Spring 2019 (Volume 29, Number 1)
The New Miracle or
a Placebo Pandemic?
By Mary-Ann Fitzcharles, MD, FRCPC
He is 57 years old, and one day may commit suicide
because of intolerable neuropathic pain in the
right knee, following multiple orthopedic procedures
and finally a total knee replacement. He was detoxed
from opioids at a morphine equivalent of over 500 mg/day,
but the pain was so excruciating that a team decision was
taken to reintroduce opioids in limited dose to a morphine
80 mg/day. He smokes 1.5 g of cannabis daily,
obtained from a buddy who grows it illegally. As a Christmas
gift he received a “green bottle” labelled “CBD 500 mg
in 30ml”, costing his friend $100. After one day administration
of three drops tid, there has been a miraculous improvement
in his pain, but he has not reduced his current
opioid dose. He still paces the corridor incessantly when
waiting for his appointment. He required a refill of his opioid
prescription that has been stable for four years, and the
urine drug screen was negative for substances other than
opioids and cannabinoids.
Prompted to do some sums, if the label on the “green
bottle” is correct, then each ml of liquid contains 16.6 mg
of cannabidiol (CBD), and each drop which is 0.02 ml to
0.05 ml contains CBD 0.33 mg to 0.83 mg. Therefore, nine
drops of liquid from the “green bottle” amounts to about
CBD 3-8 mg/day. As his treating physician, I have some
questions. How can this miracle be explained? Does the label
on the “green bottle” accurately identify the contents?
Is the product in the “green bottle” safe for my patient? Has
my patient been fleeced of his meagre income by charlatans?
Let us explore some of these questions.
Dosing of cannabis
It is beyond understanding how a seemingly homeopathic
dose of CBD oil could give such astounding effects, especially
in the setting of moderately high-dose opioids as
well as daily smoked cannabis. There is limited information
on dosing regimens for cannabis, but gleaning from the
literature, doses of CBD in the order of 50-200 mg/day
are suggested for some medical conditions; children with
Dravet syndrome have received CBD up to 50 mg/kg/day;
nabiximols, marketed as the pharmaceutical preparation
Sativex, contains CBD 2.5 mg and Δ9-tetrahydrocannabinol
(THC) 2.7 mg a puff, with studies reporting 6-8 puffs in
a day. Google tells us to “begin with CBD 10 mg, although
micro-dosing of 2.5-5 mg is sometimes used.” Google further
states that some patients may use up to 1,000 mg a
day, but in that case it is best to get advice from a “cannabis-savvy”
doctor. Google does not define the qualifications or
competencies of a “cannabis-savvy” doctor. There must be
something truly magic in the “green bottle” that defies my
Is the “green bottle” label accurate?
Testing of medical cannabis products (oils, flowers and
edibles) from the U.S. and the Netherlands have shown
important inaccuracies in the labelling of over 50% of
products, with under-, over- and mis-labelling of CBD and
THC.1-4 Other than a Marketplace study in Canada in 2016
with similar reports of inaccuracy, there has been no study
published regarding accuracy of the content of medical
cannabis in Canada. There are also currently no universal
industry testing standards for identifying molecular content
of medical cannabis. Regulations regarding quality
control for cannabis in Canada are focused toward ensuring
good practices in handling of product, record-keeping
and ensuring absence of contaminants, but with little attention
paid to ensuring accuracy of the molecular content
of cannabis products. Therefore we must question the labeling
of molecular content in the “green bottle” and others.
This leads to the question of safety of the substance in
the “green bottle”. The honest response is that we truly do
not know what is being sold to our patients, from both the
viewpoint of molecular content as well as safety. We can,
however, anticipate that patients will increasingly turn to
less costly products, obtained from suspect sources that are
Is there such a thing as a mass placebo effect?
A further thought to ponder is whether we might be in
the throes of a population mass placebo effect that has
been primed by the media. A placebo effect may be further
promoted by patients’ perceptions of personal control
in choosing a treatment, a practice increasingly prevalent
in our patients. The media has powerfully propagated the
message of medical cannabis with copious reports attesting
mostly to the successes and positive effects. We are
bombarded with images of pristine cultivation facilities,
staff clad in sterile outfits, and the smiling faces of persons
claiming treatment success. The occasional report of admissions to emergency rooms for those experiencing adverse
effects, especially children, are often tucked away and
given less prominence.5-8 Patients search for a magic potion,
and perhaps the medical community has been amiss
in failing to recognize the potential benefits of cannabis.
