Cannabinoids, the active components of Cannabis sativa (marijuana) and their endogenous counterparts, exert their effects by binding to specific G-protein-coupled receptors that modulate adenylyl cyclase and ion channels. Recent research has shown that the CB1 cannabinoid receptor is also coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis and ceramide synthesis de novo. Sustained ceramide accumulation in tumor cells mediates cannabinoid-induced apoptosis, as evidenced by in vitro and in vivo studies. This effect seems to be due to the impact of ceramide on key cell signalling systems such as the extracellular signal-regulated kinase cascade and the Akt...

Normal tissue toxicity limits the efficacy of current treatment modalities for glioblastoma multiforme (GBM). We evaluated the influence of cannabinoids on cell proliferation, death, and morphology of human GBM cell lines and in primary human glial cultures, the normal cells from which GBM tumors arise. The influence of a plant derived cannabinoid agonist, D9 -tetrahydrocannabinol (D9 -THC), and a potent synthetic cannabinoid agonist, WIN 55,212- 2, were compared using time lapse microscopy. We discovered that D9 -THC decreases cell proliferation and increases cell death of human GBM cells more rapidly than WIN 55,212-2. D9 -THC was also more potent at inhibiting the proliferation of...