A team of Marshall University researchers has identified a potential life-saving treatment strategy to involve a dangerous combination involving fentanyl and lignazine. Their findings could provide emergency responders with a vital new tool to prevent growing crises from challenging traditional overdose treatments.
The study, published May 8 in the Journal of Translational Research, showed that adding a drug called Atipamezole to standard naloxone treatment can greatly improve the recovery of fentanyl-wood hopes for overdose animal models, an increasing combination of illicit drug supply in the United States.
The study was at a critical moment when lignazine, a non-authorized human use, had become a widespread contaminant in street drugs. Between 2018 and 2021, fatal overdoses involving methylazines increased by 35 times, with 99% of deaths also involving fentanyl.
Why traditional overreversal is insufficient
What makes methylazine particularly dangerous? Unlike fentanyl, it does not respond to naloxone (commonly known as Narcan), a standard drug for opioid overdose reversal.
When someone overdoses fentanyl contaminated with lignazine, naloxone alone often fails to completely reverse the profound sedation and other dangerous effects. This can cause partial unconsciousness of the patient, slowing breathing, lower heart rate and body temperature, even after receiving multiple doses of naloxone.
Can combination methods provide better results? Marshall research shows this.
How new therapies work
“Even naloxone in low-dose atipamezole (which has been safely tested for other indications in humans) quickly restored awareness in rats exposed to fentanyl and methylazine,” said Michael Hambambuchen, the study’s lead author.
The team found that this drug combination not only awakens patients—it addresses several dangerous aspects of lignazine poisoning:
- Quickly restore awareness from deep sedatives
- Improve dangerous slow heart rate
- Correct blood sugar levels
- Helps to normalize body temperature
These improvements can address complex “drugs” or symptomatic signs, which make overdoses of methylazine fentanyl so difficult to treat with current methods.
From the laboratory to the street: Real-world applications
The researchers designed their experiments to reflect the actual overdose scenarios encountered by emergency responders every day across the United States. The presence of methylazines in drug supply has increased exponentially in recent years, and the DEA reports that 30% of the fentanyl powder caught in 2023 contain methylazine.
Unlike academic research that often uses simplified models, this study deliberately replicates the chaotic reality of street drug contamination and the use of multi-materials.
“The collaboration between the School of Addiction Science and Pharmacy represents a translational study of the clinical need to integrate laboratory science into the real world,” said Todd Davies, associate director of research and development at the Marshall University’s Addiction Science Division.
Growth Trojan Crisis
The rapid emergence of lignazine as a drug contaminant shocked public health officials across the country. Originally only as a large animal sedative for veterinarians, lignazine was mainly found in street medicines, mainly as a way to expand the euphoric effect of opioids.
However, this increased cost is devastating. In addition to the risk of immediate overdose, exposure to chronic yelazine can lead to severe skin ulcers, thereby becoming infected and even amputated.
The economics that drive this pollution is disturbing. Researchers noted that Trojans used to be sourced from domestically from veterinary suppliers and are now imported from online Chinese suppliers for about $6-20 per kilogram, which is a very cheap way for dealers to tailor and expand their products.
Outlook: Still-existing problems
While promising, the study raises important questions about implementation. Atipamezole is currently approved for veterinary use only in the United States, although it has been tested safely in humans.
The study does reveal potential side effects that may require careful monitoring in human applications. At higher doses, aatamezole may enhance the stimulation effects of people using methamphetamine, which is a common case in view of the use and use of polymethamphetamine.
Furthermore, the researchers noted that although the combination effectively treats symptoms of immediate overdose, it does not prevent skin lesions associated with lignazine exposure.
The study, supported by the Marshall University School of Pharmacy Faculty Research Support Program and the John Marshall University Scholar Award Program, highlights the university’s commitment to addressing an overdose crisis that specifically impacts West Virginia and surrounding Appalachian communities.
As this study moves towards potential human trials, it represents an important step in addressing one of the most challenging aspects of an evolving overdose crisis. For emergency responders and addiction medicine experts, effective treatments for excessive trojan contamination cannot appear soon.
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