Xylazine bottle

Photo by Dr. Wendy Smith Wilson

A go-to animal sedative used by many large animal and wildlife veterinarians, xylazine (pictured) has drawn the scrutiny of lawmakers and law enforcement for its role in a growing number of opioid overdose deaths in the United States.

Multiple times a day, Dr. Victoria Bentley reaches for the drug xylazine. "It's my primary go-to for sedation for anything that's potentially going to be short or not really painful," Bentley, a veterinarian who works with horses in Western New York, told the VIN News Service. So she's concerned that lawmakers in her state and others are considering classifying the veterinary sedative as a controlled substance due to its skyrocketing illicit use by people as a street drug. 

She worries the classification, which could come with increased security and documentation requirements, will make using xylazine too cumbersome and inefficient for farm visits involving multiple horses.

If xylazine became a controlled substance, she would have to unlock a drug safe every time she needed it and log every single injection in every horse. Instead, she said, she might turn to alternatives that are less well-suited to quick treatments like floating sharp teeth, suturing wounds and taking X-rays. She explained that if she used a related drug, which wears off more slowly than xylazine, someone would be required to watch the patient for up to an hour after treatment — a treatment that, alone, might take just a few minutes.

Hoping to persuade legislators not to pass laws that make it difficult for veterinarians to use xylazine, she said, "I sent letters to everybody remotely votable."

Bentley's efforts are not singular. Other veterinarians and professional organizations are urging lawmakers to find the middle ground between protecting the use of xylazine in veterinary patients and effectively curbing illicit use.

A White House announcement on Wednesday designating fentanyl combined with xylazine as an "emerging drug threat" will likely put additional pressure on those efforts. It is the first time the White House Office of National Drug Control Policy has ever identified a substance for that designation, and it requires the administration to develop a wide-ranging response for prevention, treatment and supply reduction.

OK for some animals but not humans

A non-opioid, xylazine has been an essential veterinary tranquilizer, sedative, analgesic and muscle relaxant with potential use in all types of practice, but especially large animals and wildlife. It is also used in cats and dogs, although less commonly.

Increasingly in recent years, drug traffickers and dealers are combining low-cost xylazine with fentanyl, cocaine, benzodiazepines and heroin to enhance and extend their psychoactive effects.

It makes for a dangerous cocktail. Xylazine is not approved for use in humans due to hazardous side effects, including severe sedation, low blood pressure and slow heart rate. Experts say that xylazine might increase the chance of fatal overdoses when combined with drugs like fentanyl because it can exacerbate the respiratory depression that opioids cause. Injected drug mixtures containing xylazine can lead to gruesome wounds, as well.

Worse yet, naloxone, a drug used to reverse opioid overdoses, is ineffective against xylazine.

Supplies of xylazine for the street-drug market apparently come chiefly, if not exclusively, from non-veterinary sources. A U.S. Drug Enforcement Agency Joint Intelligence Report from October 2022 said that xylazine is readily available from internet sites, often with no association with the veterinary profession. The report refers to Chinese suppliers selling online. A 2022 Illinois Department of Health memorandum stated that there is no indication that xylazine is being diverted from veterinary providers, clinics or pharmacies.

Making xylazine a controlled drug at the federal level will help the DEA track any diversion from legal channels, which is one of its functions under the Controlled Substances Act. The DEA enforces CSA rules for the manufacture, importation, possession, use and distribution of certain potentially dangerous substances. It classifies drugs in one of five schedules, according to how dangerous they are, their potential for abuse and addiction, and whether they are deemed to possess medical value. The most dangerous substances with the greatest restrictions and no accepted medical value are Schedule I; the least dangerous with medical value are Schedule V.

Lawmakers crack down

Three states already have classified xylazine as a controlled substance. Florida was first, making it a Schedule I drug in 2016. West Virginia followed this year, in late March, classifying it as Schedule IV. Around the same time, Ohio's governor by executive order directed the state pharmacy board to immediately classify it as Schedule III.

At least four more states are considering legislation:

• Illinois has two slightly different bills: SB 2089, which would make xylazine a Schedule I drug; and HB 3873, which would make it Schedule II.
• New York, through SB 5439 and AB 5914, would make xylazine Schedule III.
• Louisiana, through HB 106, would designate the drug as Schedule II.
• Rhode Island, through HB 5922 and SB 738, would classify xylazine as Schedule V. 

None of the bills directly addresses veterinary use. The same is true of the laws in Florida and West Virginia. Only the governor's executive order in Ohio acknowledges the use in animal patients. It provides a temporary enforcement waiver for veterinary clinics. They have until June 30 to obtain a Category 3 Terminal Distributor of Dangerous Drugs license, which will allow them to continue ordering xylazine from a licensed wholesaler. No DEA registration is required.

