Nature Communications - The Consciousness Library

The mPFC-reuniens-hippocampus pathway links brain circuitry and neural plasticity in antidepressant response

Nature Communications September 1, 2026 Maxime Veleanu, Louise E. Schuberth, Antje Kilias et al.

The pathophysiology of depression involves multiple biological processes, including circuit dysfunction and impaired neuroplasticity, yet an integrative view linking these processes remains elusive. Here, we identify a convergent circuit for antidepressant response and plasticity modulation. We demonstrate that chemogenetic activation of the infralimbic cortex (IL) exerts rapid...

DOI: 10.1038/s41467-026-77248-y Full text

Psilocybin enhances sociability only in altered behavioural state and does not need an awake experience to be effective

Nature Communications August 27, 2026 Chenchen Song, Tinya Chang, Tobias Buchborn et al.

Psilocybin, a psychoactive compound contained in certain mushrooms, can provoke profound psychedelic experiences and also exerts established and controversial therapeutic efficacy in clinical depression and other neuropsychiatric conditions respectively. Here we report that a single systemic administration of the serotonergic psychedelic psilocybin can durably promote social behaviour in the...

DOI: 10.1038/s41467-026-77238-0 Full text

Serotonergic psychedelics induce distinct patterns of metabolic activity and covariance within biologically informed rat brain networks

Nature Communications August 3, 2026 Frederik Gudmundsen, Julia Czurylo, Daniel Ryskamp Rijsketic et al.

Serotonergic psychedelics show therapeutic potential across neuropsychiatric disorders despite transient acute effects. These compounds share serotonin 2 A receptor agonism but differ in broader pharmacology, motivating a systematic comparison of their neurobiological effects. Here, we use [18 F]FDG-PET in rats to assess acute and one-week effects of psilocybin, LSD, and 2C-B on brain metabolic...

DOI: 10.1038/s41467-026-75890-0 Full text

Multi-metric evaluations of acute psychedelic effects on fMRI brain entropy

Nature Communications June 24, 2026 Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al.

A prominent theory of psychedelics is that they increase brain entropy. Thirteen studies have evaluated psychedelic effects on fMRI brain entropy, each applying a distinct measure. Here we evaluated these metrics in an independent 28-participant healthy cohort with 121 pre- and post-psilocybin fMRI scans. We assessed relations between brain entropy and objective and subjective psychedelic drug...

DOI: 10.1038/s41467-026-74215-5 Sample entropy Voxel Neuroimaging Pattern recognition psychology +3

A week in the life of the human brain reveals stable states punctuated by chaotic-like transitions.

Nature Communications June 5, 2026 Maxwell B Wang, Max G'Sell, James F Castellano et al.

Critical real-world neurocognitive processes, such as settling into a conversation and neurophysiological fluctuations, vary over minutes-to-days in real-world environments. We harnessed simultaneous multi-electrode intracranial and video recordings in twenty people during a week of unconstrained, spontaneous behavior. Using dynamical deep learning algorithms, we found neurodynamics linked to...

DOI: 10.1038/s41467-026-73347-y Full text

The act of detecting a stimulus contaminates measures of conscious experience with decision biases.

Nature Communications May 8, 2026 Nicolás Sánchez-Fuenzalida, Chris Jungerius, Stephen M Fleming et al.

A central challenge in consciousness research is determining whether observers have a conscious experience of a stimulus. However, present/absent detection judgments are often biased by contextual factors, making it difficult to isolate conscious perception from non-perceptual influences. Traditional psychophysical methods struggle to disentangle these components. To address this, we conducted...

DOI: 10.1038/s41467-026-72567-6 Full text

Human brain changes after first psilocybin use.

Nature Communications May 5, 2026 T Lyons, M Spriggs, L Kerkelä et al. 19 citations

Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain...

DOI: 10.1038/s41467-026-71962-3 Full text

Sex-specific increased reactivity of the PVT and prolonged PVT→CeA circuit engagement following psilocin administration.

Nature Communications April 10, 2026 Devin P. Effinger, J L Hoffman, Sema G. Quadir et al. 1 citation

The psychedelic psilocybin has shown therapeutic potential, yet underlying neural mechanisms remain poorly understood. We investigated the impact of psilocin-the active metabolite of psilocybin-on basal activity and reactivity within the paraventricular nucleus of the thalamus (PVT) and PVT projections to central amygdala (CeA) in rats. Psilocin administration increased PVT c-Fos expression and...

