Page 10 - The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews

8 Page 10 of 12 Curr Neurol Neurosci Rep (2018) 18:8

symptom profiles. This may make it difficult to find an effect considerable efficacy for multiple sclerosis, studies with active
on secondary outcome measures when symptoms are not comparators will be critical in further informing clinical
found in all study participants. The seriousness of adverse decision-making about the use of cannabinoids.
effects may also vary with patients’ presenting symptoms. For
example, those with cognitive impairment may be more sus-
ceptible to potential cognitive effects of cannabinoids [28•]. Conclusions
A further challenge identified in the systematic reviews
was a lack of harmonisation across the studies in the outcome In conclusion, reviews identified evidence that would support
measures used. This makes synthesis of findings challenging. a trial of cannabinoids for pain or spasticity in a patient with
Finally, the cannabinoid products evaluated were considered multiple sclerosis. Effect sizes are generally small suggesting
suboptimal. Newer cannabis products may have different risk- only modest effects may be expected. Adverse events were
benefit profiles. generally mild to moderate, although caution is warranted in
There are some limitations with the current review. Some specific populations of patients with multiple sclerosis with
of the evidence considered in the reviews came from well- greater vulnerability to adverse effects from cannabinoids.
conducted RCTs, including some with large samples sizes.
This was supplemented by weaker evidence from studies with Acknowledgements The editors would like to thank Dr. John Brust and
smaller sample sizes and subject to possible biases from weak Dr. José Biller for taking the time to review this manuscript.
study design. Different reviews reported on different outcome
Funding Funding was received from the Commonwealth Department of
measures relating to symptoms of multiple sclerosis. In some
Health and the NSW Government Centre for Medicinal Cannabis
cases, this explained why reviews came to different conclu- Research and Innovation, who determined the topics and scope of the
sions on the efficacy of cannabinoids despite including the reviews to be conducted and funded the salary of MW. SN and LD are
supported by NHMRC research fellowships (no. 1132423 and no.
same studies.
1041472). The National Drug and Alcohol Research Centre at the
Some reviews argued that the risk versus benefit decision University of New South Wales is supported by a funding from the
for patients with multiple sclerosis may need to be made at the Australian Government under the Substance Misuse Prevention and
individual rather than the population level. Their use may Service Improvements Grant Fund.
depend on which symptoms are most problematic for the pa-
tient, and on how the adverse effects of cannabinoids affect Compliance with Ethical Standards
their quality of life. Most adverse events and most benefits
Conflict of Interest SN, MF and LD have all been investigators on untied
reported in systematic reviews are likely to be noted within a
investigator-driven educational grants funded by Reckitt Benckiser. MF
short period of time. This facilitates individualised decision- and LD have received untied educational grant from Mundipharma for
making by means of a time-limited therapeutic trial. One study post-marketing surveillance studies of new opioid medications. SN, MF
reported that benefits of cannabinoids are generally observed and LD have been investigators on untied investigator-driven educational
grants funded by Indivior and Reckitt-Benckiser. NB is a member of the
in the first 4 weeks of the study [35]. If so, a trial of 4–6 weeks medical cannabis expert panel for New South Wales Health. WH provided
may enable patients and their physicians to assess whether evidence to parliamentary committees on medical uses of cannabis in
their symptoms will respond to cannabinoids. If benefits are Australia and the United Kingdom and is a member of the Australian
not observed in this time, there is little benefit expected from Advisory Council on Medical Uses of Cannabis. SN, WH, MF, MW and
LD have previously published manuscripts on the topic of therapeutic use
continued use [35]. of cannabis. Other authors declare no conflicts of interest.
Few reviews drew any conclusions on use with symptoms
other than pain or spasticity and some which reported benefits Human and Animal Rights and Informed Consent This article does not
in spasticity found detriments in other domains, complicating contain any studies with human or animal subjects performed by any of
the authors.
general statements about the risk/benefit ratio of cannabinoids
for individuals.

References
Further Research Papers of particular interest, published recently, have been
highlighted as:
One area in which further research is required is the possible • Of importance
role of cannabidiol in disease progression. One review report- •• Of major importance
ed that the THC:CBD combination may have adverse effects
and showed more disease progression compared with THC 1. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):
1502–17. https://doi.org/10.1016/S0140-6736(08)61620-7.
alone [31]. Further, few studies used active comparators, and
2. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple
no review commented on if cannabinoids could be considered sclerosis. Nat Rev Immunol. 2015;15(9):545–58. https://doi.org/10.
as a monotherapy. Given that there are other treatments with 1038/nri3871.