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

Key Points Activation of cannabinoid receptor 1 (CB 1 R) by endocannabinoids or synthetic ligands mediates acute haemodynamic effects and might contribute to pathology in cardiovascular disease; activation of cannabinoid receptor 2 (CB 2 R) exerts anti-inflammatory effects The psychoactive constituent of marijuana, Δ 9 -tetrahydrocannabinol (THC), exerts its cardiovascular effects via CB 1 R activation; at low doses it might have beneficial properties via partial activation of CB 1 R and CB 2 R, and unrelated mechanisms The composition of marijuana (THC–cannabidiol ratio, terpenoids) can influence its therapeutic and cardiovascular adverse effects, with marijuana smoke being as harmful as tobacco smoke Most synthetic cannabinoids used for recreational use are full agonists of CB 1 R (THC is a partial agonist) with up to several hundred-fold higher potency and efficacy than THC, causing more dangerous adverse effects In parallel with a tenfold increase in the THC content of marijuana and the widespread availability of synthetic cannabinoids for recreational use, the number of serious cardiovascular adverse effects reported has markedly increased Clinicians should be vigilant to recognizing potential cardiovascular effects of marijuana and synthetic cannabinoids; controlled clinical trials should determine the long-term consequences of the use of medical marijuana on cardiovascular morbidity and mortality Over the past decade, marijuana has been legalized for medicinal purposes or recreational use in many countries, and the potency of marijuana and synthetic cannabinoids has substantially increased. In this Review, Pacher and colleagues summarize the role of the endocannabinoid system in cardiovascular health and disease, and critically discuss the beneficial and detrimental cardiovascular effects of marijuana and synthetic cannabinoid use. Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CB 1 R and CB 2 R) has been implicated in a variety of cardiovascular pathologies. Activation of CB 1 R facilitates the development of cardiometabolic disease, whereas activation of CB 2 R (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, Δ 9 -tetrahydrocannabinol (THC), is an agonist of both CB 1 R and CB 2 R, and exerts its psychoactive and adverse cardiovascular effects through the activation of CB 1 R in the central nervous and card