Neuropharmacology
December 27, 2022
Robin Carhart‐Harris, Shamil Chandaria, David Erritzøe et al.
106 citations
A theoretical model proposes that psychopathology arises from a defensive process called canalization, which narrows an individual's range of thoughts, feelings, and behaviors by increasing precision or reducing variance in neural responses. This contrasts with an early form of plasticity, TEMP (Temperature or Entropy Mediated Plasticity), which increases variance and learning rate. Canalization entrenches pathology as the agent develops expertise in their disorder, while TEMP, combined with gentle psychological support, may counter this entrenchment. The model distinguishes adaptive from maladaptive canalization and suggests concrete experiments to test its hypotheses.
Trends Cogn Sci
February 3, 2023
Manesh Girn, Fernando E. Rosas, Richard E. Daws et al.
76 citations
Psychedelics reduce the functional segregation of large-scale brain networks, but findings have been largely inconsistent. A complexity-science perspective that emphasizes the distributed, interactional, and dynamic nature of brain function may explain these inconsistencies. The authors propose that psychedelics induce a mode of brain function that is more dynamically flexible, diverse, integrated, and tuned for information sharing, consistent with greater criticality. This 'meta' perspective can unify past findings and guide intuitions toward compelling mechanistic models.
J Psychopharmacol
April 22, 2021
Robin L Carhart-Harris, Anne C Wagner, Manish Agrawal et al.
54 citations
Psychedelic therapy is experiencing a resurgence due to favorable regulations, policy changes, and positive trial results, but current confirmatory trials may not fully address safety and best practice. The authors recommend supplementing these trials with pragmatic trials, real-world data initiatives, and digital health solutions to discover optimal and personalized treatment protocols. These steps aim to develop safe, effective, and cost-efficient psychedelic therapy, which is susceptible to hype and regulatory challenges given its history.
Am J Geriatr Psychiatry
May 19, 2024
Hannes Kettner, Leor Roseman, Adam Gazzaley et al.
18 citations
Guided psychedelic group sessions improve well-being in older adults (age 60+) similarly to younger adults, but through different mechanisms. Acute psychedelic effects are less intense in older adults and do not predict later well-being changes, whereas relational experiences before and after the sessions do predict improvements. Among older adults, having a lifetime psychiatric diagnosis was linked to greater well-being increases at the four-week follow-up. These findings suggest that the social and relational aspects of psychedelic group therapy may be especially important for older adults, warranting further research into psychedelic interventions for this population.
bioRxiv (Cold Spring Harbor Laboratory)
November 9, 2023
Fernando E. Rosas, Pedro A. M. Mediano, Christopher Timmermann et al.
14 citations
preprint
Autonomic signals can reveal aspects of subjective and neural states. A Bayesian framework estimated heart rate entropy under psychedelics. Across four drugs—LSD, DMT, psilocybin, and ketamine—mean heart rate, high-frequency heart rate variability, and heart rate entropy consistently increased during the psychedelic experience. These changes predicted various dimensions of the experience. Heart rate entropy increases correlated with brain entropy increases, while other autonomic markers did not. Cost-efficient autonomic measures can reveal detail about subjective and brain states, opening new research avenues in neuroscience.
Research square
March 8, 2024
Hannes Kettner, Leor Roseman, Adam Gazzaley et al.
5 citations
Older adults (age 60+) who participated in a guided psychedelic group retreat showed significant improvements in well-being, with larger gains among those with a prior psychiatric diagnosis. Compared to younger adults, older adults experienced weaker acute psychedelic effects, and these effects did not predict well-being changes. Instead, a sense of communitas—the relational or social connection during the group session—predicted well-being improvements in older adults, suggesting that the social context of psychedelic therapy may be especially important for this age group.
