EClinicalMedicine
February 1, 2023
Robin von Rotz, Eva M Schindowski, Johannes Jungwirth et al.
345 citations
A single, moderate dose of psilocybin (0.215 mg/kg body weight) significantly reduced depressive symptoms compared to placebo in adults with major depressive disorder. Over two weeks, depression severity scores dropped by 13.0 points on the MADRS and 13.2 points on the BDI in the psilocybin group, with improvements significantly larger than in the placebo group. 54% of participants receiving psilocybin met remission criteria. No serious adverse events occurred. The findings suggest psilocybin offers rapid antidepressant effects, though larger, longer-term trials are needed.
Biological psychiatry
February 1, 2023
Devon Stoliker, Leonardo Novelli, Franz X Vollenweider et al.
49 citations
Under the peak effect of LSD, the inhibitory influence from the salience network to the default mode network becomes excitatory, and inhibition from the default mode network to the dorsal attention network weakens. These changes in effective connectivity between resting-state networks may reduce their normal anticorrelation, offering a neural mechanism for ego dissolution—the blurring of the boundary between self and world. The findings suggest that alterations in the sense of self across different conscious states depend on the organized balance of effective connectivity among these networks.
iScience
May 19, 2023
Andres Ort, John W Smallridge, Simone Sarasso et al.
47 citations
Classical psychedelic drugs like psilocybin induce profound changes in consciousness, including heightened sensory-emotional awareness and arousal, accompanied by increased spontaneous EEG signal diversity. By combining Transcranial Magnetic Stimulation (TMS) with EEG, this work shows that psilocybin creates a state of increased chaotic brain activity, which is not due to altered complexity in causal interactions between brain regions. The study also maps regional effects of psilocybin on TMS-evoked activity, identifying changes in frontal brain structures that may relate to the phenomenology of psychedelic experiences.
eLife
April 17, 2024
Flora Moujaes, Jie Lisa Ji, Masih Rahmati et al.
23 citations
Ketamine is a promising treatment for treatment-resistant depression, but why people respond differently is poorly understood. In a single-blind placebo-controlled study, 40 healthy participants received acute ketamine. Using data-driven global brain connectivity, the neural and behavioral effects of ketamine were found to be multi-dimensional, reflecting robust inter-individual variability. Ketamine's principal neural gradient matched somatostatin and parvalbumin cortical gene expression patterns, while the mean effect did not. Behavioral symptom variation mapped onto distinct neural gradients resolvable at the single-subject level. These results highlight the importance of individual variation for developing precise pharmacological biomarkers in psychiatry.
Molecular psychiatry
April 1, 2025
Devon Stoliker, Katrin H Preller, Leonardo Novelli et al.
19 citations
Psilocybin, the active compound in magic mushrooms, alters visual perception by changing how brain regions communicate. Under psilocybin, early visual areas and higher visual-association regions showed increased self-inhibition, reducing sensitivity to incoming neural signals. At the same time, top-down feedback from visual-association areas to earlier visual regions was enhanced. This shift in balance—less bottom-up sensitivity and stronger top-down influence—may explain the vivid eyes-closed imagery characteristic of psychedelic experiences. The findings come from a double-blind, placebo-controlled study of 24 healthy adults using functional MRI and dynamic causal modeling, and they advance understanding of both basic visual perception and potential clinical applications.
Translational psychiatry
December 4, 2024
Kenneth Shinozuka, Katarina Jerotic, Pedro Mediano et al.
17 citations
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and may help treat depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—subjective experience, neuroimaging, and molecular pharmacology—reveals that medium and high doses of LSD produce 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 exist in receptor selectivity among the drugs. The analysis finds high heterogeneity and risk of bias, calling for standardized methods and more research.
Scientific reports
October 14, 2023
Nathalie M Rieser, Ladina P Gubser, Flora Moujaes et al.
14 citations
Psilocybin alters cerebral blood flow in the brain, and the magnitude of these changes depends on individual baseline psychological and neurobiological characteristics. In a placebo-controlled study of 70 healthy participants given one of three oral doses of psilocybin, reductions in relative cerebral blood flow correlated with both baseline traits and the intensity of the subjective psychedelic experience. The findings demonstrate that inter-individual heterogeneity in the neural response to psilocybin is linked to pre-existing differences, helping to identify biomarkers for a personalized medicine approach in psychedelic-assisted therapy.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Mihai Avram, Felix Müller, Katrin H Preller et al.
13 citations
In a double-blind, placebo-controlled, crossover study with 25 healthy participants, LSD, MDMA, and d-amphetamine all increased effective connectivity from the thalamus to specific unimodal cortices while reducing the influence of those cortices back onto the thalamus, indicating stronger bottom-up and weaker top-down information flow. For transmodal cortices, including parts of the salience network, amphetamines showed opposite effects. LSD uniquely increased effective connectivity from the thalamus to both unimodal and transmodal cortices, suggesting a breakdown in the hierarchical organization of brain activity. These findings refine models of how psychedelics alter brain connectivity.
Neuroscience and biobehavioral reviews
August 1, 2025
Lucie Berkovitch, Baptiste Fauvel, Katrin H Preller et al.
