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

Key Points

  • Activation of cannabinoid receptor 1 (CB1R) by endocannabinoids or synthetic ligands mediates acute haemodynamic effects and might contribute to pathology in cardiovascular disease; activation of cannabinoid receptor 2 (CB2R) exerts anti-inflammatory effects

  • The psychoactive constituent of marijuana, Δ9-tetrahydrocannabinol (THC), exerts its cardiovascular effects via CB1R activation; at low doses it might have beneficial properties via partial activation of CB1R and CB2R, 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 CB1R (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

Abstract

Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CB1R and CB2R) has been implicated in a variety of cardiovascular pathologies. Activation of CB1R facilitates the development of cardiometabolic disease, whereas activation of CB2R (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, Δ9-tetrahydrocannabinol (THC), is an agonist of both CB1R and CB2R, and exerts its psychoactive and adverse cardiovascular effects through the activation of CB1R 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.

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Figure 1: Pathophysiological effects of the endocannabinoid system in health and disease.
Figure 2: Reported cardiovascular adverse consequences of recreational marijuana and synthetic cannabinoid use.
Figure 3: Adverse cardiovascular consequences of synthetic cannabinoids.

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Acknowledgements

The authors are supported by the Intramural Program of the NIAAA/NIH.

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P.P. and S.S. researched data for the article. All the authors discussed the content of the manuscript. P.P., S.S., and G.K. wrote the article, and P.P., G.H., T.H.S., and G.K. reviewed/edited the manuscript before submission.

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Correspondence to Pal Pacher.

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Pacher, P., Steffens, S., Haskó, G. et al. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol 15, 151–166 (2018). https://doi.org/10.1038/nrcardio.2017.130

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