bioRxiv (Cold Spring Harbor Laboratory)
November 7, 2024
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
4 citations
preprint
Psilocybin induces fast and sustained improvements in mental well-being, yet its long-term mechanisms are not fully understood. Four weeks after a full dose, fronto-striatal-thalamic (FST) circuitry—involved in goal-directed behavior and motivation—shows increased dynamic activity and flexibility in healthy volunteers. Computational modeling indicates that reduced structural constraints on functional dynamics cause this increased flexibility. Long-term changes include increased bottom-up and reduced top-down information flow, mediated by serotonergic (5-HT2A) and dopaminergic (D2) receptor systems. This functional re-organization of FST circuits may represent a common mechanism underlying clinical improvements across neuropsychiatric disorders such as substance abuse, major depression, and anorexia.
bioRxiv : the preprint server for biology
August 12, 2024
Lorenzo Pasquini, Alexander J Simon, Courtney L Gallen et al.
4 citations
preprint
The psychedelic DMT rapidly alters consciousness, producing physical transcendence, vivid auditory distortions, and visual imagery. Using simultaneous fMRI and EKG data from 14 healthy volunteers before, during, and after intravenous DMT (versus placebo), a brain substate emerged immediately after injection characterized by deactivations in the hippocampus and medial parietal cortex alongside increased superior temporal lobe activity. Hippocampal and medial parietal deactivations correlated with disruptions in the sense of time, space, and self-referential processes, reflecting a deconstruction of ordinary consciousness. Superior temporal lobe activations correlated with audio/visual hallucinations and the experience of "entities.
Imaging Neuroscience
April 16, 2025
Lorenzo Pasquini, Alexander J. Simon, Courtney L. Gallen et al.
1 citation
DMT rapidly induces a short-lasting altered state of consciousness marked by physical transcendence, vivid auditory distortions, and visual imagery. Using simultaneous fMRI and EKG data from 14 healthy volunteers before, during, and after intravenous DMT or placebo, a brain substate emerged immediately after DMT injection, characterized by deactivations in the hippocampus and medial parietal cortex and increased activity in the superior temporal lobe. Hippocampal and medial parietal deactivations correlated with altered sense of time, space, and self-referential processes, reflecting a deconstruction of ordinary consciousness. Superior temporal lobe activations correlated with audio/visual hallucinations and the experience of "entities.
Hum Brain Mapp
July 1, 2026
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
A computational model predicts that a single dose of psilocybin can produce lasting changes in the dynamic activity and effective connectivity of fronto-striatal-thalamic brain circuits. The modeling suggests that psilocybin may strengthen connectivity between the prefrontal cortex and striatum while altering thalamic gating, effects that persist beyond the acute drug experience. These changes could underlie the sustained therapeutic benefits observed in clinical settings, such as reduced depressive symptoms and increased psychological flexibility. The findings provide a mechanistic framework for understanding how psilocybin induces long-term neural plasticity and highlight potential circuit targets for treating psychiatric disorders.
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.
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.
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.
October 14, 2024
Terence J. Lyons, Merle Spriggs, Leevi Kerkelä et al.
preprint
A single high dose of psilocybin (25 mg) produced lasting functional and anatomical brain changes in healthy, psychedelic-naive adults, detected from one hour to one month later. Diffusion imaging showed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity, which in turn correlated with improved well-being. Increased cortical signal entropy shortly after dosing predicted better psychological well-being at one month, with next-day psychological insight mediating this relationship. No such effects occurred with a 1 mg placebo dose. Cognitive flexibility, psychological insight, and well-being also increased at one month.
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.
Consciousness and cognition
May 1, 2015
Christina Merrick, Melika Farnia, Tiffany K Jantz et al.
The stream of consciousness, often seen as free and whimsical, is actually more open to external influence than previously thought. An experimental manipulation successfully triggered not just one but two involuntary thoughts in participants: they were asked to avoid subvocalizing the names of visual objects and to avoid counting the number of letters in those object names. On many trials, participants experienced both types of involuntary thoughts, which arose from distinct high-level processes (naming and counting). This is the first demonstration of inducing two involuntary thoughts into the stream of consciousness, with stimulus word length systematically affecting the results. The findings have implications for attention, imagery, and action control.