By combining AI, clinical testing and computer analysis of vast amounts of biomedical knowledge and electronic health records, researchers at Case Western Reserve University have found that ketamine could be an effective treatment for cocaine use disorders.
Currently, there are no FDA-approved treatments for cocaine-use disorders, despite more than two million people in the US regularly using the substance.
Around one in every five drug overdose deaths in the US involves cocaine, and its consistent use contributes to an array of serious health issues such as heart attack and stroke.
Corresponding author, Professor Rong Xu, and her colleagues, have determined ketamine held the greatest potential as a treatment by developing novel AI-based drug discovery algorithms to identify promising candidates from all FDA-approved drugs, reviewing top drug candidates by expert panels of addiction experts such as the University of Cincinnati’s T. John Winhusen.
Xu, professor of biomedical informatics and founding director of the Center for AI in Drug Discovery at the Case Western Reserve School of Medicine, commented: “Ketamine, a small synthetic organic molecule used clinically as an anaesthetic and a depression treatment, was found to be associated with significant improvement in remission among people with cocaine-use disorders.”
The team evaluated the potential clinical effectiveness of ketamine in improving remission rates among patients with cocaine-use disorders by analyzing tens of millions of electronic health records. They found that cocaine-use disorder patients administered ketamine for pain or depression experienced two to four times higher remission rates.
The authors write: “The mechanism of action analysis revealed that ketamine directly targets multiple CUD-associated genes (BDNF, CNR1, DRD2, GABRA2, GABRB3, GAD1, OPRK1, OPRM1, SLC6A3, SLC6A4) and pathways implicated in neuroactive ligand-receptor interaction, cAMP signaling, and cocaine abuse/dependence.”
While a few previous studies have found increased efficacy of ketamine in treating cocaine use disorder, the researchers have said that the groups involved were largely homogenous.
The Case Western Reserve study not only included a greater diversity of participants by race and gender, but also those suffering from additional medical and psychiatric conditions.
“This study is a great example of addressing an intractable problem by the creative use of AI using different sources of data,” added study coauthor Pamela Davis, the Arline and Curtis Garvin Research Professor at the School of Medicine. “It is our hope that this approach will suggest therapeutic approaches for other difficult problems.”
While this study substantially strengthens the argument for the use of ketamine in treating cocaine-use disorder, the researchers emphasise that additional clinical trials are required to assess ketamine’s potential impact more thoroughly.
The study, funded by the National Institute on Drug Abuse Clinical Trial Network, has been published in the journal Addiction.
The work was conducted at the Center for AI in Drug Discovery by research associate ZhenXiang Gao and medical school student Maria Goreflo, in collaboration with Davis, Winhusen, David Kaelber from MetroHealth and Case Western Reserve and Udi Ghitza from the National Institute on Drug Abuse Clinical Trial Network.
