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Coca leaf (“chewed” by indigenous Andean peoples) and cocaine (the notorious modern illicit drug trafficked from the Andes) are deeply emblematic of South America, but neither has attracted the in-depth archival research they deserve. Their two modern histories are closely linked. Coca leaf, a part of Andean indigenous lifeways for thousands of years, is the raw ingredient for the alkaloid drug cocaine, discovered in 1860, and illicit peasant coca plots in the western Amazon of Peru, Bolivia, and Colombia have been the source for the infamous illicit cocaine “cartels” since the 1970s. The two drugs’ fates have both had surprisingly shifting trajectories and meanings across the colonial, national, and modern eras. They have also distinctively linked the Andes to the outside world and national political cultures of the three chief Andean states. Bolivia has the most continuous history with coca, related to the highland geography of its indigenous majority, though coca leaf only became a “nationalist” symbol over the past fifty years or so. Peru was home to the world’s first legal cocaine industries, starting in the 1880s, and coca and illicit cocaine have interacted in complex ways ever since. Colombia had the least coca traditions, and was the last nation to develop illicit cocaine exports in the 1970s and 1980s, although with a dramatic impact on Colombia and the world. This largely unknown and changeable history underlies the present-day crossroads of coca and cocaine: will the US-abetted Andean “drug wars” against cocaine continue, despite their long failures, and will coca’s place as a symbol of cultural and national pride in the Andes be fully restored?