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.
European Neuropsychopharmacology
August 9, 2024
Friederike Holze, M. Madsen, Claus Svarer et al.
16 citations
Ketanserin, a drug that blocks the serotonin 2A (5-HT2A) receptor, occupies this receptor in the human brain in a dose-dependent manner. In a positron emission tomography (PET) study with healthy participants, oral doses of 10, 20, or 40 mg of ketanserin led to a plasma concentration-related increase in receptor occupancy. The half-maximal effective concentration (EC50) was 2.52 ng/mL, corresponding to about a 10 mg oral dose. These findings clarify how ketanserin works in the brain, aiding its use as a research tool and suggesting potential for treating bad psychedelic experiences.
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.
Neuropsychopharmacology
August 25, 2020
M. Madsen, Gitte M. Knudsen
15 citations
No Summary
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.
Neurosci Appl
January 11, 2024
Drummond E-Wen McCulloch, Matthias E. Liechti, Kim PC. Kuypers et al.
10 citations
Psychedelic drugs like psilocybin and LSD are being tested in clinical trials for psychiatric and neurological conditions, with phase 2 studies showing particular promise for depression. At a 2023 European College of Neuropsychopharmacology meeting, experts identified key knowledge gaps that need addressing for successful medical implementation. These include understanding how these drugs work in the body (pharmacokinetics and pharmacodynamics), comparing different psychedelics, exploring the link between the duration of subjective effects and therapeutic outcomes, studying polypharmacology, and assessing the role of psychological support. The article also presents perspectives from the European Medicines Agency and Health Technology Assessors on what is most needed for medical adoption in Europe.
Journal of Psychopharmacology
September 6, 2016
Helle Ruff Laursen, Susanne Henningsson, Julian Macoveanu et al.
8 citations
Prolonged recreational use of MDMA (ecstasy) alters serotonin neurotransmission, similar to a depleted state. In this fMRI study, 14 ecstasy users and 12 non-users viewed faces expressing anger, disgust, fear, sadness, or no emotion while their amygdala activity was measured. Serotonin transporter binding, assessed via PET, correlated negatively with amygdala activity in users. Greater lifetime ecstasy intake was associated with increased amygdala activity during angry face processing, while longer time since last use showed a trend toward decreased activity during angry and sad face processing. The results indicate dose-dependent effects of long-term serotonin depletion on emotional face processing.
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.
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.
Molecular Psychiatry
July 8, 2026
Granville J. Matheson, Johan Lundberg, Martin Gärde et al.
The serotonin 1B receptor (5-HT1BR) can be imaged in living humans using a PET tracer called [11C]AZ10419369 and is linked to major depressive disorder (MDD) and its treatment. Ketamine and electroconvulsive therapy (ECT) are rapid-acting antidepressants that raise serotonin levels, but whether they directly alter serotonin receptors was unclear. Reanalyzing 222 PET scans from three centers—including MDD patients before and after ketamine (19 completers), saline placebo (10), or ECT (13 completers)—using a hierarchical Bayesian method, the authors demonstrate large increases in 5-HT1BR binding after both ketamine (6.4%, 95% CI: 3.1–9.6%) and ECT (9.3%, 95% CI: 4.3–14.2%).
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.
bioRxiv
April 13, 2026
Anders S. Olsen, Kristian Larsen, Drummond E-W. McCulloch et al.
Psilocybin, a serotonergic drug, alters brain function and connectivity as measured with fMRI, but whether these effects are frequency-specific was unknown. In 28 healthy volunteers scanned after oral psilocybin (0.2–0.3 mg/kg), psilocin (the active metabolite) was associated with a selective reduction in low-frequency spectral power (0.01–0.06 Hz) and an increase in spectral entropy, with strongest effects in transmodal networks. Low-frequency connectivity energy explained by the unimodal/transmodal axis also decreased. These findings demonstrate that psilocin induces spatially distributed, frequency-dependent alterations, suggesting broadband fMRI analyses may obscure low-frequency dynamics and that frequency-resolved approaches offer greater sensitivity.
Research Square
October 10, 2025
Gitte M. Knudsen, Annette Johansen, Pontus Plavén‐sigray et al.
A single dose of psilocybin increases synaptic density in the frontal cortex and hippocampus of healthy individuals, but the magnitude of this effect depends on the environment in which the experience occurs. Participants who took psilocybin in a therapeutic-like room reported more intense mystical-type experiences, longer-lasting psychological benefits, and showed greater increases in synaptic density compared to those dosed inside an MRI scanner. These findings indicate that psilocybin's neuroplastic effects are modulated by environmental context, with implications for psychedelic-assisted therapies.
medRxiv
June 18, 2025
Drummond E-Wen Mcculloch, K. M. Larsen, Annette Johansen et al.
preprint
Lysergic acid diethylamide (LSD) increases global cerebral blood flow and internal carotid artery flow without affecting artery diameter, effects opposite to those of psilocybin. Functional connectivity analyses show decreases in global connectivity (GCOR), which is negatively correlated with the increase in cerebral blood flow. An anticlockwise hysteresis loop between plasma drug levels and subjective effects suggests atypical pharmacodynamic mechanisms. These findings, derived from simultaneous PET-MRI in seven healthy volunteers, establish the dose-occupancy relation of LSD at cerebral serotonin 2A receptors and highlight neurophysiological differences from related psychedelics, providing insights for clinical development.
Research Square
January 12, 2024
Erik Kaadt, Rolf Søkilde, Hanne D. Hansen et al.
A single dose of psilocybin alters the expression of specific microRNAs (miRNAs) in the prefrontal cortex and hippocampus of pigs, brain regions central to depression. One day after administration, 12 miRNAs were dysregulated in the prefrontal cortex and 2 in the hippocampus; after one week, only 4 dysregulated miRNAs remained in the hippocampus. Nine of the 18 identified miRNAs have been previously linked to depression. Two miRNAs, miR-212-3p and miR-107, showed robust acute regulation in the prefrontal cortex and are known to exert anti-inflammatory effects, mirroring previously reported effects of psilocybin. These results suggest psilocybin may exert its molecular effects through miRNA regulation.
Journal of Psychopharmacology
July 14, 2019
Livia Ng, Luca Pani, Anaïs Soula et al.
Claims about the positive effects of microdosing psychedelics on mood and cognition have entered public discussion, but scientific studies are scarce and no consensus on what microdosing means exists. This critique identifies questions future research must answer and offers guidelines, focusing on psilocybin due to its potential clinical approval and short-lasting effects. While anecdotal reports emphasize benefits, the paper concludes that future studies should also investigate potential risks of repeated low-dose administrations. Preclinical and clinical research examining biological measures like heart rate and receptor turnover, as well as cognitive parameters such as memory and attention, is needed to uncover possible negative consequences.