110 results found
Kaertner L, Steinborn M, Kettner H, et al., 2020, “Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing”, Scientific Reports, ISSN: 2045-2322
Sanz C, Pallavicini C, Carrillo F, et al., 2020, The entropic tongue: Disorganization of natural language under LSD., Conscious Cogn, Vol: 87
Serotonergic psychedelics have been suggested to mirror certain aspects of psychosis, and, more generally, elicit a state of consciousness underpinned by increased entropy of on-going neural activity. We investigated the hypothesis that language produced under the effects of lysergic acid diethylamide (LSD) should exhibit increased entropy and reduced semantic coherence. Computational analysis of interviews conducted at two different time points after 75 μg of intravenous LSD verified this prediction. Non-semantic analysis of speech organization revealed increased verbosity and a reduced lexicon, changes that are more similar to those observed during manic psychoses than in schizophrenia, which was confirmed by direct comparison with reference samples. Importantly, features related to language organization allowed machine learning classifiers to identify speech under LSD with accuracy comparable to that obtained by examining semantic content. These results constitute a quantitative and objective characterization of disorganized natural speech as a landmark feature of the psychedelic state.
Rosas FE, Mediano PAM, Jensen HJ, et al., 2020, Reconciling emergences: An information-theoretic approach to identify causal emergence in multivariate data, PLOS COMPUTATIONAL BIOLOGY, Vol: 16, ISSN: 1553-734X
Leptourgos P, Fortier-Davy M, Carhart-Harris R, et al., 2020, Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison., Schizophr Bull, Vol: 46, Pages: 1396-1408
The recent renaissance of psychedelic science has reignited interest in the similarity of drug-induced experiences to those more commonly observed in psychiatric contexts such as the schizophrenia-spectrum. This report from a multidisciplinary working group of the International Consortium on Hallucinations Research (ICHR) addresses this issue, putting special emphasis on hallucinatory experiences. We review evidence collected at different scales of understanding, from pharmacology to brain-imaging, phenomenology and anthropology, highlighting similarities and differences between hallucinations under psychedelics and in the schizophrenia-spectrum disorders. Finally, we attempt to integrate these findings using computational approaches and conclude with recommendations for future research.
Andersen KAA, Carhart-Harris R, Nutt DJ, et al., 2020, Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies, ACTA PSYCHIATRICA SCANDINAVICA, ISSN: 0001-690X
Luppi AI, Mediano PAM, Rosas FE, et al., 2020, A Synergistic Workspace for Human Consciousness Revealed by Integrated Information Decomposition
<jats:title>Abstract</jats:title><jats:p>A central goal of neuroscience is to understand how the brain synthesises information from multiple inputs to give rise to a unified conscious experience. This process is widely believed to require integration of information. Here, we combine information theory and network science to address two fundamental questions: how is the human information-processing architecture functionally organised? And how does this organisation support human consciousness? To address these questions, we leverage the mathematical framework of Integrated Information Decomposition to delineate a cognitive architecture wherein specialised modules interact with a “synergistic global workspace,” comprising functionally distinct gateways and broadcasters. Gateway regions gather information from the specialised modules for processing in the synergistic workspace, whose contents are then further integrated to later be made widely available by broadcasters. Through data-driven analysis of resting-state functional MRI, we reveal that gateway regions correspond to the brain’s well-known default mode network, whereas broadcasters of information coincide with the executive control network. Demonstrating that this synergistic workspace supports human consciousness, we further apply Integrated Information Decomposition to BOLD signals to compute integrated information across the brain. By comparing changes due to propofol anaesthesia and severe brain injury, we demonstrate that most changes in integrated information happen within the synergistic workspace. Furthermore, it was found that loss of consciousness corresponds to reduced integrated information between gateway, but not broadcaster, regions of the synergistic workspace. Thus, loss of consciousness may coincide with breakdown of information integration by this synergistic workspace of the human brain. Together, these findings demonstrate that refining our understanding
Brouwer A, Carhart-Harris RL, 2020, Pivotal mental states., J Psychopharmacol
This paper introduces a new construct, the 'pivotal mental state', which is defined as a hyper-plastic state aiding rapid and deep learning that can mediate psychological transformation. We believe this new construct bears relevance to a broad range of psychological and psychiatric phenomena. We argue that pivotal mental states serve an important evolutionary function, that is, to aid psychological transformation when actual or perceived environmental pressures demand this. We cite evidence that chronic stress and neurotic traits are primers for a pivotal mental state, whereas acute stress can be a trigger. Inspired by research with serotonin 2A receptor agonist psychedelics, we highlight how activity at this particular receptor can robustly and reliably induce pivotal mental states, but we argue that the capacity for pivotal mental states is an inherent property of the human brain itself. Moreover, we hypothesize that serotonergic psychedelics hijack a system that has evolved to mediate rapid and deep learning when its need is sensed. We cite a breadth of evidences linking stress via a variety of inducers, with an upregulated serotonin 2A receptor system (e.g. upregulated availability of and/or binding to the receptor) and acute stress with 5-HT release, which we argue can activate this primed system to induce a pivotal mental state. The pivotal mental state model is multi-level, linking a specific molecular gateway (increased serotonin 2A receptor signaling) with the inception of a hyper-plastic brain and mind state, enhanced rate of associative learning and the potential mediation of a psychological transformation.
