PsyArXiv
October 17, 2023
Alessia Marrocu, Hannes Kettner, Brandon Weiss et al.
9 citations
preprint
About 16% of people who used psychedelics in naturalistic settings experienced a clinically meaningful decline in psychological well-being four weeks later. Those with a prior personality disorder diagnosis were disproportionately affected, making up 31% of negative responders and facing more than a four-fold elevated risk of adverse psychological responses. The findings suggest that personality disorders may heighten vulnerability to negative outcomes from psychedelic use, highlighting the need for careful screening and robust psychological support.
PsyArXiv
April 13, 2023
Lisa Xiaolu Luan, Emma Eckernäs, Michael Ashton et al.
9 citations
preprint
A within-subjects, placebo-controlled study tested a novel method of administering N,N-Dimethyltryptamine (DMT) by combining a bolus injection with a constant-rate infusion to extend the experience to 30 minutes. The method effectively maintained stable and tolerable subjective effects over the infusion period. Anxiety ratings remained low, and heart rate habituated within 15 minutes, indicating psychological and physiological safety. Plasma DMT concentrations increased consistently starting ten minutes into administration, while psychological effects plateaued, suggesting acute psychological tolerance to DMT. These findings demonstrate the safety and effectiveness of continuous intravenous DMT administration for basic and clinical research.
Psychopharmacology
May 1, 2018
Mendel Kaelen, Bruna Giribaldi, Jordan Raine et al.
9 citations
correction
Music plays a central role in psychedelic therapy by helping to guide and support the therapeutic process. The article synthesizes evidence that music can influence emotional states, facilitate psychological insights, and enhance the overall therapeutic outcome when combined with psychedelic substances. The authors argue that music acts as a "hidden therapist" by directing the trajectory of the psychedelic experience, promoting emotional release, and supporting the integration of the experience afterward. This suggests that careful selection and use of music is crucial for optimizing the therapeutic benefits of psychedelic therapy.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
May 1, 2025
Paolo Cardone, Pablo Núñez, Naji L N Alnagger et al.
7 citations
A patient in a minimally conscious state plus received psilocybin, a classic psychedelic, for the first time. No increase in overt behavioral repertoire was observed on validated scales, but new spontaneous behavior not previously seen emerged, and brain complexity, measured by the Lempel-Ziv complexity index, increased with changes in underlying periodic rhythms. This case report contributes to future investigations of psychedelics for disorders of consciousness and the link between brain complexity and consciousness.
George Deane, Jonas Mago, Aikaterini Fotopoulou et al.
7 citations
preprint
A computational theory called adaptive narrative control explains how subpersonal processes shape conscious experience to enable adaptive behavior. Systems with an attention schema can anticipate the epistemic and pragmatic consequences of attentional states, using mental action—endogenous control of attention—to regulate affective states. This capacity also produces avoidant mental action or motivated inattention, which is argued to be a core mechanism underlying psychopathology, leading to rigid belief formation, reduced emotional recognition (alexithymia), and decreased subjective well-being under certain environmental conditions. The account partially echoes Freudian defense mechanisms and introduces a computational unconscious. It refines the REBUS model of psychedelic therapy and explains improvements in well-being from meditation.
Communications biology
March 11, 2025
Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini et al.
6 citations
The transition into a psychedelic brain state is often overlooked in favor of static descriptions of acute effects. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the work shows that a transient of heightened reactivity in fronto-parietal regions and visual cortices correlates with serotonin 5HT2a receptor density. Simulated perturbations suggest that minimal disturbances can achieve maximal effects during this brief period, and the temporal evolution of these features aligns with pharmacokinetics. These findings indicate a mechanism for how short psychedelic episodes may exert a lasting influence over time.
Research Square
October 26, 2022
Rubén Herzog, Pedro A.M Mediano, Fernando E. Rosas et al.
