Proc Natl Acad Sci U S A
April 11, 2016
Robin L. Carhart-Harris, Suresh Muthukumaraswamy, Leor Roseman et al.
887 citations
LSD produces marked changes in brain activity that correlate with its psychological effects. Increased blood flow in the visual cortex, decreased alpha power there, and an expanded functional connectivity profile of the primary visual cortex strongly correlated with visual hallucinations, suggesting that intrinsic brain activity influences visual processing more during the psychedelic state. Decreased connectivity between the parahippocampus and retrosplenial cortex correlated strongly with ego-dissolution and altered meaning, indicating this circuit's role in maintaining the self and processing meaning. Different imaging metrics showed strong relationships, allowing firmer inferences about their functional significance.
Frontiers in Pharmacology
November 2, 2018
Adam D. G. Hampshire, Christopher Timmermann, Christopher Timmermann et al.
422 citations
Psychological well-being increased two weeks after a psychedelic experience and remained elevated at four weeks. Higher ratings of a 'mystical-type experience' positively influenced this change in well-being, while 'challenging experience' and 'visual effects' did not. Having 'clear intentions' for the experience fostered mystical-type experiences. A positive 'set' and recreational intentions reduced the likelihood of a challenging experience. The trait 'absorption' and higher drug doses amplified all aspects of the acute experience. Baseline traits had the strongest effect on well-being change, underscoring the importance of extra-pharmacological factors in shaping responses to psychedelics.
Sci Rep
November 19, 2019
Christopher Timmermann, Leor Roseman, Michael Schartner et al.
325 citations
Intravenous DMT, a fast-acting psychedelic, markedly reduces alpha and beta brain wave power and increases spontaneous signal diversity in the human brain, as measured by EEG. The emergence of delta and theta oscillatory activity correlates with the peak of the subjective experience, especially its eyes-closed visual component. Relationships between changes in subjective experience and brain activity were observed across time, linking specific brain changes to specific aspects of the experience.
Neuroimage
May 25, 2019
Louis-David Lord, Paul Expert, Selen Atasoy et al.
249 citations
Brain function can be understood as the exploration of a repertoire of metastable connectivity patterns that underlie different mental processes. Intravenous infusion of psilocybin rapidly modulates how the brain dynamically explores these resting-state networks. Using a data-driven approach focused on the leading eigenvector of BOLD phase coherence at single-TR resolution, recurrent BOLD phase-locking patterns were assessed pre- and post-infusion. A frontoparietal subsystem pattern was strongly destabilized after psilocybin, while a pattern characterized by global BOLD phase coherence became more probable. These results demonstrate network-specific neuromodulation by psilocybin, bridging molecular pharmacodynamics and whole-brain network dynamics.
Curr Biol
September 27, 2018
Gustavo Deco, Josephine Cruzat, Joana Cabral et al.
246 citations
A whole-brain model integrating anatomical, functional, and neurotransmitter data explains how serotonin 2A receptor stimulation with LSD alters brain dynamics. The model combines diffusion MRI, functional MRI, and PET scans of serotonin 2A receptor density to simulate resting-state activity and music listening effects. It shows that LSD's effects arise from non-linear interactions between anatomical connectivity, the brainwide distribution of 5-HT2A receptors, and neuromodulation of neuronal gain. Accounting for neuromodulatory activity in brain models can yield insights into brain function and aid drug discovery for neuropsychiatric disorders.
Neuropharmacology
December 27, 2017
Leor Roseman, Lysia Demetriou, Matthew B. Wall et al.
239 citations
In an open-label study, 20 individuals with moderate to severe, treatment-resistant depression received two doses of psilocybin with psychological support. Nineteen completed fMRI scans before and after treatment. Depressive symptoms improved rapidly and enduringly. Right amygdala responses to fearful and happy faces increased after psilocybin, and increased responses to fearful versus neutral faces predicted clinical improvement at one week. This contrasts with SSRIs, which typically reduce amygdala responses, suggesting psilocybin may help patients confront and work through emotions rather than dampen them. The authors propose psilocybin with psychological support revives emotional responsiveness in depression.
