcare access, may be particularly effective in mitigating the adverse cardiovascular effects of cannabis use in vulnerable populations[15].

The co-diagnosis of CUD and AF has risen substantially from 2008 to 2018, with over a 3-fold relative increase and a nearly 5-fold absolute increase[12]. However, previous studies have not considered the confounding effect of TUD, which has profound cardiac adverse effects[12]. Moreover, smoking is associated with a 2-fold increased risk of AF attributed to current smoking and a trend towards a lower incidence of AF amongst smokers who quit[16]. With the legalization of cannabis across many states, this trend is expected to increase and have a growing impact on inpatient healthcare utilization and costs[12]. However, the cost of care for these CUD patients with AF was substantially higher in this study, suggesting a pathologic interaction that results in more severe AF requiring intensive treatment. As these younger patients with CUD and AF age, they may develop risk factors like hypertension and coronary disease that promote AF progression and complications like stroke.

Further research is needed to characterize CUD patterns, mechanisms, and outcomes in AF patients. This includes a detailed assessment of cannabis use history, arrhythmia phenotype, longitudinal outcomes, and potential treatment implications such as cannabis cessation. A focus on evaluating women, Hispanics, and other minority populations will also expand the generalizability. Future research should aim to explore these regional differences in more detail in order to gain a comprehensive understanding of the complex relationship between cannabis use, cardiovascular health, and geographic factors. Further study of the CUD-AF relationship offers significant potential to understand and reduce population health burdens related to cannabis use and AF.

Additional research using longitudinal designs is needed to clarify the temporality and quantify the magnitude of the association between cannabis use and AF risk. Understanding these relationships has important public health implications, given rising rates of cannabis use and growing awareness of AF-related morbidity in young people. Future studies should employ geospatial analysis techniques to map the distribution of CUD and AF across different regions and to identify hotspots where targeted interventions may be most effective[17]. Collaborations between researchers, policymakers, and healthcare providers will be essential in developing region-specific strategies to address the CUD-AF relationship and to promote cardiovascular health in communities most affected by cannabis use[18].

In addition to AF, CUD is also associated with increased risk of anxiety and other mental health condition. Recent evidence presented at the 2023 Cannabis Clinical Outcomes Research Conference highlights the complex relationship between cannabis use and mental health outcomes. While some studies suggest potential therapeutic benefits of cannabis for certain mental health conditions, such as insomnia[18], others have found no significant improvement in pain, anxiety, or depression among adolescents and young adults[18]. These findings underscore the need for further research to elucidate the effects of cannabis on mental health and cognition across different populations and contexts.

Recent studies have also suggested a potential link between cannabis use and COPD exacerbations. In a study by Chatkin et al[19], patients with COPD who reported using cannabis had a higher risk of exacerbations compared to non-users. Similarly, Tan et al[20] found that heavy cannabis use was associated with an increased risk of COPD exacerbations in a population-based cohort. Our study found a relative incremental association between cannabis use and COPD exacerbation rates similar to the potential for increased risk reported in other studies[19,20].

This study has limitations, including reliance on administrative data lacking clinical granularity, diagnostic coding inconsistencies, and the inability to infer causation due to the cross-sectional design. Other unmeasured confounders may include healthcare access and substance use patterns. Nonetheless, these findings highlight CUD as an emerging risk factor for AF among young adults, particularly in minority populations at elevated risk of AF complications. Additional longitudinal research is warranted to elucidate the temporal associations and detailed mechanisms linking cannabis use and arrhythmogenesis across demographically diverse populations.