Cocaine use continues to be a public health problem, yet despite concerted efforts, no drugs have been approved to resolve cocaine addiction. Research suggests that the attention-deficit/hyperactivity disorder drug methylphenidate (MPH; Ritalin) could serve as a cocaine-replacement therapy, but clinical results have been mixed. Although several labs have produced MPH derivatives for testing, parts of the molecule remained chemically inaccessible. Now, researchers reporting in ACS Central Science have cleared that hurdle.

According to the Centers for Disease Control and Prevention, more than 5 million Americans reported actively using cocaine in 2020, and almost 25,000 Americans died of a cocaine-related overdose in 2021. Although small-molecule drugs have proven effective in treating other drug addictions—for example, methadone as a therapy for heroin abuse—no such medication exists for cocaine abuse.

MPH has been considered a potential treatment because it behaves similarly to the illicit drug, increasing dopamine levels in the brain by blocking dopamine reuptake. Additionally, clinical studies have shown that MPH has a lower risk of abuse than cocaine.

The results of a human study carried out by an international research team have provided valuable new insights into the activity of the brain’s noradrenaline (NA) system, which has been a longtime target for medications to treat attention-deficit/hyperactivity disorder, depression, and anxiety. The study employed what the researchers claim is a groundbreaking methodology, developed to record real-time chemical activity from standard clinical electrodes implanted into the brain routinely for epilepsy monitoring.

The results offer up new insights into brain chemistry, which could have implications for a wide array of medical conditions, and also demonstrate use of the new strategy for acquiring data from the living human brain.

“Our group is describing the first ‘fast’ neurochemistry recorded by voltammetry from conscious humans,” said Read Montague, PhD, the VTC Vernon Mountcastle research professor at Virginia Tech, and director of the Center for Human Neuroscience Research and the Human Neuroimaging Laboratory of the Fralin Biomedical Research Institute at VTC. “This is a big step forward and the methodological approach was implemented completely in humans – after more than 11 years of extensive development.” Montague is senior, and co-corresponding author of the researchers’ published paper in Current Biology, which is titled “Noradrenaline tracks emotional modulation of attention in human amygdala.” In their paper the authors concluded, “By showing that neuromodulator estimates can be obtained from depth electrodes already in standard clinical use in the conscious human brain, our study opens the door to a new area of research on the neuromodulatory basis of human health and disease.”