Hunting down an antidote to the opioid crisis

Thanks to seed funding from the Research Innovation Council at St. Michael’s Hospital Foundation, Dr. Gaspard Montandon is getting closer to keeping people who need painkillers safe.

International Overdose Awareness Day on August 31 aims to overcome the stigma of drug-related death. We spoke with Dr. Gaspard Montandon about his bold biological research to prevent the tragedy of overdose.  

Each year, nearly 4,000 people die in Canada from opioid overdoses—and that number is climbing. We are now in the midst of a full-blown opioid crisis. It’s nothing less than a public health emergency. 

When opioids, which include street drugs like heroin and prescription drugs like oxycodone and fentanyl, are taken in a quantity or combination that exceeds what the body can handle, they can stop a person’s breathing and cause death. Dr. Gaspard Montandon, who joined St. Michael’s Hospital in 2017 as a staff scientist in the Keenan Research Centre for Biomedical Science, wants to save lives by finding new therapies that prevent “respiratory depression” without reducing the pain-killing effects of opioids. He’s on a mission to change how we address the opioid epidemic.

First, we need to dispel a few common misconceptions about addiction and opioid overdose. One is that the majority of people with an addiction don’t have the willpower to resist opioids—it’s their own fault. In reality, says Dr. Montandon, “a large proportion of people who become addicted are prescribed opioids to deal with acute or chronic pain. Because they need to use opioids regularly, they progressively become addicted. If their supply of legal drugs is cut off, they try to access an unsafe supply on the streets, which increases their risk of overdose.” In fact, an alarming 40 per cent of opioid-related deaths in 2016 were a result of prescription drugs.

A second misconception is that if we treat the addiction, we can reduce the number of deaths due to opioid overdoses. The reality is that more people are dying because the powerful new synthesized opioids stop them from breathing. “Drug addiction is a serious mental health issue that needs to be addressed,” Dr. Montandon says, “But we should also be looking at how to make opioid drugs safer.” 

As for naloxone, the “opioid antagonist” designed to temporarily reverse the effects of opioid overdose, it is indeed a life-saving antidote, according to Dr. Montandon. “But it can only be taken after the overdose happens, and is often administered too late, when the damage has already been done,” he says. Even the aggressive campaigns against overprescribing are not a magic bullet, because, he explains, “if you reduce the supply of opioid prescriptions, drug users will look for illegal and unsafe opioids which are often laced with the powerful opioid fentanyl and have severe risks of respiratory depression.”

Dr. Montandon believes that to tackle the opioid epidemic head on, we need to address the side effects of opioids to develop safe painkillers.

The first step, he explains, is to understand what happens in the human body during an overdose. “We know that during an overdose, breathing slows down and sometimes stops entirely. However, we only recently discovered which brain cells controlling breathing are sensitive to opioids.”

The next step is to identify a drug that targets these areas of the brain to prevent the lethal side effects of respiratory depression while preserving their analgesic properties. Here at St. Michael’s Hospital, Montandon is leading a research program combining basic research and drug discovery in zebrafish to identify potential new drugs. 

“Using zebrafish, we have been successful in developing models of opioid overdose where we can replicate what happens to breathing and pain in human beings. We can quickly test thousands of new drugs to find those that protect against respiratory depression,” he says.

The quest to identify solutions is urgent, because one person in North America dies of opioid overdose every 15 minutes. 

Dr. Montandon’s approach is bold and would not have been possible without seed funding from the Research Innovation Council (RIC), created by three St. Michael’s Hospital Foundation board members. In fact, he was the RIC’s first recipient. 

The RIC accelerates breakthroughs. It supports promising new projects that challenge the status quo and are not yet sufficiently advanced to win grants from government funding agencies. The RIC’s flexible support is especially critical for a young investigator, says Dr. Montandon. “It helped me build the research program. It enabled me to hire a postdoctoral fellow and graduate student, and purchase equipment I couldn’t have otherwise. It gave me the time necessary to develop techniques that didn’t exist before and get lots of data that we’re now ready to publish.” Importantly, it helped him to secure a bigger grant from the Canadian Institutes for Health Research, and enlarge the team to battle this epidemic.  

Dr. Montandon is confident that they will find the right painkiller that is effective and reduces the risk of lethal overdose—and defeat the opioid crisis. More information about Dr. Montandon’s research and team can be found here:


In the world of health-care research, there is no such thing as an overnight success story. 

Discoveries that save lives, treat diseases and improve our quality of life take time, tenacity and an influx of funding. Introducing St. Michael’s Research Innovation Council (RIC), founded by a trio of St. Michael’s Hospital Foundation Board members: Gwen Harvey, John Hunkin and Melissa Martin. It’s a different approach to funding research, because donors choose which scientists and projects receive an annual pool of funds. Donors are then immersed in the discovery experience. They develop a personal stake in scientific breakthroughs. They go behind the scenes and inside the lab to see early-stage research and make funding decisions that could bring the next medical invention to life. Our Research Innovation Council makes medical ingenuity possible. 

Click here to learn more about the Research Innovation Council.