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.
bioRxiv
April 13, 2026
Anders S. Olsen, Kristian Larsen, Drummond E-W. 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.