- Researchers cautioned to avoid LP-funding for clinical trials, if they also want government money.
- New cannabis research licenses from Health Canada are proving hard to obtain.
- The risks related to CBD are not properly understood.
Despite the huge amount of money and interest pouring in the cannabis sector, researchers still know remarkably little about the drug, its positive and negative impacts on human health and society, and even how certain cannabinoids actually work.
That was the takeaway from an event held on Thursday in Toronto to mark the launch of the Toronto Cannabis and Cannabinoid Research Consortium, a group of University of Toronto scientists and researchers at its affiliated hospitals.
"All of a sudden society is asking us scientists to answer questions, and because of restrictions that have been put upon us by the law, we are unable to answer many of them,” said Dr. Daniele Piomelli, the director of the University of California Irvine’s Centre for the Study of Cannabis, and the event’s keynote speaker. “This has put everybody in the science environment… in a state of fibrillation.”
Researchers spoke of a lack of knowledge on everything from the impact of cannabis use by new mothers on breastfeeding infants, to how second-hand cannabis smoke travels between apartment units. Even basic information about effective dosing for medical cannabis remains elusive, despite increasing interest in new cannabis drug development to treat a variety of health problems.
“I’ve heard over and over again from pharmacists and physicians and nurses, ‘so what’s the right dose for this indication? How much is too much? How do I know how much to give or to authorize?’ It’s remarkable that we have this substance, and yet we don’t have dosing guidelines,” said Dr. Bruna Brands, a senior science adviser with Health Canada and a member of the World Health Organization’s Expert Committee on Drug Dependence.
Here a few takeaways from the event:
Federal funders are wary of LP-backed clinical research
LPs are increasingly putting money into clinical research as they pursue drug identification numbers (DIN) for their medical products. DINs are required to make health and efficacy claims for drugs.
A representative of the Canadian Institutes of Health Research (CIHR), the federal government’s main federal funding agency for health research, however, cautioned researchers at the event about participating in LP-funded clinical research.
It’s unlikely that initiatives funded by LPs would be eligible for government funding as well, said Dr. Eric Marcotte, associate director of the CIHR’s Regenerative Medicine and Nanomedicine Initiative.
“There's always going to be that concern if the funding is coming from private industry sources that it could be biased, or perceived as biased,” Dr. Eric Marcotte said. “The advice I give to investigators looking at this is try to keep your [funding] streams somewhat separate if you can... It's the same for institutions.”
When CIHR began funding cannabis-related research, the agency was more open to working with LPs, similar to how it works with pharmaceutical companies, Dr. Marcotte said. Over the past year, however, the move by LPs into the recreational market and the increasing investment by alcohol and tobacco companies in the space has muddied the waters.
“We would love to be able to treat them as pharma companies. But as soon as you have tobacco or alcohol owning even part of that, it now moves into the other category,” he said.
Dr. Marcotte, however, encouraged public-private research partnerships to help solve common problems around “cultivation, growing, standardization of processes, and not so much on the clinical trial side.”
New cannabis research licenses have been hard to obtain
Under the new cannabis licensing regime, there is a separate licence category just for research. Securing one of these licenses appears to be challenging.
"The intent of the federal government was to lower the barriers to doing research in Canada on cannabis, that was the intent of the new system. I've heard from a lot of researchers that they're feeling the opposite, that it's actually gotten more complicated, more burdensome, more difficult," said Dr . Hanan Abramovici, manager and senior science advisor with Health Canada’s Cannabis Legalization and Regulation Branch.
The problem, he said, is mostly due to transitioning older licences to into the new system.
“Initially, when the transition happened on October 17, there was a need to migrate an enormous number of licences from the old system, and map that to the new system, and not all the mapping is as easy as one would think,” Dr . Abramovici said.
The delays, however, are not all on the Health Canada side, he said: “Scientists are inputting information into the CTLS, but sometimes or often that information is incomplete, so there's a lot of back and forth; that happened under the old system as well.”
There are also issues at the institutional level, he said, where “some institutions are grappling with how to manage those licences, how to authorize research within their own institutions."
Potential risks related to CBD are being overlooked, as the cannabinoid is little understood
In the rush to market cannabidiol (CBD) in both the U.S. and Canada, people are overlooking potential harms associated with the non-intoxicating cannabinoid, said Dr. Piomelli, one of the world’s leading experts on the pharmacological effects of cannabis.
"I'm not one for fostering any paranoias, I think we already have plenty of those. But there is a need to take a pause, and think about CBD a little bit more. Because I think we are cutting CBD too much slack,” he said.
The problem, he said, is that scientists don’t actually know how CBD works. Researchers have a fairly good idea how THC interacts with the human endocannabinoid system. CBD, in contrast, does not appear to interact directly with endocannabinoid receptors.
"We don't know the mechanism of action of CBD. That ignorance is a real problem. Because if we knew the way it worked, we would know the risk it carries,” he said.
“In fact... if you ask people who are in the business of selling CBD, the last thing they want is an understanding of how CBD works. I’m not being facetious. It is actually true. Because they realize that if the mechanism is discovered, and that mechanism carries a specific liability, then the FDA will be asking questions about the specific liability,” he said.
It was pointed out that the WHO’s Expert Committee on Drug Dependence recently said CBD should not be a scheduled substance. Dr. Brands, who has chaired the expert committee, said that their review of existing literature did not find any risk of addiction or abuse with CBD. But she agreed that more research into the long-term impact of CBD use is needed.
Watch out for pseudo-scientific marketing, like “entourage effect”
The marketing push behind CBD wasn't the only thing Dr. Piomelli cautioned against. He also pointed out certain pseudoscientific terms, such as the much-touted “entourage effect,” being used to market cannabis.
“Pharmacology knows something called synergism, which is just the opposite of antagonism, so things when put together do a lot more than each of them separately. But the entourage effect is today used more as a magic term, just basically a marketing scheme, to convince people that some particular type of cannabis is so much better than another," he said.
“The phrase ‘entourage effect,’ which was introduced originally by [Dr. Raphael] Mechoulam... was introduced in a completely different context. Raffi was trying to explain why along with endocannabinoids we have a whole ocean of other molecules that kind of look like the cannabinoids and they work in an ancillary manner to the cannabinoids. He said, ‘well they work as an entourage.’ Which was just a nice phrase to say, we don’t know how they work."