Page 8 - The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews

8 Page 8 of 12 Curr Neurol Neurosci Rep (2018) 18:8

with a pooled effect size for cannabinoids of 0.08 (95% CI − Bladder Function
0.74 to 0.89) [26], though noted positive results were observed
when only studies of central pain were considered. The Four reviews considered evidence on the effects of cannabi-
highest quality review (AMSTAR score of 10) did not report noids on bladder function in multiple sclerosis [28•, 29, 31,
conclusions for the outcome of pain in multiple sclerosis, al- 33](see Supplementary Table 8). In most of these reviews,
though it concluded that cannabinoids may reduce spasticity this was not the primary outcome, and few reviews reported
[30••] which is associated with pain. conclusions on the clinical use of cannabinoids for this indi-
cation. One review concluded that there was evidence that
Spasticity THC:CBD oromucosal spray was probably effective, whereas
oral cannabinoid extracts and THC were probably not effec-
Seven reviews examined the effects of cannabinoids on spas- tive in reducing bladder symptoms [28•].
ticity in multiple sclerosis [24, 25, 28•, 29, 30••, 31, 33](see In general, the reviews provided some evidence, in-
Supplementary Table 7). Many reported outcomes on the cluding positive findings from high quality RCTs, that
Ashworth Score, a measure of spasticity on a 5-point scale THC and THC:CBD had positive effects on bladder
using subjective clinical assessments of tone ranging from symptoms. The latter included fewer voids, reduced fre-
0—‘no increases in tone’ to 4—‘limb rigid in flexion or ex- quency of nocturia and improved incontinence-related
tension [abduction/adduction]’ [34]. quality of life measures. These effects were not consis-
In general, results were inconsistent between studies iden- tently observed across studies in the reviews and positive
tified in the reviews, with many reporting positive effects on findings from smaller studies were not confirmed in larg-
some, but not all measures of spasticity. Reviews reported that er, high quality studies.
many studies did not find an effect of cannabinoids on spas-
ticity using the Ashworth scale, one of the most widely used Ataxia and Tremor
measures for this outcome. Positive effects were reported,
however, on patient-rated measures of spasticity. Four reviews considered evidence on the effects of cannabi-
One review conducted a meta-analysis of outcomes of noids on ataxia and tremor with use of dronabinol, nabilone,
spasticity measured on the Ashworth scale [30••]. This meta- nabiximols and THC:CBD extracts [23, 27, 28•, 33](see
analysis demonstrated a trend towards an improvement (re- Supplementary Table 9). In most reviews this was not a pri-
duced score on the Ashworth scale) but did not detect a sta- mary outcome so few reported on the clinical use of cannabi-
tistically significant effect, either when cannabinoid types noids for this indication. One review concluded that THC and
were examined alone or when all studies were considered oral cannabinoid extracts were probably ineffective, and
together. In a total of 1134 participants, the mean difference nabiximols were possibly ineffective for tremor [28•]. A sec-
was − 0.12 units on a five-point scale (95% CI – 0.24 to 0.01). ond review stated that no conclusions could be made of the
A meta-analysis of three studies found nabilone and efficacy of cannabinoids on the treatment of movement disor-
nabiximols were associated with a greater average improve- ders, with studies failing to demonstrate a significant effect on
ment on spasticity measured with a numerical rating scale tremor. [27]. Studies identified in reviews were generally
(mean difference, − .76, [95% CI − 1.38 to − .014]). From small and not likely to have had the power to detect anything
these results, the authors concluded that there was moderate but very large effects.
quality evidence to suggest cannabinoids may reduce spastic-
ity [30••]. Sleep
Three other reviews also concluded favourably on the use
of cannabinoids to treat spasticity. Ben Amar [33] concluded Three reviews reported on the effects of cannabinoids on mea-
that cannabinoids objectively showed a small noticeable ben- sures of sleep [29, 31, 33] (see Supplementary Table 10).
eficial effect on spasticity, and Koppel et al. [28•] concluded Sleep was also not a primary outcome in any review and no
that THC:CBD extracts are effective, and THC/nabiximols are review reported a conclusion on the clinical use of cannabi-
probably effective in treating painful spasticity. A similar con- noids to improve sleep in people with multiple sclerosis.
clusion was reached by Lakhan and Rowland [25] in their
review of whole plant extracts. Karst et al. [29] concluded Quality of Life
there was evidence of efficacy but a narrow therapeutic index
limiting use. Overall, most reviews found evidence that THC Four reviews examined the effect of cannabinoids on overall
and THC:CBD products may reduce spasticity or concluded quality of life or other measures of general functioning in
that it generally favoured cannabinoids to treat spasticity patients with multiple sclerosis [23, 29, 30••, 33](see
based on the results of individual studies or trends towards Supplementary Table 11). Reviews provided evidence of
significant effects [25, 28•, 29, 30••, 33]. mixed findings on the effect of cannabinoids on quality of life,