Validation of the Imperial Psychedelic Predictor Scale - CORRIGENDUM.
Psychol Med August 26, 2025 Michael Angyus, Sarah Osborn, Eline Haijen et al.
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Robin Carhart-Harris
Imperial College London, Multidisciplinary Association for Psychedelic Studies
351 papers in the library · 30,431 citations · publishing 2007-2026
Papers
Correction: Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises.
Mol Psychiatry July 1, 2025 Rebecca Harding, Neomi Singer, Matthew B. Wall et al. correction
In a study comparing psilocybin therapy (PT) to escitalopram for depression, brain responses to unexpected musical notes were measured. After PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions. This suggests PT alters brain processing of unexpected events differently than escitalopram, potentially contributing to its therapeutic effects.
Detecting neuroplastic effects induced by ketamine in healthy human subjects: a multimodal approach
bioRxiv Preprint Server May 1, 2025 Claudio Agnorelli, Joseph Peill, Gabriela Sawicka et al. preprint
A single psychedelic dose of ketamine (1 mg/kg, intravenous) alters brain chemistry and connectivity in healthy people for at least one to eight days. After the dose, glutamate levels in the anterior cingulate cortex rose significantly. Functional connectivity decreased within high-order networks such as the default mode network, while integration between low- and high-order networks increased. Increases in a PET marker of synaptic plasticity correlated with reduced intrinsic activity in default mode network regions and a diminished influence of the posterior cingulate cortex on global network dynamics. The posterior cingulate cortex appears to be a central hub through which ketamine may reshape brain hierarchies over the long term.
Revealing Changes in Linear and Nonlinear Functional Connectivity After Psilocybin and Escitalopram Treatment in Patients with Depression
bioRxiv (Cold Spring Harbor Laboratory) March 10, 2025 Shaun K.l. Quah, Cameron C. Glick, Leor Roseman et al. preprint
People with major depression who responded to either psilocybin or escitalopram showed distinct changes in brain network connectivity compared to non-responders. Responders had increased linear connectivity within the ventral attention network and greater nonlinear connectivity within the default mode and ventral attention networks. Psilocybin responders showed enhanced coordination between higher-order networks, while escitalopram responders showed reduced connectivity within networks linked to self-referential thought and salience processing. These patterns suggest the two antidepressants work through different mechanisms, with nonlinear connectivity analyses revealing effects not captured by traditional linear measures.
Perturbing whole-brain models of brain hierarchy: an application for depression following pharmacological treatment
bioRxiv (Cold Spring Harbor Laboratory) January 2, 2025 Marcel Socoró-garrigosa, Yonatan Sanz Perl, Morten L. Kringelbach et al. preprint
Using whole-brain models guided by the Thermodynamics of Mind framework, the authors estimated the brain hierarchy of specific brain states and simulated transitions between states. Applying this to major depressive disorder, they built models of depressed patients before and after psilocybin and escitalopram treatments. Dynamic sensitivity analysis showed that susceptibility to change was on average reduced by escitalopram and increased by psilocybin, and both treatments promoted healthier transitions. These results align with the post-treatment plasticity window opened by serotonergic psychedelics and with the similar clinical efficacy of both drugs observed in clinical trials.
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 January 1, 2025 Sorcha O'Connor, Kate Godfrey, Sara Reed et al. correction
A protocol describes a planned study testing whether a low-moderate dose of psilocybin (10 mg), combined with non-interventional therapy, can improve cognitive flexibility and neuroplasticity in people with obsessive-compulsive disorder (OCD). Twenty blinded participants will receive an active placebo (1 mg psilocybin) in a first session and 10 mg in a second session four weeks later. Cognitive flexibility will be measured with the intradimensional-extradimensional shift task two days after each session, and neuroplasticity will be assessed via electroencephalography immediately after each session. Secondary outcomes include OCD symptom severity and patient-reported measures. The results are expected to clarify neural mechanisms and guide a future randomized controlled trial.
Human neuroimaging: fMRI.
