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

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.