Young cannabis smokers showed significantly heightened atherosclerosis markers compared to non-users, with monocyte foam cell formation increased 1.36-fold and transendothelial migration up 1.13-fold among 134 participants aged 21-30. Co-use with nicotine e-cigarettes amplified these effects further, pushing foam cell formation to 1.83-fold higher than controls. The study used novel ex vivo assays measuring two key early steps in arterial plaque development using participants' own blood cells and plasma. This represents some of the first mechanistic evidence linking cannabis combustion to cardiovascular risk in humans, addressing a critical gap as cannabis use surges among young adults. The findings suggest that inhaling combusted plant material—regardless of whether it's tobacco or cannabis—may trigger similar inflammatory pathways leading to heart disease. However, this cross-sectional preprint awaiting peer review cannot establish causation, and the relatively small sample size limits generalizability. The work provides concerning early signals about long-term cardiovascular consequences of cannabis smoking, particularly when combined with vaping, though longitudinal studies are needed to confirm whether these acute changes translate into clinical heart disease.