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

Ayahuasca, a psychoactive beverage made from Banisteriopsis caapi and Psychotria viridis, showed moderate activity against Trypanosoma cruzi trypomastigotes in vitro (IC50 95.78 μg/mL), compared to the reference drug benznidazole (IC50 2.03 μg/mL). The β-carboline alkaloid harmine, isolated from B. caapi, was active (IC50 6.37 μg/mL), while the tryptamine DMT from P. viridis was moderately active (IC50 21.02 μg/mL). In vivo, harmine alone reduced parasitemia in a dose-responsive manner (10 and 100 mg/kg) without toxic effects. Ayahuasca and the harmine-DMT combination worsened parasitemia, suggesting immune modulation via increased IgG and IgG1 antibodies. Molecular docking indicated harmine binds to trypanothione reductase, a promising drug target absent in humans. The findings support ayahuasca's potential against Chagas disease and internal parasites.

Study at a glance

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.