Psychology Colloquium: The ‘light’ and ‘dark’ sides of addiction: animal models, psychological processes, and the development of novel pharmacotherapies.
Dr Nicholas Everett, The Brain and Mind Centre, School of Psychology, University of Sydney.
While psychosocial interventions for substance use disorders can be effective for some, they are inaccessible for the many, and relapse occurs in 60-80% of people despite successful abstinence. Unfortunately, addiction medicine is in its infancy, with very few therapies approved for use, and even fewer which are effective long-term. This is at least partially due to a lack of understanding of the psychological and neural processes which underpin the distinct symptoms which drive, maintain, and trigger relapse to substance use disorders. Additionally, within the psychological, neuroscience, and drug-discovery fields, there has been an overwhelming focus on the ‘light’ side of addiction, characterised by drug-induced euphoric highs, positive reinforcement, and incentive sensitisation. In contrast, only recently has significant attention been given to the ‘dark’ side of addiction, characterised by drug- and withdrawal-induced dysphoria and negative reinforcement. Together, these (and other) issues have precluded the development of pharmacotherapies which specifically target the neurobiology underpinning these problematic affective and motivational states.
Here, I will present my work using rodent models of opioid and methamphetamine use disorders to develop novel pharmacotherapies for treating the dark and light behavioural symptoms and neural markers of addiction. I will discuss the therapeutic effects and neural mechanisms of administered oxytocin for methamphetamine addiction, including potential solutions to its translational hurdles, and will present research using a novel clinical-stage molecule, KNX100, for treating both opioid and methamphetamine use disorder.
Nick is a post-doctoral researcher at The Brain and Mind Centre in the School of Psychology, with A/Prof Michael Bowen. His research using preclinical rodent models of behaviour and neurobiology, in the context of normal function and psychiatric disease states spans a range of themes including pavlovian and operant conditioning, social motivation, substance use disorders (particularly methamphetamine and opioids), nucleus accumbens function, and oxytocin neurobiology. Overarching these themes is a focus on the discovery and development of novel brain-targeting molecules which interact with disease-relevant neural systems, to treat intractable psychiatric diseases. Recently, through A/Prof Bowen’s start-up, Kinoxis Therapeutics, Nick’s industry-sponsored development of KNX100 for treating the negative affective symptoms of opioid withdrawal has helped to progress this potentially first-in-class therapy to Phase-I clinical trials. Nick’s translational work continues to progress KNX100 and other novel molecules towards clinical trials for methamphetamine use disorder, and to discover translatable biomarkers of addiction symptomology and of therapeutic intervention, while his basic psychology and neuroscience research continues to understand how neural systems (e.g. oxytocin) contribute to normal and aberrant motivational states. Across these projects, Nick uses a combination of contemporary neural recording and manipulation techniques including in vivo calcium imaging, chemogenetics, optogenetics, neuropharmacology, immunohistochemistry, in combination with pavlovian conditioning tasks (e.g. conditioned place aversion, sign-tracking), and operant tasks of intravenous drug self-administration and social motivation (behavioural economics), and mutually exclusive choice between drugs and social rewards (modelling the Community Reinforcement Approach). Nick also co-supervises PhD candidates in the School, spanning topics including: novel cannabinoid-based therapies for opioid use disorder; the neurobiology of social fear; the interactions between oxytocin, sleep deprivation, and social motivation; and improving the translation of oxytocin for treating methamphetamine use disorder. Nick serves on the executive council for the International Behavioral Neuroscience Society and on the USYD Animal Ethics Committee. Nick is eager to collaborate with other School of Psychology researchers.
This is a Hybrid event so you can join in person or via the Webinar link below:
HEYDON LAURENCE LECTURE THEATRE 217 (DT ANDERSON) (You are encouraged to please wear a mask if attending in person)
Zoom Webinar Link: https://uni-sydney.zoom.us/s/88411869946