BRAIN FUNCTIONAL CONNECTIVITY CHANGES AFTER A LOW DOSE OF AYAHUASCA INTAKE IN EXPERT USERS

Ayahuasca is an indigenous sacramental brew from the Amazon region that has a sinergetic serotonergic action. Ayahuasca is chemically composed of: N,N-dimethyltryptamine (DMT), which is an agonist to 5HT2A receptors; harmine and harmaline, inhibitors of monoamine-oxidase-A (iMAO-A); and tetrahydroharmine (THH), weak serotonin reuptake inhibitor. It promotes increases in brain activity at frontal and subcortical brain regions including visual perception, emotions and cognition, while reducing activity of the default mode network (DMN). Recently, evidences support its therapeutic potential in cases of refractory depression, however the understanding of the mechanisms involved in this process is still unknown. The goal of this study is to evaluate the acute effects of a low dose of Ayahuasca at the main brain functional networks in expert users.

Nineteen (19) expert volunteers underwent two neuroimaging examinations using functional MRI (fMRI), before and after Ayahuasca intake. They were all instructed to maintain their eyes closed, to stay relaxed and not to keep a specific thought. FSL software was used to preprocess all images and also to perform an Independent Component Analysis (ICA). Results were expressed in p value corrected for family-wise error (FWE). For the psychometric scales, a t test was performed for each category of the scale, using Prisma software, version 6. The procedures and experimental design of this study were approved by the research ethics committee of the Hospital Universitario Clementino Fraga Filho of the Universidade Federal do Rio de Janeiro (UFRJ) - CAAE: 34772414.9.0000.5257.

On the ICA, only two networks increased their activity: the salience network (p-FWE = 0.05) and the executive control network (p-FWE = 0.03). Both visual and sensorimotor networks had no increase or decrease in activity. No other networks were identified in this analysis including DMN. In psychometric scales analysis, decreases in anxiety and mental sedation (p <0.01) were observed after Ayahuasca intake.

As self reported by most subjects, ICA results also suggest that they didn't experienced visual psychedelic effects with a lack of perceptual changes on both visual and sensorimotor networks. On the other hand, the increase in activity of the salience and executive control networks corroborate findings in the literature that show Ayahuasca effects on cognitive and emotional processes. These are further reinforced by the psychometric reporting reduction in anxiety and mental sedation. Besides, promoting stronger salience network connectivity among its parts including anterior cingulate cortex, amygdala and insula may represent improvements in brain functions responsible for many complex functions related to sensory, emotional and cognitive processing. These findings contribute to a better understanding of the Ayahuasca effects on the human brain as well as to show a cognitive-emotional regulation, that may have therapeutic use in future research.

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