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Wednesday, October 31, 2018

Cannabinoids Provide Limited Efficacy in Treating Multiple Sclerosis Symptoms


Medicinal cannabinoids had limited efficacy in treating certain symptoms in adult patients with multiple sclerosis (MS) but overall were safe compared with placebo, according to a meta-analysis and systematic review published online in JAMA Open Network on October 12.

The cannabinoids produced a mild reduction of subjective spasticity, pain, and bladder dysfunction ([standardized mean differences] SMD of -0.25, -0.17, and -0.11, respectively), compared to placebo. And although cannabinoids were associated with a higher total number of adverse events, the differences were not significant.

MS patients experienced side effects including dizziness or vertigo, dry mouth, fatigue, intoxication, impaired balance or ataxia, memory problems, and sleepiness.

The researchers used both objective assessments and patient self-reports in their analysis. "None of the interventions demonstrated a clear efficacy in the treatment of spasticity when evaluated in a more objective form (ie, the Ashworth and Modified Ashworth scales)" the researchers, led by Mari Carmen Torres-Moreno, PhD, of the Universitat Autònoma de Barcelona, Spain wrote. "To our knowledge, this is the most complete systematic review and meta-analysis of the effect of cannabinoids on MS."

Cannabinoids act as neuromodulators of the endocannabinoid system, the study authors explained. They noted that cannabinoids (nabiximols) are approved in some countries for the symptomatic treatment of MS spasticity and neuropathic pain in cases where medication was deemed ineffective, they noted.

However, systematic reviews and meta-analyses have not shown clear or complete efficacy in treating MS symptoms including spasticity, pain, and bladder dysfunction.

The researchers reviewed 17 clinical trials involving 3,161 adult patients with MS. Clinical trials included assessments of oral cannabis extract—containing tetrahydrocannabinol and cannabiniol from the cannabis sativa plant—oromucosal cannabis extract (nabiximols [Sativex]), dronabinol (Marinol), and nabilone (Cesamet). Dronainol and nabilone are oral synthetic versions of THC.

Overall, the researchers found that cannabinoids performed statistically better than placebo for pain and bladder dysfunction. Subjective reports (from patient reports) were significantly better for cannabinoids, though that was not true for objective measures.

In regard to tolerability, the researchers found an relative risk of 1.72 patient-years (95% CI, 1.46 - 2.02 patient-years) in the total adverse events analysis and 2.95 patient-years (95% CI, 2.14 - 4.07 patient-years) in withdrawals due to adverse events.

The researchers performed further analysis to exclude studies potentially influenced by pharmaceutical industry funding. No differences were found between nabiximols and placebo in efficacy outcomes.

The researchers encouraged further studies on the combination of cannabinoids and other therapies for MS patients to yield more concrete results.

Limitations included the small number of studies assessed and the differences in lengths of treatment. The researchers also cited potential publication bias as several studies were funded by the pharmaceutical industry, especially those involving nabiximols.

The study was partly funded by the Ministerio de Sanidad and MINECO/Instituto de Salud Carlos III.

The researchers reported no conflicts of interest.


Torres-Moreno MC, Papaseit E, Torrens M, et al. Assessment of efficacy and tolerability of medicinal cannabinoids in patients with multiple sclerosis: A systematic review and meta-analysis. JAMA Network Open 2018; Epub 2018 Oct 12.