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Background: Cannabis use has increased among young individuals in recent years. Although dependent cannabis use disorder (CUD) has been associated with various cardiac events, its effects on young adults without concurrent substance use remain understudied., Aim: To examine trends in hospitalizations for major adverse cardiac and cerebrovascular events (MACCE) in this cohort., Methods: We used the National Inpatient Sample (2016-2019) to identify hospitalized young individuals (18-44 years), excluding those with concurrent substance usage (tobacco, alcohol, and cocaine). They were divided into CUD+ and CUD-. Using International Classification of Diseases-10 codes, we examined the trends in MACCE hospitalizations, including all-cause mortality (ACM), acute myocardial infarction (AMI), cardiac arrest (CA), and acute ischemic stroke (AIS)., Results: Of 27.4 million hospitalizations among young adults without concurrent substance abuse, 4.2% (1.1 million) had co-existent CUD. In CUD+ group, hospitalization rates for MACCE (1.71% vs 1.35%), AMI (0.86% vs 0.54%), CA (0.27% vs 0.24%), and AIS (0.49% vs 0.35%) were higher than in CUD- group ( P < 0.001). However, rate of ACM hospitalizations was lower in CUD+ group (0.30% vs 0.44%). From 2016 to 2019, CUD+ group experienced a relative rise of 5% in MACCE and 20% in AMI hospitalizations, compared to 22% and 36% increases in CUD- group ( P < 0.05). The CUD+ group had a 13% relative decrease in ACM hospitalizations, compared to a 10% relative rise in CUD- group ( P < 0.05). However, when adjusted for confounders, MACCE odds among CUD+ cohort remain comparable between 2016 and 2019., Conclusion: The CUD+ group had higher rates of MACCE, but the rising trends were more apparent in the CUD- group over time. Interestingly, the CUD+ group had lower ACM rates than the CUD- group., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflicts of interest regarding the publication of this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)