COM M E N TA RY

Cannabis industry and medical

D
uring the 2017-2018 fiscal year, the number of cannabis improves PTSD symptoms among veterans.4
Canadians authorized to receive medical canna- However, these studies are not reflective of the wider
bis (ie, products derived from the cannabis plant, body of literature. A recent systematic review7 of sys-
as opposed to the pharmaceutical cannabinoids nabilone tematic reviews, clinical trials, and observational stud-
and nabiximols) increased from 174 503 to 296 702, and ies with control groups identified 2 systematic reviews
that number continues to climb.1 In this commentary, we and 3 primary studies on cannabis and PTSD. Both sys-
argue that the evidence for the therapeutic benefits of tematic reviews8,9 concluded that there was insufficient
medical cannabis is very limited, and that this evidence evidence to draw any conclusions about the efficacy of
is misrepresented by the medical cannabis industry. We cannabis in PTSD treatment. One of the 3 primary stud-
further argue that the lack of regulation and oversight of ies, a retrospective cohort study of more than 2000 US
medical cannabis clinics by Health Canada has allowed veterans who were assessed before and after attending
clinicians to prescribe unsafe doses. We comment on the residential treatment for PTSD, found that those who
influence that the medical cannabis industry has had on started or continued using cannabis had worse PTSD
the public’s perception of cannabis and consider the effect symptoms, more violent behaviour, and greater alcohol
that this influence has within the context of legalization. use compared with those who never used or stopped
Finally, we outline strategies that family physicians can using cannabis.10 In the other 2 studies, cannabis use
use to protect their patients from the harms of cannabis. was not associated with severity of PTSD symptoms.11,12
Another review of cannabis and PTSD concluded that
Evidence of benefit for medical cannabis
Advocates claim that cannabis is effective for a variety of marijuana use has been linked to … depression, anxi-
medical and psychiatric conditions; however, the only con- ety, psychosis, and substance misuse. Marijuana use
ditions for which cannabis has credible evidence of ben- is also associated with worse treatment outcomes in
efit are neuropathic pain, spasticity from multiple sclerosis, naturalistic studies .… Known risks of marijuana thus
palliative care, and chemotherapy-induced vomiting.2 currently outweigh unknown benefits for PTSD.13
In spite of a lack of supporting evidence, the medical
cannabis industry commonly makes exaggerated claims A broader literature review shows that the evidence for
about the therapeutic benefits of cannabis. A website cannabis as a treatment for PTSD is far from conclusive,
belonging to a chain of cannabis clinics provides a list of indicating that the cannabis company’s claim about recent
“common conditions treated with cannabis” that includes studies showing promise4 is misleading and disingenuous.
several conditions that have little to no evidence and Furthermore, when considering the evidence for medi-
for which clinical guidelines do not recommend the cal cannabis, it is important to distinguish pharmaceutical
use of cannabis. These conditions include back pain, cannabinoids from other preparations: cannabis advo-
headaches, anxiety, and posttraumatic stress disorder cates tend to equate the benefits and safety of medical
(PTSD).3 To take PTSD as an example, medical cannabis cannabis with that of pharmaceutical cannabinoids, yet
has been promoted as a viable treatment without a rea- the 2 have different effectiveness profiles. Evidence for
sonable body of evidence behind its use. A prominent medical cannabis is far weaker than for the pharmaceuti-
medical cannabis company states the following: cal cannabinoids nabiximols and nabilone, in part because
of the difficulty of designing a trial of sufficient quality for
We’ve heard from a number of our patients that suffer inhaled cannabis. In a systematic review of cannabinoids
from PTSD that medical cannabis is very effective at for neuropathic pain, inclusion criteria were met by 10
helping find relief …. More and larger studies need to randomized controlled trials (RCTs) on nabiximols, 3 RCTs
be done on the effects of cannabis on treating PTSD, on nabilone and dronabinol, and only 2 on medical canna-
although recent studies are showing that there is bis.14 A systematic review of 11 high- and moderate-quality
much promise in this form of treatment.4 systematic reviews of RCTs and prospective long-term
observational studies on the effectiveness of cannabinoids
The company bases this conclusion on 2 studies of (both pharmaceutical cannabinoids and cannabis) in pain
uncertain relevance to medical cannabis—one on nabi- management15 found no evidence of benefit for medical
lone5 and the other on pure oral tetrahydrocannabinol cannabis (and limited evidence of benefit for nabiximols in
(THC)6—and on anecdotal evidence from studies that the management of neuropathic pain).

