Launching Pot Into The Unknown

"Now is when we need to be doing this research, and the money is just not there. If we're going to be the only North American country that has full legalization, there's no reason that we shouldn't become global leaders."
"We're in a weird situation where we're about to legalize a drug and we have no idea what the downstream molecular signalling pathways are: what it's doing in the brain."
Steven Laviolette, professor, Departments of Anatomy and Cell Biology and Psychiatry, Western University Schulich School of Medicine and Dentistry

"I think at the end of the day everyone agrees that the best medical care is based in evidence. And unfortunately we just don't have enough for many conditions to guide us."
"Really, science has been stuck for the past 80 or 90 years or so, unable to do many of these tests."
"Hopefully when it is legalized many of those barriers will fall away. Unfortunately, cannabis has developed a bit of a reputation as a panacea in some groups. We need to really test cannabis, develop good medical evidence, so people know whether or not this hope and optimism is warranted."
Dr. M-J Milloy, professor, Department of Medicine, University of British Columbia; research scientist B.C. Centre on Substance Use

"If you make the statement that cannabis is safe,  you're then asking, 'Well what's safe? Is it a 50-50 combination of THC and CBD? Or high THC? And who is it safe for'?"
"People  are constantly asking the questions, and they want a definitive answer. We just can't give a definitive answer, even on age."
"Targeted funding [for research] would be incredibly helpful, but of course research takes time. We're not going to have these answers instantly."
Dr. Ruth Ross, professor, Pharmacology and Toxicology, University of Toronto

A protester lights a joint during a 4-20 marijuana rally on Parliament Hill in Ottawa on Friday, April 20, 2012. (Sean Kilpatrick/The Canadian Press)

These scientists are absorbed in the study of many addictive substances, one of which in their view it has become imperative to study the long-term effects of, but the funding for this critical research is absent, at a time when that substance, marijuana, is on the cusp of being legalized in Canada. Legislation legalizing marijuana will come before the Members of Parliament and the Senate of Canada because the current government is on a trajectory to enacting legislation legalizing it.

What disturbs these medical professionals who study the effects of marijuana on the human body and the brain in particular which is known to undergo changes associated with the mind-altering ingredient THC in marijuana, is that no focus has been given to the imperative of studying the very drug that will soon become legal in Canada, extending its use for medical purposes to recreational purposes. Even if researchers have funding for study purposes, to access marijuana for their experiments, applications must be submitted for exemptions from Health Canada, setting out the purpose of the study for each individual compound meant to be studied, and there are hundreds.

The paperwork alone is daunting, then throw in a shortage of funding for the study and its effects in a country prepared to legalize a drug whose use is endemic in Canada, despite a lack of legalization, and researchers' frustrations can be imagined. There is an impetus from within the scientific community to commit to studying how cannabis impacts human health, behaviour and the brain, particularly in the teenage years, but no stream of funding allocated to do so.

A large crowd filled Dundas Square in Toronto as pot smokers gathered on April 20, 2011. (Peter Power/The Globe and Mail)

 

The plant in question contains over 100 chemical compounds called cannabinoids. THC is the chemical known for its psychoactive effects, while CBD is another compound that has, like THC, been the subject of some study, though neither has been as exhaustively studied as the scientists would like. These compounds are known to have therapeutic effects, yet solid evidence that marijuana helps in a wide range of health conditions is lacking.

A report by the U.S. National Academies of Sciences, Engineering, and Medicine confirms that cannabis and compounds derived from it are deemed to represent an effective therapy supported through "conclusive or substantial evidence" only for three specific problems: chronic pain in adults, chemotherapy-induced nausea, and spasticity in multiple sclerosis. Yet the list of therapies for which which people claim cannabis has given them huge relief, lacks evidence of its usefulness in conditions such as Tourette's syndrome, traumatic brain injury, epilepsy, and ALS.

AIDS patients who in the 1990s had few other tolerable treatments, began to agitate for medical marijuana to ease their symptoms and pain associated with them, which placed the focus on marijuana and began its popularization as a pain reliever. The Task Force on Cannabis Legalization and Regulations mandated to consult widely and to give advice to the Canadian government has admitted to a lack of evidence existing for the wide approval of marijuana for medicinal purposes.

And precisely as a result of lack of evidence on marijuana's risks, benefits, optimum dosages or potential interactions with other drugs, reflecting basic data available for any other prescription drugs, physicians have been led to object to having been given the status of fulcrum for the dispensing of medical marijuana, and nor does the Canadian Medical Association support the use of marijuana in clinical settings, for the very same reasons.

The intersection of marijuana with other drugs, leading to such issues as alcohol addiction, and binge drinking creating ill health, costly in law enforcement and lost employment, and the growing use of prescription opioids becoming a worrying source of overdoses and deaths only adds to the confusion and the concern. On the other hand there is hope that binge drinkers and those addicted to opioids might switch to marijuana, a legal source of pain relief for medicinal purposes and an alternative to gaining a buzz satisfying to the recreational user.

The cannabis-psychosis link has long been a chicken-or-egg question, since people with schizophrenia are known to self-medicate by smoking pot. (Kevin Frayer/The Canadian Press)

 

There are stirrings from Colorado and Washington, two American states where marijuana was legalized in 2012, that lead to the belief that patients are making the choice to substitute opioids with marijuana. But the data cannot be viewed as reliable since no comparative data is available from before the legalization of marijuana took place. Still, providing a lesson to Canada; that government would be well advised to launch a search for data from before legalization for after legalization comparison.

There is a recognition that the broad understanding that marijuana is harmless is simply untrue, since marijuana affects cognitive performance and memory, and it also increases psychosis risk. Furthermore an estimated eight to nine percent of users will develop a lifetime dependence on the drug. But it is the large body of evidence in existence that links adolescent THC exposure to the risk of developing schizophrenia, that is most troubling. The human brain undergoes major remodelling where synapses are pruned and other neuronal connections are formed from a period predating the teens up to mid- to late-twenties.

It thus becomes imperative to gain a fuller understanding of the basic neurobiology of cannabis, since that understanding should be in place ideally before the legalization of the drug takes place. Biomarkers for modest risk should be taken into account, and maximum THC and minimum CBD content could be established using gathered, reliable data. Ruth Ross at U of T, points out that while it is known which receptors in the brain THC acts on, it is not understood what all of CBD's targets are.

So it came as a bit of a relief when the Canadian Institutes of Health Research announced a one-year $1-million "catalyst grant" to aid researchers in the development of studies in the impact of legalization, in the hope that "evidence gaps" relating to the health effects of cannabis and its behavioral, social and economic implications can be identified. It may not be much, and may not go far enough, but it's a start even though it's in the ballpark of too-little-too-late.