Elife
October 12, 2020
Andrea Alamia, Christopher Timmermann, David Nutt et al.
86 citations
The psychedelic drug DMT rapidly induces a highly immersive state of consciousness with vivid visual imagery. In a study of participants who received DMT or placebo (saline) while keeping their eyes closed, brain electrical activity showed a pattern of cortical travelling waves similar to that normally seen during visual stimulation. The typical alpha-brainwave rhythms of eyes-closed rest were significantly reduced, while forward-directed waves from lower to higher brain regions increased. These findings support the idea that psychedelics reduce the brain's reliance on prior expectations, shifting the balance from top-down to bottom-up information processing, which may be a key mechanism underlying altered states of consciousness.
Neuropharmacology
November 20, 2017
Christopher Timmermann, Meg J. Spriggs, Mendel Kaelen et al.
83 citations
LSD reduces the brain's automatic neural adaptation to familiar sounds and blunts the neural 'surprise' response to unexpected sounds. Using magnetoencephalography and dynamic causal modeling, the authors found that LSD modulates backward (top-down) connectivity within a fronto-temporal network and intrinsic connectivity in the primary auditory cortex. These patterns resemble those seen in schizophrenia, ketamine states, and reduced consciousness, suggesting that backward connectivity may reflect altered perceptual learning common to multiple altered states rather than a direct marker of conscious level. The findings challenge top-down hypotheses of consciousness and indicate that several altered states may share this biophysical mechanism.
Frontiers in Psychiatry
October 20, 2021
Meg J. Spriggs, Hannah Douglass, Rebecca J. Park et al.
78 citations
Anorexia nervosa is a severe psychiatric condition with few approved treatments. This paper describes how individuals with lived experience of anorexia nervosa helped shape a pilot study of psilocybin-assisted therapy through two online focus groups involving eleven people, and presents the protocol for that study at Imperial College London. Twenty female participants aged 21–65 with a body mass index of 15 kg/m² or above will receive three oral doses of psilocybin (up to 25 mg) over six weeks, supported by psychological preparation and integration, with a 12-month remote follow-up.
Frontiers in Psychology
October 12, 2018
Taylor Lyons, Robin Carhart-Harris
78 citations
Patients with treatment-resistant depression showed a significant pessimism bias when predicting future life events, which was linked to the severity of their depressive symptoms. One week after receiving two doses of psilocybin (10 and 25 mg) with psychological support, this pessimism bias decreased significantly, depressive symptoms greatly improved, and patients became more accurate at predicting future events. No such change occurred in non-depressed controls. The findings suggest that psilocybin with psychological support might correct pessimism biases in treatment-resistant depression, enabling a more positive and accurate outlook.
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.
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.
Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences
May 23, 2022
Pedro A. M. Mediano, Fernando E. Rosas, Andrea I. Luppi et al.
73 citations
Emergence—how galaxies form or consciousness arises from neurons—lacks formal tools for rigorous study. This article summarizes, elaborates, and extends a recent formal theory of causal emergence based on information decomposition, which is quantifiable and empirically testable. The theory links emergence to information about a system's temporal evolution that cannot be obtained from its parts separately. The article provides an accessible but rigorous introduction to this framework, discussing its merits in various scenarios, interpretation issues, and potential misunderstandings, highlighting the distinctive benefits of this formalism.
J Psychopharmacol
February 10, 2021
Carla Pallavicini, Federico Cavanna, Federico Zamberlán et al.
73 citations
Inhaled N,N-dimethyltryptamine (DMT) in natural settings reduces alpha brainwave power (8-12 Hz) across the scalp while increasing delta (1-4 Hz) and gamma (30-40 Hz) power. Gamma power increases correlate with reports of mystical-type experiences. DMT also raises global synchrony and metastability in the gamma band and lowers them in the alpha band. These findings align with prior lab-based psychedelic research and suggest EEG markers for mystical experiences in real-world contexts, underscoring the value of studying psychedelics in natural settings.
Neuroscience of Consciousness
January 1, 2019
Gregory Scott, Robin Carhart-Harris
72 citations
The classic psychedelic psilocybin may increase conscious awareness in patients with disorders of consciousness, based on its ability to increase brain complexity—a reliable index of conscious level. The authors propose testing this hypothesis but also confront the considerable ethical and practical challenges that must be addressed for direct assessment.
Prog Brain Res
October 25, 2018
Selen Atasoy, Jakub Vohryzek, Gustavo Deco et al.
