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.
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.
The Lancet
February 11, 2023
Florence Butlen‐ducuing, Drummond E-Wen Mcculloch, Marion Haberkamp et al.
28 citations
No Summary
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.
Comprehensive psychoneuroendocrinology
February 1, 2023
Daniel Rødbro Burmester, Martin Korsbak Madsen, Attila Szabo et al.
24 citations
A single dose of psilocybin did not significantly change peripheral biomarkers of inflammation—high-sensitivity C-reactive protein (hsCRP), tumor-necrosis-factor (TNF), and soluble urokinase plasminogen activator receptor (suPAR)—in 16 healthy individuals one day after administration. All effect sizes were small (Cohen's d ≤ 0.31) and p-values were ≥ 0.23. These findings do not support that a single dose of psilocybin reduces inflammation in healthy people, though future studies should examine additional markers and clinical populations where effects may be more detectable.
Frontiers in Psychology
November 17, 2022
Catharina Messell, Lisa Summer, Lars Ole Bonde et al.
22 citations
A new music program, the Copenhagen Music Program, has been developed to accompany the 4–6 hour sessions of medium/high dose psilocybin therapy. The program uses the Guided Imagery and Music framework to choose and sequence music, and the Taxonomy of Therapeutic Music to rate each piece's psychological intensity. Detailed procedural steps and examples are provided to guide others in creating music programs for psychedelic interventions, with the aim that informed music selection can support therapeutic dynamics during the drug's acute effects.
BMJ Open
October 1, 2022
Mathias Ebbesen Jensen, Dea Siggaard Stenbæk, Tobias Søgaard Juul et al.
21 citations
A planned clinical trial will test whether psilocybin-assisted therapy, compared to a placebo, reduces heavy drinking in people with alcohol use disorder. Ninety treatment-seeking adults aged 20–70 will be randomly assigned to receive either psilocybin or placebo alongside psychological support. The main outcome is the change in percentage of heavy drinking days from baseline to 12 weeks after dosing. Secondary outcomes include total alcohol consumption, a blood biomarker for alcohol, the active drug metabolite in blood, the subjective drug experience, and brain responses to alcohol cues measured with functional MRI one week after dosing. The trial is registered and has ethical approval.
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.
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.
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.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
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.
Journal of Psychopharmacology
September 12, 2025
Stephan Tap, Kelan Thomas, Tomáš Páleníček et al.
5 citations
Classic psychedelics like psilocybin are being studied for psychiatric disorders. Current protocols typically require patients to stop antidepressants (ADs) for at least two weeks before psychedelic use to avoid serotonin syndrome and preserve efficacy, but discontinuation can worsen depression and increase suicidal ideation. This scoping review of 18 studies found that using ADs alongside classic psychedelics is generally safe and tolerable, with no increased risk of serotonin syndrome, especially with psilocybin. Some studies showed significant improvements in depression and other symptoms. Although some evidence suggests a potential reduction in acute subjective psychedelic effects, this was not consistent. The authors conclude that maintaining ADs may improve patient access and avoid discontinuation risks.
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.
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.
European Neuropsychopharmacology
January 1, 2019
M. Madsen, Daniel Burmester, Dea Siggaard Stenbæk et al.
3 citations
No Summary