Ayahuasca, a psychoactive beverage containing DMT and β-carboline alkaloids, was administered to female Wistar rats at doses 15X, 30X, and 50X the typical ritual dose. The lethal oral dose exceeded 50X (15.1 mg/kg DMT). At 30X, ayahuasca reduced locomotion in open field and elevated plus-maze tests and increased swimming in the forced swimming test, suggesting antidepressant-like effects. Neuronal activation increased in serotonin-related brain areas, with some brain injury but no permanent damage. These findings indicate antidepressant properties at high doses, warranting further study.
Ayahuasca, when given orally to pregnant rats from gestation days 6 to 20 at doses one to eight times the average human ritual dose, caused maternal death and kidney injury at higher doses. Surviving rats at the highest dose showed neuronal loss in the hippocampus and raphe nuclei, and those at twice the human dose showed neuronal loss in the CA1 region. The highest dose also delayed intrauterine growth, increased embryo deaths, and raised the occurrence of fetal anomalies. At non-lethal doses, ayahuasca increased embryo deaths and the incidence of fetal soft-tissue and skeleton anomalies. The findings suggest ayahuasca is developmentally toxic and that daily use during pregnancy may pose risks to the developing offspring.