European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
September 1, 2021
Martin K Madsen, Dea S Stenbæk, Albin Arvidsson et al.
132 citations
Psilocybin, a novel therapeutic, is metabolized to psilocin, which alters brain function by engaging serotonin receptors. In fifteen healthy individuals, a psychoactive dose (0.2-0.3 mg/kg) reduced the integrity and segregation of brain networks, including the default mode network, while increasing connectivity between networks like the executive control and dorsal attention networks. These changes correlated with plasma psilocin levels and subjective drug intensity. The findings link psilocin's time course to shifts in brain functional architecture and subjective experience, offering insight into the neurobiological mechanisms of psychedelic effects and consciousness.
J Psychopharmacol
February 28, 2019
David Erritzøe, James Smith, Patrick M Fisher et al.
95 citations
People who use psychedelics recreationally tend to score higher on the personality trait openness, which involves being open-minded, curious, and receptive to new experiences. This study examined whether this link might be explained by differences in the brain's serotonin system, a key chemical system affected by psychedelics. Using brain imaging, the researchers measured serotonin markers in recreational users and non-users. The findings suggest that higher openness in psychedelic users is not directly tied to these serotonin markers, indicating that other factors may underlie the personality differences.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
February 26, 2025
Kristian Larsen, Ulrich Lindberg, Brice Ozenne et al.
9 citations
Psilocybin, the active compound in magic mushrooms, reduces blood flow in the brain. In a study of 28 healthy volunteers, psilocybin decreased cerebral blood flow by about 11.6% at peak effect, while the serotonin blocker ketanserin had no significant effect. Psilocybin also constricted the internal carotid artery by 10.5%, whereas ketanserin did not. These findings suggest that psilocybin's effects on brain blood flow involve the serotonin 2A receptor and may help explain its therapeutic potential for conditions like depression.
Neuroscience Applied
December 30, 2023
Sophia Armand, Kristian Larsen, Martin K Madsen et al.
7 citations
The psychedelic drug psilocybin acutely reduces amygdala reactivity to angry faces in healthy individuals, while its subjective intensity is linked to reduced amygdala response to fearful faces. In 26 participants, fMRI scans showed that amygdala response to angry faces was significantly lower under psilocybin compared to baseline. No significant changes occurred for fearful or neutral faces. Higher subjective drug intensity was associated with weaker amygdala response to fearful faces, but plasma psilocin levels showed no such link. These findings align with prior work, suggesting psilocybin alters emotion processing in the brain, with potential implications for treating depression.
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.
International review of neurobiology
January 1, 2025
Paul Cumming, Klemens Egger, Gitte M Knudsen
2 citations
Molecular brain imaging techniques such as PET and SPECT have been used since the 1980s to study psychostimulants, and more recently to investigate psychedelics. Most published research involves SPECT studies of cerebral blood flow and PET studies of metabolism and neuroreceptors, particularly the 5-HT2A receptor, which is primarily responsible for the effects of classical psychedelics. Some evidence documents interactions at dopamine D2/3 receptors in the striatum, but many other potential molecular targets remain unexplored. The growing therapeutic use of psychedelics for neurological and psychiatric disorders highlights the need for broader, systematic investigation of their effects on brain function.
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.
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.
Journal of neuroscience research
May 1, 2013
Martin A Santini, Cecilia Ratner, Susana Aznar et al.
Subchronic administration of phencyclidine (PCP) to mice increases the sensitivity of serotonin 2A receptors (5-HT2A Rs) in the frontal cortex. Mice treated with PCP (10 mg/kg) for 10 days, followed by a 5-day washout, showed a stronger head-twitch response and greater expression of immediate-early genes (Arc, c-fos, egr-2) after a challenge with the 5-HT2A R agonist DOI, compared to saline-treated mice. These functional changes occurred without alterations in 5-HT2A R binding or in binding of the 5-HT1A receptor or serotonin transporter. Basal Arc mRNA levels were also elevated in the prefrontal cortex. The findings suggest that PCP-induced changes enhance 5-HT2A R-mediated neurotransmission, which may contribute to behavioral deficits in this schizophrenia model.