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.
Neuropharmacology
December 25, 2017
James J.H. Rucker, Jonathan Iliff, David J. Nutt
339 citations
Classical psychedelics like psilocybin, LSD, and mescaline were widely used in psychiatry before being placed in Schedule I of the UN Convention on Drugs in 1967. Pre-prohibition studies indicate these drugs are not helpful for people with established psychotic disorders and should be avoided in those at risk. However, individuals with psychoneurotic disorders sometimes benefited considerably from the drugs' tendency to loosen fixed, maladaptive patterns of cognition and behavior, especially in a supportive therapeutic setting. A recent systematic review in unipolar mood disorder and a meta-analysis in alcoholism have both suggested efficacy. Serious adverse events appear to be low. Since 2006, pilot trials and randomized controlled trials using psychedelics (mostly psilocybin) in various non-psychotic psychiatric disorders have provided encouraging results, though regulatory and legal hurdles to licensing remain formidable.
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.
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.
Eur Neuropsychopharmacol
April 12, 2016
Mendel Kaelen, Leor Roseman, Joshua Kahan et al.
143 citations
Psychedelic drugs like LSD are being re-examined for therapeutic use, often combined with music during psychotherapy. In a placebo-controlled fMRI study with 12 healthy volunteers, researchers investigated how LSD and music together affect mental imagery. They found that the combination of LSD and music increased functional connectivity and information flow from the parahippocampal cortex to the visual cortex. This enhanced connectivity correlated with stronger eyes-closed visual imagery, including autobiographical imagery. The findings suggest a neural mechanism by which music and LSD synergistically enhance subjective experiences that may be valuable in therapeutic settings.
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.
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.
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 (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.
BJPsych Open
January 18, 2022
Zach Walsh, Özden Merve Mollaahmetoğlu, Joseph Rootman et al.
28 citations
No Summary
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.
Imaging Neurosci (Camb)
January 3, 2025
Kenneth Shinozuka, Prejaas K.b. Tewarie, Andrea Luppi et al.
9 citations
LSD weakens the brain's usual hierarchy of information flow by making neural communication more balanced between sending and receiving signals. Using magnetoencephalography (MEG) data from 16 healthy adults given 75 micrograms of LSD intravenously, researchers measured directed functional connectivity under four conditions (eyes-closed with or without music, eyes-open with or without video). Across the whole brain, LSD reduced the asymmetry of directed connectivity over time. Machine learning classifiers distinguished LSD from placebo more accurately using hierarchy metrics than traditional connectivity measures. These results indicate that LSD flattens the brain's hierarchical information processing by increasing the balance between senders and receivers of neural signals.
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.
Neuropharmacology
August 23, 2018
David J. Heal, Jack Henningfield, Bruno G. Frenguelli et al.
7 citations
Psychedelic compounds can temporarily alter brain connectivity, potentially re-opening periods of heightened plasticity that allow rigid neural patterns to be reshaped. This process may facilitate cognitive shifts, including new perspectives and changes in emotional processing, which could underlie therapeutic breakthroughs for various mental health conditions. The text suggests that by disrupting entrenched brain networks, psychedelics enable a reconfiguration of neural pathways, offering a mechanism for lasting improvements in mental well-being.
Nat Med
June 1, 2021
David J. Nutt, Harriet de Wit
6 citations
The text is a brief, playful title that reinterprets the abbreviation MDMA, suggesting a connection to medical doctors (MD) rather than providing substantive content. It does not present a finding, argument, or data.
bioRxiv
March 20, 2024
Valerie Bonnelle, Amanda Feilding, Fernando E. Rosas et al.
5 citations
preprint
Intense positive emotional experiences induced by psychedelics, known as 'peak experiences', are strong predictors of positive outcomes in psychedelic-assisted therapy. This study investigated how the autonomic nervous system (ANS) relates to such experiences. Analyzing electrocardiogram data from 17 participants who received DMT or placebo, researchers found that coactivation of the sympathetic and parasympathetic branches of the ANS during the DMT experience was strongly correlated with ratings of 'Spiritual Experience' and 'Insightfulness', and also linked to improved wellbeing two weeks later. Additionally, the balance between these branches before DMT injection predicted 'Insightfulness' scores. These findings demonstrate the ANS's involvement in psychedelic-induced peak experiences and suggest potential for biofeedback tools to enhance therapy.
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.
