Dazed + Confused
Illustrations by Suharu Ogawa
It can cause intense bouts of vomiting — but might also relieve nausea. It can worsen anxiety — or reduce it. It can stifle motivation or give back the will to live.
If you’re confused about cannabis, welcome to the club.
By Carolyn Morris
But if you’re at all relieved about its upcoming legalization for recreational use in Canada — at the prospect of no longer having to stand between patients and pot — you might want to reconsider.
With legalization, health-care professionals will need to think and talk much more about cannabis, not less.
This despite limited and unclear evidence, dissenting views around its benefits and harms, and huge commercial interests at play.
No longer a ‘dirty little secret’
About 10 years ago, Dr. Lloyd Gordon (MD ’76) began seeing people arrive at the Humber River Hospital’s emergency department who were vomiting repeatedly. With standard anti-vomiting medications proving futile, the perplexed physicians carried out all sorts of tests and procedures, trying to understand what was going on.
It turned out this cyclical vomiting was tied to chronic cannabis use. And cannabinoid hyperemesis syndrome has only become more common in emergency rooms.
“I used to see one case every six months, but now I often see one or two every shift — usually among people in their 20s,” says Gordon.
If we look to places like Colorado, which are a few years ahead in legalizing recreational cannabis, we can expect these types of emergency visits to increase — at least in the beginning. One of the trends there was an initial spike in hospital visits for cannabis-related ills including cyclical vomiting, accidental ingestion of edibles by children and intoxication among adolescents — before a return to pre-legalization rates.
“Health-care providers will need to manage harms from use — and also be able to detect signs of misuse,” says U of T professor Peter Selby (PGME ’95, MHSc ’99), an addiction specialist at the Centre for Addiction and Mental Health (CAMH). It’s estimated that close to 10 per cent of users will develop addiction, with warning signs including regular or daily use and a reduced ability to function.
It’s hard to ignore the benefits reported by patients, especially around pain relief. But even occasional use comes with potential dangers, including health effects of smoking, excessive intoxication due to the delayed high of edibles, unintentional poisoning incidents among kids and impaired driving. There are also serious but rare side effects like the triggering of psychosis among adolescents and young adults, and even death from suicide.
One positive side of legalization, Selby believes, will be new regulation and standardization of cannabis products, both recreational and medicinal. In addition to preventing social harms of criminalization, this was among the central reasons CAMH called for legalization. It might take a while, but he expects dosage and delivery will become increasingly clear and straightforward — just as prohibition-era home brew or hooch gave way to alcohol with standardized concentrations.
While concerned about the implicit green light that comes with legal status, addictions expert and U of T family medicine professor Anita Srivastava (MD ’96, PGME ’98, MSc ’05) believes one possible benefit could be patients feeling more comfortable talking about their cannabis use — and physicians being more open to asking.
“We ask patients about smoking and alcohol use, but tend to ask about illegal substances less,” she says. “When it’s legal, it won’t feel like a ‘dirty little secret’ anymore.”
For U of T psychiatry professor Joanna Henderson (BA ’92, MA ’94, PhD ’03), the most important thing for doctors to do is to check their biases and take the time to listen to their patients, to learn what purpose cannabis might be serving for them. Even when it comes to adolescents, who are particularly at risk of harm related to mental health and brain development.
“We should be asking patients about cannabis the same way we would with a rash,” says Henderson, who is also director of the Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health at CAMH. “We shouldn’t just assume they are using it for recreation.”
These conversations, however, may be precisely what some medical professionals want to avoid. Since medical marijuana first became legal in Canada in 1999, physicians have struggled to navigate limited and conflicting evidence, along with requests for prescriptions from patients. Many are eager to get out of the middle.
We should be asking patients about cannabis the same way we would with a rash. We shouldn’t just assume they are using it for recreation.
But Srivastava expects questions about cannabis will only increase. Primary health care providers should be keeping up with the literature now more than ever, she argues, even if it is only to correct misconceptions.
There are few easy answers. For instance, when Gordon began telling patients with repeated vomiting that cannabis was the cause, they would almost always reply: “But it’s the only thing that helps my vomiting!”