International review of neurobiology January 1, 2025 Matthew B. Wall, Robin Carhart-Harris
Functional MRI has been central to recent psychedelic research in healthy and clinical populations. Classic psychedelics such as psilocybin, LSD, and DMT acutely and profoundly disrupt normal resting-state brain connectivity, an effect likely linked to their subjective experiences and longer-term positive emotional impacts. This chapter outlines fMRI methodology and reviews current knowledge from task and resting-state studies in both non-clinical and clinical groups. Current limitations include small datasets and lack of standardization; future work should provide more data, standardize acquisition and analysis, conduct multi-modal imaging, and share data openly. fMRI remains a key tool for understanding psychedelic mechanisms and developing psychedelic-based treatments.
Diminished functional gradient of the precuneus during altered states of consciousness
bioRxiv December 17, 2024 Dian Lyu, Ram Adapa, Robin Carhart-Harris et al. preprint
The default mode network (DMN) and frontoparietal control network (FPCN), typically anticorrelated at rest in healthy brains, show continuous rather than absolute anatomical boundaries in the posterior precuneus. Connectivity differences along the dorsal-ventral axis follow linear slopes, forming functional gradients that exist only within each network's territory. These gradients flatten in altered states of consciousness (ASC), with the gradient magnitude similarly impaired across different ASC types, while spatial entropy differs between psychedelic and sedative states. The findings suggest the DMN and FPCN, though appearing distinct, may originate from a single integrated mechanism, and the loss of functional differentiation between them characterizes altered conscious states.
Reply to Letter to the Editor: "Psychedelics in Older Adults: Difficulties of a Clear Therapeutic Evidence".
Am J Geriatr Psychiatry September 26, 2024 Hannes Kettner, Leor Roseman, Adam Gazzaley et al.
A reply to a letter to the editor addresses difficulties in establishing clear therapeutic evidence for psychedelics in older adults. The response likely discusses challenges such as study design, sample size, and confounding factors that complicate the interpretation of clinical data on psychedelic treatments for this population. It emphasizes the need for rigorous research to clarify the potential benefits and risks of psychedelic therapy in geriatric mental health care.
Transient destabilization of whole brain dynamics induced by DMT
bioRxiv January 29, 2024 Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini et al. preprint
The brain state induced by psychedelic drugs is often studied as a static snapshot, but this work focuses on the transition itself. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the authors show that the drug briefly pushes the brain near a critical point where it becomes maximally responsive to perturbations. This heightened reactivity is concentrated in fronto-parietal regions and visual cortices and correlates with serotonin 5HT2a receptor density. The findings suggest that even a short psychedelic episode can have a lasting influence because minimal perturbations during this transient achieve maximal effect, with the temporal evolution aligning with the drug's pharmacokinetics.
Statistical diversity distinguishes global states of consciousness
bioRxiv December 7, 2023 Joseph Starkey, Robin Carhart-Harris, Andrea Pigorini et al. preprint
A measure of 'statistical complexity' that calculates the diversity of statistical interactions in neural activity, removing randomness, was tested on human brain data from different sleep stages and from people under ketamine, LSD, and psilocybin. Statistical complexity differentiated sleep stages similarly to the standard Lempel-Ziv complexity measure and increased relative to placebo for all three psychedelic substances. The measure is a useful alternative for investigating neural activity complexity across states of consciousness.
A critique of: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds
May 10, 2022 Robin Carhart-Harris, Richard E. Daws, David Nutt preprint
The authors respond to a critique of their earlier work that questioned whether psilocybin truly opens depressed minds. They address the skeptic's arguments, defending their original evidence and conclusions about psilocybin's effects on depression. The response clarifies methodological points and reaffirms the potential of psilocybin as a treatment for depression, while acknowledging the need for further research to address lingering doubts.
4 Psychedelics: therapeutic mechanisms
Journal of Neurology Neurosurgery & Psychiatry July 20, 2020 Robin Carhart-Harris
Psychedelics like LSD, psilocybin, MDMA, and DMT work in the brain through a multi-level mechanism. Classic serotonergic psychedelics act on the serotonin 2A receptor, whose function and evolutionary purpose are illuminated by this pharmacology. Brain imaging reveals acute effects that increase entropy, supporting the entropic brain hypothesis. The REBUS model explains how psychedelics relax prior beliefs, allowing for predictive processing changes that map onto the acute experience and therapeutic outcomes. Current evidence supports psychedelic therapy, including a clinical trial of psilocybin for treatment-resistant depression and an ongoing comparison with escitalopram for major depressive disorder.
