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.
Journal of Vision
September 1, 2016
Leor Roseman, Martin I. Sereno, Robert Leech et al.
4 citations
Under LSD, the visual cortex's resting-state functional connectivity (RSFC) becomes more dependent on its intrinsic retinotopic organization, as if the brain were processing actual visual input despite closed eyes. In 10 healthy subjects, RSFC between non-adjacent patches of V1 and V3 that represent congruent parts of the visual field (both horizontal or both vertical meridians) was significantly stronger than connectivity between incongruent patches (horizontal-vertical), compared to placebo. The difference between congruent and incongruent connectivity was greater under LSD (Cohen's d=1.6), suggesting that psychedelic imagery involves transient local retinotopic activation similar to that from visual stimulation.
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.
June 30, 2022
Matthew B. Wall, Rebecca Harding, Rayyan Zafar et al.
3 citations
preprint
Psychedelic therapy shows potential for treating psychiatric disorders like depression, addiction, and PTSD. Classic serotonergic psychedelics such as psilocybin, LSD, DMT, and 5-MeO-DMT are the main focus, along with ketamine, MDMA, and ibogaine. The concurrent use of advanced neuroimaging methods, particularly PET and MRI, has allowed precise assessment of brain effects, benefiting the development of these treatments. The text identifies gaps in knowledge that future multimodal imaging studies could address, providing a stronger foundation for psychedelic therapy.
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.
Drug Science Policy and Law
January 1, 2022
Rayyan Zafar, Dustin Sulak, Jaime Brambila et al.
3 citations
A 49-year-old woman with metastatic breast cancer (ER+, PR-, HER2+, BRCA-) received targeted chemotherapy and a ketogenic diet for 26 months, then added a high-dose cannabinoid regimen (CBD and THC) and psilocybin-assisted psychotherapy. After five months, PET/CT scans showed no evidence of metastatic disease, and chemotherapy was stopped. A one-year follow-up CT found no residual or recurrent disease. Recurrence appeared at 18 months, when the cannabis dose had been reduced to 60% of the initial protocol; increasing it back to the original dose was followed by receding cancer progression over 16 months. The case suggests potential therapeutic utility of adjunctive cannabinoids and psychedelics in metastatic breast cancer.
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.
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.
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.
October 19, 2022
Stefan Baumann, Robin Carhart-Harris, David Nutt et al.
2 citations
preprint
In a placebo-controlled citizen science trial with 240 participants, microdosing tolerance was assessed by tracking whether correct guesses of receiving a microdose decreased with more doses taken. Correct guess probability declined overall, indicating tolerance developed. This tolerance was specific to LSD and LSD-analogue microdoses, not psilocybin microdoses. The findings suggest that microdosers may need to periodically suspend their routine to avoid tolerance and that psilocybin may be better suited for long-term protocols.
Prometheus
September 1, 2010
David Nutt
2 citations
In October 2009, the UK home secretary requested David Nutt's resignation as chair of the government's advisory council on the misuse of drugs after the publication of his paper arguing that ecstasy and LSD are less dangerous than alcohol. Nutt had previously clashed with the Home Office over an editorial comparing the harms of ecstasy unfavorably to those of horse riding. The incident highlighted tensions between academic publication and scientific advice to government. Nutt now chairs the Independent Scientific Committee on Drugs.
bioRxiv (Cold Spring Harbor Laboratory)
June 16, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Gorka Zamora‐lópez et al.
1 citation
Psilocybin and the conventional antidepressant escitalopram produce opposite changes in the brain's hierarchical non-equilibrium dynamics when treating major depressive disorder. Using resting-state fMRI before and after treatment, researchers built whole-brain models and measured how much each patient's brain activity deviated from the fluctuation-dissipation theorem. Baseline measures distinguished treatment responders from non-responders within each group. The deviation from the fluctuation-dissipation theorem may serve as a marker to differentiate the brain effects of psilocybin and escitalopram, contributing to understanding how these treatments work for depression.
Psychological Medicine
July 19, 2023
Brandon Weiss, Induni Ginige, Lu Shannon et al.
1 citation
No Summary
BMJ
May 2, 2023
Leslie A. King, David Nutt, David E. Nichols
1 citation
The authors argue that regulations governing clinical research on Schedule 1 drugs, which are classified as having high abuse potential and no accepted medical use, should be reassessed. They contend that such classification unnecessarily impedes scientific investigation into substances with therapeutic potential, such as certain psychedelics. The piece advocates for a review of the scheduling system to facilitate research that could lead to medical treatments, while maintaining appropriate controls to prevent misuse.
Neuroscience Applied
January 1, 2023
Hannah Douglass, Merle Spriggs, Kate Godfrey et al.
1 citation
No Summary
June 30, 2022
Sandeep M. Nayak, Bilal A. Bari, David B. Yaden et al.
