Although cannabinoids are among the oldest known
medicinal compounds, their chemistry, pharmacology, and clinical effects have only been recently studied. There is also an increasing recognition of their therapeutic potential in multiple clinical scenarios.
Cannabinoids, the active ingredients in marijuana, are
derived from the hemp plant Cannabis sativa. Different
parts of this plant, including leaves, flowers, and resin
extract, have been used for euphoric effects for centuries.
The use of cannabinoids as herbal medicine as an analgesic, muscle relaxant, appetite stimulant, and bronchodilator can be traced back 5000 years in China.
In a research made by Dr.
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.
Based on the studies discussed in the research, modulation of the cannabinoid system holds promise in preventing the progression of atherosclerosis.
In another Research made by Naghum Alfulaij, Franziska Meiners, Justin Michalek, Andrea L. Small‐Howard, Helen C. Turner, and Alexander J. Stokes called Cannabinoids, the Heart of the Matter they discuss about the various Cardiovascular disease (CVD) , including the contributing pathologies within CVD, and current therapeutic approaches.
That is followed by the review of the Endocannabinoid System (ECS) and its physiological and pathological roles, and details the receptors involved in the ECS. and discuss the connection of CVD to the ECS and delve into the possible manipulations of these pathways that could be employed for future therapeutic approaches, but we are going to focus on Atherosclerosis for this Article.
Atherosclerosis is an inflammatory condition in which the concentration of immune cells is elevated, and vascular smooth muscle cell expression is changed. CB2 receptors promote monocyte chemotaxis, infiltration and activation; leading to vascular inflammation, plaque development, and vascular smooth muscle cell proliferation.
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 angina indicating that receptor expression, and thereby theoretical endocannabinoid‐receptor interaction, is directly linked to disease severity in patients with atherosclerosis.
CB1 agonism reduces the blood pressure significantly more in spontaneously hypertensive rats than in normotensive rats, and CB1 receptor expression is higher in the heart and aortic endothelium in spontaneously hypertensive rats compared with normotensive rats. In addition, ∆‐9‐THC‐stimulated human T‐cells show less proliferation and inhibition of interferon‐gamma production, as well as downregulation of T‐helper 1 cells that are present in atherosclerotic lesions and which contribute to the inflammatory state of the lesions.
The endocannabinoid system (ECS) and cannabinoid receptors (both CB1 and CB2) are highly active in cells found in atherosclerotic plaques such as macrophages and vascular smooth muscle cells, Macrophages are activated by oxidized LDL through increased (anandamide) and 2‐arachidonoylglycerol (2‐AG) concentration, as well as upregulation of CB1 and CB2, thus initiating cholesterol accumulation in immune cells, affecting endothelial cells, and vascular smooth muscle cells.
In summary, the endocannabinoid system is highly active in cardiovascular disease states. Modulation of the ECS, CB1, and TRPV1 antagonism, as well as CB2 agonism, have proven to modulate disease state and severity in CVD. Studies are underway to develop drugs to change the course of cardiovascular diseases. Areas of promise include: CB1 antagonism which has an anti‐inflammatory effect and reduces smooth muscle cell proliferation, as well as CB2 agonism which results in decreased expression of adhesion molecules, reduced inflammatory response, reduced plaque size in atherosclerosis and inhibits the action of oxidized LDL. Of particular interest is the fact that TRPV1 antagonism protects the heart from heart failure‐associated remodeling, especially given the plethora of available TRPV1 antagonists tested in Phase II clinical trials for pain, and other indications.
Although cannabinoids are among the oldest known
medicinal compounds, their chemistry, pharmacology, and clinical effects have only been recently studied. There is also an increasing recognition of their therapeutic potential in multiple clinical scenarios.
Cannabinoids, the active ingredients in marijuana, are
derived from the hemp plant Cannabis sativa. Different
parts of this plant, including leaves, flowers, and resin
extract, have been used for euphoric effects for centuries.
The use of cannabinoids as herbal medicine as an analgesic, muscle relaxant, appetite stimulant, and bronchodilator can be traced back 5000 years in China.
In a research made by Dr.
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.
Based on the studies discussed in the research, modulation of the cannabinoid system holds promise in preventing the progression of atherosclerosis.
In another Research made by Naghum Alfulaij, Franziska Meiners, Justin Michalek, Andrea L. Small‐Howard, Helen C. Turner, and Alexander J. Stokes called Cannabinoids, the Heart of the Matter they discuss about the various Cardiovascular disease (CVD) , including the contributing pathologies within CVD, and current therapeutic approaches.
That is followed by the review of the Endocannabinoid System (ECS) and its physiological and pathological roles, and details the receptors involved in the ECS. and discuss the connection of CVD to the ECS and delve into the possible manipulations of these pathways that could be employed for future therapeutic approaches, but we are going to focus on Atherosclerosis for this Article.
Atherosclerosis is an inflammatory condition in which the concentration of immune cells is elevated, and vascular smooth muscle cell expression is changed. CB2 receptors promote monocyte chemotaxis, infiltration and activation; leading to vascular inflammation, plaque development, and vascular smooth muscle cell proliferation.
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 angina indicating that receptor expression, and thereby theoretical endocannabinoid‐receptor interaction, is directly linked to disease severity in patients with atherosclerosis.
CB1 agonism reduces the blood pressure significantly more in spontaneously hypertensive rats than in normotensive rats, and CB1 receptor expression is higher in the heart and aortic endothelium in spontaneously hypertensive rats compared with normotensive rats. In addition, ∆‐9‐THC‐stimulated human T‐cells show less proliferation and inhibition of interferon‐gamma production, as well as downregulation of T‐helper 1 cells that are present in atherosclerotic lesions and which contribute to the inflammatory state of the lesions.
The endocannabinoid system (ECS) and cannabinoid receptors (both CB1 and CB2) are highly active in cells found in atherosclerotic plaques such as macrophages and vascular smooth muscle cells, Macrophages are activated by oxidized LDL through increased (anandamide) and 2‐arachidonoylglycerol (2‐AG) concentration, as well as upregulation of CB1 and CB2, thus initiating cholesterol accumulation in immune cells, affecting endothelial cells, and vascular smooth muscle cells.
In summary, the endocannabinoid system is highly active in cardiovascular disease states. Modulation of the ECS, CB1, and TRPV1 antagonism, as well as CB2 agonism, have proven to modulate disease state and severity in CVD. Studies are underway to develop drugs to change the course of cardiovascular diseases. Areas of promise include: CB1 antagonism which has an anti‐inflammatory effect and reduces smooth muscle cell proliferation, as well as CB2 agonism which results in decreased expression of adhesion molecules, reduced inflammatory response, reduced plaque size in atherosclerosis and inhibits the action of oxidized LDL. Of particular interest is the fact that TRPV1 antagonism protects the heart from heart failure‐associated remodeling, especially given the plethora of available TRPV1 antagonists tested in Phase II clinical trials for pain, and other indications.
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