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.
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.
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.
Journal of Chromatography B
January 29, 2005
Sys Stybe Johansen, Jytte Lundsby Jensen
41 citations
A liquid chromatography-tandem mass spectrometry method was developed to measure LSD, iso-LSD, and the metabolite 2-oxo-3-hydroxy-LSD in forensic samples. The procedure extracts the compounds from whole blood or urine, then uses electrospray ionization and multiple reaction monitoring for detection and quantification. The method is linear over 0.01-50 µg/kg for LSD and iso-LSD, with a quantification limit of 0.01 µg/kg. Applied to a homicide investigation of a 26-year-old man, blood concentrations were 0.27 µg/kg for LSD and 0.44 µg/kg for iso-LSD; the metabolite was detected in urine, confirming LSD use. The case highlights the need to separate isomers before detection because they produce identical fragment ions.
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.
Scandinavian Journal of Clinical and Laboratory Investigation
October 21, 2008
Sys Stybe Johansen, Jakob Jornil
25 citations
A quantitative gas chromatography–mass spectrometry method was developed to measure amphetamine, methamphetamine, MDA, and MDMA (ecstasy) in human hair. The procedure uses liquid-liquid extraction of hydrolyzed hair with deuterated internal standards and derivatization with perfluorooctanoyl chloride. Validation showed a linear range of 0.25 to 25 ng/mg, intra-day precision of 3–6% RSD, inter-day precision of 3–17% RSD, and trueness between 96% and 106%. Detection limits ranged from 0.07 to 0.14 ng/mg and quantification limits from 0.24 to 0.46 ng/mg. Applied to 40 authentic hair samples, concentrations ranged up to 3.2 ng/mg for amphetamine, 0.4 ng/mg for MDA, and 5.9 ng/mg for MDMA; methamphetamine was detected once at trace level. The method is simple, robust, and sensitive enough for measuring these drugs in abusers' hair.
Neuropsychopharmacology
March 8, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
21 citations
correction
No Summary
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.
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
Frontiers in psychiatry
January 1, 2026
Sivert Drange, Jacob Cohen, Sys Stybe Johansen et al.
1 citation
In identical twins discordant for obsessive-compulsive disorder, the affected twin self-administered low doses of psilocybin (1–5 mg every third day) while the unaffected twin did not. The affected twin reported notable reductions in OCD symptoms, improved emotional regulation, and better well-being. However, cognitive flexibility, measured with a set-shift task, remained impaired compared to the unaffected twin. Low-dose psilocybin may alleviate some OCD symptoms but does not fully address underlying cognitive deficits.
December 30, 2024
Sivert Drange, Jacob Cohen, Sys Stybe Johansen et al.
1 citation
preprint
In a pair of identical twins where one had obsessive-compulsive disorder and the other did not, the affected twin self-administered low, non-psychedelic doses of psilocybin. After the regimen, the affected twin reported a notable reduction in OCD symptoms, improved emotional regulation, and greater well-being. However, cognitive flexibility deficits—the ability to shift thinking—remained compared to the unaffected twin. This suggests that microdosing psilocybin may help relieve some OCD symptoms but does not fully address underlying cognitive impairments. Larger, longer studies are needed to understand how these low doses work and their potential as a treatment.
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.
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.