Using cannabinoids to treat the symptoms of multiple sclerosis is controversial. This week, JAMA Network Open has published a systematic review and meta-analysis that might help settle the debate.
Multiple sclerosis (MS) involves an autoimmune response, in which a person's immune system attacks the myelin sheaths that coat and insulate nerves.
Globally, this degenerative condition affects an estimated 2.5 million people.
Symptoms include bladder dysfunction, pain, and spasticity, wherein muscles are stiff and tight, making movement and speech more difficult.
To date, there is no cure for MS. Current treatments focus on relieving symptoms and reducing the risk of relapse.
Researchers have studied cannabinoids, a class of drugs that act on cannabinoid receptors in the body, for their potential use in MS.
Because cannabinoid receptors are involved in the immune responses, some believe that they could help reduce the autoimmune attack that MS causes.
Cannabinoids and MS
In some countries, people use cannabinoids in order to treat MS-associated spasticity and pain. For instance, nabiximols — an extract of cannabis — is marketed in the United Kingdom, Spain, Canada, and elsewhere for individuals who have tried other MS drugs without success.
Despite this, evidence that cannabinoids might reduce MS symptoms is not particularly strong.
Recently, investigators dipped into the findings of previous studies; they combined the data in an attempt to draw a more solid conclusion. They set out "to evaluate the therapeutic efficacy and tolerability of medicinal cannabinoids to treat the symptoms of spasticity, pain, and bladder dysfunction in patients with MS."
The analysis used 17 trials including a total of 3,161 patients. All studies that the experts re-analyzed compared cannabinoids against placebo and were double-blind, randomized trials.
The studies used four cannabinoids: cannabis extracts, nabiximols, dronabinol, and nabilone. Once they had completed the analysis, the scientists came to the following conclusion:
"The results suggest a limited efficacy of cannabinoids for the treatment of spasticity, pain, and bladder dysfunction in patients with MS."
They noted some side effects, including dry mouth, fatigue, feeling drunk, and dizziness. In all, they documented 325 serious adverse events. Though they attributed more of these adverse events to cannabinoid treatment than placebo, the difference was not statistically significant; so, overall, the researchers concluded that "[t]herapy using these drugs can be considered as safe."
The scientists believe that this study is the "most complete systematic review and meta-analysis of the effect of cannabinoids on MS."
The authors are confident that the analysis is robust. They point out that the largest study included in their analysis, which involved more than 500 patients, found that placebo had a greater effect than cannabinoids.
Are these findings conclusive?
Their paper appears alongside an editorial by Drs. Marissa Slaven and Oren Levine. In it, they point out some concerns with the analysis. One major issue is the heterogeneity of the studies that they analyzed. In other words, the studies were very different and, therefore, difficult to compare.
The authors write that "if the trials that are pooled are very different [...] the validity of the final results of the meta-analysis can be of concern."
In the recent meta-analysis, the study designs varied, they used different types of cannabinoids at different doses, and patient demographics also differed between studies.
Drs. Slaven and Levine write that, because there are few effective drugs to treat MS and because cannabinoids are relatively safe, it is no surprise that they have drawn interest from researchers.
They think that focusing on "different cannabis components" would be a sensible approach, and that they might find a more effective intervention once they understand which cannabinoids are most potent at treating MS.
The editorial concludes that the researchers "have conducted a methodologically sound meta-analysis; however, this does not overcome the limitation of the relatively weak trials that were included."