Page 9 - The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews

Curr Neurol Neurosci Rep (2018) 18:8 Page 9 of 12 8

with reviews reporting data from studies that found both pos- General Conclusions of the Reviews
itive and negative effects on quality of life. One review report-
ed that cannabinoids can lead to a moderate improvement in One recent high quality review [30••] concluded that there
general well-being [33]. was sufficient evidence to support the clinical use of
nabiximols, nabilone, THC/CBD capsules, and dronabinol
Adverse Effects in treating symptoms of multiple sclerosis (see
Supplementary Table 13). This review received an
Eight reviews reported data on adverse effects (AEs) of can- AMSTAR score of 10 and reported on 7 studies in patients
nabinoids in treating multiple sclerosis [25, 26, 28•, 29, 30••, with multiple sclerosis involving a total of 1218 participants.
31–33] (see Supplementary Table 12). This included one sys- Four other reviews similarly concluded that there are pos-
tematic review of the adverse effects of therapeutic cannabi- sibly or probably beneficial effects on some outcomes (such as
noids, from which we extracted data on studies in patients pain, spasticity and bladder symptoms) [25, 28•, 29, 33]. A
with multiple sclerosis [32]. further four reviews concluded that there was insufficient ev-
Most reviews identified similar AEs from cannabinoids that idence to make any recommendations [23, 24, 27, 31]. The
were most frequently described as ‘mild’ to ‘moderate’.They scope of these latter reviews was often narrower (e.g. limited
included dizziness, dry mouth, euphoria, diarrhoea, and diffi- to a specific symptom such as ataxia, or to a specific cannabi-
culty concentrating. Adverse effects were consistently rated as noid, such as cannabidiol). One review was focused on ad-
more commoninstudyparticipants whoreceivedcannabinoids verse effects as opposed to clinical efficacy [32].
than placebo. Most reviews did not draw conclusions on wheth- No reviews made a recommendation on where cannabi-
er any of these adverse effects precluded clinical use. noids would fit in the therapeutic hierarchy in treating differ-
No specific cannabinoid was identified as having a more ent symptoms of multiple sclerosis, i.e. whether cannabinoids
serious adverse effect profile than another. Whiting et al. should be used as first line or later line treatments only after
[30••] noted that no cannabinoid or route of administration other treatments had been tried. No review recommended their
was associated with any specific adverse event. Their meta- use as a monotherapy.
analyses of adverse events over a range of cannabinoids and
medical conditions found that an adverse event was around
three times more likely to occur with a cannabinoid than pla- Discussion
cebo (OR 3.03, 95% CI 2.42–3.80). There was a slightly
greater odds of a serious adverse event (OR 1.41, 95% CI We reviewed the findings of 11 systematic reviews of evi-
1.04–1.92), and three times the odds of patients withdrawing dence on the potential benefits of cannabinoids for multiple
due to adverse events with patients receiving cannabinoids sclerosis. Recent high quality reviews supported the clinical
rather than placebo (OR 2.94, 95% CI 2.18–3.96). They noted use of cannabinoids for spasticity and pain in multiple sclero-
the lack of long-term follow-up data on adverse events. sis. The findings were inconclusive on use to treat other com-
Karst et al. [29] concluded that the risk to benefit profile mon symptoms (e.g. bladder control, ataxia and tremor).
was not optimally balanced with existing cannabinoid prod- Some positive findings appear to support clinical use of can-
ucts. Koppel et al. [31] noted that adverse effects were a con- nabinoids in spasticity, although the magnitude of the effect
cern in patients with multiple sclerosis. One specific concern was generally small. Few reviews could conduct meta-
raised was the potential cognitive impairing effects of canna- analyses because the measures used and outcomes examined
binoids in patients with pre-existing cognitive dysfunction were not standardised.
[28•]. Other reviews expressed caution about use of cannabi- Reviews identified potentially negative effects in a small
noids in the elderly and persons with a psychosis [33]. number of studies, often of low quality. A potential negative
Review findings were inconsistent on the effect of the effect of cannabinoid use on disease progression warrants fur-
addition of CBD to THC on the adverse effect profile of ther research especially as many of the positive studies only
THC. Some reviews identified evidence of an attenuation measured short-term outcomes (i.e. up to 12 weeks).
of adverse effects related to THC, while other reviews Beneficial effects on bladder function and sleep were iden-
identified greater adverse effects from THC:CBD combi- tified by some reviews. Because these symptoms were rarely
nations than THC [25, 31]. Adverse effects with oral THC/ the primary focuses of reviews, no reviews offered clinical
dronabinol were dose dependent. One review identified recommendations on the use of cannabinoids for these indica-
that at least 10 mg of THC was reported as required to tions. Future research may evaluate the effects of cannabi-
reduce spasticity and adverse effects were observed with noids in patients who report that these are their symptom of
doses of 15 mg and above [29]. Reviews were not able to greatest concern.
compare side effects of cannabinoids with those of other One challenge in studying the effects of cannabinoids on
active treatments because of a lack of such studies. multiple sclerosis is that patients have heterogeneous