New imaging technique used to study effects of caffeine on brain chemistry

For some, coffee is the perfect stimulant to wake up in the morning, get through the afternoon or stay alert in the evening. Yet for others, coffee or other caffeinated products cause feelings of anxiety and discomfort. New UW research provides direct evidence from humans that caffeine can have different chemical effects on brain activity - effects that vary for regular caffeine consumers, people “taking a break” from caffeine and those who avoid caffeine due to unpleasant side effects such as anxiety or discomfort.

Dr. Stephen Dager, professor of psychiatry and behavioral sciences, radiology and bioengineering at the School of Medicine, and colleagues report on the use of a rapid chemical imaging technique to measure people’s brain chemical responses to caffeine — the most widely used psychostimulant in the world. The research is reported in the February issue of the American Journal of Psychiatry.

Researchers used a modified form of magnetic resonance imaging called proton echo-planar spectroscopic imaging (PEPSI). PEPSI allows for rapid “snapshots” of human brain chemistry, similar to a MRI, that provides quantitative information about brain chemical composition or metabolism. This new imaging technique is able to simultaneously measure changes in brain metabolism or chemical status in multiple regions of the brain. The technique was developed at the UW in collaboration with Dr. Stefan Posse with the Institut for Medizin in Julich, Germany.

Brain lactate levels for caffeine intolerant subjects and regular caffeine users at rest and following a caffeine challenge.

The study involved nine people who were caffeine intolerant and nine regular caffeine users (who consumed five or more cups of coffee, or its equivalent, daily). After having their resting brain chemistry imaged with PEPSI, research participants drank a dose of caffeine equivalent to five to eight shots of espresso depending on their weight. Subjects then had continuous images of their brain activity recorded for the following hour.

Investigators found that the caffeine-intolerant individuals had substantial increases in brain lactate (a metabolic product of energy expenditure), demonstrating a distinct anatomical pattern of metabolic changes in the brain. Only slight brain chemical changes were detected among the regular caffeine users.

Brain lactate levels for regular caffeine users during first study and then when rechallenged following a caffeine holiday.

“These results were consistent with what we had predicted,” said Dager. “But, we wanted to further ascertain whether the regular caffeine drinkers would lose their tolerance once they stopped drinking coffee.”

To assess the effects of a caffeine holiday, six of the regular coffee drinkers abstained from caffeine-containing products for one to two months and were then re-tested with the same caffeine dose. Researchers measured a threefold increase in brain chemical response to caffeine - a response even greater than observed among the caffeine-intolerant individuals.

In contrast to the symptoms of anxiety or physical discomfort experienced by caffeine intolerant individuals, these subjects did not report any discomfort.

“These results demonstrated that regular caffeine users experience a loss of tolerance to the brain metabolic effects of caffeine when they take a break from coffee,” Dager said. “These findings suggest that mechanisms other than exaggerated brain metabolic responses are responsible for caffeine intolerance in individuals who experience discomfort from consuming caffeinated products.” ¶

Julie Rathbun