The Biochemist
March 25, 2024
David J. Nutt
3 citations
Natural psychedelics like magic mushrooms have been used for at least 7000 years, with a resurgence in the 1950s and 1960s after LSD was synthesized and used therapeutically. Non-medical use led to a global ban in the early 1970s. Over the past 20 years, research has revived, showing that psychedelics act as agonists of the serotonin 5-HT2A receptor, altering neuro-circuitry to produce more integrated and flexible brain activity. These changes, observed in healthy volunteers, predicted benefits for mental illnesses like depression and addiction, confirmed by subsequent trials. A single psychedelic experience can yield very long-lasting improvements across several mental illnesses. Given these consistent positive outcomes, psychedelic therapy will likely soon be widely approved in Western medicine, as it already is in Australia for treatment-resistant depression.
J Psychopharmacol
October 27, 2025
David J. Nutt, Celia Morgan, David Erritzøe et al.
2 citations
Ketamine, originally developed as an anesthetic, has emerged as a promising treatment for severe depression and other psychiatric conditions, particularly in patients who have not responded to traditional therapies. The compound can provide rapid relief from depressive symptoms, often within hours, which contrasts with conventional antidepressants that may take weeks to work. This surprising discovery has opened a new frontier in mental health treatment, offering hope for those with challenging mood disorders. However, the use of ketamine in psychiatry also raises concerns about its potential for abuse and long-term side effects, necessitating careful clinical oversight.
bioRxiv Preprint Server
December 9, 2024
Clayton R. Coleman, Kenneth Shinozuka, Robert Tromm et al.
1 citation
preprint
Lysergic acid diethylamide (LSD) alters consciousness by affecting brain connectivity, particularly in the dorsolateral prefrontal cortex (DLPFC). Using fMRI and MEG data from healthy participants, the study found that ego dissolution—a hallmark of the psychedelic experience—was positively correlated with increased functional connectivity between the left and right DLPFC, thalamus, and fusiform face area. Emotional arousal was linked to stronger connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory analysis supported these findings. MEG data showed that LSD increased directed information flow from the thalamus to the DLPFC in the theta band, suggesting disrupted thalamic gating contributes to ego dissolution. These results indicate a key role for the DLPFC in LSD-induced states of consciousness.
Br J Psychiatry
July 8, 2026
Hannah M. Douglass, Meg J. Spriggs, Kate Godfrey et al.
In a small pilot study, 21 women with anorexia nervosa received three doses of psilocybin (COMP360) over six weeks, combined with talk therapy and usual care. The treatment was well tolerated; common side effects were headache, nausea, and dizziness. Two serious adverse events (suicide attempts) occurred in one participant during the 6–12 month period. Eating disorder symptoms significantly improved at six months, and motivation to change improved at twelve months, though individual responses varied widely. The findings provide preliminary support for the feasibility and safety of psilocybin therapy in this population, but larger, more rigorous studies are needed.
Hum Brain Mapp
July 1, 2026
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
A computational model predicts that a single dose of psilocybin can produce lasting changes in the dynamic activity and effective connectivity of fronto-striatal-thalamic brain circuits. The modeling suggests that psilocybin may strengthen connectivity between the prefrontal cortex and striatum while altering thalamic gating, effects that persist beyond the acute drug experience. These changes could underlie the sustained therapeutic benefits observed in clinical settings, such as reduced depressive symptoms and increased psychological flexibility. The findings provide a mechanistic framework for understanding how psilocybin induces long-term neural plasticity and highlight potential circuit targets for treating psychiatric disorders.
PLoS ONE
June 18, 2026
Elisa Liberati, Hv Curran, Peter Fonagy et al.
MDMA-assisted psychotherapy shows promise for treating PTSD, but the psychological mechanisms behind its effects are not well understood. This qualitative study will have approximately 25 experienced psychodynamic psychotherapists receive two doses of MDMA (80-120 mg, oral) in an open-label design. Participants will complete interviews before, during, and after MDMA sessions, plus daily journals. Researchers will use phenomenological and thematic analysis, along with grounded theory, to develop a model of MDMA's psychological mechanisms of action. The study treats therapists as expert observers of their own psychological processes, aiming to generate insights that can inform future treatment models and offer a framework for qualitative mechanistic research on psychedelics.
Neuropsychopharmacology
October 31, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region involved in reward and motivation—communicates with other areas. Using resting-state fMRI data from prior studies, researchers examined striatal connectivity after acute drug administration. Neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connections between the limbic striatum and the amygdala, while LSD increased connections between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, supporting the idea that psychedelics reduce the brain's usual network segregation, potentially explaining their therapeutic and psychological effects.