Pubdate: Mon, 19 Aug 2019
Source: Canadian Medical Association Journal (Canada)
Copyright: 2019 Canadian Medical Association
Contact:  http://www.cmaj.ca/
Details: http://www.mapinc.org/media/754
Author: Mary-Ann Fitzcharles, Yoram Shir and Winfried Hauser

MEDICAL CANNABIS: STRENGTHENING EVIDENCE IN THE FACE OF HYPE AND PUBLIC 
PRESSURE

Canada has been at the forefront of cannabis research, education and
regulation for the past 2 decades, yet uncertainty remains about how
the drug should be used in medicine. Physicians lack evidence-based
information and formalized training about cannabis, which stems, in
part, from the drug's previously illegal status that hindered
research. Among the public, however, many perceive cannabis as a
natural and safe medical treatment. Patients increasingly seek advice
about cannabis from physicians, request prescriptions or experiment
with cannabis for medical problems on their own. However, physicians
must adhere to good medical practice regardless of public pressure and
provide counselling to patients based on up-to-date knowledge and
evidence. Now that cannabis is legal in Canada more research should be
forthcoming, but the evidence base remains weak.

Medical cannabis is unique in that it bypassed the process of due
diligence required for drug registration and entered the therapeutic
domain buoyed mostly by advocacy. Positive effects of cannabinoids
have been reported for severe childhood epilepsy and
chemotherapy-induced nausea, and as palliation at end of life, but
data are limited. For other conditions commonly believed to improve
with cannabis use, such as pain relief or mood disorder, the evidence
is less convincing. A 2018 systematic review and meta-analysis of the
effect of cannabis-based medicines on chronic noncancer pain reported
a number needed to benefit of 24, whereas the number needed to harm
was A randomized controlled trial (RCT) in the Netherlands that
involved women with fibromyalgia who were treated with
pharmaceutical-grade inhaled cannabis in various concentrations of
[delta]9-tetrahydrocannabinol (THC) and cannabidiol (CBD) found that
none of the treatments had an effect greater than placebo on
spontaneous pain, and reduced pain scores were significantly
correlated with the extent of drug high.5 Furthermore, CBD increased
plasma concentrations of THC but reduced THC's analgesic effects,
which emphasizes the complexity of THC-CBD interactions and the
possible role of psychotropic mechanisms on symptom relief.

Patients often seek treatments that offer better symptom relief than
their current medications. Some hope that medical cannabis could be a
less-harmful alternative to opioid medication and could aid harm
reduction. The perception of cannabis as being safer than opioids may
have been reinforced by its recent legalization for recreational use
in some jurisdictions. Media promotion, replete with images of
pristine cultivation facilities, personal testimony and vocal medical
advocacy, has done much to influence this perception. Patients are
often primed by the media to believe medical cannabis is a valid
treatment for many symptoms. Medication beliefs influence treatment
adherence and efficacy, with personal choice reinforcing positive
expectations.6 The ability to choose a treatment and manipulate dosing
or method of administration may foster a sizable placebo effect, which
may be further reinforced by financial commitment when there is no
reimbursement. It is possible that medical cannabis does not
meaningfully affect the medical condition other than through subtle
psychoactive effects that bring comfort.

Patients who want to try cannabis as a treatment often seek medical
advice about dosages, choice of specific products and method of
administration. Other than broad recommendations that cannabis should
not be smoked and to use products with low THC and high CBD levels, no
regulatory or medical body has provided specific guidance.This
provides the perfect setting for an emergent medical cannabis
industry, with self-styled medical and nonmedical experts projecting
an image of knowledge and promise of personalized medicine. Although
more than 90% of dispensary staff in the United States reported
providing advice to patients, only 20% had (unspecified) medical
training and 13% had scientific training.The medical advice that was
given was often not evidence based.

Many people feel secure in a medical setting, which has opened the
door for cannabis clinics staffed by physicians who are savvy about
cannabis. Yet the concept of a physician focusing treatment strategies
on a single product is peculiar and contrary to medical care
standards. The notion that a "cannabis expert" can identify the ideal
strain or molecular content for a specific condition for a specific
patient is not backed by concrete evidence. Furthermore, the accuracy
of the labelling of cannabis products is questionable, and regulations
regarding both quality control and labelling are insufficient.To save
costs, many patients may choose to access cannabis illegally,
compounding risks related to unknown molecular content, quality and
safety, especially since the concentration of THC offered as a
medicinal product by Canadian growers has reportedly increased in
recent years.

Despite advocacy, politics and commerce having outpaced sound clinical
evidence regarding the use of medical cannabis, physicians must
provide advice based on valid science, not pseudoscience or hype.
Therefore, there is an urgent need to generate better evidence about
the benefits and risks of medical cannabis. Preclinical study should
be used as a guide to identify molecular compositions of cannabis that
may be effective for a specific indication and warrant further testing
in the clinical setting. The gold standard of RCTs may, however, be
less realistic for accumulating evidence for using medical cannabis
for reasons that include variability in molecular content (even within
specific strains of the plant product), current prevalent use by many
patients, issues of effective blinding and the need for long-term study.

Observational studies involving cohorts of patients being managed in
usual clinical care, but not those conducted by cannabis growers or in
cannabis clinics or dispensaries, will generate real-world
information. Investigator-initiated studies that are financially
supported by the cannabis industry should adhere to the regulatory
standards required for pharmaceutical products.

Governments and regulators worldwide have a moral obligation to
support the scientific study of cannabis to protect the well-being of
patients and avert a potential disaster similar to the opioid epidemic
in North America. Although some patients may benefit from cannabis in
the short term, long-term consequences of its use are not yet known.
Until the evidence base is strong enough to support sound decisions
about the use of cannabis as a medical treatment, the well-being of
patients will continue to come second to profit-motivated parties.
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MAP posted-by: Matt