Ozempic® & Addiction: How GLP-1s May Work in the Brain

Medically reviewed by: Kristin Baier, MD

GLP-1 medications like Ozempic® (semaglutide), Wegovy® (semaglutide), and Mounjaro® (tirzepatide) are by now well-known for their efficacy in managing blood sugar and weight. Recent research, however, reveals that these drugs may reduce cravings beyond food—even showing potential in the treatment of alcohol use disorder and drug dependence. 

This discovery points to the medication’s potentially more profound effect on the brain’s reward pathways, making GLP-1s a promising area of study for substance use disorders. Read on to learn more about the research and what it tells us. 

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How GLP-1s affect the brain: A focus on reward pathways

Earlier clinical studies have found that GLP-1 drugs (glucagon-like peptide-1 receptor agonists) work by mimicking our natural gut hormones (glucagon-like peptide-1s, among others) that regulate blood sugar levels and signal fullness. This helps to curb appetite and slow the movement of food through the digestive system. 

Some individuals who struggle with weight or who have type 2 diabetes may produce fewer natural GLP-1s, or those that they produce may be less effective. For them, GLP-1 medication acts as a boost and might help lower the body’s set point—the weight one’s body fights to maintain—while regulating blood sugar and insulin response. 

It turns out, however, that GLP-1 drugs have effects that go beyond just this mechanism, and may be more complex than originally suspected: 

New research shows that these medications can also access GLP-1 receptors within the brain’s mesolimbic system, an area responsible for regulating both pleasure and impulse control. By reaching these brain regions, GLP-1s may reduce not only food intake but also help curb cravings tied to addiction, including those for alcohol and opioids.

A recent, widely-circulated article published by The Atlantic discussed the research and its potential impact for those struggling with drug and alcohol cravings. As author Sarah Zhang highlights in “The Science Behind Ozempic Was Wrong,” GLP-1 receptor agonist medications are further-reaching than their naturally-produced counterparts—and thus may suppress certain addictive and compulsive behaviors, not just appetite. 

“By indiscriminately flooding the body with long-lasting molecules, the injections likely allow engineered GLP-1 drugs to penetrate parts of the body that the natural gut hormone cannot—namely, deep in the brain,” Zhang explains. 

The potential of GLP-1 medications for treating addiction presents exciting new avenues for both research and treatment, yet it raises several critical questions that warrant further exploration:

One pressing area of investigation is understanding how GLP-1s might impact different types of addiction. Thus far, only nicotine, alcohol and opioid addiction have been studied. Another, and perhaps more significant, is the long-term impact of GLP-1 therapy on brain pathways. Scientists still need to determine the effects of prolonged GLP-1 receptor activation in these areas.

Let’s take a closer look at the research to date. 

GLP-1 drugs for strong urges like alcohol: The growing body of evidence

In her Atlantic article, Zhang cites an influential study from the medical journal Addiction, published October 2024, which demonstrated a 50% reduction in alcohol intoxication and a 40% decrease in opioid overdose among individuals taking either combined GIP/GLP-1 (such as Mounjaro®, the brand name for tirzepatide) or GLP-1 (such as Wegovy® or Ozempic®, brand names for semaglutide) prescriptions. 

The large-scale observational study examined more than 500,000 individuals with opioid and alcohol use disorders. It found that the protective effects of combined GIP-GLP-1 and/or GLP-1 medications were consistent across subgroups, “including patients with comorbid type 2 diabetes and obesity.”

The authors of this study suggest that GLP-1s may reduce the urge for substances like alcohol and opioids by modulating reward processing in the brain. Specifically, GLP-1 receptors in areas like the nucleus accumbens and the ventral tegmental area are believed to alter dopamine transmission—a neurotransmitter critical to reward and pleasure. 

Earlier research supports these findings: A 2021 review published in the British Journal of Pharmacology highlighted studies where liraglutide and semaglutide reduced alcohol consumption and drug-seeking behaviors in rodents. Here, too, scientists pointed to GLP-1 medications’ regulation of dopamine activity in the mesolimbic system. This area is thought to create a “brake” on the excessive motivation for alcohol, essentially blunting the intense drive associated with alcohol-seeking behavior. 

