In recent years, recreational cannabis use among young adults has significantly increased with changing legal policies and its widespread availability. As we see this rise in cannabis consumption, there is a need to pay attention to its impact on health, particularly cardiovascular health. In this study, we examined the rates and trends of MACCE in young hospitalized adults with CUD in the absence of concomitant tobacco, alcohol, or cocaine use from 2016 to 2019. We observed that rates of MACCE (1.71% vs 1.35%) were higher in cannabis users than non-users. The trends in MACCE hospitalizations among cannabis users had a 5% relative increase from 2016-2019, which is consistent with a previous study that reported increasing trends in MACCE among CUD+ during 2010-2014[8]. It is imperative to consider the neurobiological underpinnings that may predispose this population to both increased health risks and the sustenance of CUD. The process of myelination in the brain, wherein a protective layer forms around axons to expedite nerve impulse transmission, is critical for neural efficiency and functionality. Notably, young brains, particularly those under 25 years of age, have not yet achieved complete myelination, rendering them more susceptible to the influences of external substances. This developmental stage is crucial because neurons that are simultaneously active tend to forge stronger connections, adhering to the principle that “cells that fire together wire together”[9]. This mechanism is thought to underlie the formation of addiction pathways; hence, repeated cannabis use during this formative period can result in myelination patterns that inadvertently promote and sustain cannabis addiction. This neurobiological perspective provides a plausible explanation for the observed phenomenon that individuals initiating cannabis use before the age of 18 years are significantly more likely to develop a CUD compared to those who start in adulthood. Understanding these mechanisms is essential for interpreting the trends observed in our research.

Cannabinoid-1 receptors are mainly located in the cardiovascular system, the central nervous system, and peripheral vasculature, play a critical role in mediating the cardiovascular effects of THC[10]. Acute exposure to THC leads to a dose-dependent rise in blood pressure and heart rate, a reaction to which cannabis users may quickly develop tolerance, often resulting in the consumption of higher doses more frequently. Such increased usage has been linked to a higher incidence of cardiac arrhythmias and myocardial infarction[10]. Additionally, long-term THC use is associated with a more frequent occurrence of angina, potentially due to lowered angina thresholds and compromised autonomic nervous system functioning. This includes reduced efficiency in sympathetic and parasympathetic nervous system signaling, increased levels of serum aldosterone, and both central and peripheral vasoconstriction, culminating in hypertension[10]. Low to moderate doses lead to increased heart rate and blood pressure due to increased sympathetic activity. In contrast, high doses or chronic use cause decreased heart rate and blood pressure by increasing parasympathetic activity[11]. In our study, the prevalence of AMI was higher (0.86% vs 0.54%) among cannabis users as compared to non-users, and the trends in AMI hospitalizations among cannabis users had increased by 22% from 2016 to 2019. These findings align with previous studies that indicate cannabis use is associated with an increased prevalence of AMI, particularly among younger age groups[12]. Furthermore, AMI-related hospitalizations have seen a rise in cannabis users, even after accounting for confounding factors such as tobacco, alcohol, and other stimulant drug abuse[13]. It leads to dose-dependent changes in heart rate and blood pressure in most individuals. Moreover, CUD leads to higher levels of carboxyhemoglobin, which reduces the blood’s ability to carry oxygen[14]. It also promotes platelet aggregation and activates factor VII, which can potentially contribute to blood clot formation. These changes may trigger an AMI by increasing the myocardial oxygen demand while decreasing its supply[14].

Another finding is that the prevalence of AIS was higher in cannabis users than non-users. Many recent studies also reported that cannabis use is associated with a higher prevalence of stroke even after adjusting for confounding factors like tobacco smoking[15]. Heavy cannabis users in the general community also have a higher rate of AIS, particularly among the young, with nearly three times the odds compared to non-users[16]. A prospective study by Wolff et al[17] revealed that cannabis use was associated with multifocal intracranial angiopathy leading to ischemic stroke in young individuals. Possible mechanisms for cannabis-induced stroke were abnormal blood flow regulation through sympathetic activity inhibition, symptomatic cerebral vasospasm, and embolism from cardiac arrhythmias[18]. In the central nervous system, THC has been observed to enhance cerebral vasculature tone and elevate central blood pressure, subsequently leading to a reduction in cerebrovascular blood flow. This diminished flow is linked to a heightened risk of cerebral vascular accidents (CVA) and TIAs, indicating a relationship between TIAs and a reversible impact of cannabis on cerebrovascular health, potentially due to temporary vasospasm and/or increased central blood pressure reducing cerebral circulation[10]. Additionally, it has been proposed that cannabis usage could elevate CVA risk in individuals predisposed to cardiovascular disease, regardless of secondary prevention with the use of anti-platelet drugs[10].