6 citations
Psychedelic drugs like LSD, which activate serotonin 2A receptors, dramatically alter subjective experience and offer a window into the neurobiology of consciousness. A key signature of these drugs is increased entropy—or randomness—in spontaneous brain activity, but why this occurs was unclear. Using a computational model of serotonin's effects on the whole brain, researchers reproduced the entropy increase seen in living brains, providing the first model-based explanation. Entropy rose across all brain regions but was most pronounced in visual and occipital areas. Surprisingly, this pattern was not tied to the density of serotonin receptors but instead linked to the brain's structural connectivity network. The findings clarify how psychedelics reconfigure brain activity.
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
August 29, 2022
Giulio Ruffini, Giada Damiani, Diego Lozano-Soldevilla et al.
5 citations
preprint
Using fMRI data from fifteen people who took LSD or a placebo, researchers modeled brain dynamics with an Ising spin model to test whether psychedelics push the brain into a more disordered state. LSD increased the Ising temperature of brain activity, moving it further away from a critical point (the edge between order and disorder) into a more disordered, paramagnetic phase. This shift was accompanied by a decrease in interhemispheric connectivity, especially between corresponding regions in the two hemispheres. Algorithmic complexity of brain signals also increased with LSD. The findings suggest LSD loosens homotopic connections, driving the brain into a more flexible, complex state, consistent with theories that psychedelics increase neural entropy.
Andrea I. Luppi, Pedro Mediano, Fernando Rosas et al.
5 citations
preprint
Consciousness can be understood not as a single unified thing but as composed of distinct information-theoretic elements. A new approach called Integrated Information Decomposition (ΦID) shifts from measuring how much integrated information a system has to analyzing its composition. This provides a formal way to determine whether consciousness is an emergent phenomenon based on that composition. Two organisms can have the same amount of integrated information yet differ in its composition. A new measure, ΦR, and the ΦR-ing rate quantify how efficiently an entity uses information for conscious processing. This decomposition identifies qualitatively different 'modes of consciousness,' enabling mapping between phenomenology and information-theoretic structure, starting with selfhood.
Nat Med
February 16, 2026
David Erritzøe, Tommaso Barba, Tiffanie Benway et al.
4 citations
A single 21.5-mg intravenous dose of the psychedelic DMT, given with psychotherapeutic support, produced a rapid and significant reduction in depressive symptoms in adults with moderate-to-severe major depressive disorder. In a double-blind, placebo-controlled trial with 34 participants, those receiving DMT showed a greater decrease in depression scores at two weeks compared to placebo. Antidepressant effects persisted up to three months in an open-label phase. Adverse events were mostly mild to moderate, and no serious adverse events occurred.
PsyArXiv
May 14, 2025
James W. Sanders, Raphaël Millière, Ema Demšar et al.
4 citations
preprint
Under DMT, immersive experiences and perceived presences follow a consistent structural pattern: bodily sensations arise first, then visual and auditory elements, and only after multisensory integration and 3D spatial characteristics develop do perceived sentient presences emerge. Micro-phenomenological interviews with 23 participants who received intravenous DMT (20mg) during fMRI-EEG recordings identified 125 phenomenological categories structuring immersion, including modal sensory dimensions, amodal feelings, self/world configurations, and social engagement modes. Perceived presences varied in sensory manifestation, semantic complexity, and social interaction modes. The findings advance understanding of non-ordinary states of consciousness and support future neurophenomenological research.
Human brain mapping
April 1, 2025
Clayton R Coleman, Kenneth Shinozuka, Robert Tromm et al.
4 citations
LSD alters consciousness by changing connectivity between the dorsolateral prefrontal cortex (DLPFC), thalamus, and visual areas. In healthy participants, stronger functional connectivity between the left and right DLPFC, thalamus, and fusiform face area correlated with greater ego dissolution. Emotional arousal was linked to increased connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory reverse analysis supported these findings. Magnetoencephalography data showed that LSD increased theta-band information flow from the thalamus to the DLPFC, supporting the idea that disrupted thalamic gating underlies ego dissolution. The results clarify the DLPFC's role in LSD-induced altered states.
bioRxiv
February 8, 2025
Mona Irrmischer, Marco Aqil, Lisa Luan et al.