Perhaps the effect is not so much on the underlying medical
condition, but rather a surreptitious psychoactive effect
that gives a sense of relaxation and calm; perhaps not such
a poor payoff for many.
Who gives advice about medical cannabis?
The internet and media are awash with advice, favourable
reports and details about medical cannabis. Dispensary
staff, with less than 20% reporting any medical training,
are freely advising patients in the U.S.9 In Canada, agents
for the producers provide similar advice, but without documentation
of the training of these persons. Advice regarding
the ideal molecular content, dosing schedules and adjustments
for a particular condition to a specific patient
represents the ideal of patient-tailored treatment. This notion
has echoes of the old-fashioned apothecary, mixing a
little of this and that to obtain the perfect mix. This sense
of highly personalized medicine is promoted by the salespersons
of producers as well as “cannabis-savvy” doctors. It
is puzzling to understand how physicians in this day project
themselves as experts in the administration of a single substance.
Is the ideal of medical care not to address the whole
person? Could it be that today’s “cannabis clinics” are not
dissimilar from the medical “opioid mills” in North America that have been a cause of extreme suffering?
There is no turning back as cannabis is a legal medical
and recreational substance in Canada, with easy access for
those who hold hope for medical relief. Who are the winners
in this game? The industry is clearly thriving; Canadian
politicians are lauded as forward thinking; Canada is
proud to be a leader in this field; cannabis news sells well,
but what about our patients? Perhaps some patients will
truly find a magic treatment, but clearly the financial interests
of stakeholders will be substantial. As physicians who
practice evidence-based medicine, is it not aberrant that
we swivel 180-degrees, and simply embrace anecdotes and
popular beliefs, throwing aside rational judgement?
Cannabis, now embedded into clinical care, may be
a truly neglected panacea for many ills; or perhaps physicians
are on the brink of an epidemic of pseudoscience
that is promoted by a handful of “cannabis-savvy” doctors
who base their competence on “clinical experience,” poor
science and vigorous promotion to a vulnerable patient
population. How this epic will play out in time remains
to be seen. Will cannabis emerge as a truly neglected but
welcome addition to the physicians’ armamentarium, will
the current enthusiasm just blow over, or are we opening a
frightening Pandora’s Box? I, however, pity those with limited
income who are enticed to spend precious dollars on a
possible modern-day snake oil. Are we in the calm before
the storm erupts?
The views expressed in this article are those of the author, supported by scientific
references and vast clinical experience. They should not be taken to represent an
official position of the CRA, CRAJ or STA Communications.
1. Jikomes N, Zoorob M. The cannabinoid content of legal cannabis in Washington State varies systematically
across testing facilities and popular consumer products. Sci Rep 2018; 8:4519.
2. Hazekamp A. The trouble with cbd oil. Medical cannabis and cannabinoids 2018; 1:65-72.
3. Vandrey R, Raber JC, Raber ME, et al. Cannabinoid dose and label accuracy in edible medical
cannabis products. JAMA 2015; 313:2491-3.
4. Bonn-Miller MO, Loflin MJE, Thomas BF, et al. Labeling accuracy of cannabidiol extracts sold online.
5. Vo KT, Horng H, Li K, et al. Cannabis intoxication case series: The dangers of edibles containing
tetrahydrocannabinol. Ann Emerg Med 2018; 71:306-13.
6. Thomas AA, Mazor S. Unintentional marijuana exposure presenting as altered mental status in the
pediatric emergency department: A case series. J Emerg Med 2017; 53:e119-e23.
7. Wang GS, Le Lait MC, Deakyne SJ, et al. Unintentional pediatric exposures to marijuana in Colorado,
2009-2015. JAMA Pediatrics 2016; 170:e160971.
8. Rao DP, Abramovici H, Crain J, et al. The lows of getting high: Sentinel surveillance of injuries
associated with cannabis and other substance use. Can J Public Health 2018; 109:155-63.
9. Haug N KD, Sottile J, Babson K, et al. Training and practices of cannabis dispensery staff. Cannabis
and cannabinoid research 2016; 1:244-51.
Mary-Ann Fitzcharles, MD, FRCPC
Associate Professor of Medicine,
McGill University Health Centre