J Psychoactive Drugs
April 26, 2017
Matthew M. Nour, Lisa Evans, Robin L. Carhart-Harris
230 citations
People who have used psychedelics in natural settings tend to hold more liberal and less authoritarian political views, score higher on the personality trait of openness, and feel more connected to nature, even after accounting for other drug use and potential confounders. The degree of ego dissolution during a person's most intense psychedelic experience also predicts these same outcomes. The findings come from an anonymous internet survey of 893 participants who reported their lifetime use of psychedelics, cocaine, and alcohol, and completed measures of personality, nature relatedness, and political attitudes. Cocaine use and weekly alcohol consumption did not show the same associations.
Sci Rep
December 15, 2017
Selen Atasoy, Leor Roseman, Mendel Kaelen et al.
225 citations
LSD alters the energy and power of individual harmonic brain states in a frequency-selective manner, leading to an expansion of the repertoire of active brain states. This expansion is non-random, suggesting a general re-organization of brain dynamics. The frequency distribution of active brain states under LSD closely follows power-laws, indicating a re-organization of dynamics at the edge of criticality. These findings provide insight into how LSD affects brain function and open new methods for understanding complex brain dynamics in health and disease.
Neuroimage
March 8, 2020
Manesh Girn, Caitlin Mills, Leor Roseman et al.
139 citations
Creativity involves alternating between generating ideas and evaluating them. A refined Dynamic Framework of Thought describes creative generation not as one mental state but as a product of many varying states. The psychedelic state is proposed as a mental state with high potential for facilitating creative generation, making psychedelic substances useful experimental tools for studying the neuroscience of creativity.
Curr Opin Psychiatry
January 1, 2019
Robin L. Carhart-Harris
138 citations
Psychedelics are reawakening interest in psychiatry and neuroscience due to promising small-scale clinical trials and brain imaging findings. This opinion piece proposes that psychedelics work through a cascade of neurobiological changes spanning multiple scales: from molecular serotonin 2A receptor agonism, to heightened anatomical and functional plasticity, increased brain entropy, and network-level disintegration and desegregation. These changes ultimately relax high-level beliefs, and psychedelic therapy aims to harness that belief-relaxation to revise pathological beliefs toward healthier ones.
Neuroimage
December 17, 2019
Lionel Barnett, Suresh D. Muthukumaraswamy, Robin L. Carhart-Harris et al.
88 citations
The psychedelic state involves a breakdown in patterns of information flow in the brain. Using MEG recordings, researchers measured functional connectivity after administration of LSD, psilocybin, and low-dose ketamine, and compared them with the non-psychedelic drug tiagabine. All three psychedelics decreased directed functional connectivity (information flow) throughout the brain, as measured by Granger causality. For LSD, this decrease was coupled with an increase in undirected functional connectivity (correlation and coherence), a surprising opposite movement that highlights the importance of comparing multiple measures of functional connectivity in neuroimaging data.
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.
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.
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.
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.
bioRxiv
November 26, 2020
Andrea I. Luppi, Pedro A.M. Mediano, Fernando E. Rosas et al.
49 citations
preprint
The brain coordinates information from many sources to create a unified conscious experience. Combining network science and information theory, the authors identify a “synergistic global workspace” where gateway regions gather synergistic information from specialized brain modules, integrate it, and then broadcast it widely via broadcaster regions. Functional MRI shows that gateway regions correspond to the default mode network and broadcasters to the executive control network. Loss of consciousness from general anesthesia or disorders of consciousness reduces the workspace’s ability to integrate information, which is restored upon recovery. This work reconciles aspects of the Global Neuronal Workspace and Integrated Information Theory.
