Ceramide: a new second messenger of cannabinoid action

Trends Pharmacol Sci. 2001 Jan;22(1):19-22. doi: 10.1016/s0165-6147(00)01586-8.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cannabinoids / metabolism
  • Cannabinoids / pharmacology*
  • Ceramides / biosynthesis
  • Ceramides / physiology*
  • Humans
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Rats
  • Receptors, Cannabinoid
  • Receptors, Drug / metabolism
  • Second Messenger Systems / drug effects
  • Second Messenger Systems / physiology*


  • Cannabinoids
  • Ceramides
  • Receptors, Cannabinoid
  • Receptors, Drug