bioRxiv (Cold Spring Harbor Laboratory)
June 26, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Robin Carhart-Harris et al.
A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and escitalopram. First, we built whole-brain models of pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) and obtained an initial generative effective connectivity (GEC) matrix for each individual.
Research Square
June 19, 2026
Aline Frick, Grace Blest‐hopley, Manesh Grin et al.
In a reanalysis of a six-week randomized controlled trial comparing psilocybin with escitalopram for moderate-to-severe major depressive disorder, sex-related patterns emerged for anxiety and anhedonia. Women receiving psilocybin showed greater reductions in anxiety than men, while women receiving escitalopram showed greater reductions in anhedonia than men. For other depressive symptoms, thought suppression, and well-being, sex differences were small and uncertain. Sexual dysfunction severity was lower overall in the psilocybin group than in the escitalopram group and lower in women than in men, though the treatment-by-sex interaction was not significant. These preliminary findings suggest that responses to these serotonergic treatments may differ between women and men, supporting the need for adequately powered, sex-balanced trials.
Curr Psychiatry Rep
June 5, 2026
Matthew J Reid, Hannes Kettner, Tessa F. Blanken et al.
correction
A correction notice was issued for a previously published article on psilocybin administration and sleep improvements. The correction addresses errors in the original text but does not provide new findings or data.
Frontiers in Pharmacology
June 3, 2026
Burton J. Tabaac, Robin Carhart-Harris, Teresa Yung
Three individuals with persistent symptoms after traumatic brain injury or hypoxic-ischemic brain injury completed a six-week protocol combining a participant-directed iboga-containing microdosing regimen (using whole root bark biomass with about 3.845% ibogaine content, yielding an estimated 3.8–38.5 mg/day ibogaine equivalent) with weekly Accelerated Experiential Dynamic Psychotherapy and supportive nutraceuticals. All three showed progressive neurological recovery; two reported complete symptom remission at long-term follow-up. Participants discontinued all prescription medications and reported resolution of headaches, brain fog, fatigue, irritability, and mood swings, with a return to regular activities and renewed enthusiasm. The authors note that the findings do not establish causality or iboga-specific efficacy due to the multimodal intervention and methodological limitations.
arXiv (Cornell University)
May 15, 2026
Jonas Mago, Edmundo Lopez-Sola, Jakub Vohryzek et al.
States of consciousness with minimal phenomenal content, such as those induced by certain meditation practices, show increased brain entropy similar to high-content psychedelic states, challenging the Entropic Brain Hypothesis that links entropy to phenomenal richness. The Complex Brain Hypothesis resolves this by proposing that brain complexity, not entropy, better indexes the richness of experience. Complexity is modulated by the grain of inference the brain uses to resolve uncertainty: fine-grained inference loosens constraints and proliferates content, as in psychedelic states; coarse-grained inference simplifies experience into contentless awareness, as in minimal phenomenal experiences. Both regimes can elevate entropy but differ in phenomenology and perturbational signatures, refining the Entropic Brain Hypothesis and highlighting minimal phenomenal experiences as a test case for computational theories of consciousness.
May 13, 2026
Robin Carhart-Harris, Richard J. Zeifman, Lorenzo Pasquini et al.
preprint
The paper argues that the term 'plasticity' in neuroscience refers to induced changes in brain function or structure, which differs from the dictionary definition of plasticity as the ability to be shaped or molded. Many biomarkers of neuroplasticity actually index processes that bias phenotypic canalization, the opposite of phenotypic plasticity, creating a paradox. The authors question extrapolating from these biomarkers to improved mental health, as the relationship is context dependent. They propose a new construct, 'mediational and recalibrative plasticity' (MR-P), which aligns with plasticity proper and can describe and predict phenotypic changes relevant to mental health.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Taylor Lyons, Joseph Marks et al.
Across three studies—a naturalistic observation, a single-arm psilocybin trial with healthy volunteers, and a randomized controlled trial comparing psilocybin to escitalopram in depressed patients—psychedelic use did not produce significant changes in authoritarian attitudes. Contrary to earlier suggestions, the evidence does not reliably show that psychedelics decrease authoritarian attitudes. Future work should use larger, more diverse samples and examine other political outcomes.
Philosophical Psychology
April 10, 2026
Eric Rundquist, Diego Nicolás Monasterio López, Juan Jonathan Oyarzo Alvarado et al.
