Cannabinoids, multiple sclerosis and neuroprotection.

The cannabinoid signaling system participates in the control of cell homeostasis in the CNS, which explains why, in different neurodegenerative diseases including multiple sclerosis (MS), alterations in this system have been found to serve both as a pathogenic factor (malfunctioning of this system has been found at early phases of these diseases) and as a therapeutic target (the management of this system has beneficial effects). MS is an autoimmune disease that affects the CNS and it is characterized by inflammation, demyelination, remyelination, gliosis and axonal damage. Although it has been considered mainly as an inflammatory disorder, recent studies have recognized the importance of axonal loss both in the progression of the disorder and in the appearance of neurological disability, even in early stages of the disease. In recent years, several laboratories have addressed the therapeutic potential of cannabinoids in MS, given the experience reported by some MS patients who self-medicated with marijuana. Most of these studies focused on the alleviation of symptoms (spasticity, tremor, anxiety and pain) or on the inflammatory component of the disease. However, recent data also revealed the important neuroprotective action that could be exerted by cannabinoids in this disorder. The present review will be precisely centered on this neuroprotective potential, which is based mainly on antioxidant, anti-inflammatory and anti-excitotoxic properties, exerted through the activation of CB1 or CB2 receptors or other unknown mechanisms.