The authors of the review also theorize that GLP-1s might reduce stress-related withdrawal symptoms by activating receptors in the nucleus tractus solitarius, a brainstem area tied to physiological stress responses, potentially making it easier for individuals to abstain long-term​.

Research on GLP-1 drugs has also expanded into nicotine addiction. A pilot study published in Nicotine & Tobacco Research tested exenatide, a since-discontinued GLP-1, as an adjunct to nicotine replacement therapy (NRT). 

Participants in the study showed an encouraging 46% cessation rate with exenatide plus NRT (using a nicotine patch) compared to 27% with NRT alone, suggesting that GLP-1 drugs could support smoking cessation by addressing multiple addictive substances in ways that standard treatments alone have not achieved. Participants also experienced reduced cravings and reduced weight gain post-nicotine cessation. 

Across these studies, authors agree that GLP-1 medications’ influence on the brain’s dopamine-driven reward systems is likely central to their potential in addiction treatment. By modulating these pathways, GLP-1 drugs could offer a powerful mechanism to reduce cravings, weaken the reward feedback loop, and support sustained abstinence.

The Calibrate approach: Integrating GLP-1s for sustainable habit change

Calibrate’s Metabolic Reset program leverages the multifaceted effects of GLP-1s as part of a broader strategy to foster sustainable health changes. 

While GLP-1s are proven effective in promoting weight loss by affecting metabolic pathways and reward systems in the brain, Calibrate’s program pairs these effects with a structured curriculum that addresses metabolic health holistically. Clinical trials have shown that, to be maximally effective, GLP-1s must be combined with ILIs (intensive lifestyle interventions)—the formal term for habit change. That’s where many prescription-only services fall short. 

Unlike traditional weight loss approaches, Calibrate is designed to address root causes of metabolic health and support behavior change beyond medication. The comprehensive, science-backed program helps participants rewire their habits for lasting health improvements, utilizing GLP-1s as a supportive tool alongside robust behavior and accountability coaching. 

Through targeted 1:1 coaching and a focus on the Four Pillars of Metabolic Health—food, exercise, sleep, and emotional health—Calibrate guides members toward healthier habits that can be sustained even after stopping GLP-1 medication.

With Calibrate, members experience higher percentage weight loss on average and more significant improvements in other health markers (such as A1c) than that seen in clinical trials of GLP-1 drugs Ozempic®, Wegovy®, and others. Learn more. 

GLP-1s and the potential for future addiction therapies

The therapeutic promise of GLP-1s extends beyond metabolic health. Novo Nordisk and other companies are exploring GLP-1 drugs’ potential to reduce alcohol consumption and treat conditions such as alcoholic liver disease and Alzheimer’s. These ongoing trials could broaden the application of GLP-1s, potentially leading to new therapies for various addiction and mental health disorders​.

All told, as new research continues to emerge, GLP-1s are reshaping how the world thinks about addiction, obesity, and metabolic health. Calibrate’s program taps into this potential, using GLP-1s in tandem with personalized coaching and lifestyle changes to support members in achieving not only weight loss but also long-term improvements across multiple health markers. 

Ready to take the first step? Join Calibrate today and start your journey to lasting, sustainable weight loss.

Sources:

• Chopping, D. (2024, October 17). Weight-loss drugs cut drug and alcohol abuse, according to new study. The Wall Street Journal. https://www.wsj.com/health/pharma/weight-loss-drugs-cut-drug-and-alcohol-abuse-according-to-new-study-dc46db68
• Zhang, S. (2024, March 5). The science behind Ozempic was wrong. The Atlantic. https://www.theatlantic.com/health/archive/2024/03/ozempic-glp1-weight-loss-brain-gut/677645/
• Klausen, M. K., Thomsen, M., Wortwein, G., & Fink-Jensen, A. (2021). 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
• Qeadan, F., McCunn, A., & Tingey, B. (2024). The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. Addiction. https://doi.org/10.1111/add.16679
• Yammine, L., Green, C. E., Kosten, T. R., de Dios, C., Suchting, R., Lane, S. D., Verrico, C. D., & Schmitz, J. M. (2021). Exenatide adjunct to nicotine patch facilitates smoking cessation and may reduce post-cessation weight gain: A pilot randomized controlled trial. Nicotine & Tobacco Research, 23(10), 1682–1690. https://doi.org/10.1093/ntr/ntab066