A cognitive-linguistic analysis of interviews with a healthy volunteer after moderate-to-high psilocybin doses reveals that the participant consistently used metaphors framing abstract introspective events in terms of concrete, visible, and interpersonal events, instantiating a cognitive frame called the Observer's Model. These metaphors imply cognitive defusion and heightened metacognitive awareness during the sessions. Literal descriptions of hallucinatory visual experiences correlated semantically with metaphorical expressions, suggesting metaphorical thinking plays a role in motivating those experiences. The findings are linked to neuroscientific research on psychedelics and have psychological and therapeutic implications.
Nature Mental Health
April 1, 2026
Saif S. Ali, Robin Carhart-Harris, Karl G. Sieg
LSD and psilocybin may help treat obsessive-compulsive disorder (OCD) by disrupting maladaptive brain circuits and enhancing neuroplasticity. OCD involves dysfunction in the cortico-striatal-thalamo-cortical circuit, default mode network, and salience network. Psychedelics acutely dysregulate the default mode network and increase connectivity between normally segregated networks, potentially breaking cycles of rumination and self-referential thought. They also modulate the cortico-striatal-thalamo-cortical circuit and rapidly promote dendritic spine formation via 5-HT2A receptors in rodents. These dual mechanisms could reset pathological patterns and support long-term restructuring of maladaptive circuits, but clinical trials with neuroimaging endpoints are needed to validate this framework.
Discover Mental Health
March 7, 2026
Nicholas Fabiano, Brendon Stubbs, David W. Lawrence et al.
More than half of people with major depressive disorder do not respond to standard treatments, prompting interest in alternatives such as exercise and psychedelics. This commentary examines how these two approaches might work together. Biologically, psychedelics briefly boost brain-derived neurotrophic factor (BDNF) signaling, while exercise provides sustained BDNF elevation; psychedelics enhance neuroplasticity mainly in the cortex, whereas exercise promotes hippocampal neurogenesis; both increase serotonin release. Psychologically, psychedelics may help people adopt exercise habits, and exercise may improve emotional resilience, potentially deepening the psychedelic experience. The authors suggest that these complementary mechanisms warrant future research on their combined efficacy, tolerability, safety, and neurobiology.
bioRxiv (Cold Spring Harbor Laboratory)
March 5, 2026
Venkatesh Subramani, Annalisa Pascarella, Jérémy Brunel et al.
Lysergic acid diethylamide (LSD) loosens the brain's usual alignment between anatomical structure and neural activity in a frequency-dependent way. Low-frequency brain waves (theta, alpha, beta) become less constrained by the structural connectome, indicating a global relaxation of large-scale dynamics. High-frequency gamma activity shows selective reorganization rather than uniform disruption. Greater gamma-band decoupling within core default-mode network regions predicts the intensity of ego dissolution across individuals. LSD does not cause indiscriminate disintegration but drives system-specific rebalancing: visual and attentional systems decouple while auditory networks strengthen coupling. These findings suggest psychedelic states emerge from frequency-dependent relaxation of structural constraints, with default-mode reorganization as a neural correlate of ego dissolution.
Behavioral Sciences
February 23, 2026
Joshua Lipson, Hannes Kettner, Robin Carhart-Harris et al.
Mood before taking a psychedelic substance and factors like social connectedness, mindfulness, and spirituality influence how the experience unfolds. People with higher baseline depression and anxiety tend to have more challenging experiences but not more mystical ones, while those with greater wellbeing report more mystical and fewer challenging experiences. Mindfulness and spirituality are linked to more mystical experiences, and social connectedness and mindfulness are linked to fewer challenging ones. Mystical and challenging experiences were weakly but positively correlated overall.
medRxiv
February 19, 2026
Amanda Gow, Emily Shih, Ryan Reid et al.
Under Oregon's regulated psilocybin program, adults who consumed an average of 27.8 mg of psilocybin showed significant improvements in depression, anxiety, and well-being 30 days after a session, including those concurrently using psychiatric medication. Of 88 participants (median age 43, 52% male, 64.8% with prior psychedelic experience), two reported symptoms of hallucinogen persisting perception disorder one day after the session, but none at 30 days. The findings suggest that legal psilocybin services can produce clinically meaningful mental health benefits.
Neuroscience of Consciousness
January 1, 2026
Jonas Mago, George Deane, Lars Sandved-Smith et al.
