European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
September 1, 2021
Martin K Madsen, Dea S Stenbæk, Albin Arvidsson et al.
132 citations
Psilocybin, a novel therapeutic, is metabolized to psilocin, which alters brain function by engaging serotonin receptors. In fifteen healthy individuals, a psychoactive dose (0.2-0.3 mg/kg) reduced the integrity and segregation of brain networks, including the default mode network, while increasing connectivity between networks like the executive control and dorsal attention networks. These changes correlated with plasma psilocin levels and subjective drug intensity. The findings link psilocin's time course to shifts in brain functional architecture and subjective experience, offering insight into the neurobiological mechanisms of psychedelic effects and consciousness.
Frontiers in Pharmacology
March 9, 2022
Drummond E-Wen Mcculloch, Maria Zofia Grzywacz, Martin Bruun Madsen et al.
91 citations
Psilocybin, a psychedelic drug, can produce lasting positive psychological changes in healthy people. In 28 healthy volunteers who received 35 medium-high doses, the intensity of the acute mystical experience, measured by the Mystical Experience Questionnaire, predicted positive persisting effects three months later. Specifically, the subscales for positive mood and mysticality were linked to later benefits, while transcendence of time/space and ineffability were not. Qualitative reports described themes of connection with the Universe, familial love, and profound beauty. The type of acute experience appears important for predicting enduring positive outcomes.
NeuroImage
October 27, 2022
Anders Lykkebo-Valløe, Brice Ozenne, Sophia Armand et al.
44 citations
Psilocybin's acute perceptual psychedelic effects may arise from drug-level decreases in the occurrence and duration of lateral and medial frontoparietal connectivity motifs. The authors apply and argue for a modified approach to modeling eigenvectors from LEiDA that more fully acknowledges their underlying structure. These findings contribute to a more comprehensive neurobiological framework underlying acute effects of serotonergic psychedelics.
Frontiers in Psychology
October 5, 2022
Anna Søndergaard, Brice Ozenne, Sophia Armand et al.
35 citations
People who took psilocybin showed significantly higher trait mindfulness three months later, and the size of this increase was linked to how intense their mystical-type experience was during the drug session. Higher trait mindfulness before taking psilocybin was associated with lower serotonin 2A receptor binding in the right amygdala, a brain region involved in emotional processing. These findings suggest that the acute, mystical quality of the psilocybin experience may help shift awareness in ways that support mindful living, and that pre-existing mindfulness relates to specific brain receptor patterns.
bioRxiv (Cold Spring Harbor Laboratory)
February 5, 2021
M. Madsen, Dea Siggaard Stenbæk, Albin Arvidsson et al.
27 citations
preprint
Psilocybin, a psychedelic drug, produces its effects through its active metabolite psilocin, which activates serotonin 2A receptors in the brain. In fifteen healthy individuals given a moderate oral dose (0.2–0.3 mg/kg), higher plasma psilocin levels and stronger subjective drug intensity correlated with reduced integrity and segregation of brain networks, particularly the default mode network, and with increased connectivity between networks such as the executive control and dorsal attention networks. These changes in functional brain architecture tracked the time course and magnitude of the psychedelic experience, linking network desegregation to altered consciousness.
medRxiv
July 3, 2023
Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al.
20 citations
preprint
Psychedelics like psilocybin are thought to increase brain entropy, but previous findings have not been replicated. In 28 healthy participants with 121 fMRI scans taken before and after psilocybin, brain entropy was measured alongside plasma psilocin levels, serotonin 2A receptor occupancy, and subjective drug intensity. Shannon entropy of path-length and instantaneous correlation distributions showed significant positive associations with drug effects, while sample entropy showed divergent associations depending on time-scale. However, 8 of 13 entropy metrics showed no significant effects, and the metrics correlated poorly with each other. The results suggest a nuanced acute effect of psilocybin on brain entropy and highlight specific metrics that may mediate clinical effects.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
February 26, 2025
Kristian Larsen, Ulrich Lindberg, Brice Ozenne et al.