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 Cannabis industry and medical cannabis clinics need regulation COMMENTARY

Pharmaceutical cannabinoids also have a different cannabis clinics have not published the indications, con-
safety profile than cannabis. Smoking is the most com- traindications, or dosing protocols for the products they
mon route for cannabis ingestion among US adults,16 prescribe. The College of Family Physicians of Canada,
and cannabis smoke contains multiple toxins, some in its 2014 guidance document,25 recommends restrict-
of which are carcinogenic and atherogenic. Smoking ing the prescribing of dried cannabis to patients with
delivers very high concentrations of THC to the brain severe neuropathic pain unresponsive to all first-line
within seconds, which can cause acute cognitive impair- medications. It also recommends a maximum dose of
ment and increase the risk of motor vehicle accidents.17 700 mg of dried cannabis with 9% THC per day. However,
Smoking 2 g of cannabis containing 20% THC, a concen- in 2017, the average daily dose of prescribed medical
tration that is high but available for purchase from pro- cannabis in Canada was 2.3 g,1 well in excess of this
ducers of medical cannabis, will deliver up to 400 mg of recommended maximum. The average concentration
THC to the brain (although some THC will be lost through of THC prescribed has not been reported, but many of
side smoke), whereas 12 sprays of nabiximols, the maxi- the industry’s cannabis products contain concentra-
mum daily dose, only delivers 33 mg of THC. Creating an tions of THC that are far above the 9% recommended
equivalency between these 2 different products is mis- by the guidance document, with some containing con-
leading to consumers and contributes to a lack of public centrations of 20% or more. To discourage inappropri-
knowledge about the effects of medical cannabis. ate prescribing, some US states have imposed medical
requirements on cannabis clinics, including mandatory
Cannabis and opioids training in cannabis prescribing, prescriptions lasting no
Invoking a public health angle, advocates have asserted that more than 30 days, and a requirement to closely follow
cannabis can help prevent or treat opioid use disorder.18 the patient to ensure the safety and effectiveness of the
This claim is based on a study that found that US states that cannabis prescription.26
had legalized cannabis had reductions in opioid overdose The provincial regulatory colleges have put out posi-
rates.19 However, this is an ecologic study that did not ana- tion statements on medical cannabis. For example, the
lyze individual-level data on cannabis use and overdose risk. College of Physicians and Surgeons of Ontario position
Other factors not related to cannabis laws might have con- statement27 advises physicians that they must do a com-
tributed to lower overdose rates, such as prescription moni- prehensive assessment before prescribing cannabis and
toring systems or the crackdown on “pill mills.” A recent identify patients at high risk of cannabis-related harms,
analysis of statewide long-term time trends in overdose such as psychosis or mood disorders. The college also
deaths found that the states that had legalized cannabis had recommends that prescribers use a low dose and monitor
lower rates of prescription opioid overdose before legaliza- for complications such as cannabis use disorder (CUD).
tion, and controlling for this eliminated the association.20 However, evidence from the United States suggests
Contrary to advocates’ claims, observational stud- that physicians frequently prescribe medical cannabis
ies have found a positive association between cannabis to patients who have conditions for which cannabis is
use and opioid use disorder. A review of observational contraindicated, such as CUD. In a US survey study, fam-
studies concluded that opioid misuse is more common ily doctors reported that 31% of their patients who were
among cannabis users than among nonusers,8 and a prescribed medical cannabis by another doctor had a
large American epidemiologic survey found that can- medical condition that could be worsened by cannabis.28
nabis use was associated with nonmedical prescription Another large-scale epidemiologic study found that, out
opioid use (odds ratio of 5.78, 95% CI 4.23 to 7.90) and of a total of 3784 respondents with past-year cannabis
with opioid use disorder (odds ratio of 7.76, 95% CI 4.95 use, 32% of medical cannabis users had past-year CUD,
to 12.16)21; other studies have had similar results.22 compared with 25% of recreational cannabis users.29 A
Medical cannabis users have self-reported that canna- US study of at-risk youth in Denver and San Francisco
bis has helped them reduce their use of prescription opioids found that CUD was significantly (χ2 = 22.8, P < .001) asso-
for pain,23 but there is no objective evidence that cannabis ciated with having a medical cannabis card.30 A review
reduces use of opioid analgesics. In a 4-year Australian of US medical cannabis programs noted that
cohort study of 1500 patients taking opioids for chronic
pain, frequent cannabis users had higher pain scores, higher in many states people receive authorizations for medi-
pain interference scores, and lower pain self-efficacy scores; cal marijuana from physicians whom they have seen for
and they were not using lower opioid doses and did not a single visit …. Initial studies have shown that the typi-
have higher rates of opioid discontinuation.24 cal medical marijuana patient in these states is a young
male with a nonspecific indication of chronic or severe
Regulation and oversight pain and a history of recreational marijuana use.26
of the medical cannabis industry
There is little transparency about the clinical practices of Health Canada is responsible for ensuring that phar-
medical cannabis clinics. To our knowledge, Canadian maceutical products are safe and effective. It approves