4 citations
preprint
The psychedelic DMT shifts brain oscillations away from criticality—a state thought to support healthy brain function—in alpha and adjacent frequency bands, moving toward subcritical regimes. Entropy increases while complexity decreases during this shift. The magnitude of the criticality shift in alpha and theta bands correlates with the intensity of ego-dissolution, a core feature of the psychedelic experience. These results suggest that altered proximity to critical brain dynamics may underlie the neurological and subjective effects of psychedelics, with implications for understanding altered states of consciousness.
PsyArXiv
October 20, 2024
Hugh McGovern, Marco Aqil, Selen Atasoy et al.
4 citations
preprint
Archetypes, as described by Carl Jung, can be understood through modern neuroscience. The article proposes that archetypes arise from a three-part interaction: subcortical systems provide an affective core, altered states like those induced by psychedelics generate archetypal imagery, and higher cortical areas encode archetypal stories. The Free Energy Principle and Predictive Processing are used as foundational frameworks. Archetypes may be transmitted socially, forming a collective unconscious through learning and attunement. The work offers testable hypotheses about the neurological bases of archetypes, aiming to bridge Jungian psychology with neuroscience and encourage empirical investigation.
bioRxiv
July 18, 2019
Christopher Timmermann, Leor Roseman, Michael Schartner et al.
4 citations
preprint
Intravenous DMT, a fast-acting psychedelic, markedly alters human brain activity. Compared with a placebo, DMT reduced oscillatory power in alpha and beta brainwaves and increased spontaneous signal diversity. Time-referenced analyses linked changes in subjective experience to changes in brain activity. Emergence of delta and theta frequency oscillations correlated with the peak of the experience, particularly its eyes-closed visual component. These findings advance understanding of the neurobiological underpinnings of immersive states of consciousness.
Annals of the New York Academy of Sciences
July 21, 2025
Marcel Socoró-garrigosa, Yonatan Sanz Perl, Morten L Kringelbach et al.
3 citations
The scale at which the brain represents information remains a key question in neuroscience. Evidence shows that information is encoded not just in localized areas but across distributed, hierarchical networks. The hierarchy of causal influences shaping brain activity patterns is a signature of different brain states, relevant to neuropsychiatric disorders. Using whole-brain models guided by the thermodynamics of mind framework, researchers estimated brain hierarchy and studied in-silico transitions in static functional connectivity. Applying this to major depressive disorder, they built resting-state whole-brain models of depressed patients before and after treatment with psilocybin or escitalopram.
bioRxiv
March 24, 2025
Kenneth Shinozuka, Mattia Rosso, Clayton R. Coleman et al.
3 citations
preprint
LSD profoundly alters consciousness by reorganizing brain networks in specific frequency bands. Analyzing MEG data from 14 healthy participants, the substance enhances high alpha (12.1, 13.3 Hz) activity across all conditions and high beta (25.3 Hz) in three conditions, while suppressing low beta (18.1, 19.3 Hz) and low alpha (8.5 Hz). LSD also shifts network spatial distributions: low alpha moves anteriorly toward the motor cortex, high alpha becomes more localized to the visual cortex, and low beta expands over temporal and occipital cortices. These frequency- and region-specific changes add nuance to theories of network disintegration under psychedelics.
PsyArXiv
December 29, 2024
James W. Sanders, Raphaël Millière, Zachary G. Daily et al.
