Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) that leads to a progressive functional decline. Symptoms vary widely from person to person and include fatigue, muscle spasticity, weakness, chronic neuropathic and musculoskeletal pain, mobility restrictions, visual impairment, depression, anxiety, and bladder and bowel dysfunction.

The endocannabinoid system has been shown to be modulated in MS patients. Chiefly anandamide (AEA) levels, but not 2-AG (2-arachidonoylglycerol) levels, were found to be elevated in the cerebrospinal fluid (CSF) of Recurrent Remitent MS patients experiencing a current relapse.

Medical cannabis refers to the use of the Cannabis plant or cannabinoids as a medical therapy to relieve symptoms. There are several routes of administration for cannabis, including inhalation, oral, oromucosal, sublingual, transdermal, eye drops, topical, and rectal. Depending on the mode of administration, the onset and duration of cannabis effects may vary. Oral and oromucosal administration result in a slow onset of action but a longer duration of action. The median dose in clinical trials for people with MS is eight sprays per day.

International guidelines have reached different recommendations on the use of cannabinoids in people with MS, but it depends on the country whether or not it is allowed. There are differences between countries in the legal authorization and use of cannabinoid-based medicines for MS.

The aim of this study is to assess the benefits and harms of cannabinoids, including synthetic,  herbal, and plant-derived cannabinoids, for symptomatic treatment of MS. The authors included 25 studies (18 parallel RCTs and seven cross-over RCTs). Participants ranged in age from 18 to 60 years.

Despite the high level of heterogeneity of the pooled estimate, the authors did not downgrade for inconsistency because the direction of effect across the studies consistently favoured cannabinoids compared with placebo. We found that nabiximols probably reduce spasticity severity as perceived by patients at time points up to 14 weeks (moderate-quality evidence). For the important outcome of Patient Global Impression Change they found moderate-certainty evidence of the benefit.

The authors are moderately confident in the effect estimate of an important reduction in spasticity in the cannabinoid group compared with the placebo group. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

This review provides moderate-certainty evidence for an antispastic effect of nabiximols (as an add-on therapy to antispasticity medications) compared with placebo in people with MS in spasticity outcomes at 6 to 14 weeks. An important clinical indication for nabiximols in MS would be where spasticity is moderate to severe and other pharmacological and rehabilitation treatments are not effective.

María Soriano Micó