Toxicity of ayahuasca after 28 days daily exposure and effects on monoamines and brain-derived neurotrophic factor (BDNF) in brain of Wistar rats

Abstract

Ayahuasca is a hallucinogenic beverage that affects the serotonergic system and have therapeutic potential for many diseases and disorders, including depression and drug addiction. The objectives of this study were to evaluate the potential toxic effects of ayahuasca on rats after chronic exposure, and the levels of monoamines, their metabolites and the brain-derived neurotrophic factor (BDNF) in the brain. Female and male rats were treated orally for 28 days with H₂O (control), fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, or ayahuasca (Aya) at doses of 0.5X, 1X and 2X the ritualistic dose (7 to 10 animals/group). Clinical, hematological and macroscopic results showed that ayahuasca was safe to the rats. Behavior tests conducted one hour after the last treatment showed that male rats from the Aya1 group explored the open field central area less than the control group, and the number of entries in the central area compared to total locomotion was also significantly lower in this group and in the FLX group. The hippocampus was removed for BDNF analysis and the remaining brain was used for monoamine analysis by HPLC-FL. Serotonin levels were significantly higher than control only in the Aya2 female group, while a significant reduction of its metabolite 5-HIAA was observed in the FLX group. Dopamine levels were similar among the experimental groups, but the levels of its metabolite DOPAC increased significantly in the Aya1 and Aya2 groups compared to controls, especially in females, and the DOPAC/dopamine turnover was significantly higher in Aya2 group. The levels of HVA, another dopamine metabolite, did not change with the treatments compared to controls, but HVA/DOPAC ratio was significantly lower in all ayahuasca male groups. Norepinephrine was not detected in any brain sample, and the levels of its metabolite MHPG did not change significantly among the groups. BDNF levels in the hippocampus were significantly higher in the FLX and Aya2 female groups compared to controls when expressed in relation to the total brain weight. The mechanisms involved in the increase in serotonin, dopamine turnover and BDNF levels observed in ayahuasca treated animals should be further investigated in specific brain areas.

Keywords: Ayahuasca; BDNF; Brain; Depression; Dopamine; Serotonin.