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.
Journal of Cerebral Blood Flow & Metabolism
April 30, 2014
Anders Ettrup, Sofi Da Cunha‐bang, Brenda Mcmahon et al.
106 citations
A new radioactive tracer, [11C]Cimbi-36, was tested in 29 healthy volunteers for brain imaging using PET scans. This tracer binds to serotonin 2A receptors, which are involved in mood and perception, and is an agonist, meaning it activates the receptor rather than blocking it. High uptake in the brain matched known locations of these receptors. A two-tissue compartment model using arterial blood samples gave the most accurate measurements. In five subjects given a blocker drug (ketanserin), tracer binding decreased in cortical areas but not in the cerebellum, confirming the tracer's specificity and that the cerebellum can serve as a reference region. This is the first agonist PET radioligand to successfully image these receptors in humans.
Archives of General Psychiatry
June 6, 2011
David Erritzøe, Vibe G. Frøkjær, Klaus K. Holst et al.
86 citations
MDMA use, but not hallucinogen use, is linked to changes in the brain's presynaptic serotonin system. Because hallucinogens primarily act on serotonin 2A receptors, the negative association between MDMA use and serotonin transporter (SERT) binding is likely due to MDMA's direct presynaptic effect rather than its serotonin 2A agonistic actions. Cross-sectional data suggest that subcortical, but not cortical, SERT binding may recover after several months of MDMA abstinence.
Neuropsychopharmacology
March 8, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
21 citations
correction
No Summary
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.
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.
European Neuropsychopharmacology
January 1, 2019
M. Madsen, Daniel Burmester, Dea Siggaard Stenbæk et al.
3 citations
No Summary
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.
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.