People under the influence of psychedelics often report encountering autonomous entities such as spirits, elves, or ancestors. A neurocomputational model, grounded in the active inference framework, explains these experiences by proposing that psychedelics reduce the predictability of sensory perceptions, leading the brain to interpret both internal and external perceptions as coming from non-self agents. The model synthesizes earlier theories including the entropic brain model, computational accounts of felt presence, and sensory attenuation theories of self-other discrimination. It aims to account for how the brain supports entity encounters and for the diversity and similarity of these experiences across cultural contexts.
Mol Psychiatry
December 1, 2025
Ross J. Purple, Rahul Gupta, Christopher W. Thomas et al.
correction
A correction notice addresses an error in a previously published article: the author's name Robin Carhart-Harris was incorrectly written as Robin Carhartt-Harris. The original article has been corrected.
bioRxiv
November 26, 2025
Rui Dai, Rodrigo Cofré, Christopher Timmermann et al.
preprint
Classical psychedelics (DMT, LSD, psilocybin) and non-classical ones (nitrous oxide, ketamine) all disrupt local synchrony in small brain regions (<1 cm³) in humans, as measured by functional magnetic resonance imaging. This disruption occurred extensively in cortical regions and sparsely in subcortical regions. As local synchrony declined, large-scale functional connectivity increased. For classical psychedelics, the disruption was most strongly associated with 5-HT receptors; for nitrous oxide and ketamine, it was most strongly associated with NMDA receptors. Both neuronal and non-neuronal cell types were linked to these changes. The findings suggest diverse molecular events converge on a common outcome of disrupted local synchrony, which then mediates drug-specific global connectivity changes.
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.
bioRxiv (Cold Spring Harbor Laboratory)
November 21, 2025
Joseph C. C. Chen, Gabriella Mace, Avery Ostrand et al.
preprint
Awe, a positive emotion linked to well-being and social behavior, was studied using EEG and autonomic physiology in 23 healthy older adults watching a nature film. Awe was the dominant emotion reported, though joy was also common. During awe events, skin conductance decreased, and EEG alpha and theta power decreased—changes associated with low arousal and positive emotion. Awe also increased Lempel Ziv Complexity (LZC), a measure of neural signal entropy linked to richer conscious experience. LZC correlated positively with awe intensity and negatively with skin conductance. Three additional datasets using different induction methods (video clips and DMT) showed similar occipital LZC increases, suggesting LZC may be a generalizable neurophysiological marker of awe.
Transl Psychiatry
November 13, 2025
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. 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.
Translational Psychiatry
November 13, 2025
Bruna Giribaldi Cunha, David Nutt, Marieke Martens et al.
In a double-blind randomized trial, patients with long-standing moderate-to-severe depression received either two doses of 25 mg psilocybin plus daily placebo or two doses of 1 mg psilocybin plus daily escitalopram over six weeks. Both treatments comparably reduced negative bias in recognizing facial emotions, a measure of emotional information processing. However, changes in this bias were not linked to concurrent depression score changes. Only in the escitalopram group did a decrease in misclassifying positive faces as negative correlate with lower depression scores at a one-month follow-up. The findings suggest overlapping cognitive mechanisms between psilocybin and escitalopram, notable given psilocybin's short dosing regimen.
Journal of Psychiatric Research
November 1, 2025
Felipe Herrmann, Grant Jones, Daniel M Low et al.
Increases in meaning in life, agreeableness, mindfulness, and extraversion are the psychological changes most strongly linked to future improvements in well-being after naturalistic psychedelic use. Increases in mindfulness, emotional stability, and extraversion are most associated with later reductions in anxiety, while increased self-esteem is most tied to decreased depression. Mindfulness was the only variable ranking among the top three predictors for all three outcomes—well-being, anxiety, and depression. These differing psychological changes may explain the mental health benefits observed after psychedelic use.
Neuropsychopharmacology
October 31, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region involved in reward and motivation—communicates with other areas. Using resting-state fMRI data from prior studies, researchers examined striatal connectivity after acute drug administration. Neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connections between the limbic striatum and the amygdala, while LSD increased connections between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, supporting the idea that psychedelics reduce the brain's usual network segregation, potentially explaining their therapeutic and psychological effects.
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.
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
correction
No Summary
Research Square
October 3, 2025
Patrick A. 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.