Xylazine

"Harms of xylazine use in humans are not well documented, but evidence suggests that combined use of xylazine and an opioid such as fentanyl may increase the risk of overdose fatality.¹ Although naloxone, the opioid overdose reversal drug, is not effective against xylazine alone, unintentional fatal overdoses with xylazine detections also had heroin and/or fentanyl detections in Philadelphia, indicating timely administration of naloxone is critical for preventing deaths. Additional treatment for xylazine poisoning may involve supportive care using intubation, ventilation and administration of intravenous fluid.¹

"Of note, as fentanyl has largely replaced the heroin supply in Philadelphia, xylazine has been increasingly found in combination with fentanyl. Some evidence suggests that the combination of xylazine and fentanyl in humans may potentiate the desired effect of sedation and the adverse effects of respiratory depression, bradycardia and hypotension caused by fentanyl alone,¹ comparable to the synergistic effects of combining benzodiazepines with heroin and/or fentanyl.⁷ While benzodiazepines were detected in 97 (58%) of the 168 unintentional overdose deaths with heroin and/or fentanyl detections in Philadelphia in 2010, this decreased to 232 (28%) of the 858 unintentional overdose deaths with heroin and/or fentanyl detections in 2019. This decline may be the result of increasing demand for xylazine among people who use drugs in Philadelphia and/or changes in the illicit drug market as drug seizure data indicate that xylazine is increasing in polydrug samples. Indeed, focus groups with people who use drugs in Philadelphia have suggested that the addition of xylazine to fentanyl “makes you feel like you’re doing dope (heroin) in the old days (before it was replaced by fentanyl)” when the euphoric effects lasted longer."

"Importantly, our results show that evidence of injection was more prevalent among decedents with xylazine and heroin and/or fentanyl detections. Despite limited literature on the health effects of chronic xylazine use, regular injection of xylazine has been associated with skin ulcers, abscesses and lesions in Puerto Rico.^{2 3} Semistructured interviews with people who use xylazine in Puerto Rico revealed that regular use of xylazine leads to skin ulcers.⁴ As skin ulcers are painful, people may continually inject at the site of the ulcer to alleviate the pain as xylazine is a potent α2-adrenergic agonist that mediates via central α2-receptors, which decreases perception of painful stimuli.¹ People may self-treat the wound by draining or lancing it, which can exacerbate negative outcomes.⁸ While Philadelphia has seen a rise in skin and soft tissue infections relating to injection drug use, it is not yet clear whether or not this is due to increased presence of xylazine in the drug supply.⁹"

"We summarize longitudinal, recent, and geographically specific evidence describing how xylazine is increasingly implicated in overdose deaths in jurisdictions spanning all major US regions and link it to detailed ethnographic observations of its use in Philadelphia open-air narcotics markets. Xylazine presence in overdose deaths grew exponentially during the observed period, rising nearly 20-fold between 2015 and 2020. Whereas the most recent national data from the State Unintentional Drug Overdose Reporting System characterized the level of xylazine-present overdoses in 2019 (Kariisa, 2021), we found that the prevalence increased by nearly 50% from 2019 to 2020 alone, indicating a need for more recent data to guide the public health response. Furthermore, we find that even looking at only 10 jurisdictions a greater number of xylazine-present overdose deaths were seen in 2020 (854), than the previous study looking at 38 states in 2019 (826) (Kariisa, 2021), implying a very fast rate of growth nationally.

"Xylazine prevalence was observed earliest and at the highest magnitude in the Northeast, and may be spreading west, in a pattern similar to the trajectory of illicitly-manufactured fentanyls in recent years (Shover et al., 2020). This similarity may not be incidental, as an analysis of the co-occurrence of fentanyl and xylazine indicates a strong ecological link, with fentanyl nearly universally implicated in xylazine-present overdose deaths. Further, ethnographic data among PWID suggests that the use of xylazine as an illicit drug additive may predominantly serve as a response to the short duration of fentanyl. By ‘giving fentanyl legs’—offering improved duration of effect—the addition of xylazine may confer a competitive market advantage for illicit opioid formulations that contain it, as it remedies one of the most commonly expressed complaints that PWID hold regarding fentanyl-based street opioid formulations."

