Federal law enforcement officials in Arkansas dealing with a wave of fentanyl use that continues unabated have expressed concern about another, potentially even deadlier wave that has emerged — fentanyl mixed with xylazine, a powerful large animal tranquilizer.

According to the Centers for Disease Control and Prevention, xylazine is a non-opioid sedative or tranquilizer approved for use only in animals. However, it is increasingly showing up in illicit drugs such as fentanyl, heroin and cocaine in order to increase the potency of the drug it is mixed with or as a cutting agent to increase the weight of the drug and thus, increase the profits — or both.

Side effects in humans include sedation, difficulty breathing, dangerously low blood pressure and slowed heart rate, as well as an increased risk of death by overdose. Another side effect is skin ulcerations that can rapidly worsen and, without treatment, require amputation.

Also, because xylazine is a non-narcotic sedative, naloxone, used to reverse an opioid overdose, has no effect on the tranquilizer.

First synthesized in 1962 by Bayer Pharmaceutics, clinical trials investigating xylazine for use in humans were terminated due to the severe, life-threatening side effects, according to an advisory issued by the Drug Enforcement Administration in May. In March, the DEA reported that xylazine-laced fentanyl has been seized in 48 states and that in 2022, about 23% of fentanyl powder and 7% of fentanyl pills seized by the agency contained xylazine.

According to the CDC, 107,735 Americans died between August 2021 and August 2022 from drug overdoses, with 66% — 71,000 — of those deaths involving synthetic opioids like fentanyl. The Sinaloa and Jalisco cartels in Mexico, using chemicals largely sourced from China, are primarily responsible for the vast majority of the fentanyl that is being trafficked in communities across the United States.

Fentanyl use in Arkansas has become so prevalent that the U.S. Attorney’s Office for the Eastern District of Arkansas has prioritized prosecutions of fentanyl offenses on a par with violent gun crimes and child sexual abuse prosecutions.

Fentanyl is a synthetic opioid that is up to 50 times stronger than heroin and 100 times stronger than morphine and is a major contributor to overdoses, both fatal and nonfatal, in the U.S., according to the CDC. Pharmaceutical fentanyl, the agency said, is prescribed by doctors to treat severe pain, especially after surgery and for advanced-stage cancer, but illicit fentanyl, which is distributed through illegal drug markets for its heroin-like effect, is often added to other drugs because of its extreme potency or made into counterfeit pills that look like pharmaceutical drugs. It is that potency, the CDC said, that makes fentanyl so dangerous.

And the introduction of xylazine, said the CDC, makes fentanyl even cheaper, more powerful, more addictive and more dangerous. Data in a CDC report released last month indicated that in the U.S., xylazine-involved overdose deaths reported in 2018 totaled 102. By 2021, just three years later, that total had risen to 3,468. Although that number is dwarfed by the total reported overdose deaths attributed to fentanyl alone, the rapid rise is concerning to law enforcement.

The dangers of xylazine and the rapid rise in illicit use of the drug prompted the Biden administration to designate the drug as an emerging drug threat in April and to issue a national response plan in July to address the threat. Among other things, the response plan calls for standardized forensic testing practices, development of rapid clinical tests and development and deployment of a test to detect xylazine in drug samples at all levels in the supply chain, from wholesale seizure quantities to retail levels within communities.

Dr. Michael Mancino, program director of the Center for Addiction Services and Treatment at UAMS, said currently UAMS has no documented cases of overdose involving xylazine-laced fentanyl, which he attributed both to the drug not yet having a firmly established presence in the state and the current lack of clinical testing ability.

“Part of the problem is we don’t have drug tests to detect xylazine as part of our typical panel of drug screen results,” he said. “It’s being identified at the crime lab for people undergoing autopsy but even then, you’re getting a limited number of people that end up at the crime lab because they just can’t do autopsies on every single person who may have died of an overdose. … But we’re not testing for xylazine as part of our drug screen panel.”

Fentanyl overdoses, however, remain at alarming levels.

“If we have 10 admissions for treatment, probably eight of them are using fentanyl,” he said. “Almost everything people are using in Arkansas is fentanyl and that’s been going on for five years now and it just becomes more and more prevalent.”

Mancino said right now, he is not aware of any plans to establish xylazine testing at UAMS, primarily because of the nature of the drug itself, which has no approved use for humans.

“Part of the issue is there’s not really anything we can do for treating it so [testing] doesn’t really provide useful information in terms of directing treatment,” he said. “There’s no medication to reverse the effect … because it doesn’t work at the view opioid receptor like fentanyl does so we don’t have any medications that could prevent or reverse it’s effects.”

