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Control of the cell survival/death decision by cannabinoids
Guzman M, Sanchez C, Galve-Roperh I.
ABSTRACT
Cannabinoids, the active components of Cannabis sativa
(marijuana), and their derivatives produce a wide spectrum of central and
peripheral effects, some of which may have clinical application. The discovery
of specific cannabinoid receptors and a family of endogenous ligands of
those receptors has attracted much attention to cannabinoids in recent years.
One of the most exciting and promising areas of current cannabinoid research
is the ability of these compounds to control the cell survival/death decision.
Thus cannabinoids 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 factors such as drug concentration, timing of drug delivery,
and type of cell 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 contrast, cannabinoids induce apoptosis of glioma cells in culture
and regression of malignant gliomas in vivo. Breast and prostate cancer
cells are also sensitive to cannabinoid-induced antiproliferation. Regarding
the immune system, low doses of cannabinoids may enhance cell proliferation,
whereas high doses of cannabinoids usually induce growth arrest or apoptosis.
The neuroprotective 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 malignant
brain tumors. Ongoing investigation is in search for cannabinoid-based therapeutic
strategies devoid of nondesired psychotropic effects.
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