Imaging Fast-Acting Drug Effects in Humans Using ¹H-MRS

Proton magnetic spectroscopy (¹H-MRS) is a noninvasive imaging technique that allows for the quantification of neurometabolic compounds at millimolar concentrations in the living human brain. This technique has been most often used to assess long-term changes in human brain metabolism in psychiatric disorders, pharmacological treatment, chronic drug use, and alcohol dependence. In contrast, the capacity of ¹H-MRS to evaluate the biochemical changes in the minutes to hours following drug consumption, which contribute to fast-acting drug-induced changes in perception, mood, cognition, and behavior, is largely unexplored. This Viewpoint highlights the utility of ¹H-MRS imaging for revealing neural mechanisms of rapid drug action in the human brain, with implications for phasic, in vivo changes in biosynthetic and catabolic pathways after drug exposure. Drawing from examples of psychostimulant drug effects, neuromodulatory input and drug-induced mood, we present strategies to optimize ¹H-MRS for noninvasively imaging fast-acting drug effects and other rapid phenomena within the living human brain. These approaches could provide powerful tools for both basic research and drug development.