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Trends Pharmacol Sci. 2001 Jan;22(1):19-22.

Ceramide: a new second messenger of cannabinoid action.

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Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040, Madrid, Spain.


Cannabinoids, the active components of Cannabis sativa (marijuana), and their endogenous counterparts exert their effects by binding to specific G(i/o)-protein-coupled receptors that modulate adenylyl cyclase, ion channels and extracellular signal-regulated kinases. Recent research has shown that the CB(1) cannabinoid receptor is coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis, and ceramide synthesis de novo. Ceramide in turn mediates cannabinoid-induced apoptosis, as shown by in vitro and in vivo studies. These findings provide a new perspective on how cannabinoids act, and raise exciting physiological and therapeutic questions.

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