Scientists have discovered that semaglutide, the widely prescribed diabetes and weight loss medication sold under brand names Ozempic and Wegovy, significantly reduces cocaine-seeking behavior in laboratory animals. The groundbreaking study, published in the September edition of European Neuropsychopharmacology, represents the first preclinical evidence that this GLP-1 receptor agonist could potentially treat cocaine dependency—a condition for which no effective pharmacological treatments currently exist.
Study Design and Key Findings
Researchers from the University of Gothenburg in Sweden and the University of Pennsylvania, led by Professor Elisabet Jerlhag, conducted experiments using male rats trained to self-administer cocaine through a lever-pressing system. An experimental group of 10 animals received semaglutide treatment before being given access to the cocaine dispenser.
The results demonstrated substantial reductions across multiple addiction-related behaviors. Cocaine self-administration dropped by 26% in semaglutide-treated animals compared to controls. More significantly, after a period of abstinence, cocaine-seeking behavior decreased by 62%, while motivation to obtain the drug was reduced by 52%.
"This is the first trial showing Semaglutide's potential as a drug for cocaine dependence," said Professor Jerlhag. "Previous results, both from our group and from other groups, have found that semaglutide can reduce alcohol consumption and craving in both humans and animals, and this work on cocaine seems to reflect these previous findings on alcohol use."
Clinical Context and Unmet Need
The research addresses a critical gap in addiction medicine. Cocaine ranks as the second most popular illegal drug in Europe, with approximately 2.7 million young adults aged 15-34 using it regularly, representing around 2.5% of that population. In the UK, cocaine use is the second highest globally, affecting about 2.7% of adults.
Lead author Cajsa Aranäs, a researcher at the Sahlgrenska Academy, emphasized the clinical significance: "Our results show that an established drug can affect key behaviors behind cocaine addiction. We hope this could open the way for new treatments, but clinical trials are needed before we know if the same effect is seen in patients."
Mechanism and Broader Implications
Semaglutide belongs to the GLP-1 inhibitor class of drugs, which have revolutionized treatment for excess weight and are showing promise in mental health applications. Scientists believe the drug may work by blunting cocaine's ability to raise dopamine levels in the brain, thereby reducing the sense of reward, though the exact mechanism remains incompletely understood.
Professor Christian Hendershot from the Institute for Addiction at the Keck School of Medicine, University of Southern California, who was not involved in the research, provided independent commentary: "This is a carefully conducted study that provides additional evidence that GLP-1 receptor agonists can reduce cocaine reinforcement. These findings have clinical implications given the challenges identifying medications for stimulant use disorder, and the increasing clinical use of semaglutide in many areas of the world."
Path Forward
Professor Jerlhag acknowledged the limitations of the current work while highlighting its potential: "This is animal work, so at the moment, we can't say that we have anywhere near a viable treatment for human cocaine dependency. We need a bigger study to confirm these results, and then we need to see if the findings also apply to humans. However, these results are very promising, underlining the need for human studies, especially since there are no existing pharmacological treatments for cocaine dependency."
Professor Elisabet Jerlhag noted the urgent clinical need: "There is a pressing demand for treatments for cocaine addiction. Currently, no drugs are available, and the risk of relapse is very high. If these findings in rats hold up in clinical trials, semaglutide could become the first pharmacological option to complement psychological therapy and support programs."
The findings encourage clinical trials of GLP-1 receptor agonists for stimulant use disorder, potentially opening a new therapeutic avenue for a condition that has long lacked effective pharmacological interventions.
