Abstract
Background: Increasing cannabis legalization has led to a surge in cannabis use. To understand the consequences for cardiovascular health, we have initiated the CANnabis: Does It Damage Endothelium (CANDIDE) study. Here, we report results of an interim analysis. Aims: To investigate the effects of chronic cannabis product use on endothelial function. Approach: We recruited 44 healthy non-tobacco smokers/vapers, 21-50 yrs, in 3 groups based on chronic cannabis use: cannabis smokers, THC edible users, and nonusers. Participants underwent assessment of brachial artery flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (PWV). Human umbilical vein endothelial cells (ECs) were exposed to sera from each individual with and without VEGF to determine serum effects on endothelial NO production. Human lung microvascular ECs were also exposed to the individual sera and cell permeability was measured by electric cell-substrate impedance sensing. Results: FMD and VEGF-stimulated NO levels were both significantly lower in cannabis smokers than nonusers (5.7±3.3% vs 12.0±8.0%, p=.037, and 1.1±0.3 nM vs 1.5±0.3 nM, p=.018, respectively; figure), comparable effects to what we have reported for tobacco smokers. In contrast, FMD, but not VEGF-stimulated NO levels, was lower in the THC edible users than nonusers (5.0±4.1% vs 12.0±8.0%, p=.031, and 1.6±0.3 nM vs 1.5±0.3 nM, p=.54). There were no significant differences in other functional properties (p>.48). CD31 and IL-1β, which are circulating inflammatory biomarkers that we showed are elevated in tobacco smokers, were not elevated in cannabis smokers. The inflammatory biomarker PTX3 was lower in cannabis smokers than nonusers (p=.038). Conclusion: Chronic cannabis use impairs endothelial function but may reduce inflammation. Our findings suggest that the impairment caused by smoking cannabis vs edible THC use occurs via distinct mechanisms differing in the involvement of endothelial NO production.
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