An in vitro and in vivo Analysis of Vascular Endothelial Function in Cannabis Users
John Blakely, MS1, Scott Brown, MD2, Mary Levine, RD1, Martin Barnes, BS3, Peter H. Lin, MD4.
1California State University Channel Island, Camarillo, CA, USA, 2University of California Riverside School of Medicine, Riverside, CA, USA, 3University Vascular Associates, Los Angeles, CA, USA, 4Baylor College of Medicine, Houston, TX, USA.
OBJECTIVES: An increased number of state legislations have legalized the use of cannabis in recent years for both medicinal and recreational purposes, and this has fueled an increase of cannabis consumption among recreational smokers. The lack of scientific literature regarding the effect of cannabis on the cardiovascular system may be falsely interpreted by the public that cannabis smoking is harmless, despite the biochemical similarity between cannabis and tobacco. In this study, we examined the vascular endothelial function in recreational cannabis users using both in vivo and in vitro analysis.
METHODS: Eight male recreational cannabis smokers (age 29.4 ± 10.6 years) and an equal number of age-matched non-smoker controls participated in the study. The baseline brachial artery reactivity studies were performed using ultrasound to determine endothelium-dependent, flow-mediated dilation and endothelium-independent nitroglycerine-mediated dilation. Plasma nitrite/nitrate, cyclic 3',5'-guanosine monophosphate (cGMP), and thromboxane (TX-B2) levels were measured. These subject’s sera were added to confluent monolayers of human umbilical endothelial cells (HUVECs) for 12 hours. Basal and substance P-stimulated nitric oxide (NO) and basal endothelin-1 (ET-1) production were measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined.
RESULTS: Both groups had similar age, body mass index, blood pressure, mean resting vessel diameters, and post-occlusion flow velocities (p=NS). Cannabis users had a significantly impaired flow-mediated dilation when compared to controls (5.68 ± 2.76 vs. 13.64 ± 6.32%, p <0.01). There was no difference in nitroglycerine-mediated dilation between the two groups (21.43 ± 4.32 vs. 20.45 ± 3.85, p=NS). Plasma levels of nitrite/nitrate, cGMP and TX-B2 were not significantly different in the cannabis and control groups. Cannabis group had significantly reduced basal- (p = 0. 02), stimulated-NO production (p = 0.02), eNOS protein (p = 0.03) and eNOS activity (p = 0.02) compared to the control group. No difference was noted in ET-1 production between the two groups.
CONCLUSIONS: Recreational cannabis smoking is associated with impaired vascular reactivity as evidenced by reduced flow-mediated dilation. These results suggest a deleterious cardiovascular risk associated with habitual cannabis exposure.
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