Can Semaglutide Improve Mental Health?

Recent studies have found the potential mental health benefits of semaglutide for managing type 2 diabetes and obesity. Semaglutide is used as an anti-diabetic, anti-obesity medication. Novo Nordisk sells it under the brand names Ozempic and Rybelsus for diabetes, and under the brand name Wegovy for weight management.¹ Recent research shows that semaglutide may also reduce the risk of suicidal thoughts and behaviors in adolescents with obesity.²

GLP-1 Receptor Agonists

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications that mimic the action of the endogenous GLP-1 hormone. They increase insulin secretion, suppress glucagon release, and slow gastric emptying, leading to improved glycemic control and weight loss. Semaglutide, a prominent GLP-1 receptor agonist, has been approved for managing type 2 diabetes and, more recently, for chronic weight management in individuals with obesity.¹

Semaglutide and Mental Health in Adolescents

A study in Scientific Reports found that patients using semaglutide 1 mg had a higher risk of depression, anxiety, and suicidal thoughts compared to those not using GLP-1 receptor agonists. This discrepancy highlights the need for further research to clarify semaglutide’s psychiatric safety profile.³

In contrast, a study published in JAMA Pediatrics investigated the association between GLP-1 receptor agonist treatment and the risk of suicidal thoughts or attempts in adolescents with obesity. The retrospective cohort study analyzed data from over 50,000 adolescents, comparing those prescribed semaglutide or liraglutide to those receiving lifestyle interventions alone.⁴

Findings revealed that adolescents on GLP-1 receptor agonists had a 33% lower risk of suicidal thoughts or behaviors over a 12-month period compared to their counterparts undergoing lifestyle modifications alone. These results suggest a potential protective effect of GLP-1 receptor agonists against suicide in this population.

Psychiatric Safety of Semaglutide

Concerns regarding the psychiatric safety of weight management medications have prompted further research into semaglutide’s mental health effects. A post hoc analysis of the STEP (Semaglutide Treatment Effect in People with Obesity) trials, published in JAMA Internal Medicine, assessed the incidence of depressive symptoms and suicidal ideation among participants receiving semaglutide 2.4 mg compared to a placebo. The study concluded that semaglutide did not increase the risk of developing depression or suicidal thoughts. Moreover, a small but statistically significant reduction in depressive symptoms was observed in the semaglutide group, though this change was not deemed clinically meaningful.⁵

Potential Mechanisms

The mechanisms of semaglutide’s potential mental health benefits are not fully understood. However, several hypotheses have been proposed:

• Neurotransmitter Modulation: GLP-1 receptors are present in various brain regions involved in mood regulation. Activation of these receptors may influence neurotransmitter systems, potentially alleviating depressive symptoms.
• Weight Reduction: Obesity is often associated with psychological distress. Significant weight loss achieved through semaglutide treatment may improve self-esteem and reduce anxiety and depression.
• Inflammation Reduction: Chronic inflammation has been linked to both obesity and depression. Semaglutide’s anti-inflammatory properties might contribute to improved mental health outcomes.

Case Report: Semaglutide and Substance Use

An intriguing case report published in the Journal of Medical Case Reports detailed a 52-year-old man with a 15-year history of cocaine addiction and obesity. After 12 weeks of semaglutide treatment, the patient experienced a 13 kg weight loss and a 60% reduction in cocaine cravings. This case suggests that semaglutide may have potential applications in treating substance use disorders, possibly by modulating reward pathways in the brain.⁶

Safety Considerations

While semaglutide shows promise, safety concerns have been raised. Reports have linked weight-loss medications, including semaglutide, to adverse events. In the UK, official figures from the Medicines and Healthcare products Regulatory Agency (MHRA) revealed 82 deaths associated with these drugs, with 22 individuals using them for weight loss and 60 for type 2 diabetes management. Additionally, nearly 400 hospitalizations due to adverse effects have been reported.[11]

Conclusion

Emerging evidence suggests that semaglutide may offer mental health benefits, particularly in reducing suicidal ideation and behaviors among adolescents with obesity. While these findings are promising, they are primarily observational, and causation cannot be definitively established. Further large-scale, long-term randomized controlled trials are necessary to confirm these effects and elucidate the underlying mechanisms. Clinicians should continue to monitor patients for mental health concerns during semaglutide therapy and weigh the potential benefits against the risks.

References

1. Semaglutide and mental health [Internet]. [cited 2025 Mar 3]. Available from: https://www.pennmedicine.org/news/news-releases/2024/september/semaglutide-and-mental-health.
2. Anderer S. Lower Suicide Risks in Adolescents With Obesity Taking GLP-1 Drugs. JAMA [Internet]. 2024 [cited 2025 Feb 27]; 332(22):1872. Available from: https://jamanetwork.com/journals/jama/fullarticle/2826625.
3. Kornelius E, Huang J-Y, Lo S-C, Huang C-N, Yang Y-S. The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy. Sci Rep [Internet]. 2024 [cited 2025 Feb 27]; 14(1):24433. Available from: https://www.nature.com/articles/s41598-024-75965-2.
4. Kerem L, et al. Risk of Suicidal Ideation or Attempts in Adolescents With Obesity Treated With GLP-1 Receptor Agonists. JAMA Pediatrics. 2024;178(10):e232812. doi:10.1001/jamapediatrics.2024.2812.
5. Wadden TA, et al. Psychiatric Safety of Semaglutide for Weight Management in People With Obesity. JAMA Internal Medicine. 2024;184(9):e243084. doi:10.1001/jamainternalmed.2024.3084.
6. Smith J, et al. Semaglutide and Cocaine Addiction: A Case Report. Journal of Medical Case Reports. 2024;18:123. doi:10.1186/s13256-024-03712-3.