Herzog R, Mediano PAM, Rosas FE, et al., 2020, A mechanistic model of the neural entropy increase elicited by psychedelic drugs, Scientific Reports, Vol: 10, ISSN: 2045-2322
Psychedelic drugs, including lysergic acid diethylamide and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain's anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.
Varley TF, Carhart-Harris R, Roseman L, et al., 2020, Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains, NEUROIMAGE, Vol: 220, ISSN: 1053-8119
Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the ‘precision-weighting of priors’, thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.
Spriggs MJ, Kettner H, Carhart-Harris RL, 2020, Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder, EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY, ISSN: 1124-4909
Zeifman R, Wagner A, Watts R, et al., 2020, Post-psychedelic reductions in experiential avoidance are associated with decreases in depression severity and suicidal ideation, Frontiers in Psychiatry, Vol: 11, Pages: 1-13, ISSN: 1664-0640
Psychedelic therapy shows promise as a novel intervention for a wide range of mental health concerns but its therapeutic action is incompletely understood. In line with acceptance and commitment therapy’s (ACT’s) transdiagnostic model, qualitative research has suggested that reductions in experiential avoidance are an important component of therapeutic outcomes associated with psychedelics. However, limited research has quantitatively explored the association between decreases in experiential avoidance and therapeutic outcomes associated with psychedelics. Therefore, in two prospective studies, using convenience samples of individuals with plans to use a psychedelic, we explored the impact of psychedelic use on experiential avoidance, depression severity, and suicidal ideation, as well as relationships between changes in these outcomes. Participants (Study 1, N=104; Study 2, N=254) completed self-report questionnaires of depression severity, suicidal ideation, and experiential avoidance: 1) before using a psychedelic (in ceremonial and non-ceremonial contexts), as well as 2) 2-weeks and 3) 4-weeks after psychedelic use. Across both studies, repeated measures ANOVAs indicated significant decreases in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Furthermore, decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may lead to significant decreases in experiential avoidance, depression severity, and suicidal ideation. Additionally, these findings imply that reduced experiential avoidance may be a transdiagnostic mechanism mediating treatment success within psychedelic therapy. We conclude that integrating psychedelics with psychotherapeutic interventions that target experiential avoidance (e.g. ACT) may enhance therapeutic outcomes.
