Role of Cannabinoid Signaling in Cardiovascular Function and Ischemic Injury

Cardiovascular disease represents a leading cause of death, morbidity, and societal economic burden. The prevalence of cannabis use has significantly increased due to legalization and an increased societal acceptance of cannabis. Therefore, it is critically important that we gain a greater understanding of the effects and risks of cannabinoid use on cardiovascular diseases as well as the potential for cannabinoid-directed drugs to be used as therapeutics for the treatment of cardiovascular dis-ease. This review summarizes our current understanding of the role of cannabinoid receptors in the pathophysiology of athero-sclerosis and myocardial ischemia and explores their use as therapeutic targets in the treatment of ischemic heart disease. Endocannabinoids are elevated in patients with atherosclerosis, and activation of cannabinoid type 1 receptors (CB1Rs) gener-ally leads to an enhancement of plaque formation and athero-sclerosis. In contrast, selective activation of cannabinoid type 2 receptors (CB2Rs) appears to exert protective effects against atherosclerosis. Endocannabinoid signaling is also activated by myocardial ischemia. CB2R signaling appears to protect the heart from ischemic injury, whereas the role of CB1R in ische-mic injury is less clear. This narrative review serves to summa-rize current research on the role of cannabinoid signaling in cardiovascular function with the goal of identifying critical knowledge gaps and future studies to address those gaps in a way that facilitates the development of new treatments and better cardiovascular health. SIGNIFICANCE STATEMENT Cardiovascular diseases, including atherosclerosis and myocar-dial infarction, are a leading cause of death. Cannabinoid drugs have well known acute effects on cardiovascular function, in-cluding tachycardia and orthostatic hypotension. The recent le-galization of marijuana and cannabinoids for both medical and recreational use has dramatically increased their prevalence of use. This narrative review on the role of cannabinoid signaling in cardiovascular disease contributes to a better understanding of this topic by integrating current knowledge and identifying critical gaps.

Automated summary

Cardiovascular disease is a leading cause of death, and the increasing use of cannabis raises the need to understand its effects and risks on cardiovascular health. This review explores the role of cannabinoid receptors in atherosclerosis and myocardial ischemia, and their potential as therapeutic targets for ischemic heart disease.