Skip to content

Robin Carhart-Harris

International Computer Science Institute, University of California, San Francisco

122 papers in the library · 6,162 citations · publishing 2014-2026

Papers

DMT-induced shifts in criticality correlate with self-dissolution.

The Journal of neuroscience : the official journal of the Society for Neuroscience November 24, 2025 Mona Irrmischer, Marco Aqil, Lisa Luan et al.

A psychedelic substance (DMT) shifts brain oscillations away from criticality—a state of balanced, complex activity—toward a quieter subcritical regime, particularly in alpha and adjacent frequency bands. This shift increases entropy while reducing complexity. The magnitude of the criticality shift in alpha and theta bands correlates with the intensity of self-dissolution, a core feature of the psychedelic experience. These findings suggest that altered proximity to critical dynamics underlies both the neurological and experiential effects of psychedelics, with implications for understanding altered states of consciousness.

Correction: Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology.

Transl Psychiatry November 13, 2025 Kenneth Shinozuka, Katarina Jerotic, Pedro Mediano et al. correction

This correction notice addresses errors in a previously published article that presented three systematic reviews and meta-analyses examining the pharmacology, neuroimaging, and phenomenology of psychedelics. The correction does not provide new findings or data but serves to amend the original publication.

Eigenmodes of the deep unconscious: the neuropsychology of Jungian archetypes and psychedelic experience.

Neurosci Conscious October 18, 2025 Hugh McGovern, Marco Aqil, Selen Atasoy et al.

Archetypes—universal symbols and patterns in the deep unconscious—can be understood through a neuroscientific lens that integrates Carl Jung's theory with the Free Energy Principle and Predictive Processing. The article proposes a three-part interplay among high-level cortex, low-level cortex, and subcortical/affective systems to explain how archetypes arise, especially during altered states like psychedelic experiences. It suggests that archetypes have an affective core in subcortical regions, emerge as imagery in altered states, and are encoded as stories in higher cortical areas. The collective unconscious may develop through social learning and attunement, transmitting archetypes between individuals. This synthesis offers testable hypotheses about the neural basis of archetypes, aiming to validate Jungian concepts and encourage further empirical research.

Cross-species mapping of psychedelic gene expression reveals links to the 5HT2A receptor, cortical layers, and human accelerated regions

Research Square October 3, 2025 Patrick McConnell, Jackson Raffety, Andrew Li et al.

Psychedelic compounds alter gene expression in the brain, and this study maps those changes across species. The gene activity patterns linked to psychedelic action are associated with the 5HT2A receptor, specific cortical layers of the brain, and human accelerated regions—genetic sequences that evolved rapidly in humans and are thought to be important for brain evolution. These findings suggest that psychedelic-induced gene expression may tap into evolutionarily recent and layer-specific brain circuitry.

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.

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.

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.

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.

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 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.

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.

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 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.

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.