June 15, 2020
A pair of researchers at Temple University will lead a study to investigate the effects of a novel therapy that could serve as an effective treatment for cocaine use disorder.
With a $1.77 million grant from the National Institute on Drug Abuse, the Temple team will explore the impact of clavulanic acid on the brain. Evidence suggests the drug could help diminish addictive behavior among cocaine users.
Clavulanic acid is part of an existing therapy known as Augmentin, which combines the drug with the penicillin-related antibiotic amoxicillin. While it typically used for the treatment of bacterial infections, emerging research suggests clavulanic acid can interfere with cravings and re-establish healthy brain function.
"Augmentin has been around since the 1980s, but interest in the clavulanic acid component as a form of treatment for drug addiction is recent," Dr. Mary Morrison, the grant's lead investigator and professor of psychiatry and behavioral science at the Lewis Katz School of Medicine, said in a statement.
Co-investigator Scott Rawls, a pharmacologist at Temple's Center for Substance Abuse Research, began examining clavulanic acid as a therapy for drug addiction in 2014.
"Much of the research in my laboratory centers on an excitatory signaling molecule in the brain called glutamate, transmission of which is significantly altered by cocaine use," Rawls added. "Our research has shown that increased glutamate transmission in the brain is associated with addictive-like behaviors."
Rawls' research suggests drugs that normalize glutamate transmission are critical to reducing cocaine craving and vulnerability to relapse.
Preclinical animal studies conducted by Rawls' lab found that clavulanic acid enhanced glutamate uptake in brain cells called astrocytes. These studies also demonstrated that clavulanic acid reduces cocaine-induced activation of biological reinforcement and motivational systems. These reward pathways are responsible for keeping cocaine users engaged in drug-seeking behavior.
Based on these previous findings, the grant-funded clinical study will use functional magnetic resonance imaging to examine the brains of people with recent cocaine addictions.
"Spectroscopy will allow us to observe changes in glutamate levels in the brain, and adding fMRI will enable us to look at associated changes in cocaine craving," Morrison said.
The first part of the study will enable the researchers to study participants who take use clavulanic acid over a period of a year as they are treated for cocaine use disorder. If the drug is found to be safe and well-tolerated, additional funding will be provided by NIDA to pursue an outpatient treatment study in multiple cities in the United States.