Marijuana use and acute myocardial infarction: Mechanistic insights, clinical implications, and emerging challenges

Marijuana, or cannabis, is the most commonly used illicit substance in the United States, with prevalence nearly doubling over the past decade. Accumulating evidence implicates cannabis use as a potentially modifiable risk factor for acute myocardial infarction, particularly among younger adults without traditional cardiovascular risk factors. Marijuana precipitates acute myocardial infarction through multiple converging mechanisms: increased myocardial oxygen demand via sympathetic activation, impaired oxygen delivery through carboxyhemoglobin elevation, coronary vasospasm, endothelial dysfunction, and a prothrombotic state characterized by enhanced platelet activation. Genetic variability in cannabinoid receptor expression and CYP2C9-mediated tetrahydrocannabinol metabolism further modulates individual susceptibility. Among patients with established coronary artery disease, population-based data suggest elevated cardiovascular risk with frequent use, though prospective cohort data remain conflicting. In post-percutaneous coronary intervention patients on dual antiplatelet therapy, cannabidiol inhibition of CYP2C19 may impair clopidogrel bioactivation, warranting consideration of alternative P2Y12 inhibitors. These findings highlight the importance of cannabis use screening in clinical practice and the need for prospective studies to guide evidence-based management.