Even when a person is experiencing an overdose of fentanyl laced with xylazine, however, Mancino said naloxone treatment to reverse the fentanyl effects should still be administered.

“If you reverse the effects of the fentanyl, the xylazine by itself may not be sufficient to result in an overdose,” he said.

Dr. Lynn Beach, a veterinarian with a practice in East End, said a worry he has about xylazine is the possibility that the legal status of the drug — which is currently not a controlled drug under federal law — could change. To date, although the federal government has not moved to make xylazine a controlled drug, five states have passed legislation doing so to varying degrees, and four others are considering it. Arkansas is not one of those states.

Such a designation, he said, could create headaches for veterinarians, such as added costs and security measures that have not been needed in the past. He agreed, however, that the drug is dangerous when not used properly and he said there is no proper use for it in humans.

“It’s highly toxic for people because it slows and even stops the respiratory system and causes a slowing of the heartbeat,” he said. “In people who already have heart issues it could cause fatal cardiac side effects … I couldn’t even tell you a dose that would be safe for humans.”

Jarad Harper, assistant special agent in charge of the Little Rock DEA office, said it’s hard to determine how long xylazine-laced fentanyl has been in Arkansas, mainly because testing for the animal tranquilizer wasn’t conducted in the state until authorities became aware of its use.

“We are starting to see more of it because the labs are aware,” he said.

Harper said the emergence of xylazine as a cutting agent in illicit fentanyl is driven by the same forces that triggered the transition from pharmaceutical opioids on the black market to fentanyl-based counterfeit drugs — profit. Just as fentanyl costs much less than pharmaceutical oxycodone but is far more potent, xylazine costs less than illicit fentanyl and provides a significant boost in potency.

“[Fentanyl is cheaper for the dealers and users like the high better,” he said. “Make no mistake, from the street dealers to the Mexican cartels, it’s all about the money, and xylazine fits that business model.”

Generally, the precursors for illicit fentanyl, Harper said, are shipped from China to Mexico where the drug is manufactured and then shipped to the U.S. both in powder form and as counterfeit pills made to look like legitimate pharmaceuticals and sent to the U.S. utilizing just about any method of transport with space to conceal illegal cargo.

The most popular counterfeit pills in Arkansas and throughout the south, Harper said, are fake 30-milligram oxycodone tablets — blue in color with an M pressed into one side and scored on the other with a 30 pressed above the score — that users take orally or crush up to be injected or snorted.

“Just looking at the DEA cases alone here in Arkansas with our state and local partners,” he said, “I’d say we’ve seized 450,000 of those in the last couple of years.”

Assistant U.S. Attorney Chris Givens, who handles many of the federal fentanyl prosecutions in Arkansas’ Eastern District, said the emergence of xylazine-laced fentanyl appears to be on the rise but agreed that it’s hard to pin down just how widespread its use has become. He said the use of the drug as an additive to fentanyl or heroin first emerged on the East Coast, “and matriculated across the country.” But, he said, understanding the true scope of the problem is a constantly shifting target.

Field drug-testing kits, he said, are engineered to detect the presence of a wide range of drugs encountered by law enforcement, such as methamphetamine, fentanyl, heroin, marijuana and other substances, but cannot gauge the purity of the drug or identify other additives such as xylazine. That, he said, requires more sophisticated laboratory analysis, which can take between six months and a year for completion of the results.

“We are just now getting lab reports positive for xylazine,” Givens said. “Based on those reports, the first known cases of xylazine in fentanyl here showed up in the summer or fall of 2022.”

According to the state Crime Laboratory, between 2019 and 2022, it has identified xylazine in a total of 64 seized drug items, with two identified in 2019, five in 2020, 10 in 2021 and 47 in 2022.

An important component of drug interdiction efforts in the state is supplied by Arkansas State Police, which, according to state police Communications Director Cindy Murphy, seized 65.84 pounds of fentanyl worth nearly $12 million in 2022, with 56 pounds of that total seized in September 2022 alone. Murphy said enforcement is complex because fentanyl transport methods continue to evolve. Fentanyl, she said, in powder and in counterfeit pill form, is shipped primarily from states that border Mexico, coming into and through the state by drug couriers known as “mules,” as well as other, widely varied smuggling methods.

“We find fentanyl in hidden compartments built into vehicles and stashed inside spare tires, seats and car doors,” Murphy said in an email, “and it is also making its way into Arkansas by passenger bus and airplanes, inside luggage or hidden on passengers. Many times, fentanyl is mailed or shipped using the U.S. Postal Service, UPS or FedEx.”