It was a watershed moment for the study of medical marijuana. This past December, Canadian university researchers, federal and provincial officials, patient advocates and industry representatives met in Vancouver to set priorities for evidence-based inquiries into a drug long overshadowed by its reputation as an illegal way to get high. The two-day, invitation-only meeting – convened by the Arthritis Society and partly funded by licensed growers of cannabis for medical purposes – is the latest sign that investigations of medical cannabis are moving into the research mainstream.

So, is the stigma lifting on the potential therapeutic value of a drug that has stirred more than its share of skepticism? Possibly, say established researchers and health advocates, but they also caution that this will only happen if all stakeholders, including federal research granting agencies, commit to removing roadblocks and boosting funding for evidence-based inquiry.

The federal Liberal government’s election promise to legalize marijuana for personal use is viewed by researchers as a separate issue from research into cannabis for medical treatment. Nonetheless, researchers say the government’s commitment is raising public awareness about the need for evidence-based research, too.

Cannabis has been available for medicinal purposes over the past 15 years under strict conditions set by Health Canada. The department’s office of clinical trials approved six clinical trials on cannabis between 2001 and 2015, including studies on chronic pain and osteoarthritis. According to the Arthritis Society, citing data from Health Canada, some 65 percent of Canadians who’ve received access to medical marijuana said they suffer from severe arthritis.

That statistic may partly explain why the Arthritis Society has emerged as a leading campaigner for research on cannabis for pain and disease management. It issued a position paper on medical cannabis in 2014, calling for clear options for arthritis patients. “We don’t have the answers,” says Joanne Simons, chief mission officer for the Arthritis Society, citing a “massive vacuum of information” on safety, efficacy and dosing. Even though cannabis is available to patients through Health Canada, the research has not caught up, she says.

“It is not like the traditional way that medicines have been brought to market with all of the rigour of clinical trials,” she observes. “We don’t actually know a number of things about medical cannabis, both for those who are using it and from the physicians’ perspective.” The Arthritis Society wants to build momentum for evidence-based inquiry and to blunt “the stigma associated with medical cannabis around people’s actual intent in using it,” says Ms. Simons.

In 2015, the charity awarded $360,000 over three years to Dalhousie University’s Jason McDougall, a professor of pharmacology and anesthesia who is examining the role of nerves in controlling joint inflammation and pain. “We are trying to understand the potential pain-relieving and anti-inflammatory effects of cannabis and cannabis-like compounds,” says Dr. McDougall, who became interested in arthritis after witnessing the excruciating pain suffered by his grandfather. In theory, Dr. McDougall’s preclinical study could lead to new treatments for knee arthritis, with chemicals from cannabis in a cream or patch applied directly to the arthritic joint to reduce the pain at its source. “Smoking, of course, is not the best way of administering any drug – not the safest way certainly,” says Dr. McDougall.

At the Vancouver stakeholder meeting, one of the keynote speakers was Ethan Russo, a pioneer in the field of cannabis research and now medical director of Phytecs, a Los Angeles-based company investigating the human body’s endocannabinoid system for new therapies. (The body’s natural compounds resemble the main psychoactive component of cannabis, explains Dr. Russo: endocannabinoids bind to cell receptors in the brain and the rest of the body, regulating mood, appetite, sleep and digestion.) Dr. Russo says the meeting was “a template for future developments internationally” and notes that Canada is already a research leader in the field.

One of the recognized Canadians is chronic-pain researcher Mark Ware, director of clinical research at the Alan Edwards Pain Management Unit of the McGill University Health Centre and an associate professor in family medicine and anesthesia at McGill. He is also executive director of the Canadian Consortium for the Investigation of Cannabinoids. In September, using funds granted in 2004 by the Canadian Institutes of Health Research, Dr. Ware and his co-investigators published the first multicentre study on the efficacy and safety of medical marijuana on chronic pain involving experienced users. “It’s a very important piece in the data bank we have around medical cannabis,” says Dr. Ware. The study found that the drug was relatively safe – for example, experienced users did not have more adverse events than the control group of non-users, an important insight for physicians and patients.

