MrNicholas Everett

Dr Nick Everett

NHMRC Emerging Leader Research Fellow, School of Psychology and Brain and Mind Centre, University of Sydney

Nick's aim is for everyone grappling with a substance use disorder to have access to an effective, evidence-based treatment that helps them lead a fulfilling, socially connected and emotionally healthy life, free from the destructive cycles of addiction. No approved pharmacotherapy exists for methamphetamine use disorder, and several other psychiatric conditions are in the same position. He leads a translational psychopharmacology laboratory which studies the neurobiology underlying those disorders and the receptor systems that new medications act through, and works closely with pharmaceutical industry partners and academic collaborators to move novel molecules toward the clinic. He supervises postdoctoral researchers, PhD, masters and honours students, and research assistants.

To study methamphetamine addiction the lab uses gold-standard models, including intravenous self-administration with jugular catheter surgery, behavioural-economic modelling of intermittent access, punished drug seeking, social-versus-drug choice, and operant tests of cognitive flexibility. Current work covers prefrontal and striatal signalling during drug seeking, the loss of sensitivity to punishment that marks compulsive use, noradrenergic mechanisms, and astrocytic contributions to reward.

For 5-HT2A, the lab asks how much receptor activation a drug needs to produce lasting plasticity, whether that threshold is the same one that produces hallucinations, and what sustained behavioural change after a single dose depends on, using head-twitch, EEG, receptor-level pharmacology and the world's first humanised 5-HT2A receptor rat across cognitive and reward-relevant tasks that have high translational validity. The oxytocin work centres on social motivation: what makes social contact worth working for, and how that changes with chronic drug exposure. Hypothalamic oxytocin neurons are switched on and off with DREADDs, and CRISPR is used to knock down oxytocin receptors in fronto-striatal circuits, to establish which cells are responsible for which aspects of motivated social behaviour. 

Changes in the brain after drug exposure or treatment are measured with immunohistochemistry and super-resolution microscopy, using Airyscan and spinning disc confocal systems to resolve dendritic spines, microglia and perineuronal nets. EEG spectral signatures recorded in rodents separate hallucinogenic from non-hallucinogenic 5-HT2A agonists and have fed into clinical trials now underway, and auditory-EEG assays measure cortical excitation and inhibition balance in animals. Freely moving fibre photometry shows how healthy and impaired behaviours are represented at the neuronal, astrocytic and neurotransmitter level. The lab is also developing blood biomarkers of central 5-HT2A engagement for use in clinical trials and to support early non-clinical development.

Nick has held past and present leadership positions at the Sydney-based biotechnology companies Kinoxis Therapeutics and Xylo Bio, built on his expertise in translational psychopharmacology, behaviour and neuroscience. He has led preclinical components of programs that progressed two novel compounds from animal models into Phase 1 and Phase 2 trials for under-served psychiatric disorders, funded by and in collaboration with the US National Institute on Drug Abuse. He has also run preclinical programs in partnership with Boehringer Ingelheim (via Kinoxis Therapeutics co-development partnership). His research is funded by an NHMRC Investigator Grant, a Cooperative Research Centres Projects grant from the Department of Industry, Science and Resources, and the Department of Education's National Industry PhD Program. He completed his PhD in neuropsychopharmacology at Macquarie University. More about the lab is at everettlab.com.