Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists

Leonid Maslov, Igor Khaliulin, Yi Zhang, Andrey Krylatov, Natalia Naryzhnaya, Raphael Mechoulam, Luciano De Petrocellis, James Downey

Research output: Contribution to journalArticle (Academic Journal)peer-review

23 Citations (Scopus)
497 Downloads (Pure)


Cannabinoids can mimic the infarct-reducing effect of early ischemic preconditioning, delayed ischemic preconditioning, and ischemic postconditioning against myocardial ischemia/reperfusion. They do this primarily through both CB1 and CB2 receptors. Cannabinoids are also involved in remote preconditioning of the heart. The cannabinoid receptor ligands also exhibit an antiapoptotic effect during ischemia/reperfusion of the heart. The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase. The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression. The delayed cardioprotective effect of another cannabinoid, Δ9-tetrahydrocannabinol, is associated with augmentation of nitric oxide (NO) synthase expression, but data on the involvement of NO synthase in the acute cardioprotective effect of cannabinoids are contradictory. The adenosine triphosphate-sensitive K+ channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury. Cannabinoids inhibit Na+/Ca2+ exchange via peripheral cannabinoid receptor (CB2) activation that may also be related to the antiapoptotic and cardioprotective effects of cannabinoids. The cannabinoid receptor agonists should be considered as prospective group of compounds for creation of drugs that are able to protect the heart against ischemia–reperfusion injury in the clinical setting.
Original languageEnglish
Pages (from-to)262-272
Number of pages11
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Issue number3
Early online date19 Oct 2015
Publication statusPublished - May 2016

Structured keywords

  • Cabot Institute for the Environment


  • Heart
  • ischemia/reperfusion injury
  • cannabinoid receptor agonists


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