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BackgroundAyahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures.MethodsUsing 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose.ResultsMagnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later.ConclusionsThese results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.

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Patients with borderline personality disorder (BPD) present dysfunctions of the default mode network (DMN). Mindfulness training has proven effective to improve the symptoms of BPD. The present study examines the effect of mindfulness training on BPD symptomatology and DMN activity during the performance of a working memory task in patients with BPD. Sixty-five individuals with BPD were randomized to receive psychotherapy with either the mindfulness module of dialectical behavioural therapy (DBT-M) or with interpersonal effectiveness module (DBT-IE).The impact of treatments was evaluated with clinical and mindfulness variables as well as with functional magnetic resonance imaging during performance of the task.Both groups showed improvement in BPD symptoms and other clinical variables after treatment. Unexpectedly, there were no between-group differences in DMN activation or deactivation. However, activation of the left anterior insula increased in both groups after the intervention. Compared with the control group, participants in the DBT-M group presented higher deactivation in a cluster extending bilaterally from the calcarine to the cuneus and superior occipital gyri. KEYWORDSanterior insula, borderline personality disorder, default mode network, mindfulness

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ObjectiveAyahuasca is a psychedelic brew that originated in the Amazon basin. The psychological effects of this drug are becoming better understood due to the growing research interest in identifying new potential therapeutic agents for the treatment of emotion dysregulation and other disorders. Previous studies suggest that ayahuasca enhances mindfulness‐related capacities (decentering, non‐judging, non‐reacting and acceptance) and emotion regulation. The aim of the present exploratory study was to determine the effects of ayahuasca on self‐compassion in a community sample.MethodsWe administered validated questionnaires (the Self‐Compassion Scale‐Short Form and Forms of Self‐Criticism and Self‐Reassurance) to evaluate pre‐post changes in self‐compassion and self‐criticism/self‐reassurance in 45 volunteers (27 women; 60%) before and after (≤24 h) an ayahuasca ceremony. Most participants (n = 29; 67.4%) had previously used ayahuasca.ResultsAyahuasca resulted in significant improvements, with medium to large effect sizes (η2 = 0.184–0.276), in measures of self‐compassion (p < 0.05), self‐criticism (p < 0.01) and self‐reassurance (p < 0.01).ConclusionsThe findings of this study suggest that ayahuasca promotes well‐being and self‐compassion, which could have a therapeutic effect on individuals with negative affect and other psychopathological conditions. Large, controlled studies are needed to confirm these findings.

Borderline personality disorder (BPD) is a severe and highly prevalent psychiatric disorder, more common in females than in males and with notable differences in presentation between genders. Recent studies have shown that epigenetic modifications such as DNA methylation may modulate gene × environment interactions and impact on neurodevelopment. We conducted an epigenome wide study (Illumina Infinium HumanMethylation450k beadchip) in a group of BPD patients with (N = 49) and without (N = 47) childhood traumas and in a control group (N = 44). Results were confirmed in a replication cohort (N = 293 BPD patients and N = 114 controls) using EpiTYPER assays. Differentially methylated CpG sites were observed in several genes and intragenic regions in the X chromosome (PQBP1, ZNF41, RPL10, cg07810091 and cg24395855) and in chromosome 6 (TAP2). BPD patients showed significantly lower methylation levels in these CpG sites than healthy controls. These differences seemed to be increased by the existence of childhood trauma. Comparisons between BPD patients with childhood trauma and patients and controls without revealed significant differences in four genes (POU5F1, GGT6, TNFRSF13C and FAM113B), none of them in the X chromosome. Gene set enrichment analyses revealed that epigenetic alterations were more frequently found in genes controlling oestrogen regulation, neurogenesis and cell differentiation. These results suggest that epigenetic alterations in the X chromosome and oestrogen-regulation genes may contribute to the development of BPD and explain the differences in presentation between genders. Furthermore, childhood trauma events may modulate the magnitude of the epigenetic alterations contributing to BPD.