JAMA Psychiatry
June 1, 2023
Jacob S. Aday, Robin L. Carhart-Harris, Joshua D. Woolley
48 citations
The abstract discusses emerging challenges for psychedelic therapy, highlighting obstacles such as regulatory hurdles, accessibility issues, equity concerns, and the need for practitioner training. It underscores difficulties in integrating psychedelic treatments into mainstream healthcare, including governance, legal frameworks, and developing accessible and equitable treatment models. The text suggests that responsible integration requires addressing these barriers to ensure safe and effective mental health care.
Psychopharmacology (Berl)
November 4, 2021
Joanna Kuć, Hannes Kettner, Fernando Rosas et al.
37 citations
People who use cannabis at the same time as a classic psychedelic report more intense subjective effects, with higher cannabis doses linked to stronger mystical, visual, and ego-dissolution experiences. The relationship between cannabis dose and challenging experiences followed a U-shaped pattern, while emotional breakthrough showed no connection to cannabis dose. The findings suggest an interaction between cannabis and psychedelics, but the study's design cannot establish cause or clinical implications.
bioRxiv (Cold Spring Harbor Laboratory)
May 17, 2021
S. Parker Singleton, Andrea I. Luppi, Robin L. Carhart-Harris et al.
30 citations
preprint
LSD and psilocybin reduce the amount of energy the brain needs to transition between different activity states, as measured by functional MRI. This flattening of the brain's control energy landscape allows for more frequent state transitions and more diverse (entropic) brain activity. The effects are linked to the spatial distribution of serotonin 2a receptors, the main target of these psychedelics. The findings suggest that these compounds make brain state transitions more facile and temporally diverse, offering a mechanistic explanation for the altered subjective experience induced by psychedelics.
International Journal of Mental Health and Addiction
March 7, 2024
Brandon Weiss, Leor Roseman, Bruna Giribaldi et al.
26 citations
Acute psychological experiences, particularly mystical experience and ego dissolution, partially account for how psilocybin therapy improves depression compared to escitalopram. In a phase 2 trial of patients with moderate-to-severe major depressive disorder, mystical experience and ego dissolution uniquely mediated the effect of treatment on depressive response. Higher levels of mystical experience, emotional breakthrough, and intense music-listening responses were also linked to greater antidepressant improvement. These findings suggest that acute psychological experiences play a causal mechanistic role in psilocybin therapy for depression.
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.
N Engl J Med
February 1, 2023
Robin L. Carhart-Harris
10 citations
A compound described as a 'nonpsychedelic psychedelic' reduced anxiety and depression in mice. This commentary questions whether findings from mouse models can reliably predict effects in humans, highlighting potential limitations in translating preclinical results to clinical treatments.
Pedro A.M. Mediano, Fernando E. Rosas, Andrea I. Luppi et al.
10 citations
A new method called Complexity via State-space Entropy Rate (CSER) estimates neural signal complexity with better temporal resolution and spectral decomposition than the standard Lempel-Ziv complexity (LZ) approach. CSER matches LZ in distinguishing conscious states but offers two key advantages: it can break complexity down by frequency bands, and it provides temporal resolution about 100 times finer. Using MEG, EEG, and ECoG data from humans and monkeys, CSER revealed that gamma-band activity primarily drives complexity changes across states of consciousness. In an auditory mismatch negativity experiment, CSER detected early entropy increases roughly 20 milliseconds before the standard event-related potential. This method enables finer-grained study of how signal complexity relates to cognitive processes and conscious states.
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.
Front Hum Neurosci
June 19, 2024
Giuseppe Pasculli, Pierpaolo Busan, Eric S. Jackson et al.
5 citations
Developmental stuttering involves speech-motor disruptions linked to metabolic and network anomalies in the brain, particularly in the default mode and social-cognitive networks. These networks also influence social anxiety and avoidance, which often accompany persistent stuttering. Psychedelic compounds can modify brain metabolism and connectivity in these networks and have shown clinical benefits for conditions like depression and PTSD that share features such as rumination and social anxiety. Although no controlled trials have been conducted, anecdotal reports suggest psychedelics might alleviate stuttering and its associated symptoms. The authors argue that psychedelics warrant investigation in randomized clinical trials for developmental stuttering.