DOI: 10.1038/s41467-026-71481-1 Full text

CB1 receptor signaling at the cingulate-striatal circuit is anxiogenic

Nature Communications April 8, 2026 Thomas J. Kelly, Xiaojie Liu, Yao Huang et al.

Cannabinoids, such as Δ9-tetrahydrocannabinol (THC), produce anxiety at high doses, yet the underlying neural mechanisms remain poorly understood. The anterior cingulate cortex (ACC) sends dense monosynaptic projections to the dorsomedial striatum (DMS). Optogenetic excitation of the ACC → DMS pathway promotes anxiolytic-like behavior, suggesting that its suppression could induce anxiogenic...

DOI: 10.1038/s41467-026-71574-x Full text Anxiogenic Cannabinoid receptor Optogenetics Endocannabinoid system +5

No evidence of immediate or persistent analgesic effect from a single dose of psilocybin in three mouse models of pain

Nature Communications January 22, 2026 Nicholas Gregory, Tyler E. Girard, Akila Ram et al. 5 citations

The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some preclinical data suggest these putative benefits derive from direct analgesic effects; however, this possibility has not been comprehensively tested in preclinical models. Here, we evaluated the analgesic properties of a single exposure to psilocybin at acute and chronic time points in...

DOI: 10.1038/s41467-026-68763-z Full text Psilocybin Analgesic Hallucinogen Anesthesia +9

An astrocytic ensemble at vHip-NAc synapses modulates cognitive impairments induced by chronic tetrahydrocannabinol exposure.

Nature Communications December 9, 2025 Cristina Martín-Monteagudo, Javier Sánchez Romero, Julia Adams et al.

Cannabis is the most widely used illicit drug, particularly during adolescence. Its consumption disrupts glutamate homeostasis and synaptic plasticity in the nucleus accumbens (NAc). Here, we identify a functionally distinct accumbal astrocytic ensemble, associated with the ventral hippocampus-NAc (vHip→NAc) circuit, that is critical for tetrahydrocannabinol (THC)-induced synaptic and...

DOI: 10.1038/s41467-025-67166-w Full text

Psilocybin alters visual contextual computations.

Nature Communications November 21, 2025 Marco Aqil, Gilles De Hollander, Nina Vreugdenhil et al. 1 citation

Psilocybin alters perception and brain dynamics. Here, we investigate the effects of psilocybin using psychophysics, ultra-high field functional MRI, and computational modeling. We find that psilocybin alters contextual perception in the Ebbinghaus illusion, as well as contextual modulation in cortical responses to visual stimuli. We propose a computational model capable of capturing and...

DOI: 10.1038/s41467-025-65150-y Full text Psilocybin research Psychedelics Hallucinogens Psychedelic action +18

Sex-specific role of the 5-HT2A receptor in psilocybin-induced extinction of opioid reward.

Nature Communications November 20, 2025 Alaina M Jaster, Thomas M Hadlock, Belle Buzzi et al. 9 citations

Emerging evidence suggests that classical psychedelics may offer therapeutic potential for opioid use disorder (OUD) by alleviating key hallmarks such as altered reward processing and dependence. However, the mechanisms behind these effects remain unclear. Our data demonstrate that a single administration of the psychedelic psilocybin (PSI) reduces conditioned behavior and withdrawal induced by...

DOI: 10.1038/s41467-025-64887-w Full text Psilocybin Opioid use disorder Neuroplasticity Psychedelic +17

Psilocybin during the postpartum period induces long-lasting adverse effects in both mothers and offspring

Nature Communications September 30, 2025 Cassandra J. Hatzipantelis, Min Liu, A. H. G. Love et al. 2 citations

Abstract Psilocybin increases social connectedness and has strong clinical transdiagnostic efficacy for mental illness, making it a candidate treatment to reduce maternal disconnect, anxiety, and blunted affect seen in peripartum mood disorders. However, the efficacy and safety of psilocybin in peripartum mood disorders has not been investigated. We used a social stress model to examine the...

DOI: 10.1038/s41467-025-64371-5 Full text

Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum

Nature Communications August 19, 2025 Maxwell B. Madden, Chloe Schaefgen, Binita Vedak et al. 4 citations

Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilocybin, which is metabolized to the...

DOI: 10.1038/s41467-025-62980-8 Full text Psilocybin Serotonin Claustrum Hallucinogen +1

A dream EEG and mentation database.

