The endocannabinoid system and autoimmune demyelination: A focus on multiple sclerosis

Autoimmune demyelination is the pathological hallmark of a number of chronic, inflammatory, and neurological conditions among which multiple sclerosis (MS) stands out as the most prevalent neurological disease causing progressive disability at multiple levels. Decades of research have demonstrated that cannabinoids and endocannabinoids attenuate neurological disability in MS patients and animal models of the disease. Therapeutic effects of (endo)cannabinoids in MS include neuroprotection, attenuation of inflammatory responses mediated by peripheral and innate immune cells as well as remyelination-promoting activities that rely on the activation of cannabinoid CB1 and CB2 receptors. Despite progress, research on the role and possibilities of the endocannabinoid system in MS has evidenced not only benefits but also limitations that need to be addressed in order to improve the efficacy of cannabinoid medications. Here we review the current state of the art of endocannabinoid research in MS and highlight the main avenues to be followed in order to improve the therapeutic potential of cannabinoid-modulating drugs in autoimmune demyelination.