Carhart-Harris R, 2020, PSYCHEDELICS: THERAPEUTIC MECHANISMS, Annual Meeting of the British-NeuroPsychiatry-Association (BNPA), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
Nutt D, Carhart-Harris R, 2020, The Current Status of Psychedelics in Psychiatry., JAMA Psychiatry
Borissova A, Ferguson B, Wall MB, et al., 2020, Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment, JOURNAL OF PSYCHOPHARMACOLOGY, ISSN: 0269-8811
Herzog R, Mediano PAM, Rosas FE, et al., 2020, A mechanistic model of the neural entropy increase elicited by psychedelic drugs, Publisher: Cold Spring Harbor Laboratory
<jats:title>ABSTRACT</jats:title><jats:p>Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, encoding both acute alterations in consciousness and mediating long-term effects. However, no clear mechanistic explanation for this ‘entropic’ phenomenon has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments <jats:italic>in vivo</jats:italic>, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.</jats:p>
Kringelbach ML, Cruzat J, Cabral J, et al., 2020, Dynamic coupling of whole-brain neuronal and neurotransmitter systems, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 9566-9576, ISSN: 0027-8424
Remarkable progress has come from whole-brain models linking anatomy and function. Paradoxically, it is not clear how a neuronal dynamical system running in the fixed human anatomical connectome can give rise to the rich changes in the functional repertoire associated with human brain function, which is impossible to explain through long-term plasticity. Neuromodulation evolved to allow for such flexibility by dynamically updating the effectivity of the fixed anatomical connectivity. Here, we introduce a theoretical framework modeling the dynamical mutual coupling between the neuronal and neurotransmitter systems. We demonstrate that this framework is crucial to advance our understanding of whole-brain dynamics by bidirectional coupling of the two systems through combining multimodal neuroimaging data (diffusion magnetic resonance imaging [dMRI], functional magnetic resonance imaging [fMRI], and positron electron tomography [PET]) to explain the functional effects of specific serotoninergic receptor (5-HT2AR) stimulation with psilocybin in healthy humans. This advance provides an understanding of why psilocybin is showing considerable promise as a therapeutic intervention for neuropsychiatric disorders including depression, anxiety, and addiction. Overall, these insights demonstrate that the whole-brain mutual coupling between the neuronal and the neurotransmission systems is essential for understanding the remarkable flexibility of human brain function despite having to rely on fixed anatomical connectivity.
Nutt D, Erritzoe D, Carhart-Harris R, 2020, Psychedelic Psychiatry's Brave New World, CELL, Vol: 181, Pages: 24-28, ISSN: 0092-8674
Close JB, Hajien EC, Watts R, et al., 2020, Psychedelics and psychological flexibility - Results of a prospective web-survey using the Acceptance and Action Questionnaire II, JOURNAL OF CONTEXTUAL BEHAVIORAL SCIENCE, Vol: 16, Pages: 37-44, ISSN: 2212-1447
Mertens LJ, Wall MB, Roseman L, et al., 2020, Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 34, Pages: 167-180, ISSN: 0269-8811
Kettner H, Gandy S, Haijen E, et al., 2019, From egoism to ecoism: psychedelics increase nature relatedness in a state-mediated and context-dependent manner, International Journal of Environmental Research and Public Health, ISSN: 1660-4601
(1) Background: There appears to be a growing disconnection between humans and their natural environments which has been linked to poor mental health and ecological destruction. Previous research suggests that individual levels of nature relatedness can be increased through the use of classical psychedelic compounds, although a causal link between psychedelic use and nature relatedness has not yet been established. (2) Methods: Using correlations and generalized linear mixed regression modelling, we investigated the association between psychedelic use and nature relatedness in a prospective online study. Individuals planning to use a psychedelic received questionnaires 2 weeks before (N = 654), plus one day, 2 weeks, 4 weeks, and 2 years after a psychedelic experience. (3) Results: Frequency of lifetime psychedelic use was positively correlated with nature relatedness at baseline. Nature relatedness was significantly increased 2 weeks, 4 weeks and 2 years after the psychedelic experience. This increase was positively correlated with concomitant increases in psychological well-being and dependent on the extent of ego-dissolution and the perceived influence of natural surroundings during the acute psychedelic state. (4) Conclusions: The here presented evidence for a context- and state-dependent causal effect of psychedelic use on nature relatedness bears relevance for psychedelic treatment models in mental health and, in the face of the current ecological crisis, planetary health.
Mertens LJ, Wall MB, Roseman L, et al., 2019, Therapeutic mechanisms of psychedelic drugs: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression, 32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S416-S417, ISSN: 0924-977X
Timmermann Slater CB, Roseman L, Schartner M, et al., 2019, Neural correlates of the DMT experience as assessed with multivariate EEG, Scientific Reports, Vol: 9, Pages: 1-13, ISSN: 2045-2322
Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.
