Researchers in Alberta have discovered that a medication once used to treat gout is effective in reducing withdrawal symptoms in opioid-dependent rodents, raising the possibility it could one day do the same for humans.
The researchers, from the University of Calgary’s faculty of veterinary medicine and Hotchkiss Brain Institute, discovered that microglia – immune cells in the brain and spinal cord – have a role in causing opioid withdrawal, said neuroscientist and lead researcher Tuan Trang.
“We then found a key target on these cells known as pannexin-1 channels,” Dr. Trang explained in a phone interview from Calgary. “We took a step back and asked: Are there drugs that are clinically approved that can block this particular target?”
They found that probenecid, a gout medication that has since been taken off the market in Canada and replaced with newer generations of drugs, produced what Dr. Trang called a “striking reduction in withdrawal [symptoms] from morphine and fentanyl” in the rodents. Probenecid is relatively inexpensive, has few side effects and – importantly – does not affect the ability of the opioids to relieve pain.
Opioids also include heroin, oxycodone and codeine. Illicit fentanyl is behind a surge in overdose deaths that reached unprecedented levels in British Columbia last year.
Should probenecid produce the same effect in humans, it could mean lessening the opioid withdrawal symptoms that can often be so debilitating that they pull people back into using: severe nausea, diarrhea, muscle aches, joint pain and chills.
“What we’re seeing is that this could be used with existing therapies,” Dr. Trang said. “It could help an individual go through the hardest, most difficult phase of withdrawal.
A person with an opioid dependency who begins taking methadone, for example, could potentially require a smaller dose of methadone if withdrawal symptoms are ameliorated by the probenecid.
Michael Salter, chief of research at the Hospital for Sick Children in Toronto, said the research “reveals a new mechanism and a potential therapeutic target” for managing opioid withdrawal.
“The findings of Dr. Trang and his team could have important implications for people on opioid therapy and those attempting to stop opioid use.”
The researchers are now working with physicians from the Calgary Pain Clinic to design a clinical trial to test the compound.
That study could still be years away, Dr. Trang said.
British Columbia and Alberta have been hard hit by the opioid crisis plaguing many regions in North America. In B.C., 914 people died of illicit drug overdoses last year – the highest death toll in 30 years of record-keeping – and fentanyl is believed to be linked to about 60 per cent of those deaths.
From January through September, 338 Albertans died from an apparent drug overdose linked to fentanyl or another opioid.Report Typo/Error