We also found that the rates of cerebral vascular (CA)-related admissions were marginally higher among cannabis users than non-users. There were reported cases of CA after cannabis use[19,20] and a few reported cases associated with synthetic cannabinoid use[21,22]. Cannabis might cause an increase in parasympathetic tone and activity, causing a sudden asystolic arrest, which may lead to sudden cardiac death[23]. The other plausible mechanistic links could be due to several interconnected mechanisms. Cannabis use may induce a sympathetic predominance, contributing to arrhythmias and blood pressure variability, thereby exerting additional strain on the cardiovascular system, especially in individuals with pre-existing cardiac conditions. Additionally, it may also trigger myocardial infarction by causing either significant coronary vasospasm or endothelial dysfunction. These factors, alone or in combination, can result in a higher risk of CA among CUD patients.

An interesting finding of this study is that cannabis users had lower rates of ACM (0.30% vs 0.44%) compared to non-users. Additionally, there was a decreasing trend in admissions for ACM among cannabis users from 2016 to 2019. Mixed results were reported on this association in the previous studies. Some have reported that cannabis use was associated with lower rates of ACM[24,25], while a few have reported that ACM was higher among young cannabis users hospitalized for AMI[8]. This can be partly attributed to the fact that cannabis users are often younger, male, and African American, with a reduced incidence of cardiovascular risk factors[26]. They have lower total cholesterol, reduced lipid accumulation, weight loss, and improved glycemic control[27]. The physiological effects of cannabinoids have been associated with metabolic processes, as evidenced by a lower prevalence of obesity and diabetes mellitus among marijuana users. Specifically, there is a correlation between cannabis use and lower waist circumference, and body mass index[28,29]. These findings imply that cannabis’ anti-inflammatory properties might help reduce the risk factors linked to cardiovascular diseases. Additionally, medical cannabis has shown promise in reducing opioid usage for chronic pain management, resulting in improved quality of life and potentially contributing to lower mortality rates associated with opioid overdose[30]. These factors appear to influence cannabis beneficial association with ACM.

Although our study observed higher rates of MACCE, AMI, CA, and AIS among young adults with CUD, the multivariable analysis revealed no significant association between CUD and these outcomes. This indicates that the observed differences in rates between CUD+ cohorts and CUD- cohorts may be attributed to confounding factors such as age, socioeconomic status, or comorbidities. After adjusting for these confounders, cannabis by itself did not emerge as a significant risk factor for MACCE-related admissions.

Treatment for CUD primarily focuses on psychosocial interventions, with cognitive-behavioral therapy (CBT) and motivational enhancement therapy (MET) standing out for their evidence-based efficacy[31]. CBT, recommended as the first-line treatment, targets the identification and management of thoughts, behaviors, and triggers related to substance use, and has been shown to significantly reduce cannabis use among patients. Similarly, MET emphasizes building motivation for treatment and abstinence, showing comparable effectiveness to CBT. Brief interventions may be beneficial, particularly for adolescents and young adults identified outside healthcare settings, involving one to two short sessions of motivational enhancement techniques, though their long-term efficacy remains uncertain[31]. For those seeking treatment, psychosocial approaches are preferred over medication due to stronger evidence of success, with treatments doubling the likelihood of abstinence at follow-up compared to no treatment, although long-term abstinence rates are generally low. Monitoring treatment progress is critical, with weekly checks initially recommended, adjusting based on patient stability and progress. If initial responses to CBT or MET are insufficient, combining these therapies or incorporating contingency management, which uses incentives to promote abstinence, may enhance outcomes[31].

This study has a few limitations. First, the study design is observational, which means causality cannot be established. Despite efforts to exclude concomitant substance abuse and adjusting cardiovascular risk factors in multivariable regression analysis, it is challenging to determine if the higher rates of MACCE in the CUD+ group could still be influenced by other residual confounding factors as with any retrospective study. Second, the study lacks detailed information on the extent and frequency of cannabis use among the participants. This limits the ability to explore potential dose-response relationships and fully understand the impact of different patterns of cannabis consumption on MACCE. Third, the study analyzes trends over a limited timeframe (2016-2019). Long-term data and follow-up would provide a more comprehensive understanding of the relationship between cannabis use and MACCE. Literature reporting CA after cannabis use was limited to case reports/series and warrant more prospective studies to compare the independent association of CUD with CA in absence of other concomitant substance abuse. Lastly, we could not take into account the impact of medication history, other laboratory parameters, and follow-up data while performing this study, and this limitation warrants more longitudinal prospective studies. Despite these limitations, it is essential to underscore the significance of this study as it examines the trends of MACCE among hospitalized young adults within the CUD group compared to their non-CUD counterparts, distinctly in the absence of other simultaneous substance abuse. The focus on young adults is particularly pertinent, given their susceptibility to developing addictive behaviors, which could adversely impact cardiovascular and metabolic health over the long term. This foundational work not only fills a critical gap in the literature but also sets the stage for future research, guiding healthcare strategies aimed at mitigating the cardiovascular risks associated with cannabis use among young adults.