9 citations
Psilocybin, the active compound in magic mushrooms, reduces blood flow in the brain. In a study of 28 healthy volunteers, psilocybin decreased cerebral blood flow by about 11.6% at peak effect, while the serotonin blocker ketanserin had no significant effect. Psilocybin also constricted the internal carotid artery by 10.5%, whereas ketanserin did not. These findings suggest that psilocybin's effects on brain blood flow involve the serotonin 2A receptor and may help explain its therapeutic potential for conditions like depression.
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.
medRxiv
December 17, 2021
Anders S. Olsen, Anders Lykkebo-Valløe, Brice Ozenne et al.
4 citations
preprint
After a psychedelic dose of psilocybin, the occurrence and duration of two brain states involving lateral frontoparietal and medial fronto-parietal-cingulate coherence decrease, while a fully connected brain state increases. These changes are associated with both the level of psilocin in the blood and the intensity of the subjective drug experience. The findings suggest that the acute perceptual effects of psilocybin may arise from a shift away from specific frontoparietal connectivity motifs toward a more uniform connectivity structure. The study also proposes an improved method for modeling brain states from dynamic functional connectivity data.
Psychiatric Research and Clinical Practice
January 14, 2026
Celia Faye Jacobsen, Dea Siggaard Stenbæk, Stig Poulsen et al.
3 citations
The Compass Psychological Support Model (CPSM) used in psilocybin trials is arguably a form of bona fide psychotherapy, not merely psychological support. Its components—psychoeducation, trust, present-moment focus, and client autonomy—align with humanistic-experiential therapies like client-centered and emotion-focused therapy. These methods, such as building therapeutic alliance and reducing experiential avoidance, have established links to improved outcomes in both general psychotherapy and psilocybin treatments. Framing the CPSM as non-therapeutic undermines methodological transparency and may obscure its contribution to efficacy. Recognizing it as psychotherapy could enable optimization of therapist skills and client factors, enhancing treatment outcomes.
December 14, 2021
Drummond E-Wen Mcculloch, Maria Zofia Grzywacz, M. Madsen et al.
2 citations
preprint
Psilocybin, a psychedelic drug, can produce lasting positive psychological changes in healthy people. In 35 sessions with 28 healthy volunteers, those who reported more intense mystical experiences—measured by the Mystical Experience Questionnaire—were more likely to report positive effects three months later. The subscales 'Positive Mood' and 'Mysticality' predicted these benefits, while 'Transcendence of Time and Space' and 'Ineffability' did not. Qualitative reports described themes of connection with the universe, familial love, and profound beauty. The type of acute experience appears important for predicting lasting positive outcomes.
Nature Communications
June 24, 2026
Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al.
A prominent theory holds that psychedelics increase brain entropy, but past studies have used many different entropy measures. This work analyzed 121 fMRI scans from 28 healthy adults before and after psilocybin, testing 14 entropy metrics with two brain-parcellation methods and seven denoising pipelines. Five metrics—including Shannon entropy of spatial eigendistribution, path-length, instantaneous correlations, brain-state switching, and sample entropy at short time-scales—consistently showed positive associations with psychedelic effects. However, eight metrics showed no significant effects, and Lempel-Ziv complexity gave inconsistent positive results. The entropy measures correlated poorly with each other, indicating that brain entropy is not a single, unified phenomenon.
Journal of psychopharmacology (Oxford, England)
May 29, 2026
Kristoffer Brendstrup-Brix, Brice Ozenne, Patrick M Fisher et al.
Patients with chronic cluster headache (CCH) suffer from poor sleep, which may affect brain microstructure and waste clearance. In 11 CCH patients, subjective sleep quality—measured by the Pittsburgh Sleep Quality Index—improved one week after three doses of psilocybin (0.14 mg/kg) given one week apart, with a mean PSQI change of -2.50 points. Before treatment, CCH patients had poorer sleep and differences in brain microstructure and water diffusivity compared to 24 healthy controls, primarily in grey matter. Psilocybin intervention was not associated with statistically significant changes in brain microstructure or water diffusivity on average, though most patients showed lower white matter diffusivity and neurite volume. Subjective sleep quality showed borderline significant correlations of moderate effect size with brain microstructure and water diffusivity.