Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review

Abstract

Multiple sclerosis (MS) is the most common chronic autoimmune disease of the central nervous system. Efficacy of treatments for MS is associated with risk of adverse effects, and effective and well-tolerated drugs remain a major unmet need. Cannabis (Cannabis sativa L., fam. Cannabaceae) and cannabinoids are popular among MS patients to treat spasticity and pain. Cannabinoids are endowed with remarkable immunomodulating properties, and in particular the non-psychotropic cannabinoid cannabidiol (CBD) is increasingly recognized as anti-inflammatory and immunosuppressive, nevertheless with excellent tolerability even at high doses. In this systematic review, we retrieved and critically evaluated available evidence regarding the immune and disease-modifying effects of CBD in experimental autoimmune encephalomyelitis (EAE) and in MS. Evidence in rodent models of EAE strongly supports CBD as effective, while clinical evidence is still limited and usually negative, due to paucity of studies and possibly to the use of suboptimal dosing regimens. Better characterization of targets acted upon by CBD in MS should be obtained in ex vivo/in vitro studies in human immune cells, and higher doses should be tested in well-designed clinical trials with clinically relevant efficacy endpoints.

Cannabidiol in Neurological and Neoplastic Diseases: Latest Developments on the Molecular Mechanism of Action

“…Moreover, the high impact of MDSCs in CBD-mediated attenuation of EAE led to the inhibition of myelin oligodendrocyte glycoprotein (MOG)-induced proliferation of T cells in vitro . Thereby, the studies confirmed that by inducing immunosuppressive MDSCs, CBD-based treatment may minimize EAR [ 47 , 77 ]. Besides the results obtained in rodent models of EAE that showed efficient action of CBD, more tests and clinical trials are needed to identify the action of CBD in human immune cells [ 47 ].…”

“…This process can clarify the lower risk of developing psychotic symptoms in patients who use preparations based on high ∆ 9 -THC and CBD ratios in comparison If conventional antispastic therapy is not efficient enough, then nabiximols, commercially known as Sativex (containing CBD and THC) were mainly recommended for the treatment of pain and spasticity in MS [72], but can also be applied in inflammatory disease therapy with demyelination and neuronal injury in the brain and spinal cord. For the treatment of spasticity, Sativex was approved for the first time by the UK in 2010; however, nowadays it is recommended in more than 25 countries [47]. Interestingly, recent reports showed that the use of Cannabis is reported by 20-60% of patients with MS [47].…”

“…Both agencies have admitted that cannabis-derived compounds, such as CBD, are of great interest in the treatment of neurodegenerative diseases. Thereupon, cannabidiol has become the first FDA plant-derived compounds that can be successfully applied for the treatment of seizures in the various, rare epileptic disorders, namely: Lennox–Gastaut syndrome (LGS) or Dravet syndrome (DS) in two-year-old children (and older) with maximum doses of 10 mg/kg twice a day, and a maximum dosage of 50 mg/kg/day in adults [ 47 ]. Furthermore, the clinical trials with Epidiolex are regarded as the first open interventional exploratory study for LGS and DS.…”

“…These results are still limited, despite the evidence in mouse studies of encephalomyelitis (EAE), which have shown CBD as a beneficial drug. Furgiuele et al [ 47 ] indicate a need for ex vivo / in vitro studies in human immune cells to better analyze the targets acted upon by CBD in MS. Filippini et al [ 74 ] have shown the benefits and safety of cannabis-based medicines for people with MS. These authors also indicate that the FDA has not approved any commercial application for CBD-based medicine for MS yet.…”

“…CBD seems to exhibit a better tolerability profile at high doses. To date, cannabis-based medicines have a great interest among MS patients to treat spasticity and pain [ 47 ]. A potential CBD-receptor-mediated signaling pathway is still unknown, but it has been confirmed that many of the CBD actions are related to both central and peripheral actions [ 76 ].…”