As the bloodshed surrounding the narcotics industry and interdiction efforts in Mexico and elsewhere continues unabated, it is more important than ever to study the global “drug problem” from all angles, and the products of culture emerging from Latin America provide a unique perspective on a constellation of issues whose complexity resists definitive theorization. The study of “narconarratives” has largely focused on an aesthetic “sobriety” that recognizes the distance between intoxication where drugs are consumed (mostly in the global North) and survival and violence where they are produced and transported. However, this investigation is based on the premise that a broadly conceived intoxication, or psychotropy, in fact intervenes at every level of culture, calling for an approach that is interdisciplinary, global, and historical, taking into account distinct modes of psychotropy with divergent psycho-social ramifications. Specifically, a dialectical relationship is proposed between, on one hand, compulsive patterns of intoxication that are built into a rigid, exclusionary self, typified by cocaine abuse but also linked to the psychology of consumerism, and, on the other, a defamiliarizing type of intoxication—having deep roots in indigenous practices but also being a potentiality of aesthetic experience—that increases cognitive and experiential flexibility, destabilizing ossified patterns and opening the self toward the Other. A survey of a number of moments within a genealogy of countercultural interventions in Latin America—from the travels of outsiders like Antonin Artaud and William Burroughs to the writings of the Mexican Onda literaria—provides a historical context for the cultural coexistence and conflict between these types of intoxication. Moving ahead to the current narco era, this study examines the “Zurdo” Mendieta novels of Élmer Mendoza, which illuminate complex social realities related to the narcotics industry and interdiction, simultaneously shedding light on global patterns of intoxication and engaging reflexively with structures of addiction. Finally, Fiesta en la madriguera, by Juan Pablo Villalobos and Prayers for the Stolen, by Jennifer Clement are analyzed for the way they appropriate the perspectives of childhood for their defamiliarizing effects on the reader’s perception of the violence surrounding the Drug War.