A new clinical trial at the University of Calgary is exploring the potential of probenecid, a well-tolerated drug typically used for gout, to alleviate the debilitating symptoms of opioid withdrawal. The trial is based on recent findings shedding light on the communication between the brain and spinal cord during opioid withdrawal.
Dr. Lori Montgomery, pain clinician and clinical lead for the opioid tapering study, notes the limited options currently available to support patients reducing their opioid intake, emphasizing that "withdrawal symptoms can be crippling." The trial aims to address this unmet need by repurposing probenecid, a drug already known for its safety profile.
The research underpinning this trial was conducted by Dr. Tuan Trang and his team, who discovered in 2017 that probenecid effectively reduces opioid withdrawal in rodents. More recently, they elucidated the mechanism by which the drug disrupts the abnormal brain-spinal cord communication that occurs during withdrawal. Their findings were published in Nature Communications.
Neurobiological Basis
"During withdrawal, that center in the brain is hyperactive, contributing to the body's reaction during withdrawal," explains Trang, principal investigator of the study. This hyperactivity is linked to the autonomic system, which regulates the body's fight-or-flight response. Probenecid appears to modulate this hyperactivity, potentially mitigating the severity of withdrawal symptoms.
Clinical Trial Design
The pilot 12-week randomized control trial is recruiting individuals aged 18 and over who are motivated to reduce or discontinue their opioid use. Participants will receive probenecid at doses lower than those typically used for gout. "We start with doses that are lower than what has been used for gout. If the person is tolerating the drug well, we start to taper the opioids they are taking and measure whether they experience withdrawal," says Montgomery.
Opioid Dependence and Current Landscape
Montgomery highlights the rapid onset of physical dependence on opioids, noting that it can occur within a couple of weeks. She also points out that Canada has one of the highest rates of opioid prescription globally. The trial represents a significant step towards providing better support for individuals seeking to reduce or eliminate their opioid use.
Significance of the Research
Trang emphasizes the importance of translating scientific discoveries into potential treatments for complex societal issues, highlighting the collaborative effort of the research team. The study was supported by grants from the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), and Campus Alberta Neuroscience.
