Determination of the main compounds of Ayahuasca and the study of their cytotoxicity in dopaminergic neurons
Year: 2019
Type: dissertation
Abstract: Ayahuasca is a psychoactive beverage prepared traditionally from a mixture of the leaves and stems of Psychotria viridis and Banisteriopsis caapi, respectively, being originally consumed by indigenous Amazonian tribes for ritual and medicinal purposes. Over the years, its use has spread to other populations as a source of personal growth and spiritual connection. Also, the recreational use of the isolated compounds has become prominent. The main compounds of this tea-like preparation are N,N-dimethyltryptamine (DMT) and ß-Carbolines (B-CA) or harmala alkaloids, such as: harmine, tetrahydroharmine and harmaline. The latter are monoamineoxidase (MAO) inhibitors, thus allowing DMT to exert its psychoactive and hallucinogenic effects on the central nervous system (CNS). Although consumers defend its use, its metabolic effects and those on the CNS are not fully understood yet. The majority of studies regarding the effects of this beverage as a whole or as individual compounds are based on in vivo, clinical trials or even on surveys. Therefore, one of the objectives of this work was to develop an analytical method using gaschromatography coupled to a mass spectrometry (GC-MS) was developed to identify such compounds on five varieties of available commercial teas (P. viridis, B. caapi; P. harmala; Mimosa tenuiflora and DC AB). The developed method was fully validated in line with international guidelines for bioanalytical method validation. Linearity was obtained in a range of 0.2-20 µg/mL for all compounds, except for DMT (0.04-4 µg/mL), with determination coefficients above 0.99. In respect to precision and accuracy, the obtained coefficients of variation (CVs) were within the acceptable values (= 20 % for lowest limit of quantification (LLOQ) and = for other concentrations), both for intra- and inter-day. Recoveries ranged from 37 – 97 %. The method was considered suitable for quantify such compounds on real tea samples and P. viridis presented the highest DMT content, while P. harmala presented the highest content of B-CA. Alongside, the in vitro toxicity caused by DMT and ß-Carbolines on N27 rat dopaminergic neurons was evaluated, as well as the toxicity of harmalol, the main metabolite of harmaline. Likewise, all of the teas prepared were tested in cells. Overall, the results show that at the highest concentrations studied all compounds individually and when combined in the tea mixture exert neurotoxicity on N27 dopaminergic cells in a dose-dependent manner. This is the first study to investigate cytotoxicity of Ayahuasca compounds and commercial teas on dopaminergic cells and use GC-MS to quantify these compounds in five different teas, as well as two tea mixtures.
Author: Ana Aysa da Rocha Simão
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3034540991