Ayahuasca has shown beneficial effects in depression and increasing evidence indicates therapeutic potential in the treatment of addiction. Despite the mounting empirical evidence of its medicinal value, the mechanisms through which ayahuasca exerts its beneficial effects are still poorly understood. Objectives: In the present paper we present: a) data on post-acute changes in brain metabolism and connectivity in humans, and their association with psychological improvements; and b) data from animals showing novel effects of ayahuasca alkaloids on brain cells. Methods: Human studies were conducted using magnetic resonance spectroscopy, functional connectivity and psychological assessment. Animal studies were carried out on cultured neural stem cells. Results: In humans, ayahuasca induced a post-acute neurometabolic deactivation of a key hub of the default mode network. It also increased functional connectivity between midline brain regions, and between frontal areas and structures in the medial temporal lobe involved in memory and emotional processes. These changes in brain dynamics correlated with enhanced mindfulness capacities. Stem cell studies showed that beta-carbolines promote neurogenesis, stimulating proliferation, migration and differentiation of new neurons in the adult mammalian brain. Conclusions: These results show that ayahuasca acts at multiple levels, from the cellular to the neural and the psychological. Our results in animals open a totally new avenue of research for ayahuasca and its active principles. Potential applications would range from depression to neurodegenerative disorders.