We’re switching things up today ;

Instead of bringing you a round-up of the latest & greatest findings in the world of science, we’re doing a deep-dive on one trending topic: Ozempic.

Ozempic has jumped off of pharmacy shelves and into the public consciousness over the last few years, but recently it’s Ozempic’s potential benefits in brain health that have been making headlines.

Some studies have found that the anti-inflammatory properties of GLP-1 agonists (the chemical compound behind Ozempic) may be able to protect our brains against Alzheimers disease, and other forms of cognitive degeneration. Beyond this, the ability of GLP-1 agonists to curb cravings in food, may even reduce cravings found in some forms of addiction.

So, is this wonder-drug too good to be true? Like us, you might be wondering - what’s the catch?

This week we’ll be breaking down the emerging science behind these theories, and next week we’ll delve into the details around what these off-label uses (particularly for weight loss) mean for us as a society, and what effects drugs like Ozempic may be having on disordered eating behaviours and self-esteem beliefs.

You may have heard of GLP-1 agonist drugs by a few different names; Ozempic Wegovy, Saxenda, Mounjaro… as time goes on, so does the growing list of similar drugs!

These names are essentially just brand names for a range of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. GLP-1 agonists are compounds which work by mimicking a natural gut hormone that regulates appetite and blood sugar. Pharmaceutical companies originally developed GLP-1 agonists as a way to mimic this hormone's effects for treating diabetes and obesity. Drugs like liraglutide (Saxenda), semaglutide (Wegovy, Ozempic), and tirzepatide (Mounjaro) work by activating the GLP-1 receptors in our bodies.

While GLP-1 agonist drugs (under their many aliases) were initially developed as a treatment for type 2 diabetes, it has sparked some pretty heated debates over recent years as its popularity for ‘off-label’ uses (primarily for weight loss) has led to such high demand that many of the pharmaceutical companies that make these drugs have had shortages. The Therapeutic Good Administration of Australia (TGA) even went as far as to recommend Aussie doctors do not prescribe semaglutide to any new patients - even patients who actually have type 2 diabetes (Source: TGA).

In recent studies that have looked at various side-effects of GLP-1 agonists, researchers found evidence that they had pretty profound anti-inflammatory effects throughout the body, including in the brain (Source: Journal of Pharmacological Research; 1, 2).

Inflammation is a key driver of neurodegenerative diseases like Alzheimer's and Parkinson's. Type 2 diabetes and insulin resistance have also been associated with increased neurodegenerative disease risk due to these inflammatory factors.

By reducing brain inflammation, these weight loss drugs may help clear a path for new neuron growth and protect against the buildup of toxic proteins involved in these diseases. Alzheimers is also linked to the buildup of proteins called amyloid and tau in the brain. GLP-1 drugs have shown potential to reduce these protein deposits. Additionally, they may have anti-inflammatory effects that protect brain cells. While research is still preliminary, these findings raise hope for Ozempic as a preventative measure for Alzheimer's (Source: Cell Metabolism).

A review showed that there are currently around 20 early clinical trials exploring the potential of GLP-1 agonists as treatments for Alzheimer's and Parkinson's based on these anti-inflammatory and neuro-protective benefits (Source: Journal of Pharmacological Research). This space is evidently sparking a lot of researcher interest, and we will definitely be keeping an eye on the findings!

Researchers are also beginning to speculate that the anti-inflammatory powers of GLP-1 agonists could make them useful for other inflammation-driven conditions, including addiction (Source: Frontiers in Neuropsychology, Frontiers in Pharmacology, British Journal of Pharmacology). Certain addictive substances can trigger brain inflammation, which is thought to drive the compulsive drug-seeking behaviours that underpin substance use disorders.

One other potential model for how GLP-1 agonists could reduce addictive behaviour, is in the way these drugs weaken the association between food and pleasure. This model could also apply to the pleasure seeking behaviours associated with alcohol and other drug use.

Research in this area is emerging, however human studies into illicit substances are (naturally) highly regulated, and difficult to undertake. One current study has followed specific cases to investigate the effect of GLP-1 agonists in treating cocaine use disorder (Source: Addiction Medicine) Another study observed a reduction in the incidence and relapse of cannabis use disorder in a large dataset of patients who had used semaglutide (Source: Molecular Psychiatry), however more human trials are needed to determine if these benefits are present with different substances.

In sum, by reducing brain inflammation GLP-1 agonists may be able to disrupt the vicious cycle of addiction and cravings. While this is still highly experimental, it poses an exciting new frontier for repurposing these drugs to combat substance use disorders.

While it’s easy to get excited about the positive side effects of a treatment, it’s critical to remember that these applications are still under investigation. GLP-1 agonists are currently only approved for type 2 diabetes and some weight management cases. Using these drugs to treat addiction and Alzheimer's disease are in very early stages of research. Early research also indicates that the benefits of the drugs will end once someone stops taking them - which could pose other concerns about sustainability and supply.

More studies are needed to determine long-term efficacy and safety for these new uses.

As with any medication, the only recommended use is the one that a doctor has specifically discussed with you and aligns with your health needs.

Next week, we’ll also be taking a look at some of the negative effects of these treatments, specifically when it comes to body image, self-esteem and eating disorders.

That’s all ;

for this edition of Melon Mag.

Keep an eye on your inbox next week for the next in this series on Ozempic and the brain.

We’d love to know if you prefer this format so please take a second to hit the survey below and let us know your thoughts!

We’re always open to suggestions on what science questions you have, so drop us a line and we’ll investigate for you!

💙 The MM Team

REFERENCES

• https://www.tga.gov.au/safety/shortages/information-about-major-medicine-shortages/about-ozempic-semaglutide-shortage-2022-and-2023

• Jerlhag, E. (2023). The therapeutic potential of glucagon-like peptide-1 for persons with addictions based on findings from preclinical and clinical studies. Frontiers in Pharmacology, 14. https://doi.org/10.3389/fphar.2023.1063033

• Klausen, M. K., Thomsen, M., Wörtwein, G., & Fink‐Jensen, A. (2022). The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders. British Journal of Pharmacology, 179(4), 625–641. https://doi.org/10.1111/bph.15677

• Kopp, K. O., Glotfelty, E. J., Li, Y., & Greig, N. H. (2022). Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment. Pharmacological Research, 186, 106550. https://doi.org/10.1016/j.phrs.2022.106550

• Wang, W. Y., Volkow, N. D., Berger, N. A., Davis, P. B., Kaelber, D. C., & Xu, R. (2024). Association of semaglutide with reduced incidence and relapse of cannabis use disorder in real-world populations: a retrospective cohort study. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02498-5

• Wong, C., McLean, B. A., Baggio, L. L., Koehler, J. A., Hammoud, R., Rittig, N., Yabut, J. M., Seeley, R. J., Brown, T. J., & Drucker, D. J. (2024). Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation. Cell Metabolism, 36(1), 130-143.e5. https://doi.org/10.1016/j.cmet.2023.11.009

• Yammine, L., Balderas, J., Weaver, M. F., & Schmitz, J. M. (2023). Feasibility of exenatide, a GLP-1R agonist, for treating cocaine use disorder: a case series study. Journal of Addiction Medicine, 17(4), 481–484. https://doi.org/10.1097/adm.0000000000001147

• Yoon, G., Kim, Y., & Song, J. S. (2020). Glucagon-like peptide-1 suppresses neuroinflammation and improves neural structure. Pharmacological Research, 152, 104615. https://doi.org/10.1016/j.phrs.2019.104615