Control of the cell survival/death decision by cannabinoids

Cannabinoids, the active components of Cannabis sativa (marijuana), and the ir derivatives produce a wide spectrum of central and peripheral effects. s ome of which may have clinical application. The discovery of specific canna binoid receptors and a family of endogenous ligands of those receptors has attracted much attention to cannabinoids in recent years. One of the most e xciting and promising areas of current cannabinoid research is the ability of these compounds to control the cell survival/death decision. Thus cannab inoids may induce proliferation, growth arrest, or apoptosis in a number of cells, including neurons, lymphocytes, and various transformed neural and nonneural cells. The variation in drug effects may depend on experimental f actors such as drug concentration, timing of drug delivery, and type of cel l examined. Regarding the central nervous system, most of the experimental evidence indicates that cannabinoids may protect neurons from toxic insults such as glutamaergic overstimulation, ischemia and oxidative damage. In co ntrast, cannabinoids induce apoptosis of glioma cells in culture and regres sion of malignant gliomas in vivo. Breast and prostate cancer cells are als o sensitive to cannabinoid-induced antiproliferation. Regarding the immune system, low doses of cannabinoids may enhance cell proliferation, whereas h igh doses of cannabinoids usually induce growth arrest or apoptosis. The ne uroprotective effect of cannabinoids may have potential clinical relevance for the treatment of neurodegenerative disorders such as multiple sclerosis , Parkinson's disease, and ischemia/stroke, whereas their growth-inhibiting action on transformed cells might be useful for the management of malignan t brain tumors. Ongoing investigation is in search for cannabinoid-based th erapeutic strategies devoid of nondesired psychotropic effects.