Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. In May 2022, the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group published a new review of the effects of cannabis and cannabinoids for the treatment of people with multiple sclerosis. In this podcast, Silvia Minozzi, Co-ordinating Editor of the Cochrane Drugs and Alcohol Group and an author on the review talks with lead author and Co-ordinating Editor of the Cochrane Multiple Sclerosis Group, Graziella Filippini, about the review.

Silvia: Hello Graziella. Perhaps you could start by telling us the question tackled by this new systematic review.

Graziella: Thanks Silvia. What we set out to do was determine if cannabinoids improve symptoms such as spasticity, pain and functioning for people with multiple sclerosis, or MS, when compared to placebo or other symptomatic treatments.

Silvia: So, why is this review important?

Graziella: These symptoms badly affect the lives of people with MS. For example, spasticity is a form of increased muscle tone that is a common and serious feature of MS which can worsen with disease progression and lead to wide-ranging consequences, such as weakness, pain, fatigue and restricted joint movement. In turn, these lead to deterioration in mobility functions, activities of daily living and restriction in participation in social activities. Many medications for alleviating these symptoms are poorly tolerated or are of limited benefit and patients tend to try alternatives, including cannabis-based medicines. Different countries have different laws about this and recommendations in international guidelines on the use of cannabinoids in people with MS also vary. This makes it especially important to systematically identify and synthesize all the available evidence to come up with up-to-date conclusions.

Silvia: Did you find the evidence you needed? And, can you tell us a bit about the studies?

Graziella: We searched for research published up to December 2021 and included 25 randomised trials representing nearly 3800 people with MS. The patients ranged in age from 18 to 60 years and the proportion of women in the studies ranged from 50% to 88%. Most of the studies measured spasticity, pain, patient's global impression of health status, quality of life, and reported data about adverse effects. More than half compared a medication called Sativex, as an add-on therapy to other symptomatic medicines, against a placebo. Sativex is an oromucosal spray with a plant-derived combination of cannabinoids.

Silvia: And what did you find? Is it effective?

Graziella: We found that Sativex is likely to be effective for reducing spasticity and improving patient global impression of health status. Overall, three months after starting treatment, more people receiving Sativex reported an important reduction in the severity of spasticity and much or very much improvement in global impression of health status, than people who had no treatment. However, the effect of cannabinoids on chronic neuropathic pain and quality of life was uncertain. 

Silvia: What about the safety aspect? What evidence did you find about complications and adverse events among people who received cannabinoids?

Graziella: In the studies that reported on this, the adverse effects were mostly mild or moderate. Most commonly, these were nervous or psychiatric disorders that made it more likely that the patient would stop taking their treatment. 

Graziella: Overall, is the evidence completely clear? Are there still gaps?

Silvia: We are moderately confident that cannabinoids are better than placebo for reducing spasticity and improving patient global impression of health status. However, a lot more research is needed in this field. At the moment, there is a problem with quantity and quality and our confidence in the evidence is limited by inconsistency or imprecision in the results. About 40% of the included studies were small trials with less than 60 participants and we think that researchers should stop doing small trials and focus instead on larger, better designed studies with longer follow-up, considering comparisons with other symptomatic treatments with similar effects. There are also gaps on adverse effects, meaning that we do not know the balance between desirable and undesirable effects of the cannabinoids for people with MS.

Graziella: Thanks Silvia. If people what to read the current review and any future updates, where can they find it?

Silvia: Thanks. Our review is online at Cochrane Library dot com. If people go to the website and type 'cannabis for multiple sclerosis' in the search box, they'll see it near the top of the list.