The British Journal of Psychiatry
December 5, 2024
Emma S Høgsted, Vincent Beliveau, Brice Ozenne et al.
4 citations
A positive association between serotonin 2A receptor binding in the brain and inward-directed facets of neuroticism—depression, anxiety, self-consciousness, and vulnerability to stress—was confirmed in a new cohort of 80 healthy volunteers using the tracer [11C]Cimbi-36. This association was independent of the cortisol awakening response, an index of hypothalamic-pituitary-adrenal axis function. The findings suggest that interventions targeting the serotonin 2A receptor, such as psilocybin, might be especially effective when tailored to individuals' neuroticism profiles.
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.
medRxiv
January 16, 2026
Kristian Larsen, Patrick M. Fisher, Drummond E. Mcculloch et al.
1 citation
Classical psychedelics such as LSD, psilocybin, and mescaline produce distinct changes in brain complexity and entropy that are not seen with stimulants like MDMA or d-Amphetamine. Using resting-state fMRI data from three placebo-controlled crossover trials with 79 participants across 255 sessions, the study found that psychedelics specifically increased meta-state complexity, short-timescale multiscale entropy, and dynamic conditional correlation entropy. Both drug classes increased Lempel-Ziv and spatial complexity and decreased absolute modularity, but only psychedelics showed these unique complexity and entropy increases. These findings suggest that psychedelic-specific brain signal changes may help distinguish the acute psychedelic state from other psychoactive drug effects and could be relevant to understanding their therapeutic potential.
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.
May 28, 2024
Frederik Gudmundsen, Julia Czurylo, Camilla Trang Vo et al.
1 citation
preprint
Three serotonergic psychedelics—psilocybin, LSD, and 2C-B—produce distinct acute and long-term changes in rat brain metabolic activity and connectivity. Psilocybin uniquely alters connectivity between cortical regions including the orbitofrontal, medial prefrontal, and insula cortex, as well as with the dorsal striatum, thalamus, and hippocampus. LSD and 2C-B share more similar effects, centered on acute inhibition of the anterior cingulate cortex, increased activity and connectivity between the amygdala and hypothalamus, and heightened activity in dopamine-rich regions of the ventral tegmental area and substantia nigra. These distinct neural patterns may guide which psychedelic drug could be most beneficial for specific neuropsychiatric disorders.
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.
bioRxiv
April 13, 2026
Anders S. Olsen, Kristian Larsen, Drummond E. 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.
Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition
November 26, 2024
Ande Bagdasarian, Kristian Larsen, Patrick M. Fisher et al.
Psilocybin and lisuride produce a two-phase (bi-phasic) change in cerebral blood volume, while 25CN-NBOH produces a single-phase (monophasic) response. The bi-phasic pattern may stem from the non-selectivity of psilocybin and lisuride. Higher doses of psilocybin cause elevated cerebral blood volume that persists over time, whereas the effects of lisuride and 25CN-NBOH return toward baseline. These findings highlight the sensitivity of pharmacological MRI for evaluating drug effects on brain hemodynamics.
Translational Psychiatry
July 15, 2026
Annette Johansen, Pontus Plavén-sigray, Martin K Madsen et al.
A single dose of psilocybin (0.3 mg/kg) did not produce a statistically significant increase in synaptic density across all fifteen healthy participants. However, those who received psilocybin in a therapeutic-like room reported more intense mystical-type experiences, longer-lasting psychological benefits, and showed greater increases in synaptic density in the frontal cortex and hippocampus compared to those dosed inside an MRI scanner. The findings indicate that environmental context modulates psilocybin's neuroplastic effects, with implications for psychedelic-assisted therapies.