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Journal articleCarhart-Harris RL, Rosenblat JD, 2026, , JAMA Psychiatry, Vol: 83, Pages: 990-991
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Journal articleHancock F, Kee R, Rosas F, et al., 2026, , Neuroimage, Vol: 338
Consciousness spans a range of phenomenological experiences, from effortless immersion to disengaged monotony, yet how such phenomenology emerges from brain activity is not well understood. Flow, a phenomenological experience frequently elicited by interactive media, has drawn attention for its links to performance and wellbeing, but existing neural accounts rely on single-region or small-network analyses that overlook the brain's distributed and dynamic nature. Complexity science offers tools that capture brain-wide dynamics, but this approach has rarely been applied to flow or to its natural comparisons: boredom and frustration. Consequently, it remains unclear whether tools drawn from complexity science can objectively discriminate between these phenomenological experiences while also clarifying their neural basis. To address this uncertainty, we induced each phenomenological experience with a difficulty-titrated video game during functional magnetic resonance imaging and collected concurrent behavioral and self-report data. Our complex systems analyses revealed that flow, in this experimental setup, shows an inverse relationship to global entropy with moderate explanatory power, and is not explained by either synchronization or metastability, whereas boredom and frustration exhibit different configurations of brain-dynamics metrics. Notably, these findings integrate previously separate prefrontal and network-synchrony observations within a single dynamical systems framework and identify complexity-based markers with the potential to map the neural underpinnings of media-related benefits.
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Journal articleAustin B, Kurtin DL, Herlinger K, et al., 2026, , Imaging Neuroscience, ISSN: 2837-6056
Opioid use disorder (OUD) poses a significant public health challenge. Developing a better understanding of the brain mechanisms and potential markers of OUD would facilitate the development of therapeutic interventions. While we recently showed that between-network connectivity is disrupted in people with OUD compared with healthy controls, it remains unclear what mechanisms may drive these disruptions and how dysfunctional interactions propagate across large scale functional networks. To advance the mechanistic understanding of the disrupted processes in OUD, this study used Effective Connectivity (EC) to quantify disrupted hierarchical control among functional networks governing cognition, attention, and reward. We also explored whether whole-brain patterns of EC were effective markers to distinguish people with severe OUD from controls. We hypothesised that the ventromedial network (VMN) would drive dysfunction in cognitive and attentional networks in people with OUD. Task-fMRI data was collected from healthy controls (HC; n=22) and OUD participants on methadone maintenance treatment (OUD; n=25), during a heroin cue reactivity (CR) and monetary incentive delay (MID) task. Following brain parcellation (214 regions) and network assignment (7 functional networks), EC was quantified using large scale nonlinear Granger causality. Dimensionality reduction was performed using uniform manifold approximation and projection, followed by hierarchical density-based spatial clustering of applications with noise to assess whether EC patterns could form clusters corresponding to group labels.Contrary to our hypothesis, the VMN did not drive dysfunction in cognitive and attentional networks. Instead, edges with significantly stronger EC in HC vs OUD participants were within and between the control, somatomotor, and default mode networks. EC patterns were unable to form distinct clusters that corresponded to clinical groups; instead, clusters separated by task. Little evidence w
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Journal articleRosas De Andraca FE, 2026,
Symmetry as a common origin of hierarchical emergence and abstraction
, Science Advances, ISSN: 2375-2548 -
Journal articleOstrand AE, Nour MM, Timmermann C, et al., 2026, , J Psychopharmacol
Humphry Osmond coined the term 'psychedelic' in 1956, conjoining 'psyche' for 'soul' and 'delic' for 'to manifest' or 'illuminate'. Soul-illumination is a compound noun that describes a psychological state or process. Osmond intended for it to be a taxonomic noun-naming, not just a state-but a category of drug that can induce this psychological effect as its principal action. Consistent with the etymology of psychedelic, the present work respects the fundamental importance of phenomenology. Accordingly, we examine the main subjective effect of three different psychoactive drugs, psilocybin, ketamine, and MDMA (3,4-methylenedioxymethamphetamine) (variable label, Drug). Over 200 participants rated Delphi-generated subjective rating scale items based on their personal experiences with all 3 drugs. Factor analyses revealed three or four sufficiently independent dimensions of subjective experience (variable label, Effects). A machine-learning classifier successfully predicted Drug from Effects, validating the hypothesis that psilocybin, ketamine and MDMA have categorically distinct subjective effect profiles, differentiable by (1) visions and psychological insight (psilocybin), (2) dissociation (ketamine) and (3) pro-social and loving feelings (MDMA). We conclude that psilocybin is an exemplar psychedelic-a category of drug definable by the induction of a psychedelic state. The quintessential psychedelic phenomenon is a subjective state characterized by visions and psychological insight.
