Emotion regulation of aversive stimuli as a psychedelic therapeutic mechanism: an fMRI study of Ayahuasca effects

Sep 30, 2016

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Although psychedelics has been proposed as potentially therapeutical by anxiolitic and antidepressant effects, few studies have been carried out so far investigating their effect on brain emotional processing to support their mechanisms. The aim of this study was to measure the effect of the serotonergic psychedelic called ayahuasca on brain response to emotional aversive faces, using functional magnetic resonance imaging (fMRI). Methods: Nineteen healthy male volunteers participated in this study with at least 36 times of ayahuasca experience in one single year. They were evaluated in two fMRI sessions before and after an oral ingestion of Ayahuasca. In a blocked design task, subjects were presented with pictures of neutral (A) and aversive (B) (fearful or disgust) faces from the Pictures of Facial Affect Series (Ekman and Friesen 1976). The blocks lasted 17 seconds in a blocked design with seven blocks of aversive faces and eight blocks of neutral ones. Whole-brain images were acquired over 4.25 min for each emotion. Subjects were asked just to identify the sex of the faces. Subjective mood states were evaluated during the procedures, using a visual analogue mood scale (VAMS). Images were acquired in a 1.5 T scanner (Siemens Magnetom Avanto). Imaging data were analysed using statistical maps obtained in Brain Voyager 2.8 (Brain Innovation, Maastricht, The Netherlands), using a general linear model with random effects model. The statistical threshold was set to p < 0.05 (FDR corrected for multiple comparisons), for clusters with at least 50 mm3. Behavioural and subjective data were analyzed using Prism (version 6) considering values of p < 0.05 as significant. Results: The amygdala responded bilaterally to aversive faces of before ayahuasca intake (p < 0.05), but no activation were found after. Furthermore, after intake, Ayahuasca enhanced the activation bilaterlally in the insula, and also in the right dorsolateral prefrontal cortex (p < 0.05). In the psychometric VAMS subscale, ayahuasca attenuated self evaluation anxiety (p < 0.05), without effects on other subscales. Under the effects of ayahuasca, a negative correlation was found between cognitive impairment and the activation of dorsolateral prefrontal cortex (r = -0.58, p < 0.008), which means that as much cognitive improves as higher is prefrontal activation. Conclusions: These data suggest that ayahuasca as much as others serotonergic psychedelic can modulate brain activations to aversive stimuli in a pattern similar to emotion regulation process, reducing defensive responses in the amygdala, and enhancing cognitive responses in the insula and prefrontal cortex which suggests a potential action of ayahuasca as an effective anxiolytic. This emotion regulation process is also found in neuroimaging studies of psychotherapy and meditation practices, while it is also referred as a cognitive impairment for psychiatric disorders like depression or PTSD.

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