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.
Chronic ayahuasca exposure in male Wistar rats reduced food intake and body weight gain at higher doses and increased relative brain and stomach weight at the highest dose. Total serum testosterone increased and sperm transit time and reserves in the epididymis caudae decreased at four times the ritualistic dose, but not at the highest dose. No effects were observed on sperm motility, morphology, total count, daily production, or testis and epididymis histology. The no-observed-adverse-effect-level for chronic and reproductive effects was two times the ritualistic dose, corresponding to 0.62 mg/kg bw DMT, 6.6 mg/kg bw harmine, and 0.52 mg/kg bw harmaline. A non-monotonic dose-response suggests potential toxicity at intermediate doses.