Leila Mohammadi, Matt Springer and their colleagues at UCSF presented a study at today’s (November 13, 2023) American Heart Association Annual Scientific Sessions showing that smoking marijuana compromises blood vessel function just like smoking tobacco cigarettes does. This result is not surprising because marijuana smoke is not that different from tobacco smoke. It is also consistent with earlier results the Springer group published using rats.
Mohammadi and colleagues studied blood vessel function in people who smoke marijuana at least three times per week, people who smoke at least 5 tobacco cigarettes per day, people who avoid all kinds of smoke but take at least three THC edibles per week, and people who didn’t use any of these products. They found that the tobacco smokers had poor vascular function relative to the non-users (the arteries were less able to open up to increase blood flow when necessary), confirming what was already known from prior research. However, the marijuana smokers had the same problem.
In a surprise finding, the THC edible users also had poor vascular function, even though previous studies in rats had shown that THC is not required for marijuana smoke to impair vascular function, and vascular function is also impaired by tobacco smoke, which doesn’t contain THC. They measured how well arteries responded to increased need for blood flow by measuring how much they increased in size in the face of the need for increase blood flow (flow-mediated dilation, FMD) as well as how stiff the arteries were (measured with carotid-femoral pulse wave velocity, PWV). Both marijuana and tobacco smoking reduced FMD without affecting pulse wave velocity.
They also found that consuming marijuana edibles reduced FMD similarly to smoking.
To understand these effects Mohammadi and colleagues took blood serum samples from each person and exposed isolated endothelial cells (the cells that line the inside of blood vessels and control their function) to the serum samples in culture dishes. The serum from marijuana smokers made the cells produce less nitric oxide — the chemical that makes arteries dilate — than cells exposed to serum from non-users, but the serum from the THC edible users did not affect nitric oxide production.
They also found that markers of inflammation, which are elevated in tobacco smokers, were not elevated or were lower in cannabis smokers.
This work complements two epidemiological studies presented yesterday at the AHA meeting that linked marijuana use to cardiovascular disease in people. It also shows that earlier effects found in rats are similar to effects in people.
Here is the abstract:
Impairment of Endothelial Function by Chronic Cannabis Use: An Interim Analysis of the CANDIDE Study
Leila Mohammadi et al.
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.
