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.

Figure 1

Distribution of cannabinoid receptors in major organ systems. CB1, cannabinoid receptor type 1; CB2, cannabinoid receptor type 2.

Figure 2

Salient features of cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) receptor activation in relation to atherosclerosis. Abbreviations: AT1R, angiotensin II receptor type 1; ICAM, intercellular adhesion molecule; IFN‐γ, interferon‐γ; MAPK, mitogen activated protein kinase; MMP‐9, matrix metalloproteinase‐9; MCP 1, monocyte chemoattractant protein‐1; Ox‐LDL, oxidized low‐density lipoprotein; ROS, reactive oxygen species; SMC, smooth muscle cell; VCAM, vascular cell adhesion molecule.