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Researchers discover gout treatment drug prevents symptoms of opioid withdrawal
Old drug holds great promise for important new use.
Researchers at a Canadian university have discovered that a decades-old drug used primarily to treat gout can reduce or eliminate the debilitating symptoms of opioid withdrawal.
So far, the effects of the drug have only been tested in the lab on rodents. But those lab results are so promising that the researchers are working towards clinical trials on humans, a necessary step before the drug can be used in the real world.
The drug, called probenecid, also sold under the brand name Probalan, has been around for at least 50 years. It increases uric acid excretion in the urine to treat gout and related conditions caused by elevated uric acid in the body.
Neuroscientist Tuan Trang, PhD, and his research team at the University of Calgary’s Faculty of Veterinary Medicine (UCVM) and Hotchkiss Brain Institute (HBI), were exploring the underlying cause of opioid withdrawal symptoms at the cellular level, something that has never been fully done before.
They discovered that pannexin-1, one of a group of proteins called pannexins, is found throughout the body and, more importantly, in the brain and spinal cord, and is at least partly responsible for producing opioid withdrawal symptoms.
When they realized that the drug probenecid directly targets pannexins, including pannexin-1, the question was obvious:
Did this mean probenecid could block withdrawal symptoms?
Withdrawal not well understood
Before Trang and his team began their investigations into opioid dependence and withdrawal, the cellular mechanisms of withdrawal were not well understood. Finding a therapeutic drug that could eliminate withdrawal pain had eluded scientists for decades.
“The focus of much of the research so far has been on neurons themselves,” Trang explained. “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.”
Once they identified the pannexin-1 connection, the researchers tested probenecid, because it’s known to have non-selective pannexin-1 blocking effects. As we said earlier, it’s an old, widely approved and well-known drug, has few side effects and is relatively inexpensive.
“Opioid withdrawal is aversive, debilitating and can compel individuals to continue using the drug in order to prevent these symptoms,” Trang said. “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.”
Equally importantly was the fact that they also demonstrated that probenecid does not interrupt the pain relief offered by the opioids.
Important implications for therapy
“This is an exciting study which reveals a new mechanism and a potential therapeutic target for managing opioid withdrawal,” says Canadian pain researcher Dr. Michael Salter, Chief of Research at The Hospital for Sick Children, 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.”
Trang and team are working with Dr. Lori Montgomery and Dr. Chris Spanswick to carry out clinical trials on humans at Calgary’s Chronic Pain Center, part of the Province of Alberta’s Health Services administration.
“We now need to look to see if this works with patients as well as ensure safety,” Spanswick, the Medical Leader of the Calgary Pain Program, said. “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,” says 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.”
The side effects of withdrawal are what make it so difficult for many people to overcome their dependencies. Such a drug could have a big impact on the treatment of opioid dependence and addiction. There are very few medically supervised programs anywhere that offer significantly reduced withdrawal symptoms like do here at Novus Medical Detox Center.
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