What if we combined xylazine with fentanyl?

Answer: We’d get a drug called Tranq.

And it would be bad news. Very bad news.

Xylazine is an animal tranquilizer.

Creating Zombies

What drug users and people who work with them in Philadelphia talk about is the smell. The smell of rotting flesh from open infected wounds.

Some users say they feel ashamed of the state of their bodies, but more feel a sense of urgency. They need help. The wounds are killing them.

“It is absolutely horrible. That’s the reality, though,” said James Sherman, known as Sherm around Philadelphia’s Kensington neighborhood, where he once used drugs and where he now tries to help those still on the streets.  

The need for help has become more urgent over the last three years, as the animal tranquilizer xylazine, also called tranq, has become a bigger part of Philly’s street fentanyl supply. Xylazine can cause large wounds that won’t heal, no matter where you inject it and they can appear even if you snort it or smoke it. Infections are common and can even lead to amputations.[i] 

Heroin was edged out by the more powerful synthetic opioid fentanyl. But fentanyl’s effects don’t last as long as heroin, and so xylazine was added to street fentanyl to “give it legs,” according to Sarah Laurel, who founded Savage Sisters, the harm-reduction group that employs Sherman.

It is also being combined with heroin.[ii] 

Without the tranquilizer, fentanyl lasts about 3 hours. Then the user will have to repeat the procedure.

Xylazine is not approved for humans, but it’s widely available for veterinarians to sedate large animals like horses. Like an opioid, it can kill pain but it cannot be reversed with Narcan, also known as naloxone, which is used to treat opioid overdoses, according to the US Drug Enforcement Agency.

The drug has side effects like “tranq walk,” where people seem unaware of their surroundings, along with sores and wounds. 

Tranq can knock users out for hours.

Tranq made its mark on Philadelphia’s street drugs about three years ago. That’s when doctors, users and those who try to help them saw a difference. 

Dr. Joseph D’Orazio, an emergency physician and addiction medicine specialist at Temple University Hospital, said patients started to have major wounds that were different from typical injection drug use. “These wounds were a lot deeper, a lot more severe, there were big necrotic areas,” he said. “They were deep down into tendons. Sometimes you can see the bones, and we were starting to see more patients that were requiring amputations.” 

The decaying skin tissue is called eschar.

“The tranq dope literally eats your flesh,” says Brooke Peder, a 38-year-old tattoo artist in Philadelphia who has had a leg amputated due to an infected tranq wound, to the New York Times’ Jan Hoffman. “It’s self-destruction at its finest.”

Xylazine is in 9 out of 10 samples of lab-tested dope in Philadelphia. “What we’re seeing is the bags of fentanyl sometimes don’t have fentanyl … it’s just xylazine,” he said.

Xylazine origins

The Bayer Company first developed xylazine, an alpha-2 receptor agonist, in 1962, according to a November memo from the Drug Enforcement Administration (DEA). Ten years later, the FDA approved xylazine as a veterinarian-prescribed sedative and pain reliever for animals, reports the Times. Per the DEA, veterinarians use it to “calm and facilitate handling, perform diagnostic and surgical procedures, relieve pain or act as a local anesthetic” in various species, such as cattle, sheep, horses, dogs, cats, deer, rats and elk.

It was a sedative and muscle-relaxant.

Drugmakers studied xylazine in humans for the same purposes but ended their clinical trials, because it caused severe low blood pressure and depressed the central nervous system. Veterinarians can use substances such as yohimbine hydrochloride and tolazoline hydrochloride to help reverse xylazine’s effects in animals, however, it’s not clear if these same substances are safe and effective among humans.

Where is it?

Xylazine is most concentrated in Philadelphia, according to Dr. Rahul Gupta, director of the Office of National Drug Control Policy. But it’s in all 50 states, he told CNN.  

The highest xylazine prevalence data was observed in Philadelphia, (25.8% of deaths), followed by Maryland (19.3%) and Connecticut (10.2%).[iii]

Xylazine is cheap.

Puerto Rico is most likely where it began as an illicit drug.

A recent analysis by Brown University found xylazine in more than 40 percent of street drug samples in Rhode Island, reports ABC News’’ Nicole Wetsman.

Kicking the habit

Xylazine withdrawal can cause intense anxiety and dysphoria, D’Orazio said, and the medications used to treat opioid withdrawal don’t work well for xylazine. That’s making the public health crisis worse. “People are avoiding the hospital because they feel like withdrawal can’t be well managed,” he said. “They go longer, and the disease gets worse before they come in.”  

The bad news is that studies show roughly 90 percent of people with addiction get no healthcare at all.

Why do it?

Sarah Laurel, herself a recovering heroin addict, calls everyone she meets and tries to help in Kensington her “friend.” 

“The people that are out here numbing their pain with substances, whether it’s heroin, alcohol, cocaine, we need to address the pain, we need to stop isolating the substance and look beyond it,” she said.   

Overdose crisis

• There were 106,699 drug-involved overdose deaths reported in the U.S. in 2021 (Figure 1); 69% of cases occurred among males (yellow line). Synthetic opioids other than methadone (primarily fentanyl) were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021 (Figure 2).[iv]

Street drugs in America got even more toxic in 2022 with the spread of the synthetic opioid fentanyl. Many of those dying are young, under the age of 40.[v]

"They're zombifying people," said Marche Osborne who lives on the streets in Tacoma, Wash.

She's been addicted to opioids for 18 years and prefers heroin, but says fentanyl is now the only drug street dealers are offering.

