The opioid crisis is a serious public health issue in the United States. Synthetic opioids such as fentanyl have contributed significantly to this crisis. However, recent samples have shown the presence of xylazine, a veterinary tranquilizer, with fentanyl. Xylazine was found in almost 80% of fentanyl samples in Maryland between 2021 and 2022. Naloxone is an FDA approved treatment currently used to treat fentanyl overdoses, but naloxone cannot reverse the effects of xylazine. Thus, xylazine is exacerbating the risk of fatality due to opioid use, in particular the opioid induced respiratory depression (OIRD). In April, 2023, the White House designated fentanyl combined with xylazine as an emerging threat to the United States.
Researchers at GW found that intranasal oxytocin, also an FDA approved agent can be repurposed to reverse the respiratory depression induced by opioids such as xylazine-laced fentanyl in rats. Animals that received oxytocin had 20% higher breathing frequency and 75% reduced apneas compared to the untreated animals.
Figure. Three groups of male Sprague Dawley rats (n=8) were administered intraperitoneal (IP) fentanyl and xylazine either alone or in combination. 10-15 minutes after treatment, xylazine, like fentanyl, significantly elicits respiratory depression. Intranasal Oxytocin administered simultaneously (PREVENTION paradigm) with fentanyl, xylazine either alone or in combination significantly reversed OIRD and increased minute ventilation, breathing frequency and tidal volume, compared to untreated controls. Also, Oxytocin significantly diminished both the incidence reduction, duration of apneas and hypopneas evoked by fentanyl. Respiratory function was quantified using a whole-body plethysmography system in unrestrained and freely moving animals.
Intranasal oxytocin has potential to mitigate opioid induced respiratory depression (OIRD) in an emergency or clinical setting. In addition, GW has a related technology for treating opioid-induced respiratory depression with intranasal leptin.
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