Contradictory Cannabis
It’s not only the blurred lines between illicit drug and potential therapy that makes cannabis confusing — it is a complex and contradictory substance to its core. Medical researchers have barely scratched the surface of the plant, with its 100-plus cannabinoid ingredients, as well as its terpenes and flavonoids — a “neglected pharmacological treasure trove,” as renowned Hebrew University cannabis researcher Raphael Mechoulam put it. And they’ve discovered an entire brain pathway system along the way.
While cannabis has been used for thousands of years, its principal psychoactive ingredient tetrahydrocannabinol (THC) wasn’t discovered until 1964. That led to a surge of pre-clinical research, with cannabinoid brain receptors identified in 1988 and our body’s natural endocannabinoid system in 1992.
“Even if you take cannabis out of the picture, our cannabinoid receptors are involved in all sorts of functions, including learning and memory, mood, appetite and response to pain and stress,” says U of T pharmacology and toxicology professor and chair Ruth Ross. “This system might be overactive in some illnesses, and underactive in others.”
But introduce cannabis — with its unwieldy mélange of ingredients, wide range of doses and multiple routes of administration — and the results can be unpredictable.
Some of the cannabinoids, including THC, have a “biphasic effect” — with low doses showing one effect, and chronic use another. Add to that complexity the multitude of potential interactions among the plant’s other components, such as cannabidiol (CBD), one of the cannabinoids shown to have therapeutic properties.
Despite advances in pre-clinical and some clinical research, cannabis continues to baffle. Efforts to enhance and coordinate scientific progress are underway. At U of T, Ross is developing the Toronto Cannabinoid and Cannabis Research Consortium, set to launch later this year. Other initiatives include McMaster University’s Michael G. DeGroote Centre for Medicinal Cannabis Research and work out of McGill University’s Alan Edwards Pain Management Unit.
“There’s fuzziness all over the map when it comes to cannabis,” says McMaster professor and director of the University’s cannabis centre James MacKillop. “We need to study this drug like any other — to better understand what cannabis can do from a medical standpoint, and study its harms.”
The problem is, cannabis is not a drug like any other. And this makes clinical research that much harder, explains McGill professor and leading cannabis researcher Mark Ware.
While he has witnessed it benefit patients — it was a surprisingly healthy septuagenarian sickle cell patient in his native Jamaica who inspired him to look at the drug more closely — he notes the hurdles to studying cannabis: not only does the mixture of active ingredients complicate studies, but the high is a sheer give-away when attempting to create blind placebo control groups.
“You have a drug that has psychoactive effects — and those challenge the validity of research,” he says. In order to design double-blinded protocols, he used cannabis products in very small doses for a major study measuring pain relief. But with reduced doses, you run the risk of diluting the therapeutic benefits — or even masking potential negative effects.
Ware also points to major barriers in clinical research: the difficulty of acquiring legitimate cannabis products and the challenge of securing funding due to stigma. In addition, the over 250,000 medical marijuana users in Canada are not systematically tracked, he says. Legalization and regulation, Ware hopes, could help encourage a strong and concerted research effort.
“This is one of the biggest shifts in drug policy in generations — of a drug that has potential medicinal value and known negative effects,” he argues. “We need to up our game here.”
Big Cannabis?
Despite seeing major potential in cannabis as a medicine and the legitimate need for some form of decriminalization, Ross argues that legalization is moving ahead too fast — and without the proper safeguards in place to protect the public from a substance with serious harms.
“How can we have robust public health messaging given the profit-driven framework for recreational cannabis?” she says. “There’s real potential for financial conflict of interest, and we need to avoid repeating the mistakes made by the tobacco industry.”
There is definitely a lot of money on the line – with Canadians spending over $5.7 billion on marijuana in 2017, according to Statistics Canada. (We spent $22 billion on alcohol and $16 billion on tobacco products in the same year.)
