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Kristian Larsen

9 papers in the library · 18 citations · publishing 2023-2026

Papers

Acute psilocybin and ketanserin effects on cerebral blood flow: 5-HT2AR neuromodulation in healthy humans.

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.

Amygdala response to emotional faces following acute administration of psilocybin in healthy individuals

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.

Psychedelics distinctly alter brain entropy and complexity compared to psychostimulants

medRxiv January 16, 2026 Kristian Larsen, Patrick M Fisher, Drummond E. Mcculloch et al. 1 citation

Classical psychedelics such as LSD, psilocybin, and mescaline produce distinct changes in brain complexity and entropy that are not seen with stimulants like MDMA or d-Amphetamine. Using resting-state fMRI data from three placebo-controlled crossover trials with 79 participants across 255 sessions, the study found that psychedelics specifically increased meta-state complexity, short-timescale multiscale entropy, and dynamic conditional correlation entropy. Both drug classes increased Lempel-Ziv and spatial complexity and decreased absolute modularity, but only psychedelics showed these unique complexity and entropy increases. These findings suggest that psychedelic-specific brain signal changes may help distinguish the acute psychedelic state from other psychoactive drug effects and could be relevant to understanding their therapeutic potential.

Neurochemical characterization of 5-HT 2A R partial agonists with simultaneous PET-MRI

Journal of Cerebral Blood Flow & Metabolism November 29, 2024 Frederick A. Bagdasarian, Kristian Larsen, Deng Hong et al. 1 citation

Psilocybin, lisuride, and 25CN-NBOH, three serotonin 2A receptor agonists with different pharmacological profiles, produce distinct brain blood flow patterns in anesthetized nonhuman primates. Psilocybin and lisuride, which are mixed partial agonists, caused biphasic cerebral blood volume changes, while the selective agonist 25CN-NBOH produced monophasic increases. Cortical receptor occupancy for psilocybin plateaued at 60 µg/kg (32%), similar to that of a lower dose of lisuride (31%). 25CN-NBOH had lower occupancy (7%) but larger blood volume changes. The relationship between blood volume and receptor occupancy appeared linear for lisuride and 25CN-NBOH but not for psilocybin. These differences may stem from the mixed affinity profiles of the agonists, providing insights for developing psychiatric therapeutics.

Psilocybin acutely reduces low-frequency BOLD power and frequency-specific connectivity

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.

LSD 5-HT2A receptor occupancy and global functional connectivity effects

Figshare January 1, 2026 Kristian Larsen

LSD occupies the serotonin 2A receptor (5-HT2AR) and alters global functional connectivity in healthy human participants. The figure shows occupancy and connectivity effects for both LSD and psilocybin. Acquisition, preprocessing, and statistical modeling procedures were pre-registered and detailed in a study protocol.

Acute psilocybin effects on CBF and ICA diameter

Figshare January 1, 2026 Kristian Larsen

Psilocybin reduces whole-brain cerebral blood flow and constricts the internal carotid artery in a dose-dependent manner. In 28 healthy participants given 0.2–0.3 mg/kg psilocybin, arterial spin labelling MRI showed widespread cortical blood flow decreases at peak plasma psilocin levels. Higher plasma psilocin concentrations correlated with lower cerebral blood flow and smaller carotid artery diameter, indicating that the drug's vascular effects are tied to its active metabolite.

LSD and psilocybin effects on cerebral blood flow and global functional connectivity

Figshare January 1, 2026 Kristian Larsen

LSD and psilocybin produce distinct changes in cerebral blood flow and global functional connectivity across the human brain. Peak drug effects were observed in both measures, and within-subject associations between blood flow and connectivity were assessed using Spearman's rank correlation. The findings characterize how these hallucinogens alter brain activity at the population level in healthy participants.

Neuroimaging of Serotonergic and Psychedelic Agonist Drug Challenges in Non-Human Primates

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.