Compound in rosemary extract may reduce sensitivity to cocaine

A team of researchers led by the University of California, Irvine, has discovered that an antioxidant found in rosemary extract can reduce voluntary cocaine use by moderating the brain’s reward response, offering a new therapeutic target for treating addiction.

The study, recently published in the journal Neurondescribes the team’s focus on a brain region called the globus pallidus externus (GPe), which acts as a gatekeeper regulating how we respond to cocaine. The team found that within the GPe, parvalbumin-positive neurons play a crucial role in controlling the response to cocaine by altering the activity of neurons that release dopamine, a pleasure molecule.

“There are currently no effective treatments for addiction to psychostimulants such as cocaine, which, along with opioids, represent a substantial health burden,” said corresponding author Kevin Beier, associate professor of physiology and biophysics at UC Irvine. “Our study advances our understanding of the fundamental brain mechanisms that increase vulnerability to substance use disorders and provides a basis for the development of new interventions.”

The results in mice revealed that parvalbumin-positive cells in the globus pallidus externus, which indirectly influence dopamine release, became more excitable after exposure to cocaine. This led to a decrease in the expression of certain proteins encoding membrane channels that typically help control the activity of globus pallidus cells. The researchers found that carnosic acid, an isolate of rosemary extract, selectively binds to the affected channels, providing a pathway to reduce drug response in a relatively specific manner.

“Only a subset of individuals are likely to develop a substance use disorder, but we cannot yet identify them. If globus pallidus cell activity can effectively predict response to cocaine, it could be used to measure likely responses and thus serve as a biomarker for those most vulnerable,” Beier said. “Additionally, it is possible that carnosic acid could be given to high-risk individuals to reduce response to cocaine.”

The next steps in this research will be to thoroughly evaluate the negative side effects of carnosic acid and determine the ideal dosage and timing of administration. The team also wants to test its effectiveness in reducing the desire for other drugs and develop more potent and targeted variants.