Publications

Journal article

Subramani V, Nest T, Pascarella A, Brunel J, Mantilla Ramos YJ, Harel Y, Muthukumaraswamy S, Carhart-Harris R, Lioi G, Farrugia N, Jerbi Ket al., 2026,

LSD reconfigures cortical dynamics through faster brain rhythms and increased fractal dimension.

, Commun Biol, Vol: 9

Lysergic acid diethylamide (LSD) profoundly alters conscious experience, yet the electrophysiological mechanisms by which it reshapes neural dynamics remain incompletely understood. A hallmark of psychedelic states is widespread cortical desynchronization, typically inferred from reductions in spectral power, but whether such effects reflect genuine weakening of neural oscillations or are confounded by shifts in oscillatory peak frequencies remains unresolved. We combine source-resolved magnetoencephalography (MEG), spectral parameterization, temporal complexity metrics, and interpretable machine learning in an LSD versus placebo design, with and without music. We show that LSD induces robust, spatially structured increases in alpha and beta peak frequencies alongside genuine attenuation of oscillatory power, with partly dissociable cortical patterns. Beyond rhythmic activity, LSD is associated with flattening of the aperiodic 1/f spectral slope and increased neural signal fractality and complexity, preferentially affecting sensory, language, emotion, and imagery-related networks while sparing motor cortex. Machine-learning analyses identify peak-frequency shifts, aperiodic parameters, and complexity measures as key discriminators of the psychedelic state. Music does not robustly amplify these neural signatures and instead shows a trend toward attenuation. These findings provide an electrophysiological account of how LSD reorganizes large-scale human brain dynamics and highlight features that may differentiate its neural signature from other psychedelics.

Journal article

Carhart-Harris RL, 2026,

The entropic brain today.

, Brain, Vol: 149, Pages: 3362-3378

Introduced in 2014 and revised in 2018, the entropic brain hypothesis has accrued a wealth of supportive evidence. The hypothesis states that-along a dimension of 'the size of phenomenal consciousness'-expansive states reliably exhibit increased brain entropy, whereas the inverse applies for states of no or reduced consciousness. Examples of expansive states include expert meditation, flicker-light stimulation, near-death-like experiences, atypical breathing, REM sleep, the pre-ictal aura, unmedicated early psychosis and psychedelic drug states. Examples of states of no or reduced consciousness with low brain entropy, include disorders of consciousness, deep sleep, the anaesthetized state, seizure, post-stroke, ageing, cognitive impairment and neurodegenerative illness. It is shown that the entropic brain has convergent, correlative, predictive, discriminative and external validity. Regarding its predictive validity, increased brain entropy under psilocybin (in a supportive context) predicts subsequent improvements in mental health (improved well-being 1-month post-dose). Regarding its discriminative validity, changes in brain entropy selectively index the 'breadth of subjective experience' versus alternative dimensions, such as arousal. Regarding portability/external validity, an entropy-related function is applied in generative artificial intelligence. In conclusion, the entropic brain is a useful model of conscious states.

Journal article

Kroupi E, Araujo H, Oosterveld C, Timmermann C, Rosas F, Carhart-Harris R, Ruffini G, Soria-Frisch Aet al., 2026,

Higher signal diversity, network dysregulation, and increased well-being under DMT administration: An EEG study.

, Brain Res, Vol: 1892

N,N-Dimethyltryptamine (DMT), a potent serotonin-2A receptor agonist, elicits intense psychedelic experiences and has become a focus of interest in neuroscience and mental health research. While EEG studies of psychedelics typically report reduced alpha power, increased delta power, and enhanced signal complexity-primarily assessed using Lempel-Ziv complexity (LZc)-less is known about DMT's effects on other complexity metrics, EEG-based connectivity, and emotional correlates. This study investigated the effects of intravenous DMT versus saline placebo in 13 healthy participants using EEG. We analyzed spectral power, brain signal complexity, and functional connectivity, and examined their associations with emotional responses and subjective intensity ratings. Four complexity measures were evaluated: Lempel-Ziv-Welch (LZW) complexity, Higuchi fractal dimension (HFD), permutation entropy (PE), and waveform complexity (WC). Connectivity was assessed using weighted symbolic mutual information (wSMI), with network segregation and efficiency inferred from clustering coefficient and path length. Emotional correlates included beta-to-alpha ratio (BAR, an indicator of arousal) and frontal alpha asymmetry (FAA, an indicator of well-being). DMT significantly reduced broadband wSMI connectivity, segregation, and efficiency, particularly in alpha and beta bands in posterior and frontoparietal regions. Complexity metrics positively correlated with subjective intensity; HFD and PE were the most sensitive, revealing increased complexity in beta/gamma and decreased complexity in delta/theta/alpha bands under DMT. BAR and FAA both increased under DMT, correlating with perceived intensity. These findings suggest that DMT induces greater neural unpredictability and emotional arousal, consistent with the Entropic Brain theory. The results highlight a dynamic brain state that may support therapeutic brain network reorganization relevant for psychiatric treatment.

