Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities

Abstract

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.

Emotions and brain function are altered up to one month after a single high dose of psilocybin

“…While no one brain network stood out as uniquely (or significantly) altered with respect to post-psilocybin connectivity in the current report, the pattern of increased connectivity across brain networks that was sustained 1 week and 1 month post-psilocybin is generally consistent with reported acute effects of psilocybin 41 , where connectivity between and among a number of canonical brain networks is increased. The current findings are also consistent with recent reports that demonstrated increased within-network connectivity in the DMN the day after the second of two psilocybin administrations in patients with treatment resistant depression 44 , two days after a single dose of psilocybin was administered to individuals in a 5-day meditation retreat 43 , and the day after administration of a closely related substance, ayahuasca, to healthy participants 82 . It should be noted, though, that the aforementioned reports of connectivity changes in the DMN one or two days after psychedelic drug administration were restricted to a priori analysis of the DMN, and these studies did not report on the between-or within-network connectivity of other canonical networks.…”

Disruption of the default mode network and its intrinsic functional connectivity underlies minor hallucinations in Parkinson's disease

“…Taking into account that these areas are normally anticorrelated with the PCC, 50 our results suggest that a decrease in the orthogonality between crucial areas of the DMN and the TPN could facilitate the appearance of minor hallucinatory phenomena. This functional approach between DMN and TPN in the resting state has been reported in drug-induced hallucinations 51 and also in subjects with dementia with Lewy bodies, 52 in whom hallucinations are the main clinical hallmark.…”

Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination

“…It has been observed, for example, that ayahuasca acutely enhances mindfulness-related capacities, such as decentering or acceptance 38,39 , and psychological process variables such as personal values could also be involved in therapeutic outcomes 34 . These capacities seem to be maintained during the after-glow period and also have persistent effects over the long-term 40 .…”