Opioid overdoses remain a critical public health issue, with fentanyl continuing to be the leading cause of opioid-related deaths in the United States. The most common treatment, naloxone, works by blocking opioid receptors in the brain, quickly reversing the overdose but also causing intense withdrawal symptoms. People who survive an overdose often describe the experience as traumatic, with symptoms like severe pain, vomiting, and agitation — which can make them reluctant to seek help.
A research team from the Moron-Concepcion Lab at WashU Medicine has discovered a promising new way to treat opioid overdoses without triggering severe withdrawal symptoms. Their study, “Peripheral opioid receptor antagonism alleviates fentanyl-induced cardiorespiratory depression and is devoid of aversive behavior,” published in eLife on April 1, shows that targeting opioid receptors outside the brain can effectively reverse overdose effects without causing the intense discomfort typical of current treatments.
Led by Jose Moron-Concepcion, PhD, and Brian Ruyle, PhD, they tested a drug called naloxone-methiodide, which is similar to naloxone but does not cross the blood-brain barrier and instead focuses on the body. In the study, they found that naloxone-methiodide could effectively reverse fentanyl-induced respiratory depression without triggering the severe withdrawal symptoms associated with naloxone.
“These findings have significant potential impact given that fentanyl is still the major driver for opioid-related deaths in this country,” said Moron-Concepcion. “Our new therapeutic approach shows promise in reducing the adverse effects typically seen with naloxone, offering a safer way to reverse overdoses.”
This discovery opens up the possibility of safer and more humane overdose treatments, helping to reduce the fear and stigma that often prevent people from seeking life-saving care.