The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization

Abstract

Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca is still a central element of many healing ceremonies in the Amazon Basin and its ritual consumption has become common among the mestizo populations of South America. Ayahuasca use amongst the indigenous people of the Amazon is a form of traditional medicine and cultural psychiatry. During the last two decades, the substance has become increasingly known among both scientists and laymen, and currently its use is spreading all over in the Western world. In the present paper we describe the chief characteristics of ayahuasca, discuss important questions raised about its use, and provide an overview of the scientific research supporting its potential therapeutic benefits. A growing number of studies indicate that the psychotherapeutic potential of ayahuasca is based mostly on the strong serotonergic effects, whereas the sigma-1 receptor (Sig-1R) agonist effect of its active ingredient dimethyltryptamine raises the possibility that the ethnomedical observations on the diversity of treated conditions can be scientifically verified. Moreover, in the right therapeutic or ritual setting with proper preparation and mindset of the user, followed by subsequent integration of the experience, ayahuasca has proven effective in the treatment of substance dependence. This article has two important take-home messages: (1) the therapeutic effects of ayahuasca are best understood from a bio-psycho-socio-spiritual model, and (2) on the biological level ayahuasca may act against chronic low grade inflammation and oxidative stress via the Sig-1R which can explain its widespread therapeutic indications.

Keywords: addiction medicine; ayahuasca; dimethyltryptamine; diseases of civilization; oxidative stress.

FIGURE 1

Cross-talk between receptors by dimerization. The 5-HT2A receptor mediated hallucinogen-specific intracellular pathway requires the dimerization of the 5-HT2A receptor with the mGlu2 receptor. This unique (G protein-coupled) pathway is associated only with the dimer and not activated by either receptor alone. Serotonin lacks the mGlu2 receptor binding feature and the psychotropic effects of hallucinogens are abolished by the elimination of the mGlu2 receptor. The 5-HT2A-mGlu2 dimer is the prime target of some serotonergic hallucinogens (Moreno et al., 2011).

FIGURE 2

The polygon of self-destructive forces. Every angle of this octagon represents a pathophysiological process closely related to almost all of the others, and each pathological process is known to be involved in several illnesses of civilization (see Table 1) with extensive overlap (e.g., Alzheimer’s disease has chronic low grade inflammation, increased nitric oxide signaling, calcium dyshomeostasis, apoptosis, mitochondrial dysfunction, oxidative, and endoplasmic reticulum stress in its etiopathology). The central position of the Sig-1R illustrates its significant influence in mitigating these pathological processes. The number of angles is rather arbitrary: one may add others like insulin resistance, glutamate release, plasma membrane deficiency, etc.