By contrast, a bill sponsored by a bipartisan group of U.S. senators and representatives, the Combating Illicit Xylazine Act, introduced last month, provides a veterinary carve-out. While the proposed law would make manufacturing, distributing, dispensing and possessing of illicit xylazine subject to Schedule III penalties, the legitimate importation, manufacture and dispensing of xylazine for nonhuman species would not be held to the restrictions and requirements of scheduling. Manufacturers and distributors would, however, be obligated to report sales to the DEA.

A precedent exists for making a distinction between illicit use in humans and licit use in veterinary patients.

Dr. Heather Lindell Tally, a clinical pharmacology consultant for the Veterinary Information Network, an online community for the profession and parent of VIN News, pointed out that anabolic steroids are Schedule III when used in humans. Nonhuman animal approved anabolic steroids, such as ones used in beef cattle, are not regulated as controlled substances. However, if a cattle product is used in a person, the law regards it as a Schedule III substance because the anabolic steroid is being used outside of its intended veterinary purpose.

In a March 28 blog post, the American Veterinary Medical Association gave its backing to the federal xylazine legislation. "It strikes the right balance of protecting our communities while preserving veterinary access to this critically important animal drug," AVMA president Dr. Lori Teller is quoted as saying. The blog post says the AVMA spent weeks working with lawmakers and other stakeholders on the bill.

In an open letter posted on the American Association of Bovine Practitioners' Facebook page, Executive Director Dr. Fred Gingrich said his organization worked closely with the AVMA on federal xylazine legislation. 

Gingrich said restricting the drug would have the potential of pushing it out of the market.

He wrote: "There are currently two manufacturers (Akorn previously made the drug but dissolved a few weeks ago, leaving us with two). Only one of those manufacturers has a DEA facility. With a small market drug like xylazine, the risk of losing the product if it was a scheduled drug was very concerning."

Gingrich also wrote that he has worked with several states that are trying to restrict the use of xylazine but that it "is nearly impossible to keep ahead of this as legislators try to do something at the state level for a variety of reasons without understanding the impact it will have on cattle veterinarians and producers."

AABP's main message, he added, "is that we need access to the drug and to be able to use it in our normal course of practice." He urged practitioners to do everything they can to prevent diversion and keep accurate records of use, to demonstrate good stewardship.

Dr. Jack Kottwitz, an assistant professor in both large animal clinical sciences and pharmacology and toxicology at Michigan State University College of Veterinary Medicine, described the federal bill, in an email to VIN News, "as a logical halfway point."

But he said discussions leading up to the compromise fed into confusion about the status of xylazine. "Some of that has been driven by mistaken information on the internet …" he said. "Some of that is the general concern that this compromise, which may work, will suddenly be changed if there is a large bust of xylazine-cut opioids or high-profile deaths."

Kottwitz also pointed out that wildlife veterinarians will see an outsized impact if xylazine is restricted without animal-use exceptions. "It is often overlooked by those working with domestic animals, but xylazine is labeled for administration to Cervidae (fallow deer, mule deer, sika deer, white-tailed deer and elk, as examples) making it a drug that research project and wildlife veterinarians will reach for first, compared to other alpha-2s that are not labeled for Cervidae."

(Xylazine is in a class of compounds known as alpha-2 agonists. Related drugs include dexmedetomidine and detomidine.)

Stricter regulation in Florida

Lindell Tally, the clinical pharmacologist, said making xylazine a Schedule III substance, the same as the anesthetic ketamine, seems like an appropriate level of restriction. 

If the AVMA-endorsed bill passes, Lindell Tally said she hopes states that have classified xylazine as Schedule I or II will change their laws to "harmonize" with the federal standard. 

This is especially important in the case of Schedule I controlled substances, a classification for substances that have no currently accepted medical use. When Florida designated xylazine as Schedule I, it did not address the veterinary use of the drug, creating a gray zone.

"All the veterinarians down there would be locked up if it was intended for them, but it's not — even though you can't find this anywhere [in the law], because I've looked," Lindell Tally said. "It is only by word of mouth that people say that if it is used outside of the scope of the intent, meaning veterinary use for a veterinary patient, then that misuse becomes a Schedule I, and then they prosecute it like a Schedule I product."

Dr. Rick Sutliff, past president of the Florida Veterinary Medical Association, confirmed that Florida law does not make any reference to the veterinary use of xylazine. In fact, he told VIN News, the association didn't realize until six months ago that the state regards it as a controlled substance. He and colleagues learned about it when policymakers in Washington D.C. brought up Florida as a possible model for national legislation.

Sutliff said when Florida made xylazine a Schedule I drug in 2016, it was sort of "slipped into" the legislation with no alert to the profession. Zoo and cattle veterinarians, predominantly, "were just going about their business using xylazine as they always would," he added.

Looking at the law, Sutliff said that he sees "nothing that excludes veterinarians." However, he said legal counsel at the Florida Department of Agriculture told the state VMA it was fine for veterinarians to use xylazine.

"That's what we're stuck with," he said.

If the Combating Illicit Xylazine Act passes, Sutliff said, the VMA will petition to change Florida’s law to match the federal law. He added that provisions in state law should make this a fairly simple process.