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 COMMENTARY Cannabis industry and medical cannabis clinics need regulation

products for sale after rigorous review of their safety Health Canada regulatory approval. Nonetheless, it has
and effectiveness, and it requires companies to develop the regulatory authority, and the public health obligation,
a product monograph containing the indications, con- to regulate medical cannabis just as it does with other
traindications, and dosing for the product. Companies pharmaceutical products. Health Canada should require
are not allowed to promote “off-label” uses of their the industry to produce a product monograph, stating
product (ie, for nonindicated conditions). Physicians are the evidence-based indications, precautions, contrain-
expected to be consistent with the product monograph dications, and dosing protocols for medical cannabis.
in their prescribing of the product and in their educa- Health Canada should also prevent the industry from
tional presentations on the product. However, Health making products containing levels of THC higher than
Canada does not require cannabis companies to pro- those used in trials (ie, 9%).
duce and abide by a product monograph, listing the
indications, contraindications, and dosing of their prod- Legalization
ucts. As a result, the educational programs the industry Legalization of recreational cannabis has created uncer-
sponsors have no restrictions on their claims about their tainty about the future of medical cannabis. The Canadian
product. Furthermore, Health Canada has allowed the Medical Association has recommended that the medical
companies to produce cannabis with THC concentra- cannabis program be scrapped.32 However, even if this
tions of 20% or more. Industry involvement in medical happens, the marketing of medical cannabis has enhanced
cannabis marketing and education has a very danger- the public’s perception that cannabis is safe and benefi-
ous precedent: Purdue’s marketing of OxyContin. cial, which in turn will increase the use and the harms of
Health Canada failed in its obligation to protect recreational cannabis. People who have been persuaded
the public in the OxyContin epidemic. Health Canada that cannabis will relieve their pain, anxiety, insomnia, or
approved Purdue’s product monograph even though it PTSD will purchase recreational cannabis if they cannot
contained misleading and inaccurate information. An access medical cannabis. They will also be more resistant
affidavit, submitted to the court as part of the success- to concerns from family and friends about their cannabis
ful national class-action lawsuit against Purdue,31 con- use. There is evidence of an association between positive
cluded that Purdue’s 2009, 2010, and 2011 OxyContin social attitudes about cannabis and population-level use
monographs contained inaccurate statements that of cannabis. Canada has a more positive attitude toward
encouraged physicians to prescribe very high doses of cannabis and a higher per capita use of cannabis than
OxyContin to patients at high risk of addiction, over- Sweden or Finland.33 Exposure to advertising of medi-
dose, and other harms. The monographs suggested that cal cannabis was associated with greater intention to use
OxyContin is indicated for all types of pain; they did cannabis by students in grades 6 through 8 in California.34
not provide a therapeutic range or an upper dose limit; While Canada does not permit direct advertising of can-
they did not warn physicians that high opioid doses nabis, the industry and the clinics are able to market their
are associated with an increased risk of overdose and products through media stories, websites, direct market-
addiction; and they did not warn physicians that cer- ing to physicians, and “agents” who provide advice to con-
tain patient groups were at high risk of these harms. sumers about how to access cannabis.
This allowed Purdue, in its many publications, confer- Whether or not medical cannabis is still available,
ences, and workshops, to tell physicians that OxyContin legalization will likely cause an overall increase in the
could be “dosed to effect,” with no upper limit; that it public health harms of cannabis. In Colorado, where
was effective for all types of pain; and that addiction the legal age for cannabis purchase is 21, emergency
was rare in pain patients. Purdue’s campaign profoundly department visits among adolescents for cannabis-
changed physicians’ prescribing practices and directly or related reasons rose from 1.8 per 1000 visits in 2009 to
indirectly caused the deaths of many thousands of peo- 4.9 per 1000 visits in 2015.35
ple across North America. Health Canada also allowed
Purdue to produce tablets containing up to 80 mg Managing the risks of cannabis use
of oxycodone, 16 times the amount contained in an Family physicians can help protect their patients and the
acetaminophen-oxycodone tablet, with the result that public from the harms of cannabis through the follow-
physicians began prescribing high doses of oxycodone ing steps.
even for benign pain conditions.
While medical cannabis will not lead to overdose Follow the College of Family Physicians of Canada
deaths, it could potentially cause harm and disability guidance document25 when prescribing cannabis. Use
for many. Health Canada has put strict limits on adver- pharmaceutical preparations (nabilone or nabiximols) for
tising, and has set the minimum legal age for canna- patients with neuropathic pain who have not responded
bis purchase at 18, but much more needs to be done. to a trial of adequate dose and duration of first-line
Canadians were given access to medical cannabis medications (serotonin-norepinephrine reuptake inhibi-
because of a Supreme Court decision, not because of tors such as duloxetine, tricyclic antidepressants, and