Russ SL, Carhart-Harris RL, Maruyama G, et al., 2019, Replication and extension of a model predicting response to psilocybin, PSYCHOPHARMACOLOGY, Vol: 236, Pages: 3221-3230, ISSN: 0033-3158
Lord L-D, Expert P, Atasoy S, et al., 2019, Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin, NeuroImage, Vol: 199, Pages: 127-142, ISSN: 1053-8119
Growing evidence from the dynamical analysis of functional neuroimaging data suggests that brain function can be understood as the exploration of a repertoire of metastable connectivity patterns ('functional brain networks'), which potentially underlie different mental processes. The present study characterizes how the brain's dynamical exploration of resting-state networks is rapidly modulated by intravenous infusion of psilocybin, a tryptamine psychedelic found in "magic mushrooms". We employed a data-driven approach to characterize recurrent functional connectivity patterns by focusing on the leading eigenvector of BOLD phase coherence at single-TR resolution. Recurrent BOLD phase-locking patterns (PL states) were assessed and statistically compared pre- and post-infusion of psilocybin in terms of their probability of occurrence and transition profiles. Results were validated using a placebo session. Recurrent BOLD PL states revealed high spatial overlap with canonical resting-state networks. Notably, a PL state forming a frontoparietal subsystem was strongly destabilized after psilocybin injection, with a concomitant increase in the probability of occurrence of another PL state characterized by global BOLD phase coherence. These findings provide evidence of network-specific neuromodulation by psilocybin and represent one of the first attempts at bridging molecular pharmacodynamics and whole-brain network dynamics.
Roseman L, 2019, Functional imaging investigation of psychedelic visual imagery
Psychedelics can induce eyes-closed imagery in which various visions can be experienced. These visions vary from simple geometrical patterns, to more complex imagery, to full immersion within “other realms”. Past studies suggest that the visual cortex is involved in processing these visions, yet these studies were limited into investigation of activity. In this thesis, the aim was to expand on the involvement of the visual cortex by investigating processes that are beyond simple activation maps, such as functional connectivity and dynamics. In study 1, it was hypothesized that the visual cortex will show increased functional connectivity with many cortical and subcortical regions. This was investigated with 15 subjects that were scanned using fMRI under the influence of 75 µg of LSD or placebo. The results of this study showed increased resting state functional connectivity (RSFC) between the primary visual cortex and many cortical and subcortical regions. This result correlated with subjective ratings of psychedelic imagery and with occipital alpha power suppression measured with MEG, which is a reliable neural correlate of the intensity of the psychedelic state. It study 2, it was hypothesized that connectivity within the visual cortex would match its retinotopic architecture. Retinotopic mapping is the representation of the visual field (the world we observe) in the visual cortex – e.g. areas which are near to each other in the visual field will be near each other in the visual cortex. In this study, it was found that under LSD (same procedure as study 1), with eyes closed, connectivity patterns between different subregions of the visual cortex matched the retinotopic mapping of these regions, suggesting that the visual system behaves as if it is seeing spatially localized input, with eyes-closed under LSD. In study 3, it was hypothesized that during the onset phase of psychedelic imagery, the activation of subregions of the visual cortex
Timmermann C, Roseman L, Schartner M, et al., 2019, Neural correlates of the DMT experience as assessed via multivariate EEG, Publisher: Cold Spring Harbor Laboratory
<jats:title>Abstract</jats:title><jats:p>Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT – a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the <jats:italic>alpha</jats:italic> and <jats:italic>beta</jats:italic> bands and robustly increased spontaneous signal diversity. Time-referenced analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience, and particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the relevant subjective experience and thus further our understanding of the neurobiological underpinnings of immersive states of consciousness.</jats:p>
Roseman L, Haijen E, Idialu-Ikato K, et al., 2019, Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory, Journal of Psychopharmacology, Pages: 026988111985597-026988111985597, ISSN: 0269-8811
<jats:sec><jats:title>Background:</jats:title><jats:p> Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45). </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach’s alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being ( r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores
Carhart-Harris RL, Friston KJ, 2019, REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics, PHARMACOLOGICAL REVIEWS, Vol: 71, Pages: 316-344, ISSN: 0031-6997
Scott G, Carhart-Harris R, 2019, Psychedelics as a treatment for disorders of consciousness, Neuroscience of Consciousness, Vol: 2019, Pages: 1-8, ISSN: 2057-2107
Based on its ability to increase brain complexity, a seemingly reliable index of conscious level, we proposetesting the capacity ofthe classic psychedelic, psilocybin,to increase conscious awarenessin patients with disorders of consciousness.We alsoconfrontthe considerable ethical and practical challengesthis proposal must address, if this hypothesis is to be directly assessed.
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