Neurochemical characterization of 5-HT 2A R partial agonists with simultaneous PET-MRI
Frederick A. Bagdasarian, Kristian Larsen, Deng Hong, Patrick M. Fisher, Joseph B. Mandeville, Christin Y. Sander, Hsiao‐ying Wey, Hanne D. Hansen
Journal of Cerebral Blood Flow & Metabolism November 29, 2024 DOI: 10.1177/0271678x241302937 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with simultaneous PET and phMRI Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Anesthetized nonhuman primates |
| Interventions | Psilocybin Lisuride 25CN-NBOH |
| Dose | 30, 60, and 90 µg/kg for psilocybin; 5 µg/kg for lisuride; 15 µg/kg for 25CN-NBOH |
| Topics | Serotonin |
| Keywords | Neurochemical Characterization materials science 5-HT Receptor Nuclear magnetic resonance Nanotechnology |
| Citations | 1 |
| Key findings | Psilocybin and lisuride evoked biphasic cerebral blood volume responses, while 25CN-NBOH produced monophasic increases, with occupancy and blood volume changes varying across the three agonists. |
Abstract
Understanding neuromodulatory effects of serotonin 2A receptor (5-HT 2A R) agonists with diverse pharmacological profiles is relevant to advancing psychedelic-related drug applications. We performed simultaneous positron emission tomography (PET) and pharmacological magnetic resonance imaging (phMRI) in anesthetized nonhuman primates (NHP; N = 3) to examine partial agonists with varying 5-HT 2A R affinities and selectivity profiles: psilocybin (30, 60, and 90 µg/kg), lisuride (5 µg/kg), and 25CN-NBOH (15 µg/kg). Receptor occupancy was assessed with [ 11 C]MDL-100907 PET, and cerebral blood volume (CBV) changes were measured with phMRI. Mixed partial agonists psilocybin and lisuride evoked biphasic CBV responses, whereas the selective 25CN-NBOH produced monophasic CBV increases. Cortical occupancy for psilocybin plateaued at 60 µg/kg (32%), whereas a lower dose of lisuride (5 µg/kg) resulted in similar occupancy (31%). Administration of 25CN-NBOH resulted in lower occupancy (7%) but larger changes in CBV compared to psilocybin and lisuride. The associations between CBV and 5-HT 2A R occupancy appear linear for lisuride and 25CN-NBOH, but not for psilocybin. We speculate that the temporal and spatial differences in hemodynamic responses of the three agonists could stem from mixed affinity profiles. This work provides an understanding of pharmacological impacts of mixed serotonergic agonists being pursued as therapeutics for psychiatric conditions, offering valuable insights for future drug applications and development strategies.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 20
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Global Street Food: la cocina de la calle Diseño interior 2009
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network PLoS One February 18, 2015
and 15 more in the library