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 : 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.
European Neuropsychopharmacology
December 4, 2020
Lene Lundgaard Donovan, Jens Vilstrup Johansen, Nídia Fernandez Ros et al.
45 citations
A single dose of psilocybin given to awake female pigs caused behavioral changes—headshakes, scratching, and rubbing—lasting about 20 minutes. The dose produced a 67% occupancy of cerebral 5-HT2A receptors and plasma psilocin levels comparable to those in humans during an intense psychedelic experience. One day after injection, 19 genes in the prefrontal cortex were differentially expressed; after one week, only 3 genes were. Gene set enrichment analysis showed multiple immunological pathways were regulated one week after exposure. The authors suggest that any effects on gene expression are very modest, providing a framework for future research into the lasting molecular mechanisms of a single psilocybin dose.
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.
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.
Neuropsychopharmacology
March 8, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
21 citations
correction
No Summary
Toxicology letters
October 1, 2018
Carolina Noble, Niels Bjerre Holm, Marie Mardal et al.
17 citations
Bromo-dragonfly, a potent and long-acting hallucinogen linked to severe vasoconstriction and fatal intoxications, was not metabolized in human liver microsomes, cytosol, or recombinant enzyme systems, unlike its analogue 2C-B-fly, which underwent monohydroxylation and N-acetylation via CYP2D6 and MAO-A. Bromo-dragonfly competitively inhibited monoamine oxidase A (MAO-A) with a Ki of 0.352 μM, and its IC50 suggested clinically relevant MAO-A inhibition, though further data are needed to assess its impact on serotonin levels in the body. Protein binding and pharmacokinetic parameters were also investigated.
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.
European Neuropsychopharmacology
January 1, 2019
M. Madsen, Daniel Burmester, Dea Siggaard Stenbæk et al.
3 citations
No Summary