67 citations
Psychedelics produce distinct brain activity patterns characterized by frequency-specific energy changes and an expanded repertoire of functional states, as revealed through connectome-harmonic decomposition. These neural signatures suggest that psychedelics increase the brain's flexibility and diversity of activity, which may underlie their therapeutic benefits for mental health.
Neuroimage
June 24, 2019
Carla Pallavicini, Martina G. Vilas, Mirta Villarreal et al.
66 citations
Classic serotonergic psychedelics and dissociative drugs like ketamine produce overlapping subjective effects despite different pharmacological mechanisms. Using source-localized magnetoencephalography, researchers found that LSD, psilocybin, and ketamine all caused widespread broadband reductions in spectral power. Machine learning classifiers trained on one pair of drugs could identify the third, confirming similarity. Functional connectivity analysis revealed decreases in low alpha and theta bands specific to LSD and psilocybin, linked to 5-HT2A agonism, while low beta band decreases were common to all three drugs. These findings quantify shared large-scale brain activity patterns across drug classes and suggest that beta band decoupling is an effect shared between NMDA antagonists and 5-HT2A agonists.
Science Advances
June 14, 2023
Leor Roseman, Christopher Timmermann, Daniel Golkowski et al.
65 citations
The effects of mind-altering drugs on brain function arise from complex interactions with multiple neurotransmitter systems, not just one. By linking the distribution of 19 neurotransmitter receptors and transporters (measured with PET) to changes in functional connectivity (measured with fMRI) caused by 10 drugs—anesthetics (propofol, sevoflurane, ketamine), psychedelics (LSD, psilocybin, DMT, ayahuasca), and others (MDMA, modafinil, methylphenidate)—the work shows a many-to-many mapping between drug effects and neurotransmitter systems. The drugs' impacts follow hierarchical gradients of brain structure and function, and regional susceptibility to drug-induced changes mirrors susceptibility to structural alterations from brain disorders.
Frontiers in Psychiatry
June 29, 2021
Keri Mans, Hannes Kettner, David Erritzøe et al.
65 citations
Psychedelic substances like LSD and psilocybin have regained legitimacy in clinical research. In this naturalistic observational study of volunteers intending to take a psychedelic, well-being was assessed using fourteen measures at four time points: 1 week before and 2 weeks, 4 weeks, and 2 years after the experience (sample sizes 654, 315, 212, and 64, respectively). Changes clustered into three factors: 'Being well,' 'Staying well,' and 'Spirituality.' Repeated measures analysis showed improvements in Being Well and Staying Well in the weeks following the experience, and mixed model analyses indicated these improvements remained statistically significant up to 2 years, despite high attrition. Spirituality did not show significant change.
Scientific Reports
May 24, 2022
David Wyndham Lawrence, Robin Carhart-Harris, Roland R. Griffiths et al.
64 citations
An analysis of over 3,700 naturalistic experiences with inhaled N,N-DMT posted to Reddit over a decade reveals common themes. Somatic effects like body sensations (37.5%) and auditory ringing (15.4%) were frequent, while visualizations often involved fractals, shapes, and vivid colors. Entity encounters occurred in 45.5% of experiences, most commonly with a feminine phenotype, deities, aliens, and creature-based beings. Interactions were predominantly positive or pedagogical. Descriptions of alternate dimensions, rooms including a 'waiting room,' and tunnels were common. Mystical and ego-dissolution features were frequent, along with rewarding aspects like reduced fear of death. Challenging responses were less common.
Hum Brain Mapp
April 29, 2016
Leor Roseman, Martin I. Sereno, Robert Leech et al.
63 citations
Under LSD, with eyes closed, patches of the visual cortex that represent the same part of the visual field (e.g., both representing the horizontal meridian) showed stronger functional connectivity than patches representing different parts, compared to placebo. This pattern, measured in 10 healthy subjects using resting-state fMRI, suggests that the early visual system during LSD-induced imagery behaves as if it were processing actual visual input, even when no external visual stimuli are present.
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.
Neuroscience of Consciousness
January 1, 2023
Inês Hipólito, Jonas Mago, Fernando E. Rosas et al.
60 citations
Psychedelic therapy shows promise for mental health, but the psychological mechanisms behind its benefits are unclear. This paper proposes that psychedelics act as destabilizers, both psychologically and neurophysiologically, drawing on the 'entropic brain' hypothesis and the 'RElaxed Beliefs Under pSychedelics' model. Using complex systems theory, it suggests that psychedelics disrupt fixed points or attractors, breaking reinforced patterns of thinking and behavior. The approach explains how increased brain entropy destabilizes neurophysiological set points, leading to new understandings of psychedelic psychotherapy. These insights have implications for reducing risks and optimizing treatment during both the peak experience and the subacute recovery period.
