A potential Fentanyl + Xylazine antidote

Scientists at Marshall University have identified a promising new approach to reversing overdoses involving the dangerous combination of fentanyl and xylazine. Their research, published in *The Journal of Translational Research*, suggests that combining naloxone with atipamezole could provide a more complete reversal than naloxone alone, offering hope for those affected by this escalating crisis.

Read the full article at https://www.paperleap.com/blog/articles/a-potential-antidote-for-the-fentanyl-xylazine-crisis-0cccun

Episode Transcript

Speaker 1 (00:00):
Welcome to the paper Leap podcast, where a science takes
the mic. Each episode, we discuss cutting edge research, groundbreaking discoveries,
and the incredible people behind them, across disciplines and across
the world. Whether you're a curious mind, a researcher, or
just love learning, you're in the right place before we start.

(00:21):
Don't forget to subscribe so you never miss an insight.
All the content is also available on paperleap dot com. Okay, ready,
let's start. In recent years, fentanyl has become a household word,
not because anyone wants it to be, but because it
has reshaped the opioid crisis. This synthetic opioid is so

(00:44):
potent that just a few grains can be fatal. Naloxone,
better known by its brand name Narcan, has been the
lifeline that first responders, families, and communities rely on to
pull people back from the brink of overdose. But a
new player has entered the scene. Xylazine. A veterinary sedative

(01:04):
sometimes called trenk, originally developed to calm horses and other
large animals, xylazine has found its way into the illicit
drug supply, often mixed with fentanyl. In twenty twenty three,
the US Drug Enforcement Administration reported that nearly a third
of seased fentanyl powder contains xylazine. Tragically, this dangerous combination

(01:26):
is making overdoses harder to reverse. The US recorded over
one hundred thousand overdose deaths last year, with fentanyl involved
in most of them. Adding xylosines to the mix has
created what some call a crisis within a crisis. Not
only does it raise the risk of death, but it
also causes horrific skin altars and people who inject it,

(01:48):
and makes overdoses more stubbornly resistant to naloxone. That's where
a team of scientists from Marshall University in Huntington, West
Virginia comes in. In a new study published in the
Journal of Translational Research, researchers Yosna Yalakala, Wesley R. Tacket,
Melinda E. Varney, Todd H. Davies, and Michael H. Hambuchen

(02:10):
tested a potential new antidote strategy. Their idea use a
two drug rescue approach, pairing naloxone with a lesser known
drug called atopamezzo. When naloxone is given during a fentanyl overdose,
it blocks the opioid's grip on the brain and allows
the person to breathe again, But naloxone doesn't touch silazine.

(02:32):
That means in a fentanyl xylazine overdose, a patient may
regain some breathing, but remain deeply sedated, with dangerously slowed
heart rate, low blood sugar, and unstable body temperature. In
other words, nalaxav alone is like fighting a two headed
dragon with a sword that only cuts one head. The
other head xylazine keeps roaring. This is where atapamezole comes in.

(02:56):
Already used in veterinary medicine to wake up animals after
ana nostiesia, atopamezole works by blocking the same receptors xylazine activates.
The Marshall University team wondered could combining naloxone and atopamezole
fight both fentanyl and xylozine at once. The researchers carried
out their experiments in male sprague doorly rats, a common

(03:18):
laboratory model. They first determined how much fentanyl and xylazine
together would cause severe sedation, mimicking the heavy nod seen
in humans after using contaminated drugs. When they gave naloxone alone,
the rats perked up of it but remained sluggish and
dangerously affected. But when the team added atipamesole, sedation lifted

(03:39):
dramatically and rats giving the combination became alert much faster. Also,
the results showed that slow heart rate reversed. In fact,
at higher doses, atopamezole normalized the heartbeat. Another effect was
that atopamesol corrected high blood sugar, which is a side
effect of xylazine that can stress the body. And finally,

(04:01):
low body temperature improved, though not completely. In short, the
naloxone at pamezzo duo worked far better than naloxone alone.
The team also looked at what happens when methamphetamine, another
drug often found in street mixtures, enters the picture. They
found that at lower doses, at pamezzo didn't make meths

(04:22):
jittery effects worse, but at higher doses it could amplify
stimulant driven hyperactivity. That means careful dosing would be essential
if this ever moves to human treatment. The findings from
Marshall University don't mean we found or ready made PTERR,
but they offer a proof of concept. If you want
to fight a two drug overdose, you may need a

(04:44):
two drug reversal. At to Pamezzo is not currently approved
for human use, its license only for animals, but because
it has already been studied in small human trials for
other purposes and was generally well tolerated, researchers are cautious optimistic.
This study and its results bring the hope that in

(05:04):
the future, when a paramedic encounters someone who is overdosed
on fentanyl laced with xylazine, they don't just have n
alexone in their kit. They also have a second medication
that wakes the patient, fully stabilizes their heartbeat, and prevents
dangerous lingering sedation. That future isn't here yet, but thanks
to this study, it feels a little closer. Science can't

(05:28):
solve the overdose crisis alone. Prevention, treatment, and harm reduction
are all essential, but better rescue tools could mean thousands
more lives saved. That's it for this episode of the
paper Leaf podcast. If you found it thought provoking, fascinating,
or just informative, share it with the fellow science nerd.

(05:50):
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