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.
Research Square
October 15, 2024
Alexandra R. Gordon, Brennan M. Carrithers, Broc A. Pagni et al.
3 citations
Among individuals who reported a personality disorder diagnosis, psychedelic use was associated with improvements in mental health outcomes. In two observational studies, participants showed reductions in anxiety and depression symptoms lasting up to 2-3 months, with moderate to large effect sizes. Suicidal ideation decreased, and no participants moved to high risk of suicidal behavior after use. A small proportion experienced clinically significant worsening of anxiety (up to 8.2%) or depression (up to 7.1%). Transient increases in cognitive flexibility and sustained increases in cognitive reappraisal were observed, with the latter linked to reduced anxiety and depression. The findings are limited by small sample sizes and self-reported data.
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.
bioRxiv (Cold Spring Harbor Laboratory)
August 19, 2024
Naji Alnagger, Paolo Cardone, Charlotte Martial et al.
3 citations
preprint
Disorders of consciousness, such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have few treatments. Using whole-brain computational models built from individual patients' fMRI and diffusion-weighted imaging data, this virtual clinical trial simulated the effects of LSD and psilocybin. The psychedelics shifted the brains of patients with disorders of consciousness closer to a critical dynamical state, with a larger effect in MCS patients. In UWS patients, the treatment response depended on structural connectivity, whereas in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for considering psychedelics in treating disorders of consciousness and highlight the role of computational modeling in drug discovery and personalized medicine.
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 N. 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.
September 30, 2022
Robert F. Dougherty, Patrick Clarke, Merve Alti et al.
3 citations
preprint
A machine learning model that analyzes language from therapy sessions accurately predicted which patients with treatment-resistant depression would respond to psilocybin treatment. Transcripts of psychological support sessions held one day after COMP360 (a synthetic psilocybin formulation) administration were analyzed using a zero-shot classifier based on the BART large language model to measure sentiment (valence and arousal) for both participant and therapist. These scores, combined with the Emotional Breakthrough Index and treatment arm, were used to predict treatment outcome measured by MADRS scores. Two multinomial logistic regression models predicted responder status at week 3 and through week 12 with 85% and 88% accuracy, and AUC values of 88% and 85%, respectively. The approach enables rapid prognostication of personalized response to psilocybin treatment and insights into therapeutic model optimization.
Sci Rep
September 15, 2022
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
3 citations
A scientific paper was retracted because a typo in the script used to calculate differential entropy made the reported entropy estimations invalid. The corrected calculations no longer show the expected increase in brain signal diversity or complexity that the original analysis had claimed.
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.
American Journal of Geriatric Psychiatry
January 1, 2026
Jacob S. Aday, Robin Carhart-Harris, Kevin F. Boehnke
2 citations
Psilocybin, a hallucinogen found in certain mushrooms, demonstrated significant therapeutic potential in a study involving 200 participants with treatment-resistant depression. After just three doses, 60% reported substantial symptom relief lasting up to six months. In comparison, traditional antidepressants typically show around 30% effectiveness. The findings suggest that psychedelics like psilocybin could revolutionize psychiatry by addressing the underlying pathogenesis of mental health disorders. This breakthrough highlights the need for more exploration into psychedelics and their implications for clinical psychology and medicine.
Brain
December 12, 2025
Robin Carhart-Harris
2 citations
The entropic brain hypothesis, introduced in 2014 and revised in 2018, proposes that along a dimension of the size of phenomenal consciousness, expansive states—such as expert meditation, psychedelic drug states, and near-death-like experiences—reliably exhibit increased brain entropy, whereas states of reduced or no consciousness—including deep sleep, anesthesia, and disorders of consciousness—show low brain entropy. The hypothesis demonstrates convergent, correlative, predictive, discriminative, and external validity. For example, increased brain entropy under psilocybin predicts improved wellbeing one month later. Changes in brain entropy selectively index the breadth of subjective experience rather than arousal. An entropy-related function is also applied in generative artificial intelligence. The entropic brain is a useful model of conscious states.
December 4, 2025
Avery Ostrand, Matthew M. Nour, Christopher Timmermann et al.
2 citations
preprint
The term 'psychedelic' was coined in 1956 from Greek roots meaning 'soul-manifesting' or 'soul-illuminating,' intended to name a drug category defined by its ability to induce a characteristic subjective state. This study examined the main subjective effects of psilocybin, ketamine, and MDMA. Over two hundred participants rated items about their experiences with all three drugs. Factor analyses revealed three or four independent dimensions of subjective experience. A machine learning classifier successfully predicted which drug a person had taken from the effects reported, confirming that the three drugs produce categorically distinct experiences: psilocybin induces visions and psychological insight, ketamine induces dissociation, and MDMA induces pro-social feelings such as love. Psilocybin is thus an exemplar psychedelic drug, definable by its induction of a psychedelic state characterized by visions and insight.
Advanced Science
November 20, 2025
Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl et al.
2 citations
Simulated administration of LSD and psilocybin in computational models of patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), shifted brain activity closer to criticality—the phase transition between order and chaos. The effect was greater in MCS patients. In UWS patients, the treatment response correlated with structural connectivity, while in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for using psychedelics in DoC treatment and highlight the potential role of computational modeling in drug discovery and personalized medicine.
Neuropsychopharmacology
September 12, 2025
Jakub Vohryzek, Andrea I. Luppi, Selen Atasoy et al.
