Many researchers have studied the biochemical interactions through which ayahuasca produces its psychoactive effect. The current wisdom is pretty clear. The companion plant — chacruna, sameruca, chagraponga — contains the potent hallucinogen dimethyltryptamine, and the ayahuasca vine contains ß-carboline derivatives that inhibit the monoamine oxidase-A enzyme that inactivates of the dimethyltryptamine of the companion plant.
Thus the ayahuasca drink is reduced to dimethyltryptamine, its single active molecule.
But there are several problems with the assumption that the ayahuasca experience is due to its single active molecule.
Second, emphasis on a single active molecule has prejudiced consideration of whole plants, which can contain dozens of bioactive substances. There is little doubt that every plant contains a unique mix of multiply interacting substances in complex additive, synergistic, and antagonistic relationships, presumably in a variety of feedback loops. The fact that it is difficult to describe these relationships is no reason to decide that they are unimportant.
Yet, once it has been determined that the companion plant contains DMT, the inquiry stops. But mestizo shamans select particular companion plants — and combinations of companion plants — for their specific effects. If their only function is to provide the single active molecule dimethyltryptamine, what is there to choose among them?
This difference may be because the harmala alkaloids are in different proportions in the two plants: levels of THH are higher in the ayahuasca vine, harmaline in rue. Experiential differences might also be due to the fact that rue contains tannins and quinazoline alkaloids not found in the ayahuasca vine. Thus, too, self-experimenters tend to use only the minimum amount of rue necessary to inhibit MAO; using more apparently serves no purpose other than to increase the emetic effect. But the amount of ayahuasca vine can be increased beyond the minimum necessary, and increasing the amount is claimed to add a special dimension to the experience.
Finally, the focus on single active molecules ignores context. The terms pharmacologicalism and pharmacological determinism have been coined to capture the often unstated premise that the effects of a substance are entirely determined by its chemical structure, thus ignoring the effects, among other things, of traditional ceremonial settings, the authoritative presence of a healer, social pressures both within and outside the ceremony, and expectations of particular outcomes. Expectations of what is supposed to happen during an ayahuasca ceremony may be the most powerful additive of all.