1 citation
preprint
A Bayesian reanalysis of a trial comparing psilocybin (COMP360) to escitalopram for major depressive disorder found that psilocybin outperformed escitalopram, but not by a clinically meaningful amount. The analysis also found extremely strong evidence that psilocybin is non-inferior to escitalopram. Evidence for psilocybin's superiority varied by depression scale: indeterminate for one, strong for two, and extremely strong for another. For a clinically meaningful difference, evidence was moderate against it on one scale, indeterminate on two, and moderate supporting it on one. These results provide a more nuanced interpretation and support further research.
BMJ
December 10, 2021
David Nutt
1 citation
Investing in research, new treatments, and safe injecting rooms is advocated as a necessary approach to address drug-related harms.
December 11, 2020
Balázs Szigeti, Laura Kärtner, Allan Blemings et al.
1 citation
A self-blinding citizen science study tested whether psychedelic microdosing improves well-being and cognition beyond placebo. 191 participants who already planned to microdose were randomly assigned to receive four weeks of microdoses, placebos, or a mix. All psychological outcomes—including well-being, mindfulness, and life satisfaction—improved from baseline in the microdose group, but the placebo group also improved, and no significant differences emerged between groups. Small acute differences in mood, energy, and creativity were observed, but these could be explained by participants correctly guessing whether they took a microdose. The findings suggest that the anecdotal benefits of microdosing are likely due to the placebo effect.
UNC Libraries
April 22, 2020
Peter J. Hellyer, Luke T. Williams, Ben Sessa et al.
1 citation
Lysergic acid diethylamide (LSD) in microgram doses produces profound, sometimes life-changing experiences and is a uniquely powerful psychoactive substance. In the first modern neuroimaging study of LSD, marked changes in brain blood flow, electrical activity, and network communication patterns were observed. These changes correlated strongly with the drug's hallucinatory and consciousness-altering properties. The findings have implications for understanding the neurobiology of consciousness and for potential applications of LSD in psychological research.
bioRxiv (Cold Spring Harbor Laboratory)
Hanna M. Tolle, Andrea I Luppi, Timothy Lawn et al.
1 citation
preprint
A geometric deep learning model called graphTRIP predicts post-treatment depression severity from pretreatment clinical and brain imaging data. Trained on a clinical trial comparing psilocybin and escitalopram, it achieves strong predictive accuracy (r = 0.75) and generalizes to an independent dataset. The model links better outcomes to reduced functional coupling within serotonin systems and broader serotonergic integration with sensory-motor networks. Causal analysis shows a group-level advantage of psilocybin over escitalopram but identifies individuals with specific stress-related neuromodulatory profiles who may benefit more from escitalopram, advancing precision medicine and biomarker discovery in depression.
bioRxiv (Cold Spring Harbor Laboratory)
June 26, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Robin Carhart‐Harris et al.
A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and escitalopram. First, we built whole-brain models of pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) and obtained an initial generative effective connectivity (GEC) matrix for each individual.
Research Square
June 19, 2026
Aline Frick, Grace Blest‐hopley, Manesh Grin et al.
In a reanalysis of a six-week randomized controlled trial comparing psilocybin with escitalopram for moderate-to-severe major depressive disorder, sex-related patterns emerged for anxiety and anhedonia. Women receiving psilocybin showed greater reductions in anxiety than men, while women receiving escitalopram showed greater reductions in anhedonia than men. For other depressive symptoms, thought suppression, and well-being, sex differences were small and uncertain. Sexual dysfunction severity was lower overall in the psilocybin group than in the escitalopram group and lower in women than in men, though the treatment-by-sex interaction was not significant. These preliminary findings suggest that responses to these serotonergic treatments may differ between women and men, supporting the need for adequately powered, sex-balanced trials.
Translational Psychiatry
November 13, 2025
Bruna Giribaldi Cunha, David Nutt, Marieke Martens et al.
In a double-blind randomized trial, patients with long-standing moderate-to-severe depression received either two doses of 25 mg psilocybin plus daily placebo or two doses of 1 mg psilocybin plus daily escitalopram over six weeks. Both treatments comparably reduced negative bias in recognizing facial emotions, a measure of emotional information processing. However, changes in this bias were not linked to concurrent depression score changes. Only in the escitalopram group did a decrease in misclassifying positive faces as negative correlate with lower depression scores at a one-month follow-up. The findings suggest overlapping cognitive mechanisms between psilocybin and escitalopram, notable given psilocybin's short dosing regimen.
Mol Psychiatry
July 1, 2025
Rebecca Harding, Neomi Singer, Matthew B. Wall et al.
correction
In a study comparing psilocybin therapy (PT) to escitalopram for depression, brain responses to unexpected musical notes were measured. After PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions. This suggests PT alters brain processing of unexpected events differently than escitalopram, potentially contributing to its therapeutic effects.