PsiloGambling
Research type
Research Study
Full title
PsiloGambling: Multimodal brain and physiological biomarkers of action of a 5-HT2a receptor agonist in Gambling Disorder
IRAS ID
356419
Contact name
David Erritzoe
Contact email
Duration of Study in the UK
1 years, 1 months, 31 days
Research summary
Despite growing interest in understanding how 5-HT2AR agonists such as psilocybin influence brain function and peripheral physiological processes, our knowledge of their engagement with addiction-relevant mechanisms remains limited. While previous studies suggest these compounds may alter domains such as reward processing, cognitive flexibility, and neural plasticity, the specific neurobiological and peripheral physiological pathways involved are not well characterised. To date, the relationship between 5-HT2AR agonism and human addiction-related neurobiology has not been systematically examined. Mechanistic, biomarker-driven studies can offer insights into how these probes engage neural circuits and physiological systems implicated in addiction, building on preclinical evidence within a human experimental medicine framework (Zafar et al., 2023a).
Historically, pathological gambling was classified as an impulse control disorder. However, the DSM-5 reclassified GD as a behavioural addiction, reflecting its neurobiological, clinical, and behavioural similarities with Substance Use Disorders (SUDs) (Potenza, 2008). This conceptual shift underscores the role of addiction-related mechanisms in GD, reinforcing its relevance in addiction neuroscience. However, substantial gaps remain in our understanding of the underlying neurobiological mechanisms of addiction in GD, and more broadly behavioural addictions and SUDs making it an opportune model to for experimental and mechanistic neuropsychopharmacology research.
This present study is designed to investigate these pathways to advance fundamental knowledge of brain–body mechanisms linked to addiction vulnerability and persistence, without assessing clinical efficacy or safety as a treatment (Zafar et al., 2023a, Wall et al., 2023, Erritzoe et al., 2024). This study will characterise neural, physiological and behavioural responses to a 5-HT2AR agonist, PEX010, in individuals with GD using fMRI and EEG to map functional and electrophysiological patterns, particularly in networks implicated in reward processing, salience attribution, and cognitive control (Hayes et al., 2020). This study will focus on mechanistic targets that may inform future translational research in addiction neuroscience, consistent with other established in-human experimental medicine approaches (McGonigle et al., 2017, Wall et al., 2023).REC name
London - London Bridge Research Ethics Committee
REC reference
26/LO/0415
Date of REC Opinion
7 Jul 2026
REC opinion
Further Information Favourable Opinion