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Journal articleGoodwin GM, Aaronson ST, Alvarez O, et al., 2026, , J Affect Disord, Vol: 406
INTRODUCTION: The contribution of patient support to psilocybin's antidepressant effects remains uncertain. METHODS: Relationships between therapeutic alliance (Scale to Assess Therapeutic Relationship-Patient version; STAR-P), psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire and Emotional Breakthrough Inventory; 5D-ASC and EBI) and clinical outcomes (Montgomery-Åsberg Depression Rating Scale; MADRS) were explored using correlation and path analysis for individuals with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support (N = 79). RESULTS: Change from Baseline to Week 3 MADRS scores showed weaker correlations with pre-dosing therapeutic alliance (-0.178) than with measures of the psychedelic experience: EBI (-0.637), Oceanic Boundlessness (-0.508), and Visual Restructuralization (-0.516). Path analysis showed no nominally significant direct effects of therapeutic alliance on Week 3 MADRS scores, but there were nominally significant effects of therapeutic alliance on psychedelic experience (Oceanic Boundlessness (β = 0.28), Visual Restructuralization (β = 0.27), and Auditory Alterations (β = 0.25)). Only one indirect effect of therapeutic alliance on clinical outcome reached nominal significance (via Visual Restructuralization; β = -0.15). Stronger effects were seen on clinical outcomes for psychedelic experience (EBI (β = -0.59), Oceanic Boundlessness (β = -0.53), Visual Restructuralization (β = -0.54), and Auditory Alterations (β = -0.24)). CONCLUSIONS: The therapeutic alliance appeared to facilitate the psychedelic experience, and these experiences in turn had stronger nominally significant direct effects on clinical outcomes. The effects of the alliance itself on therapeutic efficacy were either limited or absent. TRIAL REGISTRATION: EudraCT number: 2017
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Journal articleStoliker D, Novelli L, Khajehnejad M, et al., 2026, , Nature, Vol: 656, Pages: 936-947
Psychedelics can profoundly alter consciousness by reorganizing brain connectivity1,2, producing acute experiences that shape lasting psychological change3,4. Psychedelic dynamics are commonly described as desynchronized or entropically disordered5,6, yet the brain organization underlying self-dissolving and boundary-dissolving experiences that participants often report7, and how context shapes that organization8, remain unresolved. To address this, we acquired the largest single-site psychedelic neuroimaging dataset to date. Sixty-two adults underwent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) during rest and naturalistic stimuli (meditation, music and movie), before and on the day of psilocybin administration (fMRI ~ 80 min post-dose; EEG ~ 150 min post-dose). Half ranked the experience among the most meaningful of their lives7. Here, using machine learning to represent the brain dynamics of each individual as low-dimensional trajectories, we show that psilocybin reorganizes brain activity into structured, context-sensitive patterns that co-vary with the quality of subjective experience, revealing a latent order missed by time-averaged measures. Networks that ordinarily segregate internal and external processing integrated, producing cohesive context-aligned trajectories in participants reporting the felt experience of being continuous with, rather than separate from, the environment, a state we refer to as embeddedness. The strength of this context alignment scaled with both the depth of self-dissolving and boundary-dissolving experience and the next-day mindset change. Our findings recast apparent disorder as latent organization aligned with context, linking neurobiology to subjective experience and behavioural change.