Nature Communications August 13, 2025 William Wong, Rubén Herzog, Kátia Cristine Andrade et al. 10 citations

Magneto/electroencephalography (M/EEG) studies of dreaming are an essential paradigm in the investigation of neurocognitive processes of human consciousness during sleep, but they are limited by the number of observations that can be collected per study. Dream research also involves substantial methodological and conceptual variability, which poses problems for the integration of results. To...

DOI: 10.1038/s41467-025-61945-1 Full text

Nitrous oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect.

Nature Communications April 3, 2025 Joseph Cichon, Thomas Joseph, Xinguo Lu et al.

Nitrous oxide (N2O) induces rapid and durable antidepressant effects. The cellular and circuit mechanisms mediating this process are not known. Here we find that a single dose of inhaled N2O induces rapid and specific activation of layer V (L5) pyramidal neurons in the cingulate cortex of rodents exposed to chronic stress conditions. N2O-induced L5 activation rescues a stress-associated...

DOI: 10.1038/s41467-025-57951-y Full text

Structural basis for psilocybin biosynthesis.

Nature Communications March 22, 2025 Chunyan Meng, Wenting Guo, Chuan Xiao et al. 4 citations

Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynthetic approach promises rapid and efficient production of psilocybin. Understanding the enzymes that contribute to the biosynthesis of psilocybin can enhance its production process. In this study, we elucidate the crystal structures of...

DOI: 10.1038/s41467-025-58239-x Full text Psychedelics Mental health Biochemistry Pharmaceutical research +1

Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression

Nature Communications February 12, 2025 Farid Aboharb, Pasha A. Davoudian, Ling-Xiao Shao et al. 19 citations

Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in...

DOI: 10.1038/s41467-025-56850-6 Full text MDMA Psilocybin Ketamine Pharmacology +3

Measuring the dynamic balance of integration and segregation underlying consciousness, anesthesia, and sleep in humans.

Nature Communications October 24, 2024 Hyunwoo Jang, George A. Mashour, Anthony G. Hudetz et al.

Consciousness requires a dynamic balance of integration and segregation in brain networks. We report an fMRI-based metric, the integration-segregation difference (ISD), which captures two key network properties: network efficiency (integration) and clustering (segregation). With this metric, we quantify brain state transitions from conscious wakefulness to unresponsiveness induced by the...

DOI: 10.1038/s41467-024-53299-x Full text

Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models.

Nature Communications September 20, 2024 Václav Havel, Andrew C Kruegel, Benjamin Bechand et al. 18 citations

Ibogaine and its main metabolite noribogaine provide important molecular prototypes for markedly different treatment of substance use disorders and co-morbid mental health illnesses. However, these compounds present a cardiac safety risk and a highly complex molecular mechanism. We introduce a class of iboga alkaloids - termed oxa-iboga - defined as benzofuran-containing iboga analogs and...

DOI: 10.1038/s41467-024-51856-y Full text Drug discovery Pain management Drug safety

Propofol disrupts the functional core-matrix architecture of the thalamus in humans

Nature Communications September 9, 2024 Zirui Huang, George A. Mashour, Anthony G. Hudetz 23 citations

Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic...

DOI: 10.1038/s41467-024-51837-1 Full text Propofol Thalamus Core optical fiber Architecture +3

Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice.

Nature Communications August 23, 2024 David H. Sarrazin, Wilf Gardner, Carole Marchese et al. 41 citations

Depression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant...

DOI: 10.1038/s41467-024-51716-9 Full text Chronobiology Mental health Depression treatment Brain research

Existence of multiple transitions of the critical state due to anesthetics.

Nature Communications August 15, 2024 Davor Curic, Donovan M Ashby, Alexander McGirr et al. 9 citations

Scale-free statistics of coordinated neuronal activity, suggesting a universal operating mechanism across spatio-temporal scales, have been proposed as a necessary condition of healthy resting-state brain activity. Recent studies have focused on anesthetic agents to induce distinct neural states in which consciousness is altered to understand the importance of critical dynamics. However,...

DOI: 10.1038/s41467-024-51399-2 Full text Anesthesia Brain activity Consciousness Medical research

Increased reactivity of the paraventricular nucleus of the hypothalamus and decreased threat responding in male rats following psilocin administration.

Nature Communications June 22, 2024 Devin P. Effinger, Jessica L Hoffman, Sarah E Mott et al. 15 citations

Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of...

DOI: 10.1038/s41467-024-49741-9 Full text Psychedelics Anxiety disorders Stress response Psilocybin research

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