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Immunological Modulation and Control of Parasitaemia by Ayahuasca Compounds: Therapeutic Potential for Chagas's Disease

Albert Katchborian‐neto, Mário F. C. Santos, Diego Fernandes Vilas Boas, Elda Gonçalves Dos Santos, Márcia Paranho Veloso, Paula Carolina Pires Bueno, Ivo Santana Caldas, Marisi G. Soares, Danielle Ferreira Dias, Daniela Aparecida Chagas‐paula

Chemistry & Biodiversity September 26, 2022 DOI: 10.1002/cbdv.202200409 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics In vitro and in vivo experimental study Peer reviewed
Population Trypanosoma cruzi trypomastigotes and infected mice
Interventions Ayahuasca harmine DMT benznidazole
Dose 10 and 100 mg/kg
Topics Ayahuasca
Keywords In vivo Pharmacology Alkaloid Chagas disease Benznidazole Trypanosoma cruzi Harmine Ic50 Drug Traditional medicine In vitro
Citations 9
Key findings Harmine isolated from Banisteriopsis caapi showed the highest trypanocidal activity in a dose-responsive manner without toxicity, while ayahuasca and the harmine-DMT combination worsened parasitemia, indicating immune modulation.

Abstract

Abstract Ayahuasca is a psychoactive and psychedelic decoct composed mainly of Banisteriopsis caapi and Psychotria viridis plant species. The beverage is rich in alkaloids and it is ritualistically used by several indigenous communities of South America as a natural medicine. There are also reports in the literature indicating the prophylaxis potential of Ayahuasca alkaloids against internal parasites. In the present study, Ayahuasca exhibited moderate in vitro activity against Trypanosoma cruzi trypomastigotes (IC 50 95.78 μg/mL) compared to the reference drug benznidazole (IC 50 2.03 μg/mL). The β‐carboline alkaloid harmine (HRE), isolated from B. caapi , was considered active against the trypomastigotes forms (IC 50 6.37), and the tryptamine N , N ‐dimethyltryptamine (DMT), isolated from P. viridis was also moderately active with IC 50 of 21.02 μg/mL. Regarding the in vivo evaluations, no collateral effects were observed. The HRE alone demonstrated the highest trypanocidal activity in a dose‐responsive manner (10 and 100 mg/kg). The Ayahuasca and the association between HRE and DMT worsened the parasitaemia, suggesting a modulation of the immunological response during the T. cruzi infection, especially by increasing total Immunoglobulin (IgG) and IgG1 antibody levels. The in silico molecular docking revealed HRE binding with low energy at two sites of the Trypanothione reductase enzyme (TR), which are absent in humans, and thus considered a promissory target for drug discovery. In conclusion, Ayahuasca compounds seem to not be toxic at the concentrations of the in vivo evaluations and can promote trypanocidal effect in multi targets, including control of parasitaemia, immunological modulation and TR enzymatic inhibition, which might benefit the treatments of patients with Chagas’ disease. Moreover, the present study also provides scientific information to support the prophylactic potential of Ayahuasca against internal parasites.

Comparable studies

Other preclinical and animal studies on ayahuasca, most cited first.

Study Year Design Participants
Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Eight ayahuasca samples from Peru and several Banisteriopsis caapi cultivars 1984 Qualitative and quantitative chemical analysis with in vitro assay
The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains 2017 In vitro experimental study
N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice 2020 In vitro and in vivo experimental study
Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat Female Wistar rats 2015 Observational cohort
Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice Mice 2015 Experimental study

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