This chapter presents the results of an inquiry into the origins of the ayahuasca /yagé concept (América Indigena 1986; Beyer 2009, 2012; Labate and Cavnar 2014; Luna 1986; Ott 1994). Ayahuasca and yagé are analogous potions that exert their psychotropic action through the synergism of their basic component alkaloids: harmine, tetrahydroharmine, harmaline , and dimethyltryptamine (DMT). These potions have a long history of use throughout the Amazon basin. This investigation reveals, instead of a fixed recipe, a complex series of potions, each an attempt at synergy between the different component alkaloids, with an emphasis on betacarbolines (β-carbolines) and tryptamines. The components of these potions vary according to regional plant availability and perhaps what could be seen as cultural predilections for specific methods of administration (e.g., smoking, snuffing, drinking, enemas). Ayahuasca and yagé are the potions most commonly used today but not necessarily the most ancient. The beginning stages of my inquiry focused on the origins of these two pharmacologically complex beverages. However, it soon became apparent that questions of origin were not restricted to sets of specific recipes, prescriptions, and localities. Instead, a construct related to plant interaction and modulation began to emerge from this research. In addition to the ayahuasca and yagé recipes currently available, in an inquiry about origins, analogous potions and brews should be considered. An Inquiry into the Synergy between Dimethyltryptamine and Beta-Carbolines. Significant among these are vinho de jurema, yaraque, vino de cebil, and chicha with an admixture of Anadenanthera seeds (figure 9.1). Each is discussed in detail below. These potions must be seen within the total context of tryptamine activation throughout South America (smoking, snuffing, enemas, unguents). The use of psychoactive plants and preparations on the South American continent is characterized by a predilection for visionary agents containing potent, short-acting tryptamines (N,NDMT , 5-MeO-DMT, and 5-HO-DMT). The area of San Pedro cactus (Trichocereus sp.) use in northern Peru and southern Ecuador is an exception to the previous statement (figure 9.2). In this chapter I first present a survey of potions and brews that attempt to activate tryptamines by the addition of these alkaloids to a β-carboline (e.g., harmine, tetrahydroharmine, harmaline) base. Second, the antiquity of these drinks is established by reference to early colonial documents as well as ethnographic information collected in the eighteenth through twentieth centuries. Third, after the temporal data for these potions are Figure 9.1. Map of South America indicating approximate distribution of potions mentioned in the text. Constantino Manuel Torres Figure 9.2. Map of South America with approximate distribution of tryptamine use. presented, a review of pre-Columbian iconography follows in a discussion of possible use of ayahuasca-like potions in the preconquest period. Survey of Potions The vine Banisteriopsis caapi (Spruce ex Griseb) Morton (Malpighiaceae ) forms the basis of modern (post-1750) ayahuasca and yagé potions. Sometimes the potion is prepared with only the stem or bark of Banisteriopsis species, without the addition of other ingredients. In some instances (e.g., among the Piaroa), a simple Banisteriopsis tea is drank to lengthen and enhance the effect of tryptamine-containing snuff powders (Rodd 2002: 276). Most often, the leaves or bark of various other plants is added to the Banisteriopsis potion to modify the effect. The species used most frequently are Diplopterys cabrerana (Cuatrecasas) Gates (previously known as Banisteriopsis rusbyana) and Psychotria viridis Ruiz & Pav. Solanaceous additives are also common, including Nicotiana, Brugmansia, and Brunfelsia species. For convenience, and to avoid confusion, in this Inquiry into the Synergy between Dimethyltryptamine and Beta-Carbolines chapter the term ayahuasca refers to the basic mixture of Banisteriopsis caapi and Psychotria viridis (chacruna), while yagé primarily consists of Banisteriopsis caapi and Diplopterys cabrerana (ocoyagé). Ayahuasca is generally manufactured in Brazil and Peru, and yagé in Colombia and Ecuador. Approximately a hundred species from forty plant families are reported as ayahuasca/yagé admixtures, many of them also psychoactive plants (Ott 1994: 27–31). The problem of oral administration is a complex one. Psychoactive tryptamine alkaloids (e.g., N,N-DMT), such as those found in D. cabrerana and P. viridis, are deaminated by the enzyme monoamine oxidase (MAO); therefore, snuffing, smoking, enemas, and unguents are the most direct means of administration.