Journal article

Carhart-Harris RL, Rosenblat JD, 2026,

Psychedelics Trials and Outcomes-A Closer Look.

, JAMA Psychiatry, Vol: 83, Pages: 990-991

Journal article

Hancock F, Kee R, Rosas F, Girn M, Kotler S, Mannino M, Huskey Ret al., 2026,

A complexity-science framework for studying flow: using media to probe brain-phenomenology dynamics.

, 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.

Journal article

Austin B, Kurtin DL, Herlinger K, Hayes A, Hand LJ, Fonville L, Hill RG, Nutt DJ, Lingford-Hughes AR, Paterson LMet al., 2026,

Investigating hierarchical control among functional networks disrupted by Opioid Use Disorder using effective connectivity

, 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

Journal article

Rosas De Andraca FE, 2026,

Symmetry as a common origin of hierarchical emergence and abstraction

, Science Advances, ISSN: 2375-2548

Cite

Journal article

Ostrand AE, Nour MM, Timmermann C, Rosati A, Luan LX, Gomez-Emilsson A, Bornemann J, Greenway KT, Roseman L, R C-Het al., 2026,

Defining 'psychedelic'.

, 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.

Journal article

McConnell PA, Raffety J, Li A, Steinberg E, Rahim S, Valtierra C, Gazzaley A, Carhart-Harris RL, Pasquini Let al., 2026,

Cross-species mapping of acute psychedelic-responsive genes links HTR2A cortical expression, cell-type enrichment, and human cortical expression modules

, Translational Psychiatry

<jats:title>Abstract</jats:title> <jats:p> Psychedelic drugs exert rapid and profound effects on human consciousness [1–7] and are increasingly being investigated for their therapeutic potential [8–14]. Yet the transcriptional programs through which they may reshape brain function and structure remain incompletely understood, in part because the available evidence is heterogeneous and largely preclinical [15, 16]. In a structured scoping review of transcriptomic studies in animal models and neural cell cultures, we identified genes reported in the source literature to change within 3 h of classical psychedelic administration and intersected them with the Allen Human Brain Atlas to define an acute expression set. This retained set showed cortex-centered enrichment, a marker-based deep-layer projection-neuron component, and ontology enrichment for neuron projection and related synaptic terms. A smaller subset overlapped with human accelerated region-associated genes and showed greater-than-random spatial alignment with a human cortical-expansion map. The retained cortical-expression maps showed serotonergic spatial alignment in the human cortex, most prominently with <jats:italic>HTR2A</jats:italic> expression. Clustering identified three cortical spatial-expression modules, including an association/limbic-weighted module enriched for plasticity and synaptic-organization terms. Together, these findings provide a human cortical framework linking acute psychedelic-responsive transcription to cortical cell-type enrichment, <jats:italic>HTR2A</jats:italic> spatial expression, cortical spatial-expression modules, and cortical-expansion, while leaving receptor-specific, causal, translational, and cell-type-resolved mechanisms for future work. </jats:p>

Journal article

Goodwin GM, Aaronson ST, Alvarez O, Carhart-Harris R, Croal M, Feifel D, Hellerstein DJ, Husain MI, Kelly JR, Kirlic N, Licht RW, Marwood L, Nowakowska A, Páleníček T, Repantis D, Schoevers RA, Simmons H, Soares JC, Somers M, Tsai J, Wahba M, Williams E, Young AH, Young MB, Zisook S, Malievskaia Eet al., 2026,

The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis.

, 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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Symmetry as a common origin of hierarchical emergence and abstraction