Neuropsychopharmacology
January 26, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
505 citations
Psilocybin, a naturally occurring hallucinogen, demonstrated significant effects on mental health in a study with 500 participants. About 60% reported substantial reductions in anxiety and depression after just two doses. The pharmacology of psilocybin involves its interaction with serotonin receptors, influencing behavior and mood. Additionally, chemical synthesis of alkaloids in psilocybin enhances its binding potential to neurotransmitter receptors. These findings highlight the promising role of psychedelics in internal medicine and psychology, paving the way for innovative treatments in drug studies.
European Neuropsychopharmacology
March 4, 2020
M. Madsen, Patrick M. Fisher, Dea Siggaard Stenbæk et al.
189 citations
A single dose of the serotonin 2A receptor agonist psilocybin can produce lasting beneficial effects on mood and personality, and potentially on mindfulness, but the underlying mechanisms are unclear. In ten healthy, psychedelic-naïve volunteers, psilocybin (0.2-0.3 mg/kg) led to statistically significant increases in the personality trait Openness (mean change 4.2) and in mindfulness (mean change 0.5) at three months. Although average cerebral 5-HT2AR binding did not change one week after dosing, a negative correlation between changes in 5-HT2AR binding and mindfulness suggests that individual variation in receptor levels may influence long-term mindfulness effects.
Journal of Psychopharmacology
October 8, 2020
Dea Siggaard Stenbæk, M. Madsen, Brice Ozenne et al.
81 citations
People with higher levels of serotonin 2A receptor (5-HT2AR) binding in the neocortex before taking psilocybin experienced shorter peak psychedelic intensity and a longer time to return to normal consciousness. Higher pre-drug 5-HT2AR binding also predicted lower scores on a measure of mystical-type experiences. The findings reinforce that individual differences in brain 5-HT2AR levels shape the temporal and subjective features of the psilocybin experience.
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.
Headache The Journal of Head and Face Pain
January 1, 2024
Anja Sofie Petersen, Inger Marie Sørensen, Harald Schiønning et al.
29 citations
In a small open-label trial, ten people with chronic cluster headache received three doses of psilocybin (0.14 mg/kg) over three weeks. Attack frequency dropped by an average of 31% from the four-week baseline to the four-week follow-up, and one patient had 21 weeks of complete remission. Changes in hypothalamic–diencephalic functional connectivity correlated negatively with the reduction in attack frequency, suggesting this neural pathway may be involved in the treatment response. The treatment was well tolerated. The results indicate psilocybin may have prophylactic potential for chronic cluster headache, though larger controlled studies are needed.
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.
Neuropsychopharmacology
March 8, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
21 citations
correction
No Summary
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.
Neuropsychopharmacology
August 25, 2020
M. Madsen, Gitte M. Knudsen
15 citations
No Summary
Human Brain Mapping
January 11, 2019
Dea Siggaard Stenbæk, Sara Kristiansen, Daniel Burmester et al.
11 citations
Trait Openness, a personality dimension linked to curiosity and creativity, is not related to the availability of serotonin 2A receptors in the neocortex. In 159 healthy individuals, no significant association was found between receptor binding—measured with two different PET tracers—and scores on the NEO Personality Inventory-Revised. Sex did not influence the result. Although psilocybin, a serotonin 2A receptor agonist, can increase Openness, the receptor's baseline availability does not explain natural variation in this trait.
Journal of Psychopharmacology
August 13, 2024
Oliver Rumle Hovmand, Dea Siggaard Stenbæk, M. Madsen et al.
9 citations
The Danish translation of the Five Dimensional Altered States of Consciousness Questionnaire (5D-ASC) is a valid tool for measuring altered states of consciousness among Danish-speaking individuals. Confirmatory factor analysis showed that the 11 subscales fit the data well and better than the original five-dimensional solution, with good internal consistency. Total scores correlated positively with psilocybin dose in a recreative sample of 550 users, but no correlations were found with intention or setting. The questionnaire was also tested in 47 healthy volunteers receiving psilocybin in a lab setting.
Journal of Psychoactive Drugs
January 15, 2024
Oliver Rumle Hovmand, Mathias Ebbesen Jensen, Tobias Søgaard Juul et al.
6 citations
A Danish translation of the Revised Mystical Experiences Questionnaire (MEQ30) is a valid and reliable tool for assessing mystical-type experiences in Danish-speaking individuals. The questionnaire showed excellent internal reliability across three samples: healthy volunteers receiving psilocybin in a lab (N = 47), recreational users reporting on their most recent psilocybin experience (N = 834), and users reporting on their most memorable psychedelic experience (N = 500). A four-factor structure provided the best, fair fit to the data. MEQ30 total scores correlated with dose and spiritual or religious intention, but not with setting.
medRxiv
July 10, 2022
M. Madsen, Anja Sofie Petersen, Dea Siggaard Stenbæk et al.
5 citations
preprint
In a small open-label clinical trial, three low-to-moderate doses of psilocybin reduced attack frequency by an average of 30% from baseline to follow-up in patients with chronic cluster headache. One patient experienced 21 weeks of complete remission. The treatment was well-tolerated with no serious adverse reactions. Changes in hypothalamic-diencephalic functional connectivity correlated negatively with the relative reduction in attack frequency, suggesting this neural pathway is involved in treatment response. Further studies are needed to confirm safety and prophylactic efficacy.
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.
European Neuropsychopharmacology
January 1, 2019
M. Madsen, Daniel Burmester, Dea Siggaard Stenbæk et al.
3 citations
No Summary
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.