medRxiv
September 29, 2019
Lorenzo Pasquini, Fernanda Palhano-Fontes, Dráulio B. Araújo
24 citations
preprint
One day after a single session with the psychedelic ayahuasca, connectivity within and between brain networks that support interoception, emotion, and self-related thought is altered compared to placebo. In a randomized trial with 22 participants receiving ayahuasca and 21 receiving placebo, the ayahuasca group showed increased connectivity within the salience network, decreased connectivity within the default mode network, and increased connectivity between these two networks. Primary sensory networks were not affected. These connectivity changes correlated with acute subjective effects such as altered body awareness, volition, and affect. The findings suggest that ayahuasca induces subacute functional reorganization of higher-order cognitive brain networks.
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.
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.
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.
May 13, 2026
Robin Carhart-Harris, Richard 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.
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.
bioRxiv (Cold Spring Harbor Laboratory)
March 10, 2025
Shaun K.l. Quah, Cameron 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.
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.