Pharmacological MRI: Utility in Understanding Drug Mechanisms in Psychiatric Disorders

Pharmacological MRI (pharmaMRI) has emerged as a powerful tool to study how psychoactive drugs affect brain function and to uncover mechanisms of drug action in psychiatric disorders. This review provides an overview of key techniques used in pharmaMRI, including BOLD-fMRI, arterial spin labeling (ASL), and cerebral blood volume (CBV) mapping, and how they have advanced our understanding of drug-induced changes in neural activity and connectivity. We present key advances in both preclinical and clinical pharmaMRI, highlighting its value in elucidating drug mechanisms and informing psychiatric treatment development. In preclinical studies, pharmaMRI benefits from optimized hardware, the use of contrast agents such as iron oxide nanoparticles, and precise experimental control, including invasive neuromodulation techniques (e.g., opto- and chemogenetics). These studies offer critical mechanistic insights into receptor-specific and circuit-level drug effects, supporting hypothesis-driven translation to humans. Clinically, pharmaMRI has advanced our understanding of how compounds, such as antidepressants, antipsychotics, and stimulants, affect large-scale brain networks and offers potential for modeling psychiatric phenotypes and predicting treatment response. Furthermore, pharmaMRI can serve as a biomarker for target engagement and refine dose selection in early-phase trials. Despite growing interest, clinical adoption remains limited. Systematic use of both preclinical and clinical pharmaMRI could accelerate drug development, support precision psychiatry, and deepen understanding of treatment mechanisms. Finally, open science practices and large-scale datasets can help contextualize drug effects within broader neural and molecular frameworks. While these developments present some challenges, they position pharmaMRI as a critical bridge between molecular mechanisms and systems-level brain function in psychiatry. Evidence Level: N/A. Technical Efficacy: Stage 1.