Acute ayahuasca administration attenuates binge‐like eating and anxiety‐related behaviors in mice subjected to intermittent fasting

Abstract Human binge eating disorder is characterized by recurrent episodes of excessive food consumption accompanied by loss of control and is strongly associated with alterations in reward processing and emotional regulation. Ayahuasca, a psychoactive botanical preparation traditionally used in Amazonian medicine, has been shown to modulate serotonergic signaling and reward‐related behaviors and has emerged as a potential therapeutic tool for mood and substance use disorders. However, its effects on binge‐like eating behavior remain largely unexplored. In the present study, we evaluated the behavioral and metabolic consequences of a binge‐like eating model in mice and investigated the effects of a single administration of ayahuasca on food intake, sucrose consumption, and anxiety‐like behavior. Male C57BL/6 mice were subjected to an intermittent fasting protocol combined with restricted access to a standard diet and a sucrose solution for 10 days. On the eleventh day, a subgroup of binge‐exposed mice received a single oral dose of ayahuasca (1.76 mg/kg of N, N‐dimethyltryptamine). Food and sucrose intake were quantified during refeeding periods; anxiety‐like behavior was assessed using the elevated plus maze; and the expression of hypothalamic genes POMC and CART was evaluated by RT‐PCR. Mice exposed to the binge‐like eating protocol exhibited increased food and sucrose intake during restricted access periods, reduced body weight, anxiogenic‐like behavior, and reduced hypothalamic CART gene expression. Ayahuasca administration selectively reduced food and sucrose intake during the initial hour of refeeding without affecting later intake, reversed anxiety‐like behavior, and increased hypothalamic CART expression. These findings support the notion that ayahuasca acutely attenuates binge‐like eating and anxiety‐related behaviors in mice, supporting its potential relevance for investigating psychedelic‐based approaches targeting compulsive eating and associated emotional dysregulation.