Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly

Abstract

Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CBR and CBR) has been implicated in a variety of cardiovascular pathologies. Activation of CBR facilitates the development of cardiometabolic disease, whereas activation of CBR (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, Δ-tetrahydrocannabinol (THC), is an agonist of both CBR and CBR, and exerts its psychoactive and adverse cardiovascular effects through the activation of CBR in the central nervous and cardiovascular systems. The past decade has seen a nearly tenfold increase in the THC content of marijuana as well as the increased availability of highly potent synthetic cannabinoids for recreational use. These changes have been accompanied by the emergence of serious adverse cardiovascular events, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest. In this Review, we summarize the role of the endocannabinoid system in cardiovascular disease, and critically discuss the cardiovascular consequences of marijuana and synthetic cannabinoid use. With the legalization of marijuana for medicinal purposes and/or recreational use in many countries, physicians should be alert to the possibility that the use of marijuana or its potent synthetic analogues might be the underlying cause of severe cardiovascular events and pathologies.

Interplay of Liver–Heart Inflammatory Axis and Cannabinoid 2 Receptor Signaling in an Experimental Model of Hepatic Cardiomyopathy

“…It is well documented that endocannabinoids or synthetic ligands exert opposing effects through CB 1 or CB 2 receptors on multiple pathological processes in the liver and heart . CB 1 ‐R promotes hepatic steatosis, inflammation, and fibrogenesis.…”

“…Endocannabinoid–CB 1 ‐R signaling also contributes to peripheral vasodilation and cardiac dysfunction associated with liver cirrhosis . In contrast, CB 2 ‐R activation has been shown to reduce the extent of liver injury, inflammation, and/or fibrosis and to decrease cardiovascular inflammation in models of atherosclerosis or myocardial infarction by modulating interactions of activated endothelium and infiltrating immune cells . CB 2 ‐R is primarily expressed in inflammatory cells, with the highest expression in B lymphocytes, macrophages, and macrophage‐derived cells (e.g., Kupffer cells) and lower expression in other immune and activated endothelial cells .…”

“…The role of endocannabinoid–cannabinoid 1 receptor (CB 1 ‐R) signaling has been proposed in the development of liver injury–related cardiovascular pathologies . Moreover, the beneficial role of CB 2 ‐R activation has been shown in models of liver injury, inflammation, and fibrosis …”

Liquid chromatography–tandem mass spectrometry screening method using information‐dependent acquisition of enhanced product ion mass spectra for synthetic cannabinoids including metabolites in urine

“…SCs have effects similar to (−)‐trans‐Δ9‐tetrahydrocannabinol (THC), as they usually show agonistic effects at the cannabinoid receptors CB 1 and CB 2. Potency and elimination half‐life can differ significantly, however, which most probably is the reason for the higher toxicity of SCs compared to THC . Various case reports on intoxications involving SCs are available.…”

Recurrent STEMI Precipitated by Marijuana Use: Case Report and Literature Review

“…CBR1 and CBR2 also play an important role in the precipitation of acute myocardial infarction via their distribution on circulating blood cells including monocytes, macrophages, and platelets [33]. THC prolongation lipopolysaccharide-stimulated tissue factor protein expression in activated monocytes generates a THC dose-dependent procoagulant effect [34,35].…”