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Journal articleAgnorelli C, Peill J, Sawicka G, et al., 2026, , J Cereb Blood Flow Metab, Vol: 46, Pages: 2125-2137
We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and resting-state fMRI (intrinsic brain activity, functional connectivity), before and after ketamine. While group-level analyses showed no significant increases in PET synaptic markers, ketamine administration resulted in significantly elevated glutamate levels within the anterior cingulate cortex (ACC). Functional connectivity analyses revealed reduced coupling between the ACC and the dorsolateral prefrontal cortex (dlPFC) and increased coupling between the ACC and the amygdala in the days following ketamine administration. Our multimodal analysis revealed that participants showing an increase in [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, showed a correlated reduction in intrinsic activity within regions belonging to the default mode network (DMN). By linking molecular, cellular and network-level changes, our results point to the DMN as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.
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Journal articleBailey NW, Webb SL, Fitzgibbon BM, et al., 2026, , J Psychopharmacol
BACKGROUND: Research indicates psychedelics hold therapeutic potential, but possible deleterious effects have been insufficiently examined. We explored working memory (WM) performance and WM-related neurophysiological activity before and after exposure to psilocybin or 3,4-methylenedioxymethamphetamine (MDMA) in an uncontrolled study. METHODS: Healthy participants were exposed to a single dose of psilocybin or MDMA (data analysed from 29 participants for each drug, with 16 receiving both drugs after >3-month washout). One to 16 days before and 5-16 days after dosing, participants completed a 3back WM task and eyes-closed resting with electroencephalography (EEG), plus a 3back during a 3-month remote follow-up. RESULTS: After dosing, both groups showed increased alpha to gamma WM-related oscillatory power (p < 0.001). After psilocybin, participants showed steeper WM-related aperiodic slopes (p = 0.018), an effect maximal in occipital electrodes (p < 0.001, Cohen's d = 0.802, BF10 = 155.138), and significant in occipital electrodes during resting (p = 0.008). The MDMA group showed improved task accuracy in the post-dosing EEG session (p = 0.005, Cohen's d = 0.561, BF10 = 7.809). Both groups showed improved accuracy at 3-months (p-holm < 0.001, Cohen's d = 0.678, BF10 = 272.074). CONCLUSIONS: Our results are suggestive of enduring neurophysiological effects following a single dose of MDMA or psilocybin. Our results do not support concerns about cognitive impairments from single exposures to MDMA or psilocybin in controlled settings, suggesting clinical utility does not risk impairing WM. However, given the uncontrolled study design, future research is required to confirm our observations reflect drug-induced neurophysiological changes.
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Journal articleDouglass HM, Spriggs MJ, Godfrey K, et al., 2026, , Br J Psychiatry, Pages: 1-9
BACKGROUND: Anorexia nervosa is a debilitating eating disorder with high mortality and chronicity rates owing to the paucity of effective existing treatments. Several clinical trials using psilocybin therapy have demonstrated therapeutic efficacy and safety in psychiatric conditions, including anorexia nervosa. AIMS: This study aimed to further assess the safety, feasibility and potential efficacy of psilocybin therapy in anorexia nervosa. METHOD: This single-blind, within-individual pilot study recruited 21 females with anorexia nervosa, who underwent three dosing sessions with oral psilocybin (COMP360) over 6 weeks in a fixed order (1 mg, 25 mg, 25 mg), alongside talk therapy and adjunctive to treatment as usual. Adverse events were monitored throughout the study. Primary clinical outcome measures were global Eating Disorder Examination Interview (EDE) and Readiness and Motivation Questionnaire (RMQ) precontemplation scores. Primary time points for the EDE were the 6-week final visit, 3-month follow-up and 6-month follow-up; and for the RMQ, they were the 6-week final visit and comparison between dosing days. Global EDE Questionnaire scores were a key secondary outcome. Key time points were the 6-week final visit and comparison between dosing days. There was a 12-month remote follow-up. RESULTS: Psilocybin was well tolerated by all participants. The most common adverse events were headache, nausea and dizziness. Two serious adverse events (suicide attempts) were reported for one participant within the 6-12-month period. Relative to baseline, participants displayed significant improvements in their eating disorder symptoms (EDE scores: p < 0.0001, d = 0.98, 6 months) and motivation to change (RMQ scores: p = 0.0017, d = 0.65, 12 months). However, there was a large variation in improvement and maintenance during the follow-up. CONCLUSIONS: This study further provides preliminary support for the feasibility, safety and potential efficacy of this intervention to tr
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