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Neurons involved in opioid overdose deaths identified, marking first step in developing new treatment

TORONTO — A recent study has pinpointed the group of neurons that are affected during opioid overdose deaths.

Opioids affect the human body by binding onto certain proteins in the brain and nerves, called opioid receptors. When certain receptors become bound, it slows down the body’s ability to breathe. At higher doses, breathing can be disrupted altogether, which leads to overdose deaths, also known as opioid-induced respiratory depression (OIRD).

“The underlying mechanism of why opiates slow down and depress the breathing rhythm has not been fully characterized,” Salk Institute assistant professor Sung Han said in a news release on Thursday. ​

Han and his research team published their findings in the journal Proceedings of the National Academy of Sciencesback in June. They identified a group of receptors (called the μ-opioid receptors) located in the brainstem that play a critical role in the disruption of breathing due to opioids.

In Canada, there have been over 21,000 deaths due to opioid overdose between January 2016 and December 2020, according to the Public Health Agency of Canada. After the start of the pandemic, opioid overdose deaths jumped 89 per cent. In 2020 alone, there were over 6,200 deaths from opioid overdoses.

The research team examined mice that were genetically engineered to lack those receptors and compared them to mice that weren’t genetically modified. After all of the mice were exposed to morphine, they found that the genetically modified mice did not have their breathing disrupted, while the unmodified mice did.

Even without opioids, the researchers also found that inhibiting those receptors in the unmodified mice also caused overdose symptoms.

The researchers also identified several chemical compounds that could activate those receptors rather than inhibit them. When they tested these on overdosing mice, it resulted in a nearly 100 per cent recovery rate.

“We discovered four different chemical compounds that successfully activated these neurons and brought back the breathing rate during OIRD,” first author Shijia Liu said in the release.

Currently, the only medication available for opioid overdoses is naloxone. Naloxone works by attaching to the opioid receptors and blocking opioids.

However, naloxone is not without several disadvantages. It has a short duration and needs to be administered several times. It also blocks all opioid receptors, including the ones that regulate pain, and high dosages have the potential of leading to cardiac arrest.

Han hopes that this new research can be the first step in developing a new treatment that targets the specific receptors involved in overdose deaths. 

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