3 citations
preprint
DMT reliably produces profound experiences of immersion in other worlds and encounters with seemingly autonomous presences, but the lived qualities and unfolding of these experiences remain poorly understood. Micro-phenomenological interviews with twenty-three healthy participants who received DMT during fMRI scanning revealed rich dimensions of immersive experience—from multisensory engagement to radical reconfigurations of self and world—and illuminated varied ways presences can be seen, felt, or otherwise sensed. The analysis identified structural features and temporal dynamics, particularly the layering of sensory effects followed by spatial, self-related, and social effects, extending beyond traditional constructs like ego dissolution or mystical experience. This mapping advances understanding of DMT's effects and conscious experience, inviting comparisons with meditation, lucid dreaming, and presence phenomena in lab-induced hallucinations or Parkinson's disease.
medRxiv
August 28, 2024
Zishan Jiwani, Simon B. Goldberg, Jack Stroud et al.
3 citations
preprint
Most meditators who use psychedelics perceive them as beneficial for their meditation practice. Among 863 regular meditators (practicing at least three times weekly for the past year) who also used psychedelics, machine learning identified four factors most likely to predict this positive perception: greater frequency of psychedelic use, setting intentions before use, higher agreeableness, and having used N,N-Dimethyltryptamine (DMT). The model explained about 27% of the variance. The findings suggest that intentional and personality factors may shape how psychedelics influence meditation, but causality remains unestablished.
Research Square
August 8, 2024
Danilo Bzdok, Robin Carhart-Harris, Chloe Savignac et al.
3 citations
Large language models can design, annotate, and evaluate experience dimensions from psychedelic reports, producing over 2 million automatic ratings that discriminate the unique mental effects of 30 psychoactive substances. This approach offers a bottom-up complement to legacy questionnaires for measuring changes in subjective awareness.
Research Square
February 22, 2024
Martha Havenith, Max Leidenberger, Jelena Brasanac et al.
3 citations
Circular breathwork, which involves deliberate hyperventilation, can induce altered states of consciousness (ASCs) comparable to those produced by psychedelics, without the legal, medical, or financial barriers. A reduction in end-tidal CO2 pressure due to hyperventilation is instrumental in catalyzing these ASCs. The depth of the ASCs predicted psychological and physiological follow-on effects, including improved well-being and a reduction of depressive symptoms. Two popular forms of breathwork—Holotropic Breathwork® and Consciously-Connected breathwork—produced highly similar physiological, experiential, and psychological outcomes. These findings outline physiological boundary conditions for ASCs in a non-pharmacological context and suggest breathwork's potential as an accessible psychotherapeutic tool.
PsyArXiv
May 24, 2022
Balázs Szigeti, David Nutt, Robin Carhart-Harris et al.
3 citations
preprint
Blinding in medical trials is meant to distribute expectancy effects evenly across treatment arms, but it often fails. Using computational modeling, this work shows that weak blinding combined with positive treatment expectancy can create an 'activated expectancy bias' (AEB), which inflates treatment effect estimates and can produce false positive findings. To address this, the authors introduce the Correct Guess Rate Curve (CGRC), a statistical tool that estimates what a perfectly blinded trial would have found from imperfectly blinded data. Re-analyzing a self-blinding psychedelic microdose trial, they find that observed placebo-microdose differences are susceptible to AEB and may be false positives, suggesting microdosing acts as an active placebo. The results underscore the difference between trials with a placebo control group and genuinely placebo-controlled trials.
bioRxiv
June 11, 2021
Daniel Toker, Ioannis Pappas, Janna D. Lendner et al.
3 citations
preprint
During conscious states, the cortex's electrical activity operates near the edge-of-chaos critical point—the boundary between stability and chaos. Applying a new chaos test to ECoG and MEG recordings from humans and macaques across waking, seizure, anesthesia, and psychedelic states shows that unconsciousness shifts cortical dynamics away from this critical point, disrupting information processing. Psychedelics may enhance information-richness by tuning activity closer to this point. Analysis of EEG from patients with disorders of consciousness suggests that measuring proximity to the edge-of-chaos critical point could serve as a clinical biomarker of consciousness.
Journal of affective disorders
August 1, 2026
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.