Hope on the Horizon

AACP Article


A $19 million grant may help University of Florida Health researchers uncover a treatment for stimulant use disorder.

By Emily Jacobs

As many as 4.5 million Americans over age 12 may have a stimulant use disorder, according to the 2021 annual National Survey on Drug Use and Health. This includes misuse of stimulants like cocaine, ecstasy and methamphetamine, as well as legal prescription stimulants. While opioid misuse and overdose deaths have received the most attention and funding, stimulants are a growing driver of U.S. drug overdose deaths, creating greater urgency to find effective treatments. There are currently no FDA-approved medications available to treat stimulant use disorder. However, that may change thanks to new research out of the University of Florida College of Pharmacy and Sparian Biosciences.

The National Institutes of Health and the National Institute on Drug Abuse have awarded a five-year, $19 million grant to Sparian Biosciences and the University of Florida College of Pharmacy researchers. This funding will help further the development of the molecule SBS-518, which may become a novel, oral treatment for stimulant use disorder.

Dr. Christopher R. McCurdy, professor of medicinal chemistry and the Frank A. Duckworth Eminent Scholar Chair in the UF College of Pharmacy, leads the team that developed this compound. He also directs the university’s Translational Drug Development Core within the Clinical and Translational Science Institute. This core will conduct the work necessary to get the molecule out of the lab and into clinical tests.

The researchers’ aim with SBS-518 is to block or decrease the desire to use substances like cocaine or methamphetamine.

Hope in Horizon picture

McCurdy’s team, along with researchers at the National Institute on Drug Abuse, used the compound on rats that had been trained to self-administer cocaine or methamphetamine. After receiving SBS-518, the animals showed less interest in self-administering the stimulants, although they had access to the drugs. At the same time, the rats maintained a normal food intake on demand. This may indicate that the compound blocks their drug-seeking ability without blocking normal survival behaviors.

Promising Research

In seeking a treatment for stimulant misuse, previous research had attempted to imitate the structure of cocaine in a way that would block cocaine’s actions. This included targeting the dopamine transporter protein that cocaine interacts with in the body. However, these previous compounds also blocked that dopamine transporter from doing its job, just as cocaine does. This left more dopamine available to create a euphoric response, without reducing cocaine intake.

“It is very easy for us, as researchers or as educators in the basic sciences, to get lost in the science and forget that what we’re doing has a bigger purpose overall…to improve human health and improve outcomes and ultimately to make people better.”

—Dr. Christopher R. McCurdy

While SBS-518 does interact with the dopamine transporter, it also interacts with another protein called the sigma-1 receptor. This dual activity may keep the stimulant from limiting the transport of dopamine and preserve dopamine’s normal functioning. This was indicated by the dopamine levels in the lab rats given SBS-518; their brains’ dopamine levels did not rise as they normally do after administration of stimulants.

McCurdy’s team will use its new funding to convert SBS-518 into a clinical oral drug candidate. Then, the lab will conduct toxicity studies prior to clinical trials. If the drug is found to be both safe and effective in animals, it would advance to clinical trials and be a first-in-class treatment in humans for cocaine use disorder, and possibly for stimulant use disorder in general. Counseling is currently the only available treatment for stimulant use disorder. If this proves to be a safe and effective pharmacotherapy, clinicians and patients would have another valuable tool to reduce stimulant misuse.

“It is very easy for us, as researchers or as educators in the basic sciences, to get lost in the science and forget that what we’re doing has a bigger purpose overall,” McCurdy said. “And that purpose is to improve human health and improve outcomes and ultimately to make people better.”

Over the years that this project has been underway, undergraduate and graduate student pharmacists have passed through the lab to help with some of the synthesis work. McCurdy welcomes students into the lab, remembering his own life-changing laboratory experience as a student pharmacist. He initially entered pharmacy school with the intention of working in a community-based pharmacy practice, but working as a student in medicinal chemist Stephen J. Cutler’s laboratory at Ohio Northern University piqued his interest in academia and research.

“Every day had the promise of discovering something new and seeing something for the first time that no one in the world has ever seen,” McCurdy said of pharmacy research. “It was just the excitement, I think, of the discovery and the new contributions that could be made to medicine.”

While academia does not bring as much face-to-face interaction with patients as community pharmacy practice, McCurdy noted that it can have just as much of an impact on people. “By teaching in pharmacy and doing research, I could impact many more patient lives than just practicing pharmacy by myself at a single location. So if I’ve averaged teaching a hundred pharmacy students…that starts to add up to thousands upon thousands of pharmacists that I’ve had a little part of their educational background in, and they have a little part of me in their practice setting.”

That influence on future professional pharmacists can be vital for research and patient welfare. Substance use disorders of all kinds remain highly stigmatized, McCurdy pointed out. By seeing stimulant use disorder as a chronic disease and better understanding the mechanisms behind it, it may lead to better treatment plans and social supports for patients. “Most people that end up doing substance use disorder research have a personal reason why they got involved, either a family member or a friend that they knew who struggled with addiction,” McCurdy said. “It’s not just all nitty-gritty science down at the molecular level. We try to bring it up to what human impact there will be.”

Emily Jacobs is a freelance writer based in Toledo, Ohio.