Multiple transformations-referred to as "waves" in a panoply of recent public health and law enforcement publications-have rendered North American drug markets increasingly toxic since the early 2010s. The introduction of exceptionally potent synthetic sedatives and stimulants is initiating a new generation of drug injectors into co-use of opioids and methamphetamine, catapulting rates of deadly overdoses and infectious diseases. Drawing on extensive participant-observation research in Philadelphia (2007-present) and Tijuana (2018-present), we document the experience of street-based drug users across these two North American cities to focus on regional shifts in narcotics supplies and endpoint user preferences. We link the dramatic proliferation of fentanyl, methamphetamine, xylazine, and Mexican white powder heroin to: 1) pre-existing drug supply networks on the western and eastern coasts of the North American subcontinent; 2) material characteristics of local heroin supplies in pre-fentanyl opiate markets (Mexican black tar vs. Colombian off-white powder heroin); and 3) racialized repression/incarceration of drug sellers and users on both sides of the Mexico-US border. The article combines economic and medical anthropology to develop an ethnographically-informed political economy approach to an urgent public health challenge among street-based drug users with the highest overdose mortality rates in the US Northeastern Rust Belt and the Northwestern Mexican borderland metroplex anchored by Tijuana. It foregrounds street users' experiences in real time amidst rapidly shifting narcotics supply chains, linking market-driven logics of profit-seeking to the war on drugs' prohibitionist policy context, highlighting increasing toxic impacts on vulnerable sectors across regions.
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