“We were able to follow a large number of patients using cannabis in a real-world context and compare them to a group of control subjects in the same clinics who were not cannabis users.” The study includes 80 pages of supplemental raw data on cognitive function, lung function, biochemistry and hematology that could be valuable to researchers or health-care professionals in addressing patient concerns about possible side-effects of the drug. “What I’m hoping is that anyone who is serious about medical cannabis and its effects should be familiar with the contents of that paper,” says Dr. Ware. “There’s so much there that people can dive into.”

Dr. Ware was raised in Jamaica, where he saw the potential health benefits of cannabis while working as a young doctor in a sickle cell clinic in 1998. One patient, in his late 70s, appeared relatively pain-free compared with other patients with the disease. Dr. Ware says the man, a Rastafari follower, told him: “You must study the herb, Doc.” After that, Dr. Ware researched all he could about the potential medicinal benefits of cannabis, concluding that “this needs clinical trials.”

When the Liberal government under Prime Minister Jean Chrétien announced in 1999 that it would fund medical-related marijuana studies, Dr. Ware moved to Canada. Since then, court rulings and government anti-drug policies have governed the pace of research progress.

History of medical cannabis in Canada

Access to cannabis for medical use was granted in 2001 under the Medical Marihuana Access Program (the government program uses a variant spelling for marijuana). The program’s regulatory framework gave approved users limited access to the illegal substance, allowing them or their designated supplier to grow it for personal use or buy it from Health Canada’s single supplier.

Cannabis for medical use is grown according to standardized regulations imposed by Health Canada. While different varieties are approved, they all must meet quality control requirements, including limits on the level of tetrahydrocannabinol, or THC, the plant’s naturally occurring psychoactive compound.

Over the years, several court rulings improved patient access and the right to medicinal cannabis, effectively thwarting the anti-drug policies of Stephen Harper’s Conservative government. In 2014, the Harper government replaced the existing regulatory framework, which allowed individual licensed growers to supply medical marijuana, with a new system in which only large licensed companies can produce it, and only in the dried plant form. In 2015, the Supreme Court of Canada expanded the definition of cannabis for medical use to include oils, tea and brownies.

Besides treating pain from arthritis, cannabis is now being used to relieve such symptoms as severe nausea, vomiting, chronic pain and loss of appetite in cancer patients who don’t respond to conventional treatments. The drug is also treating a variety of other medical complaints, including neuropathic pain that does not respond to common painkillers; muscle spasms linked to multiple sclerosis; weight loss in HIV and cancer patients; palliative or end-of-life care; post-traumatic stress disorder; and seizures. Ultimately it is up to the physician to decide whether cannabis is appropriate to treat a medical condition, underlining the need for more research.

In 2011, two Canadian researchers – Jon Page, founder and president of Anandia Labs and an adjunct botany professor at the University of British Columbia, and Tim Hughes, professor in the Banting and Best Department of Medical Research at the University of Toronto – completed the genetic sequencing of the Purple Kush variety of marijuana. The genome mapping is now available online to researchers, allowing them to study the plant without having it in a lab and thus avoiding having to obtain the security clearance and government permits required for such research. Dr. Page says he isn’t aware of any growth chambers for cannabis at a Canadian university, likely because cannabis and its molecules are substances controlled by Health Canada.

Moreover, researchers who study controlled substances face limits on the size of the lab and who has access to it, which wouldn’t mesh well with most universities’ existing labs and facilities. “University agricultural faculties or botany departments often have greenhouses or growth chambers where they’re growing corn, canola, grapes,” says Dr. Page. “It’s very hard to lock up one of those chambers so you can grow cannabis in it.”

When approached by young researchers who are eager to begin a career studying the plant, Dr. Page says he warns them about the lengthy time needed to get approvals. “The file crosses everyone’s desk,” he says. “They have to talk about every issue, like ‘Were the RCMP notified? Is campus security aware?’” Despite these hurdles, more universities are recognizing the value of cannabis research. With the prospect of the legalization of marijuana, Dr. Page predicts that the red tape governing research on cannabis for medical purposes will also be relaxed.

Corporate sponsorship

Lately, some of the funders of cannabis researchers are neither government nor charitable foundations, but rather companies that produce medical marijuana. This past fall, M-J Milloy received $1-million from National Green Biomed Ltd., a prospective grower of medical cannabis, to research the drug’s effects on HIV/AIDS patients. Dr. Milloy, an assistant professor in the AIDS division of UBC’s department of medicine, says NG Biomed is “as committed as we are in trying to build an evidence base for cannabis and trying to figure out what risks and benefits there might be for HIV, for arthritis, for all sorts of medical conditions.”