"Anybody will do anything for a pill, it's ridiculous. They're dehumanizing people. It's not a good thing. It's not going to go anywhere good if [the spread of fentanyl] continues," Osborne told NPR.

Using data from 2021, the Centers for Disease Control and Prevention announced in late 2022 that life expectancy in the U.S. has dropped to its lowest point in two decades, in part because of street drugs.

World Stage

Collectively, smoking, alcohol and illicit drug use kills 11.8 million people each year. This is more than the number of deaths from all cancers.[vi]

We look at smoking, alcohol and illicit drugs separately in dedicated research articles. But in this meta-article we look at the combined impacts of substance use: both through indirect impacts on mortality and direct consequences from addiction and overdoses.[vii]

Conclusion

The United States exceeds all in prevalence of drug addiction. Canada, Scotland and the United Kingdom follow behind. Scotland and the United Kingdom also rank high on alcohol consumption. Indonesia and Uganda have very low rates with both.

Apparently this combination is more addictive than either agent alone. Treatment is difficult, and there is no approved “rescue” drug to address overdoses. Yohimbine hydrochloride and tolazoline hydrochloride have only been used in animals.

Interestingly, yohimbine hydrochloride (YH) is a prescription drug to treat erectile dysfunction. It also had potential in fighting high blood pressure and diabetic neuropathy as well as promoting weight loss.[viii] It will also inhibit skin melanin synthesis by inhibiting Wnt/β-catenin and p38/MAPK signal pathways.

It also could be used to supercharge people for sprinting. I kid you not. Acute YHM ingestion increases both the ability to generate and maintain power output during repeated sprints.[ix]

Tolazoline hydrochloride has been explored as a pulmonary vasodilator in potentially fatal episodes of pulmonary vasoconstriction after cardiac surgery in children.[x] Administration of tolazoline as a bolus (1--2 mg/kg) followed by infusion of 1--2 mg/kg/hour resulted in a rapid and sustained decrease in PAP/SAP, from 1.00 +/- 0.18 (mean +/- SD) to 0.40 +/- 0.09 (p less than 0.001), and was effective management for all these clinical crises. The use of tolazoline may prevent a fatal outcome from acute elevation of PVR in the perioperative period.

Aside from a rescue drug, other means need to be developed to treat and prevent this. An ounce of prevention is worth a pound of cure. If people don’t ever get a sampling of alcohol, tobacco, opioids or whatever it is, they are far, far, far less likely to get addicted and die from them.

Drug use can arise from social pressure, depression, adventurism or boredom. Pharmaceutical companies can be enriched on the front end and the back end.

One option to consider is church.

When children are involved in the church and active practitioners of faith growing up, they may be less likely to engage in substance abuse later on in life. A study on Brazilian university students compared frequent church attenders to peers who did not regularly attend church and found that substance use over the past 30 days was higher in the group that did not regularly attend church than the group that did. In fact, these students who were not attending religious services were more likely to use alcohol, tobacco, marijuana, and illicit drugs than their church-going peers.[xi]

Social support, community involvement, and fear of consequences may all be contributing factors to this connection. A study that looked at some possible explanations more closely found that regular involvement with congregational networks such as attending church services was the most consistent indicator of decreased drug use in teens.

People need to be connected to others that are leading vital lives and not ones of drug dependency. When people have something constructive to do and uplifting people to engage with, it is priceless.

[i] https://www.cnn.com/2023/03/07/health/philadelphia-xylazine-tranq-drug/index.html

[ii] https://www.smithsonianmag.com/smart-news/what-to-know-about-tranq-the-animal-sedative-infiltrating-street-drugs-180981408/

[iii] Friedman J, Montero F, Bourgois P, Wahbi R, Dye D, Goodman-Meza D, Shover C. Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis. Drug Alcohol Depend. 2022 Apr 1;233:109380. doi

[iv] https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates#:~:text=There%20were%20106%2C699%20drug%2Dinvolved,to%202021%20(Figure%202).

[v] https://www.npr.org/2022/12/31/1145797684/2022-was-a-deadly-but-hopeful-year-in-americas-opioid-crisis#:~:text=Data%20from%20the%20Centers%20for,period%2C%20a%20stunning%20new%20record.

[vi] The Lancet, 392(10159), 1736-1788″

[vii] https://ourworldindata.org/drug-use

[viii] Fu T, Qin X, Ma Y, Yuan X, Wu S, Ye X, Dang Y. Yohimbine hydrochloride inhibits skin melanin synthesis by regulating wnt/β-catenin and p38/MAPK signal pathways. J Dermatol Sci. 2022 Jul;107(1):17-23.

[ix] Barnes ME, Cowan CR, Boag LE, Hill JG, Jones ML, Nixon KM, Parker MG, Parker SK, Raymond MV, Sternenberg LH, Tidwell SL, Yount TM, Williams TD, Rogers RR, Ballmann CG. Effects of Acute Yohimbine Hydrochloride Supplementation on Repeated Supramaximal Sprint Performance. Int J Environ Res Public Health. 2022 Jan 25;19(3):1316.

[x] Jones OD, Shore DF, Rigby ML, Leijala M, Scallan J, Shinebourne EA, Lincoln JC. The use of tolazoline hydrochloride as a pulmonary vasodilator in potentially fatal episodes of pulmonary vasoconstriction after cardiac surgery in children. Circulation. 1981 Aug;64(2 Pt 2):II134-9.

[xi] https://faithinrecovery.com/2020/07/02/religion-and-drug-prevention/