Tirzepatide's dopaminergic effects in AUD brains to be investigated in crossover PET/MRI trial

Alcohol Use Disorder (AUD) is a significant health challenge, with current treatments often falling short. Glucagon-like peptide 1 (GLP-1) receptor agonists, primarily used for diabetes and weight loss, have shown promise in preclinical and limited human data for reducing cravings for drugs and alcohol. Other GLP-1R agonists like exenatide and semaglutide have demonstrated reduced alcohol consumption in trials. This study aims to explore how tirzepatide, a dual GLP-1/GIP agonist, affects brain response and dopaminergic pathways in AUD patients, addressing a critical gap in understanding its potential for addiction treatment.

This study is designed in two parts. Part 1 involves five healthy volunteers undergoing 2-3 combined PET/MRI scans with methylphenidate to establish test/retest reproducibility of brain activity measures. Part 2 is a crossover design where both healthy volunteers and AUD participants (aged 21-65, non-treatment seeking) will receive either Tirzepatide or placebo. Treatment involves once weekly subcutaneous injection for 2-3 weeks, followed by PET/MRI imaging. After a 2-3 week washout period, participants cross over to the alternate treatment arm (tirzepatide or placebo) for another 2-3 weeks, with subsequent PET/MRI scans to assess brain activity during resting state.

This study is currently recruiting participants, and as such, no findings or results are available yet. The objective is to understand how the brains of people with AUD respond to tirzepatide by assessing dopaminergic activity using PET/MRI scans. The study aims to characterize the neural mechanisms through which tirzepatide may influence alcohol-seeking behaviors and reward processing, building on preclinical evidence suggesting GLP-1 agonists can modulate the mesolimbic dopamine system. The initial phase (Part 1) focuses on establishing the reliability of the imaging techniques.