The company offered to fund Dr. Milloy’s research after he conducted an observational study (with funding from the U.S. National Institutes of Health) in which he tried to replicate an animal study that had shown monkeys given a cannabinoid before and after being infected with HIV had significantly lower viral loads and less inflammation. In his study, Dr. Milloy used medical data collected on heroin and cocaine drug users in Vancouver’s Downtown Eastside and found that marijuana users who subsequently developed an HIV infection had less inflammation and just half the viral loads of HIV/AIDS patients who had not smoked marijuana before the infection. “This is the first time we’ve found a direct impact of marijuana on the disease process itself,” he says.

At the University of Calgary, Matthew Hill is exploring the neurological effect of endocannabinoids on reducing stress. The assistant professor at the Hotchkiss Brain Institute sees growing international research interest in the potential of cannabis to address chronic pain, including inflammatory conditions, and post-traumatic stress disorder. “If you’re going to hedge your bets on a research program … I would say those conditions are front-runners,” says Dr. Hill.

Tweed Inc., a licensed producer of medical marijuana in Smiths Falls, Ont., is funding academic and industry-led studies, in addition to doing in-house research. Tweed president Mark Zekulin says the company’s own research team is “complemented by projects we’re exploring with academic partners, which are still defined by ‘what do we need to learn? What do we need to know?’ but are more ambitious, [as in] how to improve the yield of a plant by looking into its genetics.”

Despite the interest in research by corporate partners, hurdles persist. Cannabis is a controlled substance – both the plant and its molecules – so researchers must receive approval from Health Canada to use it in research. According to Health Canada, it has issued 34 licences under the Narcotic Control Regulations to conduct “regulated activities,” which include research with cannabis. It has also issued six exemptions under the Controlled Drugs and Substances Act specifically for research or clinical trials with cannabis. The department says it aims to complete the paperwork in 180 days, but researchers say sometimes it can take a year to get a licence. Once approved, researchers must establish secure labs, with video surveillance, security patrols and restricted access.

Another brake on research momentum is that the federal research granting agencies have not made medical cannabis a research priority. The Canadian Institutes of Health Research said in an email that the agency “does not currently have funding opportunities that are targeted toward marijuana,” a position echoed in an email by a spokesperson for the Natural Sciences and Engineering Research Council.

Dr. Page, the B.C. scientist and entrepreneur, would like to see a group of universities establish a multidisciplinary centre of research excellence to push ahead on cannabis research in Canada. That approach, he says, would address such issues as how to grow the plant on a university campus, how to safely store restricted materials and how to organize the various stages of research, including clinical use. Plant biologists, chemists and pharmacologists would be able to study different strains of cannabis to speed up clinical trials.

Kate Lee, vice-president of research for the Arthritis Society, similarly recommends a structured response: “The best way to remove [roadblocks] would be to have some kind of targeted program on medical cannabis.” Another impediment to developing a concerted research agenda on cannabis, she says, is “the giggle factor” because of the widespread image of cannabis as a drug for getting high.

With a growing number of licensed medical producers – 26 to date with 389 applications under review – the legitimate business and research sides of medicinal uses of cannabis are gaining traction. This past fall, Kwantlen Polytechnic University offered a 16-week online course – Intro-duction to Professional Management of Medical Marijuana for Medical Purposes in Canada – that quickly became oversubscribed, prompting a second class. The course, offered through Kwantlen’s continuing and professional studies department, has four modules – on horticulture, regulation, marketing and sales – and information on how to run research and clinical trials. The course is viewed by prospective students as preparation to apply for a production licence. The university invited Health Canada to participate and received a one-word reply: no. “The gist was that under no circumstances would you be allowed to handle any of the product,” says Jim Pelton, Kwantlen’s executive director of continuing and professional studies.

If Canada is destined to become a lead player in medical marijuana research, “the next few months are really going to tell the story,” says Ms. Simons of the Arthritis Society. The charity recently issued its second annual call for a “meritorious research project” on cannabis for medical purposes. “We obviously hope to be at the forefront,” she says, “and we will keep pushing.”