Researchers have used PET imaging to visualize the binding sites of caffeine in a live human brain for the first time, according to a study published in the November issue of The Journal of Nuclear Medicine. The study suggested a connection between typical caffeine consumption and high A1 adenosine receptor (A1AR) occupancy, which could inform future work in neurodegenerative disorders.
Caffeine is the most widely consumed psychoactive substance, and its biologic actions relate to antagonizing effects at cerebral adenosine receptors, including A1AR.
David Elmenhorst, MD, of the Institute of Neuroscience and Medicine in Jülich, Germany, and colleagues sought to calculate the occupancy of the A1AR by caffeine using PET imaging.
A total of 15 male volunteers underwent a PET scan with 18-F-CPFPX after abstaining from caffeine for 36 hours. Caffeine was administered in 1 mg/kg steps from 1 mg/kg to 4 mg/kg. The researchers estimated the occupancy of A1AR by caffeine by comparing the total distribution volume at baseline with the volume 120-140 minutes after caffeine administration. Caffeine rapidly displaced 18-F-CPFPX in all brain regions.
Elmenhorst and colleagues observed stable caffeine levels from 120 minutes onward, which correlates with its terminal half-life of five to six hours.
Based on the current study, the researchers wrote, “It is therefore likely that usually consumed amounts of coffee and caffeinated beverages result in brain concentrations of caffeine that block substantial portions of cerebral A1ARs.” They noted that the cognition-enhancing effects of caffeine are likely exerted by A1ARs.
In regular caffeine consumers, about half of the A1ARs may be occupied by caffeine, which could lead to adaptive changes and chronic alterations of receptor expression and availability, according to the researchers. They referred to epidemiologic evidence suggesting the protective effect of caffeine against Parkinson and Alzheimer disease and suggested that future research explore A1AR in the context of neurodegenerative disorders.