Active Brain & Nervous System Mental Health

Translational biomarker development for precision psychedelic medicine in addiction

In plain English

AI plain-English summary

Gambling disorder leaves specific, measurable traces in the brain’s wiring, and this project will track whether psychedelic therapy can repair them. The problem is that addiction treatments remain blunt tools. For gambling disorder—a condition affecting roughly 1–2% of the population, with no approved medications—clinicians lack objective ways to know which patients will respond to a given therapy, or how the therapy actually changes the brain. This project builds functional MRI tasks that probe the exact circuits known to malfunction in gambling disorder—those governing reward, impulse control, and decision-making—then tests whether a single dose of psychedelic therapy shifts those signals. The researchers will also compare fMRI results with EEG and blood-based markers to see which measure best captures the therapy’s effects. If the biomarkers prove sensitive, the impact is twofold. First, clinicians could one day use a brain scan to match patients to the right treatment, rather than relying on trial and error. Second, the same biomarkers could accelerate drug development by providing a rapid readout of whether a candidate therapy is hitting its neural target. This is a fundamental science study—it will not immediately change clinical practice—but it is the kind of mechanistic groundwork that, if successful, could transform how addiction trials are designed and how precision psychiatry is delivered.

View original technical description
This research aims to develop multimodal, reliable translational biomarkers to characterise addiction processes and use them to develop psychedelic therapy (PT) in addiction. Building on previous experience, this proposal seeks to develop and validate naturalistic, functional Magnetic Resonance Imaging (fMRI) tasks that probe brain systems known to be dysfunctional in individuals with a sub-category of addiction, Gambling Disorder (GD). Further, the proposal also aims to longitudinally evaluate the sensitivity of these fMRI biomarkers to PT as compared with EEG and peripheral biomarkers to explore it's putative multimodal mechanism(s) of action in a pilot, proof-of-concept, experimental medicine study. Leveraging advances in functional imaging, this initiative seeks to build on my PhD and one-year postdoctoral work that aims to transform addiction translational research by being one of the first precision psychedelic medicine studies to date in this indication, giving insights into disease mechanisms and future clinical development. Further, the accelerator award will support skills and development and training in brain imaging analysis, human experimental medicine methodology, internships in leading addiction neuroscience academic groups and exposure to industry research with a psychedelic biopharmaceutical company.

View the original record at the funder ↗

Researchers

Rayyan Zafar (EPMC Awardee)

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Original classification

Wellcome Accelerator Awards

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