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Journal articleShinozuka K, Tewarie PKB, Luppi A, et al., 2025,
LSD flattens the hierarchy of directed information flow in fast whole-brain dynamics
, Imaging Neuroscience, Vol: 3Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed functional connectivity. We measure properties of directed functional hierarchy in a magnetoencephalography (MEG) dataset of 16 healthy human participants who were administered a psychedelic dose (75 micrograms, intravenous) of lysergic acid diethylamide (LSD) under four different conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. Across the whole brain, LSD diminishes the asymmetry of directed connectivity when averaged across time. Additionally, we demonstrate that machine learning classifiers distinguish between LSD and placebo more accurately when trained on one of our hierarchy metrics than when trained on traditional measures of functional connectivity. Taken together, these results indicate that LSD weakens the hierarchy of directed connectivity in the brain by increasing the balance between senders and receivers of neural signals.
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Journal articleGodfrey K, Weiss B, Zhang X, et al., 2025,
An investigation of acute physiological and psychological moderators of psychedelic-induced personality change among healthy volunteers
, Neuroscience Applied, Vol: 4This study investigated the effects of a single high-dose of psilocybin on personality traits in psychedelic-naïve healthy volunteers. These data originate from a larger within-subjects fixed-order design trial, where a single high dose of psilocybin (25 mg) was administered in a psychologically supportive setting and was compared against a (one-month) prior, 1 mg ‘placebo’ dose. Personality shifts were assessed by the Big Five Inventory and the Big Five Aspect Scale, while the Altered States of Consciousness questionnaire (5D-ASC) and the Psychological Insight Scale gauged the acute psychological effects of the substance. Electroencephalography provided neurophysiological insights, specifically examining alpha power and Lempel-Ziv complexity (LZc). Results indicated significant reductions in neuroticism one month after 25 mg psilocybin administration, a finding consistent with prior studies. Reductions in neuroticism were moderated by the subjective meaningfulness of the psychedelic experience, as well as by the dread of ego dissolution subscale of the 5D-ASC, suggesting a relationship between acute drug effects and enduring personality alterations. Thus, this study substantiates the role of acute psychedelic states in catalysing lasting personality transformations in a generally beneficial direction, with broader implications for therapeutic applications and understanding of personality dynamics.
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Journal articleHarding R, Singer N, Wall MB, et al., 2025,
Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises
, Molecular Psychiatry, ISSN: 1359-4184Psilocybin therapy (PT) is emerging as an effective intervention for Major Depressive Disorder (MDD), offering comparable efficacy to conventional treatments like selective serotonin reuptake inhibitors (SSRIs). Music, an emotionally evocative stimulus, provides a valuable tool to explore changes in hedonic and predictive processing mechanisms via expectancy violations, or ‘surprises’. This study sought to compare behavioural and functional magnetic resonance imaging (fMRI) responses to musical surprises in MDD patients treated with either PT or the SSRI, escitalopram. In this secondary analysis of a trial, 41 MDD patients (with usable fMRI data) were randomly assigned to either PT (n = 22) or escitalopram (n = 19) treatment groups. Participants listened to music during fMRI and tracked their emotional experience, both before and after a 6-week intervention. Surprise-related valence and arousal indices were calculated. Musical surprises were entered as regressors for whole-brain and region of interest fMRI analyses. PT caused a greater decrease in anhedonia scores compared with escitalopram. While escitalopram led to reductions in surprise-related affective responses, PT showed no significant change. Escitalopram was associated with increased activation in memory and emotional processing areas during musical surprises (versus control events) when compared with PT. Following PT, there was greater activation in the ventromedial prefrontal cortex and sensory regions, and reduced activation in the angular gyrus. PT may allow for the subjective response to musical surprises to be maintained through a lasting reduction in the salience of prediction errors, or, alternatively, by increasing hedonic priors. Contrastingly, escitalopram may diminish hedonic priors, highlighting fundamental differences in treatment mechanisms.
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Journal articleO'Connor S, Godfrey K, Reed S, et al., 2025,
Correction: Study Protocol for 'PsilOCD: A Pharmacological Challenge Study Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity'.
, Cureus, Vol: 17, ISSN: 2168-8184[This corrects the article DOI: 10.7759/cureus.78171.].
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Journal articleKettner H, Roseman L, Gazzaley A, et al., 2025,
Reply to Letter to the Editor: "Psychedelics in Older Adults: Difficulties of a Clear Therapeutic Evidence".
, Am J Geriatr Psychiatry, Vol: 33, Pages: 118-119 -
Journal articleO'Connor S, Godfrey K, Reed S, et al., 2025,
Study Protocol for 'PsilOCD: A Pharmacological Challenge Study Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity'.