Scientific Reports
October 20, 2020
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
60 citations
Psychedelic drugs such as lysergic acid diethylamide, which activate the serotonin 2A receptor, produce profound changes in consciousness and increase entropy in spontaneous neural activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonergic neuromodulation. The model reproduced the overall entropy rise seen in previous experiments. Entropy changes were not uniform: some brain regions showed increased entropy while others showed decreases, indicating a topographical reconfiguration driven by receptor activation. At the whole-brain level, this reconfiguration was not well explained by receptor density but was closely related to the brain's anatomical connectivity topology.
Neuropsychoanalysis
January 1, 2007
Robin Carhart-Harris
59 citations
Four subjective states—dreaming, the dreamy state of temporal lobe epilepsy, acute psychosis, and the psychedelic state—share a common neural basis: high-voltage bursts of theta and slow-wave activity (2–8 Hz) in the medial temporal lobes. These regions are crucial for memory and emotion. In dreaming, medial temporal bursts correlate tightly with PGO waves, widely considered direct neurophysiological correlates of dreaming. All four states are viewed as allowing unconscious material to emerge into consciousness. The argument proposes that electrical bursts spreading from the medial temporal lobes to association cortices are the primary functional correlate of discharging psychical energies, experienced as unconscious material entering consciousness. The findings support the scientific legitimacy of the psychodynamic model.
BJPsych Open
September 1, 2022
Tommaso Barba, Sarah Buehler, Hannes Kettner et al.
57 citations
Psilocybin, but not the antidepressant escitalopram, reduced rumination and thought suppression in people with major depressive disorder six weeks after treatment. In a randomized trial of 59 participants, only those given psilocybin showed significant decreases in both maladaptive coping strategies. Among treatment responders, thought suppression decreased exclusively in psilocybin responders, while rumination decreased in both psilocybin and escitalopram responders. Reductions in rumination and thought suppression correlated with ego dissolution and psychological insight during psilocybin sessions, suggesting distinct therapeutic mechanisms for the two treatments.
J Affect Disord
April 1, 2018
Facundo Carrillo, Mariano Sigman, Diego Fernández Slezak et al.
57 citations
An algorithm analyzing natural speech from baseline interviews can predict which patients with treatment-resistant depression will respond to psilocybin therapy. The approach uses vocal patterns and linguistic features to forecast treatment outcomes, suggesting that speech biomarkers may enable personalized medicine in mental health. This predictive capability could help identify likely responders before treatment begins, advancing precision psychiatry for depression.
Journal of Affective Disorders
August 1, 2023
Richard J. Zeifman, Anne C Wagner, Candice M Monson et al.
56 citations
In a double-blind randomized controlled trial comparing psilocybin therapy (two 25 mg sessions plus daily placebo for six weeks) with escitalopram (two 1 mg psilocybin sessions plus 10-20 mg daily escitalopram for six weeks) among 59 individuals with major depressive disorder, reductions in experiential avoidance mediated improvements in well-being, depression severity, suicidal ideation, and trait anxiety only in the psilocybin group. Exploratory analyses indicated that these improvements (except for suicidal ideation) occurred serially through increased connectedness. Experiences of ego dissolution and psychological insight predicted reductions in experiential avoidance. The findings support reduced experiential avoidance as a mechanism underlying psilocybin therapy's positive outcomes.
Scientific Reports
July 13, 2021
Otto Simonsson, Walter Osika, Robin Carhart-Harris et al.
54 citations
Lifetime use of classic psychedelics is associated with lower odds of heart disease and diabetes. Analyzing data from the National Survey on Drug Use and Health (2005–2014), people who had ever tried a classic psychedelic had 23% lower odds of past-year heart disease and 12% lower odds of past-year diabetes. The associations persisted after adjusting for other factors. The authors suggest classic psychedelic use might benefit cardiometabolic health but call for more research on causal pathways.
J Psychopharmacol
April 22, 2021
Robin 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.
Language Cognition and Neuroscience
August 11, 2016
Neiloufar Family, David Vinson, Gabriella Vigliocco et al.
53 citations
LSD alters cognition by expanding the breadth of semantic activation. In a picture-naming task with ten participants, LSD reduced accuracy and altered error correction patterns compared to placebo, consistent with an increased spread of semantic activation. These effects align with a generalized entropic effect on the mind. The authors recommend future studies include direct neuroimaging and more naturalistic measures of semantic processing.