Brandon Warren, Ph.D., an assistant professor of pharmacodynamics in the University of Florida College of Pharmacy, has received a $2.2 million grant from the National Institutes of Health’s National Institute on Drug Abuse to study the role of the small molecule Rac1 in the behavior, structure, and activity of neurons controlling cocaine seeking and craving in patients with cocaine use disorder.
A multidimensional psychiatric disorder characterized by abnormally strong, learned associations in the brain, cocaine use disorder impacts millions of people globally, yet no pharmacological intervention exists to treat it, Warren said. His team aims to provide opportunities for developing new, experimental therapeutics that can reduce cravings, lower relapse rates, and provide improved, long-term recovery outcomes for patients with cocaine use disorder.
Using animal models, Warren’s team aims to weaken the connections in the brain that lead to craving and relapse through the manipulation of the small molecule Rac1 within those neuronal ensembles most strongly activated by cocaine.
“One of the things that happens with cocaine addiction is that you get these strong connections among neurons in the brain, which form spiny outcroppings called synapses. Cocaine increases the number of those spines, and it makes them bigger, so they go from being sort of stubby to a large, strong, mushroom-shaped spine. These synapses underlie powerful memories associated with drug use, which can ultimately lead to craving or even relapse in some individuals,” Warren explained. “Our goal is to try to reduce some of the connections between neurons that are underlying these cocaine memories. With this grant, we can now use tools to specifically affect gene expression in only the 4% of neurons that are activated by cocaine.”
Warren said receiving support for this research from the National Institute on Drug Abuse, or NIDA, is meaningful for him on both a professional and personal level.
“This support validates the collective efforts of the whole team, who has done work on this project over several years,” Warren said. “On a personal level, this grant — the Diversity R01 for New and At-Risk Investigators — highlights NIDA’s commitment to fostering diversity in science and acknowledges my personal journey from being raised poor by a single parent to ultimately becoming a neuroscientist at one of the top research institutes in the country and ultimately, the world.”
In his career at the UF College of Pharmacy and elsewhere, Warren has utilized his personal background as the fuel that keeps him inspired to conduct research aimed at changing — and saving — patients’ lives.
“Growing up, I got a lot of firsthand experience in what drugs and alcohol can do to individuals, families, and lives. That has deeply influenced my path. From a relatively young age, I was fascinated by how these small molecules can so dramatically affect cognition, motivation, and just change people,” he said. “What I find most inspiring about my work is that there is a real potential here to make a difference in people’s lives. By uncovering these new ways to treat and prevent addiction, I think we can have a profound impact.”