, Cureus, Vol: 17, ISSN: 2168-8184BACKGROUND: Obsessive-compulsive disorder (OCD) is a complex condition marked by persistent distressing thoughts and repetitive behaviours. Despite its prevalence, the mechanisms behind OCD remain elusive, and current treatments are limited. This protocol outlines an investigative study for individuals with OCD, exploring the potential of psilocybin to improve key components of cognition implicated in the disorder. The PsilOCD study strives to assess the effects of low-moderate psilocybin treatment (10 mg) alongside non-interventional therapy on several facets of OCD. The main focus points of PsilOCD are cognitive flexibility, measured with cognitive tests, and neuroplasticity, assessed through electroencephalography (EEG). METHODS: 20 blinded participants with OCD will complete two dosing sessions, separated by four weeks, where they will receive 1 mg of psilocybin on the first and 10 mg on the second. The first dose serves as an active placebo, and the latter is a low-moderate dose that induces relatively mild-moderate emotional and perceptual effects. Participants will be supported by trained psychedelic therapists, who will sit with them during each dosing session and provide virtual preparation and integration sessions over the 12-week study period. Therapeutic support will be the same for both the 1 mg and 10 mg sessions. PsilOCD's primary outcomes include scores in the intradimensional-extradimensional (ID-ED) shift task, which is an established measure of cognitive flexibility, and neuroplasticity as quantified by a visual long-term potentiation (vLTP) task. This task is delivered as part of an EEG paradigm and measures acute quantified changes in neuroplasticity in the brain's visual system. The ID-ED task will be conducted twice, two days after each dosing session, and the EEG recordings will also be taken twice, immediately after each session. Secondary outcome assessments will include OCD and affective symptom severity, as well as an array of patien
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Journal articleJiwani Z, Goldberg SB, Stroud J, et al., 2025,
Can psychedelic use benefit meditation practice? Examining individual, psychedelic, and meditation-related factors.
, PLoS One, Vol: 20INTRODUCTION: Meditation practice and psychedelic use have attracted increasing attention in the public sphere and scientific research. Both methods induce non-ordinary states of consciousness that may have significant therapeutic benefits. Thus, there is growing scientific interest in potential synergies between psychedelic use and meditation practice with some research suggesting that psychedelics may benefit meditation practice. The present study examined individual, psychedelic-related, and meditation-related factors to determine under what conditions meditators perceive psychedelic use as beneficial for their meditation practice. METHOD: Participants (N = 863) who had reported psychedelic use and a regular meditation practice (at least 3 times per week during the last 12 months) were included in the study. To accommodate a large number of variables, machine learning (i.e., elastic net, random forest) was used to analyze the data. RESULTS: Most participants (n = 634, 73.5%) found psychedelic use to have a positive influence on their quality of meditation. Twenty-eight variables showed significant zero-order associations with perceived benefits even following a correction. Elastic net had the best performance (R2 = .266) and was used to identify the most important features. Across 53 variables, the model found that greater use of psychedelics, intention setting during psychedelic use, agreeableness, and exposure to N,N-Dimethyltryptamine (N,N-DMT) were most likely to be associated with the perception that psychedelics benefit meditation practice. The results were consistent across several different approaches used to identify the most important variables (i.e., Shapley values, feature ablation). DISCUSSION: Results suggest that most meditators found psychedelic use to have a positive influence on their meditation practice, with: 1) regularity of psychedelic use, 2) the setting of intentions for psychedelic use, 3) having an agreeable personality, and 4) reported
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Book chapterCherniak AD, Carhart-Harris R, Gruneau Brulin J, et al., 2024,
Synthesizing Attachment Theory with the REBUS Model
, The Oxford Handbook of Psychedelic, Religious, Spiritual, and Mystical Experiences, Publisher: Oxford University Press, ISBN: 9780192844064<jats:title>Abstract</jats:title> <jats:p>In this chapter, the authors synthesize the relational developmental perspective of attachment theory with a neuroscientific model: the RElaxed Beliefs Under pSychedelics (REBUS). This synthesis, the authors argue, can serve as an organizing framework for psychedelic science. Attachment theory posits that people develop internal working models (IWMs) of relational experiences with close others. These IWMs function as predictive models (“priors”) that, for better and for worse, contribute to people’s social and emotional worlds and organize how they navigate them. Effective psychedelic interventions may work by inducing a hyper-plastic neural state that, supported by corrective relational experiences (with therapists, God, or others), facilitates rapid and deep learning. This can include revision of IWMs toward greater security and other psychological transformations. Based on the attachment-REBUS synthesis, the authors describe three main proposals to guide future research. First, individual differences in attachment security predict the phenomenology of psychedelic experiences and processes related to their integration. Second, increasing attachment security may be a clinical outcome of efficacious psychedelic therapy. Third, among other process-level mechanisms, the clinical utility of psychedelic treatment involves attachment-related dynamics (e.g., connectedness to others and God, alleviation of attachment-related worries and defenses). Finally, the authors provide words of caution and future directions.</jats:p>
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Journal articleShinozuka K, Jerotic K, Mediano P, et al., 2024,
Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology
, TRANSLATIONAL PSYCHIATRY, Vol: 14, ISSN: 2158-3188 -
Journal articleMeshkat S, Tello-Gerez TJ, Gholaminezhad F, et al., 2024,
Impact of psilocybin on cognitive function: A systematic review
, PSYCHIATRY AND CLINICAL NEUROSCIENCES, Vol: 78, Pages: 744-764, ISSN: 1323-1316
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