2-arachidonyl glycerol activates platelets via conversion to arachidonic acid and not by direct activation of cannabinoid receptors.

British Journal of Clinical Pharmacology
Oliver P KeownIan L Megson

Abstract

There are conflicting views in the literature as to whether cannabinoids have an impact on platelet activity and to what extent cannabinoid receptors are involved. This is an important issue to resolve because platelet effects of putative therapeutic cannabinoid inhibitors and stimulators will have an impact on their potential benefits and safety. The data presented in this manuscript clearly show that the endocannabinoid 2-arrachidonyl glycerol can activate platelet activity, but that the effects are mediated through an aspirin-sensitive pathway that is not affected by cannabinoid receptor antagonists or FAAH inhibition, but is abolished by MAGL inhibition. The findings question the role of cannabinoid receptors in platelet function and suggest that platelet function is unlikely to be directly affected by cannabinoid receptor antagonists, at least in the acute phase. Cannabinoid receptor-1 (CB(1)) antagonists suppress appetite and induce weight loss. Direct antagonism of CB(1) receptors on platelets might be an additional benefit for CB(1) antagonists, but the role of CB(1) receptors in platelets is controversial. We tested the hypothesis that the endocannabinoid, 2-arachidonyl glycerol (2-AG), induces platelet aggregation by ...Continue Reading

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Citations

Oct 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Mireille AlhouayekGiulio G Muccioli
Jan 12, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Kayte A JenkinDeanne H Hryciw
Nov 27, 2015·Drug Testing and Analysis·Daniela MarchettiNadia De Giovanni
Aug 28, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·N MurataevaA Straiker
Jan 27, 2012·Clinical Cardiology·Sandeep SinglaJawahar L Mehta
May 25, 2011·Journal of Cellular Biochemistry·Maria Grazia SignorelloGiuliana Leoncini
Oct 16, 2015·Journal of Cellular Biochemistry·Maria Grazia Signorello, Giuliana Leoncini
May 11, 2015·Cellular and Molecular Life Sciences : CMLS·Valeria GasperiMaria Valeria Catani
Jun 25, 2013·Platelets·S Annette BrantlWolfgang Siess
Jul 31, 2013·Drug Discovery Today·Mireille AlhouayekGiulio G Muccioli
May 25, 2013·Biochimie·Maria Grazia SignorelloGiuliana Leoncini
Jan 20, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Jennifer A ShearerHilary V O Carswell
Feb 12, 2021·Journal of Neuroimmunology·Durga Shankar SharmaRavi Kumar Gutti

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