12.5.1 Cardiovascular Disease

12.5.1.1 Atherosclerosis

Atherosclerosis is a chronic inflammatory disease. It is characterized by accumula-

tion of cholesterol and other substances under the intima of the vessels leading to

proliferation of the vascular smooth muscles and recruitment of inflammatory cells

which finally form atheromatous plaque that causes stiffening and narrowing of the

vessels. Atherosclerosis compromises the circulation to vital end organs like the

heart, kidney, and brain resulting in myocardial infarction, chronic kidney disease,

and strokes. Cannabinoids affect atherogenesis via modulation of immune system

response. CB1 and CB2 receptors coexist on the human macrophages. Thus, the role

of both the receptors is considered in the regulation of atherosclerosis. CB1 receptors

on activation switch on the MAPK signaling which causes the production of ROS

(reactive oxygen species) and subsequently causes the pro-inflammatory response,

whereas, CB2 receptors suppress these inflammatory pathways stimulated by CB1

receptors (Libby 2002). Oral administration of low dose of THC inhibits the

progression of atherosclerosis in a mouse model. THC does so by decreasing

monocyte adhesion and infiltrating the subendothelial region via CB2 receptor

(Steffens et al. 2005). It is demonstrated in a study by Yuan et al. that THC

downregulated the TH1 immune response (Yuan et al. 2002). Apart from THC,

WIN 55,212-2 can also activate the CB2 receptors which in response de-escalate the

pro-inflammatory cytokine gene expression and cause attenuation of the downstream

Cardiovascular disease

CNS Disorders

ROLE OF

CANNABINOID SYSTEM

Respiratory

Disorders

Asthma

Cancer

pain

nausea

appetite

mood

elevation

MS

Huntington

Alzheimer

Epilepsy

Atherosclerosis

Fig. 12.2 Overview of the role of cannabinoid system

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S. Singh et al.