Imaging rapid drug effects in the human brain

Brown University researchers outline a method of showing how drugs affect the brain within minutes to hours of being taken.

PROVIDENCE, R.I. [Brown University] — A new study reveals how a brain imaging technique can be used to understand how fast-acting drugs alter metabolism and the production of complex molecules in the human brain.

The study outlines strategies for optimizing proton magnetic spectroscopy (1H-MRS) imaging in the minutes to hours following drug ingestion. 1H-MRS imaging has been most often used to assess long-term changes in the brain’s metabolism in psychiatric disorders, pharmacological treatment, chronic drug use and alcohol dependence. This new study demonstrates the technique’s capacity to evaluate the biochemical changes in the minutes to hours following drug consumption — a new application of the technique.

The research was published on August 25 in ACS Chemical Neuroscience, a journal of the American Chemical Society. The work was led by Tara White, assistant professor of behavioral and social sciences (research) at Brown University, and Meghan Gonsalves, a Ph.D. student at Brown.

The technique described in this latest paper was first applied in a 2018 study, led by White, which found a large rise in neocortical glutamate — the major excitatory neurotransmitter in the mammalian brain and nervous system —  2.5 hours after people took drugs used to treat attention deficit hyperactivity disorder (ADHD).

“We’re interested in emotion and behavior in healthy people, so we decided to use this technique to understand what’s happening with metabolism inside the brain in response to FDA-approved drugs that we know impact emotion, cognition and behavior,” said White, who is affiliated with Brown’s Carney Institute for Brain Science and the Center for Alcohol and Addiction Studies in the University’s School of Public Health. “We saw a large effect on compounds as fundamental as glutamate, which rose after the drug compared to placebo within subjects. What we have is a snapshot in time, which indicates a rapid change in glutamate and other compounds 2.5 hours after drug ingestion in one area of the brain.”

In the new paper, White and Gonsalves provide guidance for researchers, clinicians and drug scientists for the timing of 1H-MRS imaging in drug administration protocols. They outline strategies for understanding the mechanisms through which fast-acting drugs alter emotion, behavior and cognition in humans.

“When you look at the existing literature there is a dearth of information or studies that look at the short-term effects of drugs, neurological events and neuromodulatory effects on glutamatergic compounds,” said Gonsalves, who holds both bachelor’s and master’s degrees from Brown. “1H-MRS imaging is an underutilized technique that can bust the door wide open into how metabolic concentrations change in real time in the living human brain.”

In long-term studies, researchers typically perform imaging acquisition on two groups before and after a treatment — a control group receives an inactive substance while another group is given the treatment. In the new study, however, White and Gonsalves conducted the imaging acquisition during the period in which a fast-acting drug had its immediate effects. The placebo control, which is an inactive substance, was given to the same participants in a time-locked procedure that was identical to the day in which they took the drugs.

As a next step, the researchers will establish a three-pronged research program on brain metabolites that contribute to emotions in healthy adults. White received a Zimmerman Innovation Award last year from the Carney Institute to collect the preliminary data for this project. The long-term goal, she said, is to build a research program on the neurobiology of human emotion at Brown.

The research was funded by the National Institute on Drug Abuse (DA R21 029189).