Case series of psilocybin self-medication for spinal cord injury
SSRN Electronic Journal Robin Sandell, Adele Lafrance, Olivia Gosseries et al.
In three people with incomplete spinal cord injuries who self-medicated with psilocybin, improvements in motor function, muscle activation, and strength were reported. One person with a C4–C5 injury noted better gait automaticity; another with a T7 injury regained activation of a previously non-responsive hamstring muscle; a third with a T12 injury experienced rapid strength gains and enhanced proprioceptive awareness. All three reported psychological benefits such as increased wellbeing, motivation for recovery, and improved adjustment. Benefits appeared greatest in partially innervated muscles and diminished after stopping psilocybin. Temporary spasticity was the only adverse effect. The authors suggest psilocybin may enhance recovery by amplifying existing neural pathways and call for controlled clinical trials.
Psychedelic Science of Spirituality and Religion: An Attachment-Informed Agenda Proposal
Aaron D. Cherniak, Joel Gruneau Brulin, Sebastian Ostlind et al. preprint
Our early relationships profoundly shape how we connect with others and the divine. This framework proposes that psychedelics could help relax rigid mental patterns formed by these foundational experiences. It suggests an individual's attachment security influences their psychedelic journey, and that effective psychedelic therapy may actually boost this security. The process involves fostering a deeper sense of connection and easing worries, enhancing treatment benefits.
Observational cohort study of a group-based VR program to improve mental health and wellbeing in people with life-threatening illnesses
Joe Hardy, Hannes Kettner, David R. Glowacki et al. preprint
A group-based virtual reality program called Clear Light, delivered at home over three weeks, improved anxiety, depression, and wellbeing in people with life-threatening illnesses. The program included multi-user VR experiences, video calls, and text chats designed to elicit self-transcendent experiences similar to psychedelics. In a small observational study of 15 participants, moderate improvements were seen in anxiety, depression, wellbeing, demoralization, connectedness, and spiritual wellbeing. The intervention was well-tolerated. The findings suggest potential benefits but are limited by the lack of a comparison group, indicating the need for randomized controlled trials.
The Relationship Between Changes in Mindfulness and Subsequent Changes in Well-Being Following Psychedelic Use: Prospective Cohort Study (Preprint)
Grant Jones, Felipe Herrmann, Adam Bear et al.
Changes in mindfulness predict later changes in well-being among people who recently used psychedelics. The finding suggests that increases in mindfulness may lead to improvements in well-being in this population.
A Shared Entropic Axis Spans States of Consciousness Across Pharmacological and Clinical Conditions
bioRxiv Preprint Server June 12, 2026 Dante Sebastián Galván Rial, Gabriel A. Della Bella, Lorina Naci et al. preprint
States of consciousness can be ordered along a single dimension defined by the entropy of spontaneous neural activity, as proposed by the Entropic Brain Theory. Applying the same analytical pipeline to pharmacological (psychedelics, modafinil, propofol anaesthesia) and clinical (schizophrenia) fMRI datasets, the temporal irregularity of brain network topology was quantified. Propofol anaesthesia occupied the low-entropy end; psychedelic states and schizophrenia occupied the high end. This ordering tracks combined modulations of the level and content of consciousness, from reduced awareness under anaesthesia to heightened arousal and expanded experience under psychedelics and disorganised processing in schizophrenia. The result was not reducible to fluctuations in mean functional connectivity and was supported by convergent reorganisation of higher-order association cortex.
Detecting neuroplastic effects induced by ketamine in healthy human subjects: A multimodal approach.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism March 21, 2026 Claudio Agnorelli, Joseph Peill, Gabriela Sawicka et al.
A single intravenous dose of ketamine (1 mg/kg) in eleven healthy men altered brain chemistry and connectivity days later. Glutamate levels rose in the anterior cingulate cortex (ACC). Functional coupling between the ACC and the dorsolateral prefrontal cortex decreased, while coupling between the ACC and the amygdala increased. Participants whose PET scans indicated increased synaptic plasticity showed reduced intrinsic activity in default mode network (DMN) regions. The findings suggest the DMN is a central hub where ketamine may reshape brain hierarchies, offering clues to its therapeutic mechanisms.
Micro-phenomenology of immersion and perceived presences under DMT.
