A Systematic Review of the Complex Effects of Cannabinoids on Cerebral and Peripheral Circulation in Animal Models

Abstract

While cannabis is perceived as a relatively safe drug by the public, accumulating clinical data suggest detrimental cardiovascular effects of cannabinoids. Cannabis has been legalized in several countries and jurisdictions recently. Experimental studies specifically targeting cannabinoids' effects on the cerebral vasculature are rare. There is evidence for transient vasoconstrictive effects of cannabinoids in the peripheral and cerebral vasculature in a complex interplay of vasodilation and vasoconstriction. Vasoreactivity to cannabinoids is dependent on the specific molecules, their metabolites and dose, baseline vascular tone, and vessel characteristics as well as experimental conditions and animal species. We systematically review the currently available literature of experimental results in in vivo and in vitro animal studies, examining cannabinoids' effects on circulation and reactive vasodilation or vasoconstriction, with a particular focus on the cerebral vascular bed.

The effects of nicotine and cannabis co-use during adolescence and young adulthood on white matter cerebral blood flow estimates

“…NTP use has been associated with both vasoconstrictive and vasodilatory effects, but acute nicotine administration appears to have a dose-dependent vasodilation effect on cerebrovasculature (Iida et al 1998;Toda 1975). Acute cannabis use has similarly been associated with cerebral vasodilation, yet concomitant vasoconstriction is also often observed (Richter et al 2018). Chronic effects of either substance on cerebral vasculature are even more unclear, suggesting the presence of a complex relationship between dosage, recency of use, and region-specific effects.…”

The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease

“…The administration of phyto-, endo-and synthetic cannabinoids has a diverse and sometimes polyphasic influence on blood pressure (BP) and heart rate (HR) depending on the species, route of administration, presence of anaesthesia and other experimental conditions [19]. Cannabinoids can affect cardiovascular function not only by cannabinoid receptors, but a variety of other receptors, located both in the nervous system and directly in the blood vessels and heart [19,35,71,72]. Stimulation of central CB 1 receptors causes an increase in blood pressure, whereas peripheral CB 1 receptors located presynaptically at the endings of pre-and/or postganglionic sympathetic neurons innervating the heart and vascular resistance are responsible for hypotensive effects of cannabinoids.…”

“…Activation of CB 1 receptors located in the myocardium reduces contractility. In addition, cannabinoids can stimulate or inhibit the Bezold-Jarisch reflex, characterized by short and strong bradycardia and hypotension, via TRPV1 and 5-HT 3 receptors located on sensory vagal nerve fibres [19,72]. Cannabinoids, in most cases, cause vasodilation in isolated blood vessels or perfused vascular beds, although vasoconstriction is also observed.…”

“…These effects result from direct activation of CB 1 , TRPV1, PPARs and the putative endothelial cannabinoid receptors. In addition, the role of CB 2 , GPR55 and 5-HT 1A receptors in vasoactive effects of cannabinoids has been revealed in some studies [71,72]. Cannabinoids can also activate orphan GPR18 localized peripherally in blood vessels (GPR18 was deorphanised as the endothelial cannabinoid receptor by some authors, see below) and centrally in rostral ventrolateral medulla (RVLM) which results in vasorelaxation and hypotension [35,73].…”

Role of Cannabis in the Incidence of Myocardial Infarction: A Review

“…Since these receptors are present in the body extensively, its activation affects multiple systems [7]. The molecular mechanism of the receptors involves signal transduction through modulation of adenylyl cyclase (AC), nuclear factor kappa light chain enhancer of activated B cells (NF-kb), and mitogen-activated protein kinases (MAPK) [7,14]. CB1R stimulation causes activation of the adenylyl cyclase inhibitor subunit of G-proteins (Gi/o).…”