866 Canadian Family Physician | Le Médecin de famille canadien } Vol 65: DECEMBER | DÉCEMBRE 2019
 Cannabis industry and medical cannabis clinics need regulation COMMENTARY

gabapentin or pregabalin), and if an adequate trial of no more than 9%. Family physicians should only pre-
nabilone or nabiximols is ineffective, consider a trial scribe cannabis to patients with neuropathic pain, at a
of vaporized dried cannabis slowly titrated to a maxi- maximum dose of 400 mg per day with 9% THC and an
mum dose of 400 mg containing no more than 9% THC equal amount of cannabidiol. Patients who use cannabis
and at least 9% cannabidiol.25 regularly should be assessed for CUD and given advice
on avoiding cannabis-related harms. It is not too late to
For patients who request a cannabis prescription for a impose evidence-based practice standards and guidelines
nonindicated or contraindicated condition, emphasize that can help prevent the overprescribing of cannabis.
that cannabis lacks evidence of benefit for these condi- Dr Kahan is Associate Professor in the Department of Family and Community Medicine
tions and has considerable evidence of harm, includ- at the University of Toronto and Medical Director of the Substance Use Service at
Women’s College Hospital in Toronto, Ont. Dr Srivastava is Associate Professor in the
ing motor vehicle accidents,36,37 psychosis,38,39 wor­sening Department of Family and Community Medicine at the University of Toronto and a
anxiety, 40 long-term cognitive impairment, 41 and family and addictions physician at St Joseph’s Health Centre in Toronto. Dr Clarke is
a knowledge broker for the Mentoring, Education, and Clinical Tools for Addictions:
CUD. Explain that the risk of these harms is increased in Primary Care—Hospital Integration project at Women’s College Hospital.
young patients42-44 and with high THC doses.45 Competing interests
None declared
When patients are already using cannabis for symptom Correspondence
Dr Sarah Clarke; e-mail sarah.clarke@wchospital.ca
control, assess them for CUD. Cannabis use disorder is
characterized by frequent or daily use, spending a lot of The opinions expressed in commentaries are those of the authors. Publication does
not imply endorsement by the College of Family Physicians of Canada.
time using, poor performance at work or school, dete-
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