Neuroscience of Consciousness January 1, 2026 James W. Sanders, Raphaël Millière, Ema Demšar et al.
The psychedelic compound DMT induces highly immersive experiences that often include encounters with seemingly sentient presences. Using micro-phenomenology, immersion under DMT was characterized as a structured continuum from subtle to gross forms. Twenty-three participants received 20 mg intravenous DMT during fMRI-EEG, followed by detailed interviews. Analysis yielded 125 phenomenological categories describing structural dimensions like sensory faculties, spatial organization, and self-world configuration. Bodily effects typically preceded visual and auditory ones, and perceived presences emerged only after multisensory integration and 3D spatial characteristics had developed, illustrating a hierarchical relationship between subtle and gross immersion. Perceived presences varied widely in sensory modality, semantic complexity, and relational mode, showing immersion as a dynamic, constructive process.
Ceremonial Psychedelic Experiences and Changes in Mental Health Outcomes in Those with Adverse Childhood Experiences
Psychedelic Medicine December 15, 2025 M. Mehmood, Rebecka Bremler, M. Spriggs et al.
People who experienced more adverse childhood experiences (ACEs) showed greater improvements in mental well-being, reductions in experiential avoidance, and lower trait anxiety after participating in psychedelic ceremonies compared to those with fewer ACEs. Higher ACE scores were also linked to stronger emotional breakthrough and mystical experiences during the psychedelic session. Among individuals with four or more ACEs, those who reported stronger mystical or emotional breakthrough experiences had better well-being at two and four weeks afterward, and mystical experiences were linked to less experiential avoidance while emotional breakthrough was linked to less anxiety at four weeks. However, the acute experiences did not significantly change how ACEs affected mental health outcomes overall.
Neuroplasticity and Psychedelics: a comprehensive examination of classic and non-classic compounds in pre and clinical models
arXiv Preprint Archive November 29, 2024 Claudio Agnorelli, Meg J. Spriggs, Kate Godfrey et al.
Psychedelics like LSD and psilocybin can rewire brain connections after just one dose, unlike traditional psychiatric medications. These compounds boost the brain's natural plasticity, helping neurons form new pathways and adapt to change. Studies show they create a window of enhanced learning and adaptation, leading to lasting improvements in mood and behavior.
The entropic brain - revisited.
Neuropharmacology November 1, 2018 Robin Carhart-Harris
The entropic brain hypothesis proposes that the entropy of spontaneous brain activity, within certain limits, indexes the informational richness of conscious states. Four years after its original publication, evidence from separate studies increasingly supports the principle that brain entropy is elevated in the psychedelic state, and evidence for greater brain criticality under psychedelics is also highlighted. Heightened brain criticality may make the brain more sensitive to intrinsic and extrinsic perturbations, translating as a heightened susceptibility to 'set' and 'setting'. This updated hypothesis offers more concrete information on specific measures of brain entropy and suggests new studies to scrutinize its utility for conditions such as depression and disorders of consciousness.
Enhanced repertoire of brain dynamical states during the psychedelic experience
arXiv Preprint Archive May 26, 2014 Enzo Tagliazucchi, Robin Carhart-Harris, Robert Leech et al.
Psilocybin, the active compound in magic mushrooms, dramatically expands the brain's repertoire of connectivity states, revealing how consciousness can be altered. Using advanced brain imaging, researchers tracked neural activity before and after psilocybin administration. Results showed increased signal variability in memory and emotion-processing regions, while higher brain networks displayed enhanced flexibility in their communication patterns.
Dorsal-ventral precuneus gradients organise large-scale networks and track consciousness level
Dian Lu, Adapa Ram, Robin Carhart-Harris et al.
The posterior precuneus, a key hub of the default mode network, sits at the boundary with the frontoparietal control network. Using a spatial-derivative approach across five pharmacological datasets including psychedelic and anaesthetic states, the authors show that measuring how functional connectivity changes along the precuneus's dorsal–ventral axis reveals the organization of these networks with greater anatomical specificity than connectivity alone. This functional gradient is systematically altered by consciousness level: its overall magnitude diminishes across all altered states of consciousness, while its spatial entropy increases under psychedelics but decreases under sedation. The findings suggest the precuneus embeds a continuous, anatomically constrained transition between large-scale networks sensitive to global brain-state dynamics.