ACS Chemical Neuroscience
June 25, 2024
Jingyuan Chen, Frederick A. Bagdasarian, Hanne D. Hansen et al.
11 citations
Using fMRI in nonhuman primates, this work compared how two different hallucinogens—psilocybin, a serotonergic psychedelic, and salvinorin-A, a kappa-opioid receptor agonist—alter resting-state functional connectivity. Both drugs acutely desynchronized the default mode network and affected a network involving the claustrum, prefrontal cortex, anterior cingulate cortices, and angular gyrus, supporting a cortico-claustro-cortical model for probing hallucinogen effects regardless of serotonergic activity. Thalamo-cortical changes appeared dependent on 5-HT2AR activation. The findings offer a framework for understanding mechanisms common across hallucinogenic drug classes.
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.
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.
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
August 14, 2024
Frederick A. Bagdasarian, Hanne D. Hansen, Chi‐hyeon Yoo et al.
Psilocybin, a serotonergic agonist, and Salvinorin-A, a kappa-opioid receptor agonist, both alter functional connectivity in the brains of non-human primates, but their effects overlap and differ in specific regions. Using fMRI, the study examined how these psychedelics influence connections within the default mode network and the claustrum. The findings suggest that each substance targets distinct receptor systems, leading to both shared and unique patterns of brain network activity, which may help explain their different mechanisms of action.