New Uses for Old Drugs

Treating Cocaine Use Disorder

In 2018, the United States had 2.2 million regular users of cocaine. Of those, 1 million individuals suffered from cocaine use disorder (CUD). With substantial morbidity and mortality, CUD can be devasting for the inflicted individual, friends, and family. Despite considerable advancements in psychosocial treatments for CUD, many patients do not respond to such treatments. Further, there are currently no medicinal treatments for CUD.

Spencer Huggett, PhD, postdoctoral fellow in Emory’s psychology department, and Rohan Palmer, PhD, assistant professor of psychology, have developed a groundbreaking new technology to pinpoint repurposed drugs with the potential to treat CUD.

Rohan Palmer
Rohan Palmer photo

Brain cells in those with CUD are distinct from their healthy counterparts. In particular, cells from CUD patients display differences in transcription, the process by which cells convert genetic information in DNA to instructions in messenger RNA (mRNA). Huggett and Palmer hypothesized that known medications with transcriptional profiles negatively correlated with a diseased state would revert the cells to their original state. Essentially, they created a pipeline to take large sets of scientific data and find potential treatments by targeting the biology of CUD. The identified compounds outperformed current medications undergoing clinical trials for CUD at the mRNA level.

“Drug repurposing is a promising strategy, since it can offer a faster path to market than traditional drug discovery,” commented Cale Lennon, case manager. “The advantage of our researchers’ approach is that it leverages publicly available genetic datasets to identify unexpected drug candidates for a variety of diseases. We look forward to working with Palmer and Huggett as they evaluate potential treatments for CUD, COVID-19, and others.”

substance abuse graphic

The motivation for this research presented itself long before the technology’s inception. Palmer and Huggett both have backgrounds in biology and psychology. Huggett described a personal interest in psychology, having acted as a “mental health ambassador” to his close friends and family in the past. As such, both researchers aimed to study psychology in a biological light, with the hope of having a clinical impact in the near future. Their experiences and motives uniquely positioned them to research medicinal treatments for a disorder generally approached with psychosocial methods.

Huggett’s research of CUD began with his doctoral dissertation, and the disorder has continued to be a major focus of his study. According to Huggett, the inspiration for this technology came from scientists utilizing a similar method for drug use studies in mice.

Palmer and Huggett’s approach has significant advantages. While research on substance use initiated in mice is often not successfully translated to humans, the Emory researchers’ method is anchored in human biology. At the statistical level, their technique is simple but sophisticated. It can handle popular genomic and bioinformatic datasets, accommodate complex data types and gives interpretable results. Their method also circumvents the long, expensive, and risky process of developing and gaining FDA approval for completely new medications by focusing on repurposing drugs. Initial findings from their pipeline are promising, as their top candidate for CUD had a robust effect in preclinical models of cocaine use.

A major theme in the advancements of this technology was collaboration. Both Palmer and Huggett stressed that the strides made in identifying possible medications for CUD would not have been possible without the datasets shared with them from researchers around the country and scientific partnerships created with other labs. Palmer also highlighted that their research should inform others in the future.

This spirit of collaboration that propelled their CUD research pushed them further as the COVID-19 pandemic struck. What came next was described best by Palmer: “beautiful.” As the disease hit, Palmer and Huggett made a major breakthrough in finetuning the parameters of their technology for CUD. Like so many, the researchers had been personally impacted by the pandemic. They sought to help, and in the fall, data emerged on the genetic mechanisms of COVID-19, which allowed them to apply their pipeline and search for possible treatments for severe cases of the disease. This work confirmed the efficacy of their previous research, for they found results that overlapped with other work on the lung biology of COVID-19 deaths. The psychologists have now allied with two teams of expert virologists and plan to conduct antiviral research to test their results.

Palmer and Huggett’s work is still focused on finding medicinal treatments for CUD, and their research has the potential for serious impact on the disorder. Further, their work on the coronavirus reveals the implications of the drug repurposing pipeline they created far beyond any one disease. Huggett envisions that the method has potential in identifying treatments for neurological disorders from Parkinson’s and Alzheimer’s to depression. They aim to bridge the divide between their theoretical results and actionable human treatments. Eventually, they hope to create an accesible platform of their pipeline on the internet, allowing researchers to utilize it for a variety of diseases.

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Techids: 20204, 21015