Revised: September 24, 2013
Accepted: October 16, 2013
Published online: December 28, 2013
This article reviews the role of cannabinoids in inhibiting neurodegeneration in models of multiple sclerosis (MS). MS is a chronic, debilitating disease of the central nervous system (CNS), induced by autoimmunity-driven inflammation that leads to demyelination and thus disconnection of the normal transmission of nerve impulses. Despite the use of an array of immune modulating drugs that restore blood brain barrier function, disability continues in patients concomitant with the loss of axons in the spinal cord. MS patients therefore suffer neuropathic pain, spasticity and tremor. Anecdotal evidence suggests that MS patients using cannabis, though illegal, achieve symptomatic relief from neuropathic pain and spasticity associated with MS. The discovery of the endogenous cannabinoid (endocannabinoid) system that naturally exists in the body and which responds to cannabinoids to exert their effects has aided research into the therapeutic utility of cannabinoids. The endocannabinoid system consists of two G-protein coupled receptors cannabinoid receptor type-1 (CB1) and CB2. CB1 is mainly expressed in the CNS and CB2 is predominantly found in leukocytes, while an increasing number of potential ligands and endocannabinoid degradation molecules are being isolated. Several studies have highlighted the involvement of this system in regulating neurotransmission and its ability to prevent excessive neurotransmitter release, consistent with a capacity to provide symptomatic relief. In summary, antagonism of the CB1 receptor pathway contributes to neuronal damage in chronic relapsing experimental allergic encephalomyelitis (EAE) and suppresses tremor and spasticity. The addition of exogenous CB1 agonists derived from cannabis also afforded significant neuroprotection from the consequences of inflammatory CNS disease in EAE and experimental allergic uveitis models. Although clear neuroprotective benefits of cannabinoids have been demonstrated, the unwanted psychotropic effects need to be addressed. However, manipulating the endogenous cannabinoid system may be one way of eliciting beneficial effects without some or all of the unwanted side effects.
Core tip: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and causes disability, neuropathic pain, spasticity and tremor in affected patients. Although illegal, users of cannabis report relief from pain and spasticity, probably due to the endogenous cannabinoid system that exists. Cannabinoid receptor type-1 (CB1)-deficient mice accrue greater levels of neurodegeneration and poorly tolerate inflammatory and excitotoxic insults after immune attack in a model of MS, experimental allergic encephalomyelitis. Treatment of animals affected by experimental allergic uveitis (EAU) with CB1 agonists also provided significant neuroprotection from the consequences of EAU, suggesting that cannabinoids may slow down neurodegeneration in MS.