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.
NeuroImage
August 1, 2019
Lukasz Smigielski, Milan Scheidegger, Michael Kometer et al.
261 citations
A single dose of psilocybin (315 μg/kg) combined with a 5-day mindfulness retreat altered brain connectivity in the default mode network, particularly decoupling the medial prefrontal and posterior cingulate cortices. This decoupling correlated with the subjective experience of ego dissolution during meditation. The extent of ego dissolution and brain connectivity changes predicted improvements in psycho-social functioning four months later. The findings suggest that psilocybin-assisted meditation facilitates neurodynamic changes in self-referential networks, linking altered self-experience to lasting behavioral changes.
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.
Scientific reports
March 26, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
15 citations
Brain activity patterns during meditation shift after a psilocybin-assisted retreat, especially when open-monitoring meditation is practiced. Using functional MRI and a topological data analysis method (Mapper), researchers compared experienced meditators who received psilocybin or placebo over five days. The psilocybin group showed a link between positive derealization—an altered perception that can foster insight—and a greater geometric distance between open-monitoring meditation and resting-state brain activity, as measured by optimal transport distance. This suggests that combining psilocybin with open-monitoring practice enhances meta-awareness and insight. The findings point to possible brain markers for synergistic effects between mindfulness and psychedelics.
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.
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.
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.