The Endocannabinoid System and Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease that is characterised by repeated inflammatory/demyelinating events within the central nervous system (CNS). In addition to relapsing-remitting neurological insults, leading to loss of function, patients are often left with residual, troublesome symptoms such as spasticity and pain. These greatly diminish "quality of life" and have prompted some patients to self-medicate with and perceive benefit from cannabis. Recent advances in cannabinoid biology are beginning to support these anecdotal observations, notably the demonstration that spasticity is tonically regulated by the endogenous cannabinoid system. Recent clinical trials may indeed suggest that cannabis has some potential to relieve, pain, spasms and spasticity in MS. However, because the CB(1) cannabinoid receptor mediates both the positive and adverse effects of cannabis, therapy will invariably be associated with some unwanted, psychoactive effects. In an experimental model of MS, and in MS tissue, there are local perturbations of the endocannabinoid system in lesional areas. Stimulation of endocannabinoid activity in these areas either through increase of synthesis or inhibition of endocannabinoid degradation offers the positive therapeutic potential of the cannabinoid system whilst limiting adverse events by locally targeting the lesion. In addition, CB(1) and CB(2) cannabinoid receptor stimulation may also have anti-inflammatory and neuroprotective potential as the endocannabinoid system controls the level of neurodegeneration that occurs as a result of the inflammatory insults. Therefore cannabinoids may not only offer symptom control but may also slow the neurodegenerative disease progression that ultimately leads to the accumulation of disability.

Acute and chronic cannabinoid extracts administration affects motor function in a CREAE model of multiple sclerosis

“…There are evidences that the therapeutic effect of 9 THC on the experimental autoimmune encephalomyelitis (EAE) model of MS is achieved through an inhibition of glutamate release . The 9 THC is suggested to have a neuroprotective function in MS, counteracting the glutamate-mediated excitotoxicity; again, this effect is accomplished via the activation of CB1 receptors (Fujiwara and Egashira, 2004;Jackson et al, 2005;Baker and Pryce, 2008;Cabral and Griffin-Thomas, 2008).…”

“…Thus, the endogenous cannabinoid system and cannabinoid receptors have become the target of several studies aiming to investigate the potential relevance of cannabinoids in the MS management. Clinical and experimental research demonstrated that the endocannabinoid system is altered in MS and that it partially acts via cannabinoid receptors CB1 and CB2 (Baker et al, 2001;Centonze et al, 2007;Baker and Pryce, 2008;Rossi et al, 2010).…”

“…The role of cannabinoids in the modulation of immuno and neuroinflammatory reactions in MS is well ascertained; it has in fact been demonstrated that cannabinoids are involved in cytokine regulation and in immunosuppressive processes in MS patient brains, and that these substances possess antioxidant properties (Hampson et al, 1998;Baker et al, 2007;Correa et al, 2007;Maresz et al, 2007;Baker and Pryce, 2008).…”

“…In addition, several studies reported a neuroprotective effect of cannabinoid in MS Baker and Pryce, 2008;Croxford et al, 2008). Experimental and clinical data demonstrated that cannabinoids are potentially able to slow the progressive neurodegeneration Zajicek et al, 2005;Witting et al, 2006;Docagne et al, 2007).…”

Therapeutic potential of a novel cannabinoid agent CB52 in the mouse model of experimental autoimmune encephalomyelitis

“…In addition to ameliorating the clinical symptoms in animal models (Baker and Pryce, 2008) and MS patients (Rog, 2010), cannabinoids are also being recognized for their ability to control disease progression (de Lago et al, 2010). Although much progress has been achieved over the last several decades, questions still remain regarding the protective mechanisms of various cannabinoids and the involvement of CB1 and CB2 receptors.…”