Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
Scientific reports
November 23, 2021
Christopher Timmermann, Hannes Kettner, Chris Letheby et al.
208 citations
People who use psychedelic drugs often shift away from materialist views of reality and consciousness toward panpsychism and fatalism, with most changes lasting at least six months. In a large prospective online survey, these belief shifts correlated with greater past psychedelic use and improved mental health. Emotional synchrony with others during the experience mediated the changes, and baseline impressionability moderated them. An independent clinical trial confirmed the direction of belief change, suggesting psychedelics may causally influence metaphysical beliefs away from hard materialism, though contextual independence remains uncertain.
J Psychopharmacol
January 5, 2022
Joseph M Peill, Katie E Trinci, Hannes Kettner et al.
135 citations
A new self-report questionnaire, the Psychological Insight Scale, was developed and validated to measure the degree of psychological insight people gain from a psychedelic experience. The scale was tested in a large online sample and showed strong reliability and validity, capturing a distinct aspect of psychedelic-induced change not measured by existing tools. Higher scores on the scale were associated with greater improvements in well-being and reductions in psychological distress, suggesting that psychological insight may be a key mechanism underlying the therapeutic potential of psychedelics.
Psychological medicine
June 1, 2024
Balázs Szigeti, Brandon Weiss, Fernando E Rosas et al.
74 citations
In a double-blind trial comparing escitalopram and COMP360 psilocybin for major depressive disorder, patients held higher expectations for psilocybin than for escitalopram. Higher pre-trial expectancy for escitalopram predicted better outcomes with escitalopram, but expectancy for psilocybin did not predict response to psilocybin. Pre-treatment trait suggestibility was linked to therapeutic response in the psilocybin arm but not the escitalopram arm. These findings suggest that psychedelic therapy may be less influenced by expectancy biases than previously thought, and that highly suggestible individuals may be especially responsive to psilocybin treatment.
ACS chemical neuroscience
February 7, 2024
Pedro A M Mediano, Fernando E Rosas, Christopher Timmermann et al.
60 citations
LSD increases brain entropy (neural signal diversity) across all conditions, but the effect is strongest when eyes are closed. Brain entropy changes correlate with subjective psychedelic experience ratings, except when viewing a video, possibly because external stimuli compete with LSD-induced imagery. This shows context modulates neural dynamics during psychedelic experiences, highlighting the importance of environment in psychedelic psychotherapy.
Scientific reports
April 17, 2023
Rubén Herzog, Pedro A M Mediano, Fernando E Rosas et al.
51 citations
Psychedelic drugs such as LSD, which activate the serotonin 2A receptor, produce profound changes in consciousness and are linked to increased entropy in spontaneous brain activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonin neuromodulation. The model reproduced the overall rise in neural entropy seen in prior experiments. Entropy increased across all brain regions, with the largest effects in visuo-occipital areas. At the whole-brain level, this reconfiguration was not well explained by the density of serotonin 2A receptors but was closely related to the topological properties of the brain's anatomical connectivity.
Journal of psychopharmacology (Oxford, England)
January 1, 2024
Lisa X Luan, Emma Eckernäs, Michael Ashton et al.
41 citations
A novel method of administering the psychedelic DMT via a bolus injection followed by a constant-rate infusion safely extends the experience to 30 minutes in a stable and tolerable fashion. In eleven healthy volunteers, subjective effects plateaued into a steady state while plasma DMT concentrations continued to rise, indicating acute psychological tolerance. Anxiety ratings remained low and heart rate habituated within 15 minutes, demonstrating psychological and physiological safety. This continuous intravenous administration method lays groundwork for further basic and clinical research into DMT's potential for treating mental health conditions and studying consciousness.
PLoS computational biology
February 1, 2023
Giulio Ruffini, Giada Damiani, Diego Lozano-Soldevilla et al.
28 citations
Brain dynamics under LSD become more disordered and complex, moving further from the critical point that characterizes healthy brain function. Using Ising spin models fitted to fMRI data from fifteen participants, the authors show that LSD reduces interhemispheric connectivity, especially between corresponding regions in opposite hemispheres. Ising temperatures were significantly higher under LSD than placebo, indicating a shift into a more disordered (paramagnetic) state. Algorithmic complexity of brain activity, measured by block decomposition, correlated with both Ising temperature and condition, supporting the entropic brain hypothesis that psychedelics increase neural disorder.
Scientific reports
January 29, 2025
Richard J Zeifman, Meg J Spriggs, Hannes Kettner et al.
26 citations
A preliminary test of the REBUS model found that a high dose of psilocybin (25 mg) reduced confidence in negative self-beliefs in 11 healthy individuals, both during the acute experience and four weeks later. Greater brain signal entropy and stronger subjective effects under psilocybin correlated with larger decreases in negative self-belief confidence. Decreases in negative self-belief confidence were linked to increases in well-being. The findings provide initial evidence that relaxing and revising negative self-beliefs may underlie psilocybin's positive psychological effects, with increased neuronal entropy as a possible mechanism. Replication in larger clinical samples is needed.
