Ceramide: a new second messenger of cannabinoid action

Cannabinoids, the active components of Cannabis sativa (marijuana). and the ir endogenous counterparts exert their effects by binding to specific G(i/o )-protein-coupled receptors that modulate adenylyl cyclase, ion channels an d extracellular signal-regulated kinases. Recent research has shown that th e CB1 cannabinoid receptor is coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis, a nd ceramide synthesis de nova, Ceramide in turn mediates cannabinoid-induce d apoptosis, as shown by in vitro and in vivo studies. These findings provi de a new perspective on how cannabinoids act, and raise exciting physiologi cal and therapeutic questions.