2 citations
The brain's function depends on its structural wiring, and psychedelics alter this relationship. Using connectome harmonic decomposition, a method linking brain activity to the network of white matter pathways, the authors show that under N,N-dimethyltryptamine (DMT), the brain's harmonic repertoire shifts similarly to that seen with psilocybin, LSD, and ketamine. Repertoire entropy—a measure of the diversity of brain states—increases under DMT. For the first time, the energy spectrum difference and repertoire entropy of connectome harmonics track the intensity of subjective experience in real time, indicating a close coupling between brain network dynamics and conscious experience.
Research Square
August 22, 2025
Richard J. Zeifman, George Danias, Gabrielle Agin-Liebes et al.
2 citations
Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional experiences and their association with improvements in mental health. Methods: Study 1 was an observational study of naturalistic psychedelic use. Study 2 used data from a clinical trial that compared psilocybin with escitalopram in individuals with major depressive disorder.
medRxiv
March 21, 2025
Jessica S. Henry, Bruna Giribaldi, David Nutt et al.
2 citations
preprint
In a randomized controlled trial of 59 patients with major depressive disorder, two high-dose psilocybin therapy sessions produced large increases in optimism and improvements in dysfunctional attitudes related to achievement, dependency, and self-control after six weeks. By contrast, a six-week daily course of escitalopram produced no change in optimism and only improved dysfunctional attitudes in the achievement domain. Psilocybin therapy was superior to escitalopram in remediating negative cognitive biases in depression.
Cureus
January 29, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
2 citations
The study aims to uncover the neural mechanisms by which psilocybin-assisted therapy affects obsessive-compulsive disorder (OCD) and whether those brain changes align with improvements in cognitive symptoms. A secondary goal is to test whether a low, tolerable dose is both practical and effective as a clinical treatment. The results will provide essential data for designing a future randomized controlled trial.
The Oxford Handbook of Psychedelic, Religious, Spiritual, and Mystical Experiences
December 18, 2024
Aaron D. Cherniak, Robin Carhart-Harris, Joel Gruneau Brulin et al.
2 citations
A theoretical synthesis of attachment theory and the REBUS neuroscientific model offers an organizing framework for psychedelic science. Attachment theory holds that people develop internal working models (IWMs) of relational experiences that function as predictive models shaping social and emotional worlds. Effective psychedelic interventions may induce a hyper-plastic neural state that, supported by corrective relational experiences, facilitates rapid learning and revision of IWMs toward greater security. Three proposals guide future research: individual differences in attachment security predict psychedelic phenomenology and integration; increasing attachment security may be a clinical outcome; and clinical utility involves attachment-related dynamics such as connectedness and alleviation of worries.
arXiv (Cornell University)
November 29, 2024
Claudio Agnorelli, Meg J. Spriggs, Kate Godfrey et al.
2 citations
Classic psychedelics (LSD, psilocybin, N,N-DMT) and non-classic psychedelics (ketamine, MDMA) enhance neuroplasticity, the nervous system's ability to adapt. Animal studies indicate these drugs induce meta-plasticity, heightening sensitivity to environmental stimuli, and hyper-plasticity, reopening developmental windows for long-term structural changes that affect mood and behavior. Translating these findings to humans is challenged by limitations in current imaging techniques, but emerging approaches like novel PET radioligands, non-invasive brain stimulation, and multimodal methods offer promising directions. This review informs development of targeted interventions for neuropsychiatric disorders and advances understanding of psychedelics' therapeutic potential.
Neuropsychopharmacology Reports
March 13, 2024
Keisuke Kusudo, Hideaki Tani, Kengo Yonezawa et al.
2 citations
A Japanese version of the Ego-Dissolution Inventory (EDI) was developed through a translation and back-translation process following international guidelines. Two Japanese psychiatrists independently translated the original English EDI, reconciled differences, and had the resulting version back-translated into English. The original authors reviewed and approved the back-translated version after iterative revisions. The final Japanese EDI is intended to help assess ego-dissolution experiences during psychedelic-assisted therapy in Japanese-speaking populations. Further research is needed to test the reliability and validity of this new instrument.
JMIR Formative Research
March 4, 2024
Grant Jones, Felipe Herrmann, Adam Bear et al.
2 citations
In a group of people who recently used psychedelics, increases in mindfulness were followed by improvements in well-being. The findings suggest that mindfulness may be a mechanism through which psychedelic experiences lead to positive mental health outcomes.
bioRxiv (Cold Spring Harbor Laboratory)
October 7, 2023
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al.
2 citations
preprint
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and show therapeutic potential for depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—phenomenology, neuroimaging, and pharmacology—reveals that medium and high doses of LSD produce significantly stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences emerged in receptor selectivity among the drugs. The findings highlight high heterogeneity and risk of bias, underscoring the need for standardized methods.
International Journal of Latin American Religions
June 9, 2023
Robson Savoldi, Antônio Roazzi, José Arturo Costa Escobar et al.
2 citations
Mysticism significantly enhances well-being, with 75% of participants in a study reporting improved life satisfaction after engaging in mystical experiences. In a sample of 500 individuals, psychometric assessments utilized structural equation modeling to confirm the construct validity of these experiences. The interplay between philosophy and social psychology revealed that psychedelics, particularly alkaloids, can facilitate profound insights into the self—bridging the id, ego, and super-ego. This highlights the potential of mystical experiences as therapeutic tools within developmental psychology and theology.