Research is imagining a world where painkillers are designed to keep people safe while alleviating discomfort: Looking at opioid overdose and respiratory depression

By Christina Ting

Dr. Gaspard Montandon joined St. Michael’s Hospital, now part of Unity Health Toronto, as a staff scientist in the Keenan Research Centre for Biomedical Science (KRCBS) in 2017. His work is focused on stopping the nearly 4,000 opioid-related deaths that happen in Canada every year by combining biomedical and clinical research. Since 2016, over 10,000 opioid-related deaths happened in Canada and such fatalities continue to rise annually. The growing number of overdoses and deaths cause by opioids is staggering, so much so that it has been deemed the “Opioid Crisis” and a public health emergency in Canada.

When opioids, which include street drugs like heroin and prescriptions like oxycodone and fentanyl, are taken at high doses, they can severely affect breathing, leading to death. Dr. Montandon’s research investigates how opioids affect the parts of the brain that control breathing, and how opioids can completely stop breathing during an overdose. His research ultimately aims to find novel therapies to prevent respiratory depression without reducing the pain-killing effects of opioids.

We sat down with Dr. Montandon to understand what the opioid crisis is and how his research is trying to tackle this complex public health issue.

Q. Tell us about your research.

My research focuses on understanding how people die from opioid overdose and what is happening in the human body during an overdose. It is important to understand these mechanisms so we can create solutions. For example, we know that during an overdose, breathing slows down and sometimes stops entirely. However, we only recently found which parts of the brain are responsible for depressing breathing. A better understanding of the cells sensitive to opioids will help us find new drugs that can target these brain areas and hopefully prevent the side-effects of opioids, so patients or people who use drugs won’t die of overdoses.

Q. What are some of the ongoing projects in your lab?

One project we are working on right now is to develop an ideal pain killer with no side effects so that people can have less pain but also remain safe while using it. To design a safe opioid pain therapy, we need to find a way to block the opioid side-effects only. Imagine a drug that would prevent the side-effects instead of reversing the effects of opioids. Naloxone or Narcan is a life-saving antidote, but it can only be taken after the overdose happens, and it is often administered too late, when the damage has already been done. In other words, we are looking for a life-jacket that would prevent people who use drugs from dying when they take too many opioids.

Most research done on opioids is focused on addiction. Although it is an important health issue, mortality associated with opioids is not due to addiction, but it is caused by the severe respiratory depression and ultimately a lack of oxygen to sustain body’s functions. Because new and powerful opioid drugs have been synthetized, for example oxycodone and fentanyl, opioids are more powerful than ever and can severely affect people’s capacity to breathe.

Although the number of people affected by opioid addiction has progressively increased over the last two decades, the number of opioid overdoses and deaths quickly outpaced the number of people with addiction. In other words, there are currently more people overdosing due to the powerful effects of new opioids. Therefore, we can still try to treat addiction, but ultimately this won’t solve the issue of the powerful nature of new opioids like fentanyl. Drug addiction is a serious mental health issue that needs to be treated, but we should also be looking at how to make opioid drugs safer.

Q. Why did you decide to pursue basic science and opioid research?

I like finding solutions to problems. I like to fix things!

A few years ago, I was thinking about how we can fix the opioid epidemic and make a real difference. I realized that the current opioid research was not addressing the real issues associated with opioid use, and that the mortality and morbidity due to opioid use was, to my view, the most important problem. So, I asked myself, “How can we quickly find new safe opioid pain killers?”

At St. Michael’s, we have a zebrafish facility that facilitates drug discovery. Using the zebrafish as a model system to study opioid overdose, we can quickly test thousands of new drugs to eventually find one that could protect against respiratory depression. This is critical and urgent, because every 15 minutes, one person dies of opioid overdose in North America. Solutions need to be quickly identified but more traditional research can be too slow to address the current opioid crisis.

Q. Why did you choose to work at the Keenan Research Centre?

St. Michael’s Hospital is a very friendly workplace and everyone tries to collaborate; there is a real sense of community. The second reason is that St. Michael’s Hospital’s core values are to help those most in need. Finding solutions to the opioid crisis is consistent with these values. Also, another important part of research is finding money to do it. St. Michael’s Hospital Foundation has been fantastic because they have granted me seed funding to support my new, non-traditional research, which is now supported by Canada research agencies.

Q. Is there anything else you would like to add?

Most of the research is done by trainees and staff. It takes a good team to produce quality research. I think that, by giving my team the freedom to develop their own ideas, we can find life-changing solutions.

A harmonious workplace is important to foster new ideas and solutions. The opioid crisis is at a critical point, where we can’t afford to ignore it. We need all hands-on deck to find solutions to reduce the risk of lethal overdoses. I believe that our team is taking large strides in that direction.

Dr. Montandon is a scientist at the Keenan Research Centre for Biomedical Sciences. To find more information on his research visit www.gasplab.com.

About St. Michael’s Hospital

St. Michael’s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the Hospital’s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael’s Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto.

About Unity Health Toronto

Unity Health Toronto, comprised of Providence Healthcare, St. Joseph’s Health Centre and St. Michael’s Hospital, works to advance the health of everyone in our urban communities and beyond. Our health network serves patients, residents and clients across the full spectrum of care, spanning primary care, secondary community care, tertiary and quaternary care services to post-acute through rehabilitation, palliative care and long-term care, while investing in world-class research and education. For more information, visit www.unityhealth.to.