TIP³DE
TIP³DE
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Translational Integration of Psychophysiology, Behavioral Pharmacology and Psychobiology in the Modulation of Neural Circuits for Dysfunctional Eating
Translational Integration of Psychophysiology, Behavioral Pharmacology and Psychobiology in the Modulation of Neural Circuits for Dysfunctional Eating
ABOUT THE PROJECT
ABOUT THE PROJECT
Obesity and eating disorders (EDs) represent an escalating global health crisis, with more than half of the world's population projected to be overweight or obese by 2035 and annual healthcare costs exceeding $990 billion. Both conditions are increasingly recognized as rooted in dopaminergic reward system dysregulation, with dopamine hypofunction driving compulsive overeating in obesity and binge-eating disorder and dopamine hyperfunction contributing to food avoidance in restrictive disorders such as anorexia nervosa. TIP³DE pioneers the therapeutic application of dopaminergic allosteric modulators to restore reward circuit function in individuals with dysfunctional eating behaviors.
Integrating three translational phases: preclinical mapping in animal models, human profiling and clinical trial design.
Targeting dopaminergic dysregulation with allosteric modulators that preserve natural reward sensitivity and minimize side effects.
Identifying distinct dopaminergic signatures across obesity, anorexia and bulimia to enable personalized treatment.
Building a translational pipeline that bridges preclinical and clinical research within the CIMCYC.
Why now?
Current pharmacological treatments for obesity and EDs, including GLP-1 receptor agonists such as semaglutide, offer limited long-term efficacy and carry substantial psychiatric and cardiovascular risks. Several anti-obesity drugs acting on related mechanisms have historically been withdrawn due to serious side effects, including depression and suicidal ideation, risks that are particularly concerning in ED populations where appetite-regulating drugs may intensify restrictive behaviors. This underscores the urgent need for novel, safe and circuit-specific interventions that go beyond traditional appetite-suppressant drugs.
What for?
The project aims to identify distinct dopaminergic signatures underlying disordered eating and to validate a translational framework that positions dopaminergic allosteric modulators as a cost-effective, circuit-specific alternative to current anti-obesity drugs. Results are expected to support a shift toward psychologically informed, brain-based treatment strategies for obesity and eating disorders, with strong potential for clinical and industrial application.
What's novel?
Unlike conventional full agonists or antagonists, dopaminergic allosteric modulators act in synergy with natural dopamine signaling rather than replacing it, preserving physiological reward sensitivity while reducing the risk of tolerance and psychiatric side effects. No dopaminergic allosteric modulators have yet been clinically applied to eating behavior, representing a major untapped therapeutic opportunity. TIP³DE builds a full translational pipeline, from preclinical animal models to a stratified, double-blind clinical trial protocol, around this approach.
Where?
The project is jointly led by José Luis Mata Martín (Human Psychophysiology and Health, HUM388) and María Ángeles Zafra Palma (Psychobiology, CTS430) at CIMCYC María de Maeztu Unit of Excellence, University of Granada, in collaboration with David García-Burgos (Neuroplasticity and Learning, CTS1003, CIBM) and clinical partners at the Virgen de las Nieves University Hospital in Granada.
INTERDISCIPLINARY APPROACH
INTERDISCIPLINARY APPROACH
This project integrates expertise in psychophysiology, psychobiology and behavioral pharmacology across a three-phase translational pipeline connecting animal models with clinical application.
Psychobiology & Preclinical Neuroscience
Lead the design and execution of animal model experiments, characterizing how dopaminergic allosteric modulators affect reward-related brain circuits through neuroimaging and spectroscopy.
Clinical Psychophysiology
Coordinate human profiling and behavioral interventions, integrating physiological measures such as heart rate variability, galvanic skin response and facial electromyography to identify reward-related endophenotypes.
Food-Related Learning & Experimental Psychopathology
Contribute insight into associative learning mechanisms in eating disorders, supporting the behavioral and neural paradigm design across preclinical and human phases, with access to neuroimaging and spectroscopy technologies.
Clinical Psychiatry & Eating Disorders
Provide clinical expertise and patient access through the Eating Behavior Disorders Unit (UTCA) at the Virgen de las Nieves University Hospital, supporting recruitment and diagnostic assessment for the human profiling and clinical trial phases.
CONTACT
CONTACT
José Luis Mata Martín. E-mail: matamar@ugr.es
María Ángeles Zafra Palma. E-mail: mazafra@ugr.es
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