"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.).

"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.

"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.

"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.

"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.

"Importantly, our results show that evidence of injection was more prevalent among decedents with xylazine and heroin and/or fentanyl detections.

"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.

"Although some clandestine flights have been observed along the Pacific coast of Central America, including some affecting the Mexican airspace close to the border with Guatemala,⁹⁷ and some departing from Ecuador to various destinations,⁹⁸ this mode of conveyance appears to be more pronounced along the eastern (Caribbean) coast, where flights are extensively used alongside maritime shipments to facilitate the northward flow of cocaine from South America towards Mexico.⁹⁹ Venezuela (Bolivarian Republic of) is a major point of departure for such flights.

"North America, with its large consumer base,⁶⁸ continues to be one of the main destinations for cocaine trafficked from South America. Mexico is an important transit country functioning as a gateway for cocaine reaching the United States,⁶⁹ which accounts for the majority of cocaine users in North America,⁷⁰ as well as Canada (primarily via the United States, but also directly from Mexico⁷¹).

"Cocaine use is on the rise at the global level. The number of people who use cocaine has been increasing at a faster rate than population growth. The main markets for cocaine worldwide are North America, Western and Central Europe, followed by South and Central America and the Caribbean.