According to a comprehensive 2017 report on the health effects of cannabis, published by the National Academies of Sciences, Engineering, and Medicine, conditions found to benefit from cannabinoid therapies are chemotherapy-induced nausea and vomiting, chronic pain among adults and spasticity related to multiple sclerosis.
But with anecdotal findings and various studies pointing to potential benefits, cannabis and cannabinoids are used and prescribed for many other ailments, including anxiety and epilepsy. (A recent FDA expert advisory panel recently recommended the approval of a cannabidiol medication for two rare forms of epilepsy.)
Between hesitation on one side, and haste on the other, the medical field is divided. Some believe the research simply needs to catch up to mounting anecdotal evidence, with patients needing help now. Others are wary of exaggerated claims — and even suspect “big cannabis” of helping to promote the drug.
“I get suspicious when I hear people say, ‘Let’s jettison the rational approach and just start prescribing,’” says U of T family medicine professor Nav Persaud (BSc ’02, MD ’09, PGME ’11), an outspoken critic of the medical profession’s role in the opioid crisis, egged on by industry influence. He sees disturbing similarities in cannabis.
“If there aren’t enough studies,” he says, “I think ‘Why don’t you go, do the studies, and report back?’”
But others argue that with the opioid crisis raging, we don’t have time to wait. Family physician and U of T professor Alan Bell (BASc ’76, MD ’80) stresses that he’s not a “pot doc” but has integrated cannabis into his family practice because it’s “extremely useful in a number of areas.”
Bell prescribes cannabis oils or capsules to patients for conditions including pain and chemotherapy-induced nausea and vomiting. He agrees cannabis shouldn’t be used as a first-line treatment — but surely, he argues, it should come before opioids.
“Why would we use a high-potency, high-toxicity agent before using a low-potency, low-toxicity agent?” he asks. “It does have real side effects, but you can’t die of a cannabis overdose.”
Not Cut and Dried
Persaud wasn’t always so sceptical about cannabis. In fact, he used to prescribe it. But he soon became uncomfortable with its side effects. One patient in particular would insist the drug was helping, but over time Persaud realized the patient’s life was in fact falling apart — he lost his job and was kicked out of his home.
“I’d see patients attributing everything good happening in life to marijuana,” he says, “and they’d deny it was having any negative effect.”
This is something addictions expert Anita Srivastava has seen often. Splitting her time between an addictions clinic and her family medicine practice, she notes a big divide in awareness between both groups of patients.
“In my addictions practice, most of my patients have already recognized that a substance can cause them harm,” she says. Not so in her family medicine clinic.
“Some patients might not connect the dots. They’re often surprised to hear that cannabis use could have anything to do with their anxiety, for example. So there’s definitely more education involved in family practice.”
But with so much disagreement, it’s hard to narrow in on exactly what that education looks like.
Physicians can call on a growing number of resources to help. Canada’s Lower-Risk Cannabis Use Guidelines, for instance, recommend abstaining above all. They then provide other harm-reduction options such as delaying use until later in life and choosing safer formats over smoking burnt cannabis. The Canadian Medical Association has publicly supported these.
In terms of guidance around prescribing medical cannabinoids in primary care, the College of Family Physicians of Canada has recently published a simplified guideline — strongly recommending against using cannabis for most medical conditions. For those few exceptions — neuropathic pain, chemotherapy-induced nausea and vomiting, spasticity due to multiple sclerosis or spinal cord injury — it should only be considered as a third-line therapy.
“There are very divided opinions depending on what spectrum of medicine you practise on,” says U of T professor and clinician scientist Bernard Le Foll, who helped develop the lower-risk guidelines. At CAMH, where he is based, many patients have been harmed by their cannabis use. In pain clinics, on the other hand, physicians report benefits.
Family practice is across the board — and conversations with patients can be especially tricky, especially considering the hope and the hype that builds up in the absence of strong evidence.
“It’s so difficult for family doctors,” says Srivastava. “They have patients saying ‘OK, that’s the evidence, but this is my life! I need to get to work and take care of my kids, and this works for me.’ And as a doctor you really want to help.”
The problem is that when it comes to cannabis, it can be hard to distinguish help from harm. •