8 citations
Psilocybin, a psychedelic compound, shows fast-acting and sustainable efficacy for treating psychiatric disorders. A systematic review of 81 neuroimaging studies found that psilocybin reproducibly impacts brain networks, particularly the default mode network, though other findings were inconsistent. Effects include acute alterations in self-experience, sensory and emotional processing, and sustained changes in mood, personality, and social functioning. In patients with depression, clinical outcomes correlated with brain changes. The review indicates psilocybin induces acute and long-lasting functional brain changes, shedding light on mechanisms underlying its subjective and therapeutic effects.
EClinicalMedicine
February 1, 2023
Robin von Rotz, Eva M Schindowski, Johannes Jungwirth et al.
8 citations
correction
A correction was issued for a figure in a clinical trial on psilocybin-assisted therapy for major depressive disorder. The colors representing the Psilocybin and Placebo conditions were swapped in Fig. 2; the correction aligns them with the caption and other figures. The error does not affect the results. The trial found that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to placebo for at least two weeks, with no serious adverse events. Larger, multi-centric trials with longer follow-up are needed to optimize this treatment.
Neuroscience Applied
December 30, 2023
Sophia Armand, Kristian Larsen, Martin K Madsen et al.
7 citations
The psychedelic drug psilocybin acutely reduces amygdala reactivity to angry faces in healthy individuals, while its subjective intensity is linked to reduced amygdala response to fearful faces. In 26 participants, fMRI scans showed that amygdala response to angry faces was significantly lower under psilocybin compared to baseline. No significant changes occurred for fearful or neutral faces. Higher subjective drug intensity was associated with weaker amygdala response to fearful faces, but plasma psilocin levels showed no such link. These findings align with prior work, suggesting psilocybin alters emotion processing in the brain, with potential implications for treating depression.
Current topics in behavioral neurosciences
July 31, 2024
Nathalie M Rieser, Timo T Schmidt, Katrin H Preller
5 citations
This chapter reviews current knowledge on the neural mechanisms of psychedelic drugs, focusing on human neuroimaging studies. It covers acute and subacute adverse effects and how these may inform psychiatric illness pathophysiology. The chapter examines EEG, fMRI, and PET findings, along with pre- to postdrug changes. Prevailing models discussed include the Cortico-Striato-Thalamo-Cortical feedback loop, the entropic brain hypothesis, the REBUS principle, and the claustrum hypothesis. Neural correlates of visual effects, social and emotional impacts, and ego dissolution are explored. Speculations on how acute effects relate to rare long-term adverse effects are offered, though data scarcity makes these tentative.
Neuroscience applied
January 1, 2024
Drummond E-Wen Mcculloch, Juan Pablo Lopez, Christina Dalla et al.
2 citations
Classical psychedelic drugs like psilocybin and LSD stimulate the serotonin 2A receptor and are being investigated for clinical effects in brain disorders. Experts at the ECNP 'New Frontiers meeting' in March 2023 identified key knowledge gaps in psychedelic mechanisms, including the need for appropriate behavioral models, dose optimization, molecular mechanisms, sex differences, and effects on neurotransmitter release and brain activity. The meeting highlighted the importance of preclinical and neuroimaging research to address these gaps.
Translational psychiatry
May 26, 2026
Marvin M Urban, Lea Zillich, Nathalie M Rieser et al.
1 citation
In a pilot study of 37 detoxified patients with alcohol use disorder, psilocybin (25 mg) produced changes in DNA methylation across the genome compared to placebo. One methylation site in the TLE4 gene and a differentially methylated region in RASGRP4 were linked to psilocybin treatment. Co-methylation networks related to psilocybin were associated with reductions in depressive symptoms and drinking behavior, and gene analysis pointed to involvement in neuroplasticity and immune functions. The primary trial endpoints—duration of abstinence and mean alcohol use—were not reached, so the analysis focused on secondary psychometrics. The findings suggest immunomodulatory actions of psilocybin but are limited by the modest sample size.
Journal of psychopharmacology (Oxford, England)
May 1, 2025
Niloufar Pouyan, Jacob S Aday, Steven E Harte et al.
1 citation
People with treatment-resistant conditions often see their illness as part of their identity. The pictorial representation of illness and self measure (PRISM) gauges this self-condition enmeshment. In a survey of 297 individuals who used psychedelics therapeutically on their own, most reported symptom improvement: 95.4% with depression, 98.36% with posttraumatic stress disorder, and 94.87% with anxiety. PRISM scores dropped significantly after the most salient psychedelic experience, indicating reduced identification with the condition. The decrease in PRISM scores correlated with symptom improvement across all conditions. PRISM appears useful for tracking how psychedelics affect self-perception across diagnoses, though limitations include convenience sampling, potential positive bias, and retrospective reporting.
Neuroscience and biobehavioral reviews
July 1, 2022
Drummond E-Wen Mcculloch, Gitte Moos Knudsen, Frederick Streeter Barrett et al.
A large group of psychedelic imaging researchers reviewed 42 articles from 17 unique studies that used resting-state functional magnetic resonance imaging (rs-fMRI) to examine psychedelic effects. They found that nearly all studies varied in data processing and analysis methods, two datasets underpin over half of the published literature, and key outcome terms are used ambiguously. The authors recommend guidelines to improve consistency and replicability in future research, arguing that the field must balance novel methods with standardized approaches to reliably understand the neural mechanisms of psychedelics.