Endocannabinoid System and Multiple Sclerosis

Stuart SchlossmanComplementary & Alternative therapies and devices for Multiple Sclerosis (MS)


                                                                  

  


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COMPLIMENTARY in Nature — 

The endocannabinoid system (ECS) is a group of endogenous cannabinoid receptors located in the mammalian brain and throughout the central and peripheral nervous systems, consisting of neuromodulatory lipids and their receptors. Known as “the body’s own cannabinoid system”,[1] the ECS is involved in a variety of physiological processes including appetitepain-sensationmood, and memory, and in mediating the psychoactive effects of cannabis.[2] The ECS is also involved in voluntary exercise[3] and may be related to the evolution of the runner’s high runner’s high in human beings and related aspects of motivation or reward for locomotor activity in other animals.[4]
Two primary endocannabinoid receptors have been identified: CB1, first cloned in 1990; and CB2, cloned in 1993. CB1 receptors are found predominantly in the brain and nervous system, as well as in peripheral organs and tissues, and are the main molecular target of the endocannabinoid ligand (binding molecule), Anandamide, as well as its mimetic phytocannabinoid, THC. One other main endocannabinoid is 2-Arachidonoylglycerol (2-AG) which is active at both cannabinoid receptors, along with its own mimetic phytocannabinoid, CBD. 2-AG and CBD are involved in the regulation of appetite, immune system functions and pain management.[1][5][6]


Multiple sclerosis

Historical records from ancient China and Greece suggest that preparations of Cannabis indica were commonly prescribed to ameliorate multiple sclerosis-like symptoms such as tremors and muscle pain. Modern research has confirmed these effects in a study on diseased mice, wherein both endogenous and exogenous agonists showed ameliorating effects on tremor and spasticity. It remains to be seen whether pharmaceutical preparations such as dronabinol have the same effects in humans.[50][51] Due to increasing use of medical Cannabis and rising incidence of multiple sclerosis patients who self-medicate with the drug, there has been much interest in exploiting the endocannabinoid system in the cerebellum to provide a legal and effective relief.[38] In mouse models of multiple sclerosis, there is a profound reduction and reorganization of CB1 receptors in the cerebellum.[52] Serial sections of cerebellar tissue subjected to immunohistochemistry revealed that this aberrant expression occurred during the relapse phase but returned to normal during the remitting phase of the disease.[52] Other studies suggest that CB1 agonists promote the survival of oligodendrocytes in vitro in the absence of growth and trophic factors; in addition, these agonist have been shown to promote mRNA expression of myelin lipid protein. (Kittler et al., 2000; Mollna-Holgado et al., 2002). Taken together, these studies point to the exciting possibility that cannabinoid treatment may not only be able to attenuate the symptoms of multiple sclerosis but also improve oligodendrocyte function (reviewed in Pertwee, 2001; Mollna-Holgado et al., 2002). 2-AG stimulates proliferation of a microglial cell line by a CB2 receptor dependent mechanism, and the number of microglial cells is increased in multiple sclerosis.[53]


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