Society is dealing with a crisis of opiate abuse, as discussed by the former head of the FDA in the video below. Helping addicts to stop using is a priority for the United States and Canada. Researchers working at the University of Calgary's Faculty of Veterinary Medicine (UCVM) and Hotchkiss Brain Institute (HBI) have determined that an anti-gout medication that is already available can alleviate the degree of withdrawal symptoms in rodents addicted to opioids. The findings have been reported in Nature Medicine.
"Opioid withdrawal is aversive, debilitating and can compel individuals to continue using the drug in order to prevent these symptoms," explained Trang, an Assistant Professor at UCVM and the Cumming School of Medicine. "In our study, we effectively alleviated withdrawal symptoms in rodents, which could have important implications for patients that may wish to decrease or stop their use of these medications."
Up to this point, the molecular processes underlying opioid withdrawal had not been well characterized, so there was a dearth of targets for treatment. Delving deeper into the underlying causes of withdrawal, the team of neuroscientist Tuan Trang, PhD found that a molecule called pannexin-1, which is present all over the body, including in the spinal cord and brain, produces the withdrawal effect in mice and rats.
"The focus of much of the research so far has been on neurons themselves. Our study looked at key immune cells in the nervous system - and specifically at the pannexin-1 channel on these immune cells, which is something that hasn't been explored before," said Trang.
This new knowledge could cause a paradigm shift in understanding withdrawal and opening up avenues for the alleviation of physical symptoms that accompany opiate withdrawal.
Once they identified the mechanism, the researchers were able to test an existing drug - in this case an anti-gout medication called probenecid that is known to have non-selective pannexin-1 blocking effects. The drug is Health Canada approved, is relatively inexpensive, and has few side effects. Importantly, the researchers were also able to demonstrate that the drug did not affect the ability of the opioid to relieve pain.
"This is an exciting study which reveals a new mechanism and a potential therapeutic target for managing opioid withdrawal, says renowned Canadian pain researcher Dr. Michael Salter, Chief of Research at SickKids Hospital in Toronto. "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 moving fast to try to get this relief to human patients. They have collaborated with Dr. Lori Montgomery and Dr. Chris Spanswick at the Calgary Pain Clinic to set up a clinical trial.
"We now need to look to see if this works with patients as well as ensure safety," commented Spanswick, Medical Leader of the Calgary Pain Program. "We are at the very early stages of organizing clinical research. It will be some time before this research gets off the ground and we look forward to continuing collaboration with the HBI on this and other areas of research."
"Opioids are the pharmacological cornerstone for treating chronic pain in a large variety of diseases," said Trang. "Understanding why opioid withdrawal occurs and how to alleviate it, is of critical importance in improving pain therapy and may have implications for substance abuse in opioid addicts. The potential impact is immense."
If you are curious to learn more about what withdrawal is like for an addict, check out the video below from STAT Health & Medicine News for a perspective on the experience.
Sources: AAAS/Eurekalert! via University of Calgary, Nature Medicine