PROJECT SUMMARY/ABSTRACT Serotonergic 2A receptor agonists (“classic psychedelics”) have recently been described as psychoplastogens in view of their selective modulatory effects on neural structure and function. Although this neural modulatory mechanism has been well demonstrated in animal models, researchers are only now examining its role in the living human brain. Understanding processes involving selective and adaptive modulation of neural structure may in the future catalyze important interventions into mental and physical health that harness the brain’s capacity for plasticity. The present proposal leverages a comprehensive set of methods at molecular, functional, and psychological levels of analysis to investigate whether and how psychedelic compounds produce neural plasticity, and whether neural modulatory processes underlie post- acute changes in functional activation and synchrony in regions related to the personality trait neuroticism and adaptive post-acute effects on neuroticism found in the literature. The long-term goal of this line of research is to understand processes underlying selective modulation of neural structure and function. The overall objective is to ascertain whether psychedelic compounds produce neural plasticity indexed by Positron Emission Tomography radioligand indices of synaptic density and functional Magnetic Resonance Imaging activation and synchrony, and whether these changes covary with adaptive changes in neuroticism.

PROJECT NARRATIVE This research fellowship will investigate whether serotonergic 2A receptor agonists produce neural plasticity indexed by molecular increases in synaptic density. The fellowship will furthermore investigate whether increased synaptic density is linked to changes in task- dependent functional blood-oxygenation-level-dependent activation and synchrony in neural regions related to trait neuroticism and adaptive changes in neuroticism. By understanding these neuropsychopharmacological effects, we hope to identify neurobiological processes that can be harnessed to intervene upon mental illness.