Abstract #1133

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

Ande Bagdasarian¹, Kristian Larsen^2,3, Patrick M. Fisher^2,4, Hanne D. Hansen^1,2, and Hsiao-Ying Wey¹

¹Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States, ²Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, ³Department of Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, ⁴Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark

Synopsis

Keywords: Pharmacology, Translational Studies, Psychedelics; phMRI; fMRI; Pharmacology; 5-HT2AR

Motivation: Acute effects of psychedelic drugs are under-reported in neuroimaging studies, warranting further investigation of their immediate pharmacology to explore the potential to monitor treatment response with imaging.

Goal(s): Our goal was to assess acute impacts of serotonergic (psychedelic and non-psychedelic) agonists on hemodynamics in non-human primates (NHP).

Approach: Pharmacological-MRI (phMRI) was used to measure cerebral blood volume (CBV) changes by psilocybin, lisuride and 25CN-NBOH.

Results: Psilocybin and lisuride induced bi-phasic hemodynamic response, whereas 25CN-NBOH was monophasic. Bi-phasic phenomena may be due to non-selectivity of agonist drugs. Elevated CBV at higher psilocybin doses persists longitudinally, while lisuride and 25CN-NBOH modulations trend toward baseline.

Impact: Bi-phasic signal profiles and downstream impacts to cerebral hemodynamics may reflect non-selective targeting of psilocybin and lisuride, highlighting the sensitivity of phMRI in drug evaluation.

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