Neuropsychopharmacology
January 26, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
505 citations
Psilocybin, the main psychedelic component of magic mushrooms, produces its effects by activating serotonin 2A receptors in the brain. In eight healthy volunteers who received a single oral dose of psilocybin (3–30 mg), PET scans showed dose-related occupancy of these receptors up to 72%. Plasma levels of psilocin, the active metabolite, and receptor occupancy both closely matched subjective ratings of psychedelic intensity, supporting that stimulation of serotonin 2A receptors is a key determinant of the psychedelic experience. Although psilocin levels in the blood varied over time, they were strongly linked to the intensity of the experience, which is important for designing clinical 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.
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.
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.
Journal of Psychopharmacology
June 30, 2021
Drummond E-Wen Mcculloch, Martin Bruun Madsen, Dea Siggaard Stenbæk et al.
79 citations
A single dose of psilocybin in 10 healthy volunteers who had never used psychedelics produced a significant decrease in resting-state functional connectivity within the executive control network (ECN) one week later, an effect that was no longer present at three months. No other changes in brain connectivity were observed at either time point. Exploratory analyses suggested that the decreased ECN connectivity at one week predicted increased mindfulness at three months. The findings point to modulation of the ECN during the psychedelic 'afterglow' period as a possible neural pathway for lasting positive effects on well-being, though the neural basis of personality changes seen at three months remains unknown.
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.
Social Cognitive and Affective Neuroscience
April 23, 2021
Maja Rou Marstrand-Joergensen, M. Madsen, Dea Siggaard Stenbæk et al.
20 citations
Resting-state functional connectivity within the default mode network (DMN) is negatively associated with the personality trait Openness to experience, particularly its Fantasy subfacet. Extraversion shows both negative and positive associations with connectivity between specific brain networks: negatively with visual–dorsal attention network connectivity and positively with frontoparietal–language network connectivity. These results, based on 295 healthy participants and 470 scan sessions, link personality domains to distributed neurobiological systems and suggest neural pathways that may underlie related clinical conditions and treatment responses.
The International Journal of Neuropsychopharmacology
February 14, 2014
Vibe G. Frøkjær, David Erritzøe, Klaus K. Holst et al.
19 citations
Prefrontal serotonin transporter binding is positively associated with the cortisol awakening response, a measure of hypothalamic-pituitary-adrenal-axis output, in both MDMA users and non-users. MDMA users showed a significantly higher cortisol awakening response than non-users. The findings suggest that the inhibitory control on HPA-axis output is less efficient after recent MDMA use, likely through mechanisms beyond those compensated by reduced serotonin transporter levels.
Journal of Psychopharmacology
February 28, 2025
Dea Siggaard Stenbæk, Emil Deleuran Poulsen, Marie Katrine Klose Nielsen et al.
15 citations
A single 25 mg dose of psilocybin, a psychedelic compound, safely reduced alcohol consumption in ten adults with severe alcohol use disorder. Over 12 weeks, heavy drinking days fell by 37.5 percentage points and drinks per day dropped by 3.4. Participants also reported rapid and lasting decreases in craving and increases in self-efficacy. Peak blood levels of the drug varied widely among individuals, from 14 to 59 µg/L. The open-label, single-group design lacked a placebo control, so larger randomized trials are needed to confirm the findings.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
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.
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.
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.
Journal of Cerebral Blood Flow & Metabolism
November 29, 2024
Frederick A. Bagdasarian, Kristian Larsen, Deng Hong et al.
1 citation
Psilocybin, lisuride, and 25CN-NBOH, three serotonin 2A receptor agonists with different pharmacological profiles, produce distinct brain blood flow patterns in anesthetized nonhuman primates. Psilocybin and lisuride, which are mixed partial agonists, caused biphasic cerebral blood volume changes, while the selective agonist 25CN-NBOH produced monophasic increases. Cortical receptor occupancy for psilocybin plateaued at 60 µg/kg (32%), similar to that of a lower dose of lisuride (31%). 25CN-NBOH had lower occupancy (7%) but larger blood volume changes. The relationship between blood volume and receptor occupancy appeared linear for lisuride and 25CN-NBOH but not for psilocybin. These differences may stem from the mixed affinity profiles of the agonists, providing insights for developing psychiatric therapeutics.
Research Square
August 23, 2024
Mathias E. Jensen, Dea Siggaard Stenbæk, Catharina Messell et al.
1 citation
A single 25 mg dose of psilocybin, given with preparation and integration sessions, reduced alcohol consumption in ten adults with severe alcohol use disorder. Heavy drinking days dropped by 37.5 percentage points over 12 weeks, and drinks per day decreased by 3.4 units. Participants also reported rapid and lasting reductions in craving and increased self-efficacy. Blood levels of the active metabolite psilocin varied widely between individuals, peaking from 14 to 59 µg per liter. The open-label study, which lacked a placebo group, suggests that even a single psilocybin session may be safe and effective, but larger randomized controlled trials are needed.