"At least a decade after Xylazine became a fixture in Puerto Rico, it entered the street opioid supply in Philadelphia as a more prevalent additive in the mid-2010s. The shift was noted by PWID, as well as harm reductionists and city public health officials (Johnson et al., 2021). PWID began to describe xylazine – often referred to as tranq – as a known element of specific ‘stamps’ or brands of opioid products in the illicit retail market. Opioid formulations containing xylazine, (e.g.,'tranq dope') became largely sought-after, as the addition of xylazine was reported to improve the euphoria and prolong the duration of fentanyl injections, in particular, solving 'the problem' of the 'short legs' of the otherwise euphoric effects of illicitly manufactured fentanyl."

"Prior to the widespread availability of xylazine in the Philadelphia drug supply, it was often mentioned in passing by residents of the majority Puerto Rican neighborhood where our fieldwork was based as a powerfully psychoactive additive ‘“back on the Island”.’ Xylazine was occasionally detected in fatal overdoses in Philadelphia as early as 2006 (Wong et al., 2008), but it was not common knowledge among PWID. Significantly, however, many of our long-term informants recently immigrating/returning from Puerto Rico spoke with a mix of intrigue and apprehension about the psychoactive effects and health risks of 'anastesia de caballo [horse tranquilizer]'."

"In overdose data from 10 jurisdictions – representing all four major US census regions – xylazine was found to be increasingly present in overdose mortality (Fig. 1). The highest prevalence was observed in Philadelphia, (with xylazine present in 25.8% of overdose deaths in 2020), followed by Maryland (19.3% in 2021) and Connecticut (10.2% in 2020). In 2021, xylazine prevalence also grew substantially in Jefferson County, Alabama, reaching 8.4% of overdose fatalities. Across the four census regions, the Northeast had the highest prevalence, and the West had the lowest (Fig. 2), with only six xylazine-present overdose deaths in total detected in Phoenix, Arizona, and 1 in San Diego County, California. Across jurisdictions, a clear increasing trend was noted. Pooling data for 2015, a total xylazine prevalence of 0.36% was observed. By 2020, this had grown to 6.7% of overdose deaths, representing a 20-fold increase. From 2019–2020 – the last year of data available for all jurisdictions – the prevalence increased by 44.8%."

"Xylazine is currently not a scheduled substance under the United States Controlled Substances Act, though some efforts are underway to change this (Drug Enforcement Administration, 2021; Murphy, n.d.). However, supply side efforts to control xylazine adulteration of fentanyl/heroin are unlikely to work and – similar to trends seen when trying to decrease the availability of alcohol, cannabis, and cocaine – will likely exacerbate adulteration (Cowan, 1986). Xylazine test strips, by contrast, are a demand-driven response to unwanted adulterants and may be able influence the composition of the drug supply if xylazine is linked to specific stamps (i.e., how fentanyl/heroin products are branded in Philadelphia) (Friedman et al., 2022). This new form of drug checking represents a potential tool to further empower PWUD to make informed choices about what and how they consume drugs.

"All participants who spontaneously discussed wanting xylazine test strips, or were asked if they would want them, indicated they would use them to test their fentanyl/heroin before drug consumption, if available. Xylazine test strips are not currently available and, to our knowledge, are not in development. Research is needed from broader monitoring and analysis of the drug supply to determine whether xylazine in fentanyl/heroin is pharmaceutical grade. Additionally, it is important to understand if a xylazine test strip would be capable of detecting any xylazine analogs.

"A xylazine test strip may have the potential to positively impact drug use in a similar manner to fentanyl test strips. Fentanyl test strips have been found to significantly alter drug use behavior and foster safer drug use practices with continued testing. Individuals using fentanyl test strips prior to drug use did so in order to prevent fentanyl overdose and the potential need for emergency interventions (Peiper et al., 2019). Additionally, there have been studies reporting fentanyl test strip use following drug use. Among these individuals, positive results for fentanyl were associated with use of reduced doses on subsequent drug consumption occasions (Karamouzian et al., 2018)."