Brain
January 1, 2024
Andrea I Luppi, Manesh Girn, Fernando E Rosas et al.
25 citations
Serotonin 2A receptor (5-HT2AR) signaling drives both the evolutionary expansion and ongoing modulation of the human cerebral cortex's most complex cognitive centers. The cortex is organized along a gradient from simple sensory processing to high-level integration, with the transmodal cortex at the apex—a region disproportionately enlarged in humans and rich in 5-HT2AR expression. During early brain development, 5-HT2AR signaling on neural progenitor cells stimulates their proliferation, contributing to cortical expansion. In the adult brain, 5-HT2AR agonism promotes neuroplasticity, learning, and cognitive flexibility with therapeutic potential. The receptor thus plays a dual role in enabling cortical growth and sophisticated functioning.
NeuroImage
November 1, 2022
Hardik Rajpal, Pedro A M Mediano, Fernando E Rosas et al.
23 citations
Schizophrenia and drug-induced states from LSD and ketamine both increase neural signal diversity, but they differ in brain connectivity: schizophrenia shows increased information flow from front to back of the brain, while the drugs reduce it. These differences can be modeled by altering Bayesian inference in a predictive processing framework: drug effects correspond to reduced precision of prior beliefs, whereas schizophrenia involves increased precision of sensory information. The findings clarify similarities and differences between these altered states, with implications for understanding consciousness and developing mental health treatments.
Journal of psychopharmacology (Oxford, England)
October 1, 2024
Valerie Bonnelle, Amanda Feilding, Fernando E Rosas et al.
16 citations
The joint influence of the sympathetic and parasympathetic nervous systems over cardiac activity, known as sympathovagal coactivation, is positively related to ratings of spiritual experience and insightfulness during the DMT-induced peak experience, and also to improved well-being two weeks later. The balance between the two autonomic branches before DMT injection predicted insightfulness scores and subsequent coactivation. These findings demonstrate the autonomic nervous system's involvement in psychedelic-induced peak experiences.
Journal of Psychopharmacology
November 14, 2022
Meg J Spriggs, Bruna Giribaldi, Taylor Lyons et al.
15 citations
A fixed 25 mg dose of psilocybin produces similar acute psychedelic effects and improvements in well-being regardless of body mass index (BMI). Pooling data from three therapeutic studies, results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes, or emotional breakthroughs. There was weak evidence that lower BMI participants reported greater 'dread of ego dissolution,' but BMI did not meaningfully add to predictions beyond age, sex, and study. Mystical-type experiences and emotional breakthroughs strongly predicted well-being improvements, but BMI did not. These findings suggest body weight-adjusted dosing may be unnecessary, supporting fixed dosing to reduce practical and financial burdens on psychedelic therapy scalability.
Neuroscience of consciousness
January 1, 2025
Daniel A Atad, Pedro A M Mediano, Fernando E Rosas et al.
10 citations
A scoping review of neural complexity in meditation finds that, during meditation, brain activity shows higher complexity compared to waking rest or mind-wandering, while regular meditation practice is associated with decreased baseline complexity as a long-term trait. The review disentangles different families of complexity measures, distinguishes short-term state effects from long-term trait effects, and considers differences among meditation styles. It provides a framework to guide debates and offers practical guidelines for future research on complexity and consciousness.
eLife
July 18, 2024
Andrea I Luppi, Pedro A M Mediano, Fernando E Rosas et al.
1 citation
Loss of consciousness significantly disrupts the brain's ability to integrate information. In a study involving functional MRI analysis, it was revealed that gateway regions in a 'synergistic global workspace' correspond to the default mode network, while broadcaster regions align with the executive control network. This integration breakdown occurs during general anaesthesia or disorders of consciousness, with recovery restoring functionality. The findings enhance understanding of consciousness by bridging Global Neuronal Workspace and Integrated Information Theory, highlighting the critical role of brain networks in maintaining conscious experience.
Neuroscience and biobehavioral reviews
July 1, 2022
Drummond E-Wen Mcculloch, Gitte Moos Knudsen, Frederick Streeter Barrett et al.
A large group of psychedelic imaging researchers reviewed 42 articles from 17 unique studies that used resting-state functional magnetic resonance imaging (rs-fMRI) to examine psychedelic effects. They found that nearly all studies varied in data processing and analysis methods, two datasets underpin over half of the published literature, and key outcome terms are used ambiguously. The authors recommend guidelines to improve consistency and replicability in future research, arguing that the field must balance novel methods with standardized approaches to reliably understand the neural mechanisms of psychedelics.