Trending weight loss drugs such as Ozempic and Wegovy may be highly effective at tackling obesity, but are they also carrying some darker side effects in the long run? A new study shows these medications could trigger brain changes linked to depression.
Ozempic and Wegovy are both what’s known as glucagon-like peptide-1 receptor agonists (GLP-1 drugs), so named because they mimic the natural GLP-1 hormone found in the brain, gut, and pancreas. It helps to control blood sugar and appetite, just like the natural hormone.
We also know these GLP-1 drugs influence parts of the brain rich in dopamine, a key chemical in feelings of pleasure and reward, and are already being looked at as ways of treating alcohol and drug addiction, in addition to obesity and diabetes.
In this newly published paper, an international team of researchers has connected the dopamine disruption driven by GLP-1 drugs to potential depression and suicide ideation in people genetically disposed to hypodopaminergia – low dopamine function.
“The paper provides critical evidence for re-evaluating the widespread use of GLP-1 drugs,” says psychiatrist Mark Gold of the Washington University School of Medicine.
“The FDA and other regulatory agencies should carefully consider our findings when it comes to labeling and monitoring these drugs.”
Before we get ahead of ourselves, we should note that this study relies on computer modeling: there were no lab tests or clinical trials done here. Instead, the researchers ran an analysis of GLP-1 drug genetic pathways linked to depression and suicide risk.
They found interaction with the activity of certain genes – including DRD3, BDNF, CREB1, CRH, IL6, and DPP4. These genes check two boxes: they’re associated with dopamine signaling and mood, and GLP-1 drugs could influence their behavior.
This isn’t the first time this connection has been made, either. The European Medicines Agency is already investigating how people taking GLP-1 drugs may have increased thoughts of suicide and self-harm, based on reports from health professionals in Iceland.
In 2024, a review of side effects from GLP-1 drugs found that 1.2 percent were adverse psychiatric events, with depression the most commonly reported, followed by anxiety and suicidal ideation.
This research is still at its earliest stages, so we shouldn’t jump to any conclusions yet, but given how different we all are in our genetics, our environments, and our reactions to drugs, it’s crucial to find out as much as possible about potential GLP-1 drug side effects.
These treatments are still relatively new, and with each piece of research we’re understanding more about how their chronic use may impact our health in the long run, whether that’s how they can cut down on cravings or offer cardiovascular health benefits.
“While GLP1-R drugs hold promise for treating addictive and behavioral disorders, we must remain vigilant about their potential harm,” says psychiatrist Igor Elman of Harvard University.
“This study is not intended to break the bubble of hope but to add a layer of precaution in their over-prescription.”
The research has been published in Current Neuropharmacology.
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