Grant: Project Grant

Opioid medications are widely used in pain management, but present the side-effect of respiratory depression that can be lethal with overdose. Opioid drugs induce sedation, i.e. loss of consciousness, and considerably reduce breathing. When overdosed, opioids can shut down the nervous system, completely stop breathing, induce severe hypoxemia and patients may eventually die. The current epidemic of opioid overdoses is resulting in over 2,500 in Canada according to the Public Health Agency of Canada. Opioid drugs are responsible for thousands of emergency visits every year, causing a severe health and financial burden. Nevertheless, opioids remain the pharmacological cornerstone of modern pain therapy and there are currently no treatments to prevent respiratory depression by opioids without reducing their analgesic properties. The current opioid antagonist naloxone is very effective at blocking µ-opioid receptors, i.e. the receptors that mediate respiratory depression by opioid drugs, but it also blocks opioid analgesia so it cannot be used as a preventive treatment. The development of new therapies has been hindered by a lack of knowledge about how opioid medications alter brain activity and what mechanisms underlie respiratory depression by opioids. This research program proposes to identify the mechanisms underlying respiratory depression by opioids and to find new therapeutic solutions to prevent it. Without a preventive treatment to reduce the severity of respiratory depression, opioid medications will continue to present severe health issues and the death toll associated with opioid drugs will continue to rise.