Researchers are exploring the potential of glucagon-like peptide 1 (GLP-1) receptor agonists to treat neuropsychiatric disorders such as cognitive dysfunction and alcohol use disorder, according to a panel held last week at the American Society of Clinical Psychopharmacology’s annual meeting in Phoenix.
GLP-1 receptor agonists such as semaglutide and tirzepatide mimic the effects of GLP-1, a peptide produced in the intestinal mucosa, and are known for leading to remarkable weight loss in both the general population and individuals with antipsychotic-induced weight gain.
GLP-1 medications do not increase resting metabolic rate or promote physical activity, but “they do have a very robust signal in reducing caloric intake,” explained Rodrigo Mansur, M.D., Ph.D., research scientist, psychiatrist at the University Health Network, and assistant professor of psychiatry at the University of Toronto. “Patients tell us, ‘They reduce feelings of hunger, they promote feelings of satiety.’”
These medications are believed to modulate the rewarding aspects of food—and potentially other substances. A recent Phase 2 trial found that weekly low-dose semaglutide significantly reduced the amount of alcohol consumed by adults with alcohol use disorder during a self-administration task taken after four weeks of treatment, according to panelist Christian Hendershot, Ph.D., a professor of population and public health sciences at Keck School of Medicine at the University of Southern California, who conducted the trial with colleagues.
Research on GLP-1 medications in animal models suggest the compounds also have neuroprotective and anti-inflammatory actions, which has led to expanded research on their potential to treat neuropsychiatric disorders, said Greg Nigel, Ph.D., chief of the drug design and development section at the Intramural Research Program at the National Institute on Aging. GLP-1 receptors are found throughout the brain, and studies are showing they may prove valuable in a host of neurodegenerative disorders that are prevalent in late life, such as Parkinson’s and Alzheimer’s disease.
Mansur discussed a recent randomized trial that he and colleagues undertook to explore semaglutide’s potential for improving executive function in individuals with major depressive disorder (MDD), 80% of whom had a lifetime history of suicidality. Over the 16-week trial, Mansur and colleagues found no difference in executive function scores between the semaglutide and placebo groups. However, the researchers did find a statistical improvement in global cognition for semaglutide compared with placebo—suggesting it may work in other cognitive domains.
For related information, see the Psychiatric News article “Award Winner Describes Efforts to Improve Cognition in People With Bipolar Disorder.”
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