Psychedelics and music: characterising changes in hierarchy of brain dynamics among the Santo Daime

Abstract

The last few decades have been characterised by a resurgence in research and clinical interest in classic serotonergic psychedelics including N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD) and psilocybin, with a growing body of literature pointing to their treatment potential. Ayahuasca is a psychedelic brew commonly composed of plants carrying the psychoactive compound DMT, and beta-carbolines which enable DMT action. Ayahuasca is commonly used in indigenous ritual and syncretic religious settings, within which music plays a central role. The acute and long-term effects of psychedelics are known to be shaped by set and setting, with music being an element of the setting to which great importance has been afforded across clinical as well as ritual contexts. The Santo Daime, a religious group who incorporate the regular consumption of ayahuasca within ceremonies, are a musical doctrine. Therefore, they present a compelling case for studying the role of ayahuasca, music, and the interaction of the two in shaping brain dynamics. This thesis is the first to directly examine the role of ceremonial hymns, their presence and properties, in ayahuasca-induced changes to the functional hierarchy within the unique context of pursuing the divine. We examine the effects of ayahuasca-ingestion across resting state and ritual-relevant music contexts on large-scale brain dynamics in an fMRI dataset of 24 members of the Santo Daime Church. By leveraging undirected dynamic approaches including harmonic decomposition and leading eigenvector decomposition as well as time-averaged and time-resolved wholebrain modelling-based trophic analysis measures of directed connectivity, we addressed three aims: 1) to examine ayahuasca-induced effects on large-scale brain dynamics and the functional hierarchy among members of the Santo Daime at rest, 2) to assess the consistency of observed effects across resting state and ritual-relevant music listening contexts, and 3) to explore the modulating role of ceremonial music’s familiarity and predictability on ayahuascainduced effects on the functional hierarchy. This analysis should be seen in the light of the Relaxed Beliefs Under Psychedelics (REBUS) theory which proposes that psychedelics induce a flattening of the brain’s functional hierarchy. Comparing ayahuasca to an intravenous DMT dataset serving as benchmark, in Chapter 2 we show several consistent harmonic decomposition effects following drug administration across datasets including suppression of spatially-resolved harmonic power and contraction of latent space spread. Several differences emerged between datasets, specifically in harmonics relevant to the functional hierarchy, necessitating more direct examination of hierarchical structure. In Chapter 3 this is done through the application of whole-brain modelling and trophic analyses which showed significant context-independent reduction in hierarchical coherence, average trophic level reduction, and trophic level homogenisation, consistent with REBUS. In Chapter 4 we introduce a novel state-based modelling approach through which we examine not only average hierarchy changes following ayahuasca ingestion (confirming the findings of Chapter 3), but also enhanced stability of this less hierarchical regime across time. Finally, Chapter 5 leverages the within-music two-by-two factorial design of the Santo Daime dataset in exploring the effects of musical familiarity and predictability in modulating ayahuasca-induced effects on the functional hierarchy. Our results point to reduced sensitivity of hierarchy measures to musical properties following ayahuasca ingestion, aligning with REBUS and the Predictive Coding of Music Model. Further, our results indicate a unique role of the Santo Daime’s own ceremonial music, as the only condition which showed a strengthening of the underlying hierarchy following ayahuasca ingestion. Our findings extend support for the REBUS framework, by showing consistent findings following ayahuasca ingestion among long-term users both in the presence and absence of ritual relevant music listening. Importantly, our within-music results also align with a recent extension of the REBUS framework, Altered Beliefs Under Psychedelics. This suggests a need for expansion of REBUS to account for the complexity and variability of psychedelic-induced effects on brain dynamics and the modulating role of contextual factors such as music. This thesis characterises the first attempt to systematically examine the role of ceremonial ayahuasca consumption and music in shaping the functional hierarchy. Our work goes beyond the notion of psychedelia more broadly by exploring the nature of the interaction between ayahuasca and music in the Santo Daime’s connection to the divine. These findings supporting long-standing anthropological work and theories suggesting music provides structure within the complex psychedelic state and holds a special role in connecting with God, by showing ceremonial music to uniquely enhance the brain’s hierarchical structure.