CB1 receptors are found extensively in the heart and vascular tissues. They are present in the central regulatory centers of the CV system in the brain, as well as in the sympathetic and parasympathetic nerves that link the heart and blood vessels to central regulatory centers. CB1 activation on myocardial cells leads to decreased contractility via inhibition of L-type calcium channels. CB1 activation in the paraventricular nucleus (PVN) causes a drop in blood pressure via decreased sympathetic tone but is also necessary to increase blood pressure via renin-angiotensin system. In the rostral ventrolateral medulla (RVLM), the recently characterized endocannabinoid receptor GPR18 tonically lowers blood pressure. In the solitary tract nucleus (NTS) of the medulla, the ECS suppresses all autonomic output, potentially resulting in orthostatic hypotension if overstimulated by exogenous cannabinoids. Both endogenous and exogenous cannabinoids play a complex role in coordination with the renin-angiotensin system, sympathetics and parasympathetics, alpha-adrenergic, beta-adrenergic, NMDA, and thromboxane A (2) receptors in controlling blood pressure, with most exogenous cannabinoids leading to a slight BP lowering effect. Activation of TRPV1 and PPAR gamma also appears to have BP lowering effects. Animal models demonstrate a protective role of the ECS after MI is mediated by CB1 and CB2 receptors as well as TRPV1, with CB2 potentially playing a positive role in the prevention of atherosclerosis. While the relationship between cannabis and MI is mixed and require further study, it does appear that its activation has real benefits in both progression and prognosis of heart failure.