Cannabinoids and Atherosclerotic Coronary Heart Disease

Abstract

Marijuana is the most abused recreational drug in the United States. Cannabinoids, the active ingredients of marijuana, affect multiple organ systems in the human body. The pharmacologic effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2, which are widely distributed in the cardiovascular system, have been well described. Activation of these receptors modulates the function of various cellular elements of the vessel wall, and may contribute to the pathogenesis of atherosclerosis. Clinically, there are reports linking marijuana smoking to the precipitation of angina and acute coronary syndromes. Recently, large published clinical trials with CB1 antagonist rimonabant did not show any significant benefit of this agent in preventing progression of atherosclerosis. In light of these findings and emerging data on multiple pathways linking cannabinoids to atherosclerosis, we discuss the literature on the role of cannabinoids in the pathophysiology of atherosclerosis. We also propose a marijuana paradox, which implies that inhalation of marijuana may be linked to precipitation of acute coronary syndromes, but modulation of the endocannabinoid system by a noninhalation route may have a salutary effect on the development of atherosclerosis.The authors have no funding, financial relationships, or conflicts of interest to disclose.

Cannabinoids, the Heart of the Matter

“…In the myocardium in human adipose tissue of ischemic hearts, CB1 receptor expression is upregulated, accompanied by CB2 receptor and FAAH downregulation, as well as reduced cell survival signaling 9, 71, 72. This goes along with an increase in circulating immune cells in obese patients with adverse cardiovascular events.…”

“…Coronary dysfunction is associated with elevated endocannabinoid plasma levels in obese people, due to CB1 receptor upregulation, and results in cellular dysfunction and cell death in endothelial cells and cardiomyocytes 73. The role of CB2 receptors is to decrease leukocyte infiltration and enhance pathways that contribute to survival 9, 71, 72, 74. TRP channels account for the sensing mechanisms of cardiac pain caused by myocardial ischemia 75.…”

“…CB2 receptors promote monocyte chemotaxis, infiltration and activation; leading to vascular inflammation, plaque development, and vascular smooth muscle cell proliferation 9, 71, 72, 74. Furthermore, CB1 receptor expression in macrophages and endocannabinoid concentration of anandamide and 2‐AG in the blood is meaningfully higher in patients with unstable angina compared with patients with stable angina47 indicating that receptor expression, and thereby theoretical endocannabinoid‐receptor interaction, is directly linked to disease severity in patients with atherosclerosis.…”

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

“…Interestingly, curcumin (no effect on ACAT1 or ACAT2; inhibition of oxLDL uptake and promotion of cholesterol efflux from macrophages) [256,257] and erythropoietin (increased cholesterol efflux from macrophages) [258] , were reported to suppress the formation of macrophage foam cells. Finally, it should be noted that delta 9-tetrahydrocannabinol (THC), the main constituent of marijuana (Cannabis sativa), administered by a noninhalation route may exert dose-dependent (1 mg/kg/day; low 0.6 ng/mL plasma levels with no psychotropic effects) atheroprotective effects via its immunomodulatory and antiinflammatory actions [259] , as well as inhibition of ACAT1 and ACAT2 activities [260] . In summary, ACAT2 enzyme has a longer half-life than ACAT1.…”

New medical marijuana regulations: the coming storm

“…5 There have been case reports of younger adults experiencing acute coronary events shortly after smoking cannabis. 6 Vaporizing produces much lower concentrations of exhaled carbon monoxide than smoking, but smoking remains the most popular delivery route.…”