Single exposure to Ayahuasca reverses chronic stress effects on sociability, anxiety, cortisol, and BDNF in zebrafish

Chronic stress is a risk factor for the development of anxiety, depression, and comorbid systemic conditions. Ayahuasca (AYA) has been used for hundreds of years and it elicits antidepressant and anxiolytic effects. However, it remains unknown whether AYA elicits a behavioral and biochemical protective effect in chronic stress.

Therefore, we evaluated the therapeutic potential of AYA in reversing or attenuating the behavioral and biochemical alterations induced by an unpredictable chronic stress (UCS) paradigm in adult zebrafish.

Zebrafish underwent an unpredictable chronic stress (UCS) protocol for 14 days or were left undisturbed in their tanks. On the 15th day, AYA was added to the tank at a dose of 0.5 or 1 mL/L for one hour. On day 16, fish underwent the sociability test and the novel tank test. The levels of whole-body cortisol and brain-derived neurotrophic factor (BDNF) were measured via ELISA.

AYA restored stress-induced sociability impairments, anxiety-like behavior, and stress-induced hyperlocomotion and increased moving velocity in the novel tank test. Additionally, AYA reversed the stress-induced increase in whole-body cortisol and the stress-induced decrease in whole-brain BDNF.

A single exposure of zebrafish to AYA restored the chronic stress-induced impairments in sociability, stress-induced anxiety-like behavior, and biochemical markers of stress and impaired neuroplasticity. These findings support the potential of AYA to reverse stress-induced behavioral and neuroendocrine alterations. Clinical studies are warranted to evaluate the translational relevance of these effects in individuals exposed to chronic stress.