We have all been taught to be wary of popular press reports about the effects of new illicit drugs. More often than not, they are sensational and unsupported by scientific data.
A kerfuffle broke out a few years ago over krokodil, the homemade designer opioid originating in Russia and synthesized by mixing codeine with dangerous chemicals such as red phosphorus and lighter fluid. He was invariably portrayed as a flesh eater.
Do you remember all the cases of necrotic limbs and gangrenous ulcers we saw in the 2010s that were caused by krokodil? Of course not. The National Institute on Drug Abuse investigated because reports alleged its occurrence in parts of the United States, but no cases were ever identified. (May 2015; https://bit.ly/3s8KohI.)
Xylazine not found
The press has recently become obsessed with specific adulterants that appear with increasing frequency in illicit drugs. As usual, many stories about these drugs are based primarily on interviews with users and politicians, not medical toxicologists, and often the media are wrong.
The headline, “Strong sedative in Philadelphia drug supply causes severe injuries and agonizing withdrawals,” appeared in The Philadelphia Investigator on April 10, 2022. The substance in question was xylazine, a veterinary drug typically used as a sedative, pain reliever, and muscle relaxant in large animals like horses and deer. Xylazine was studied for use in humans, but was found to be impractical due to side effects such as severe hypotension and respiratory depression. It is not classified as a federally controlled substance but cannot be purchased legally in the United States without a veterinary license.
Xylazine has been identified with increasing frequency in recent years in the blood and urine of patients who use “heroin” and other opioids. These patients were almost always positive for fentanyl as well. This association has been documented in several parts of the country, including Philadelphia, Connecticut, and Cook County, Illinois. (MMWR Morb Mortal Wkly Rep. 2022;71:503; https://bit.ly/3MI42ZF.)
Xylazine is not an opioid or benzodiazepine but an alpha-2 agonist with a similar action to clonidine. Potential adverse effects include initial hypertension due to peripheral vasoconstriction, followed by hypotension, bradycardia, altered mental status, and respiratory depression.
Anecdotal reports of soft tissue damage have been associated with xylazine exposure, as suggested by the Applicant title, but the keyword is “associated”. I could find no source establishing a direct causal relationship or persuasive mechanism that would link the drug to necrotic or gangrenous skin lesions or rule out other causes of soft tissue damage such as infection. I also haven’t been able to find any convincing reports of xylazine withdrawal.
Xylazine has been a known adulterant in opioids sold on the street since the early 2000s, when it was first identified in Puerto Rico, where it is called “anestesia de caballo” (horse anesthesia). Anecdotal reports suggest that addicts sometimes seek out preparations containing xylazine because it prolongs the typical short duration of action of fentanyl and creates an experience seemingly similar to that produced by heroin. The effects of xylazine last about four hours in animals.
Another headline, this time from Fox News on March 29, read, “Florida Warns of New Drug Far More Potent Than Fentanyl.” This article focused on the drug isotonitazene, a synthetic opioid developed in the 1950s but never marketed. The fact that it has been identified in the systems of drug users who have overdosed since 2019 is proof that illicit drug chemists scour old research papers and patent applications for potential substances that may be manufactured and distributed but not yet specifically restricted.
The Fox News article makes several sensational and false claims about isotonitazene. It quotes Florida Attorney General Ashley Moody as saying the drug is “so potent it can kill simply by coming into contact with someone’s skin or being accidentally inhaled.” This same nonsense of death by skin contact has been rumored for years regarding fentanyl, but it is not true.
The article also claims that isotonitazene is “20 to 100 times stronger than fentanyl”. That’s not true either. Laboratory studies suggest that it is actually about twice as potent as fentanyl. (Arch Toxicol. 2020;94:3819.)
It is doubtful whether isotonitazene has potent opioid effects or has been detected with increasing frequency in drug overdose deaths in Europe and the United States. It is important to remember, however, that being detected in post-mortem specimens does not mean that it actually caused the deaths.
Isotonitazene has not been studied in humans, but it is a mu receptor agonist, and would be expected to cause typical opioid-like effects such as euphoria, respiratory depression and miosis. These effects should respond to naloxone, but may require higher than standard doses.
A recent review of Cook County, IL, and Milwaukee County, WI medical examiners’ office mortality records from the first seven months of 2020 identified isotonitazene in 40 cases. (J Addict Med. 2021;15:429; https://bit.ly/3vXF3uG.) Flualprazolam, an unregistered benzodiazepine, was also detected in many of these cases. The United States Drug Enforcement Administration issued a temporary order in August 2020 classifying isotonitazene as a Schedule I drug, and that order remains in effect.
The key point is that the exact content of illicit drugs is constantly changing. Because few if any adulterants have specific antidotes, the mainstay of treatment remains good supportive care. The local poison control center can advise what substances seem to show up in recent cases and seized drug supplies.
Dr. Gussowis a volunteer attending physician at the John H. Stroger Hospital of Cook County in Chicago, assistant professor of emergency medicine at Rush Medical College, consultant at the Illinois Poison Center, and senior lecturer in emergency medicine at the University of the Illinois Medical Center in Chicago. Follow him on Twitter@poisonreview, and read his past columns onhttp://bit.ly/EMN-ToxRounds.