Summary: The weight-loss revolution is moving from the waistline to the wine cellar. A new study reveals that tirzepatide—the active ingredient in Mounjaro—significantly reduces alcohol consumption and prevents relapse-like behavior.
In animal models, voluntary alcohol intake dropped by more than half, and binge-drinking episodes were drastically curtailed. The drug appears to work by blunting the brain’s reward system, specifically targeting dopamine levels in the lateral septum, effectively muting the “buzz” that makes alcohol addictive.
Key Facts
- 50% Reduction: Animals treated with tirzepatide consumed less than half the alcohol of the control group.
- Relapse Prevention: After a period of sobriety, animals on the drug did not experience the typical “rebound” drinking; instead, their consumption remained low.
- Dopamine Blunting: Tirzepatide attenuates alcohol-induced dopamine spikes in the brain’s reward system, particularly in the lateral septum (a region linked to motivation and addiction).
- Dual Action: Unlike semaglutide (Ozempic), which targets only GLP-1, tirzepatide is a dual agonist (GIP and GLP-1), which may provide a more robust effect on addictive behaviors.
- Epigenetic Clues: The study identified changes in histone-related proteins (which turn genes on/off) in the brain, suggesting the drug may cause long-term biological shifts in how the brain processes rewards.
Source: University of Gothenburg
Researchers at the University of Gothenburg have previously demonstrated that semaglutide, found in the diabetes and weight-loss drugs Ozempic and Wegovy, reduces alcohol consumption in rats.
In the current study, published in the journal eBioMedicine, the focus shifts to tirzepatide and Mounjaro.
Voluntary alcohol consumption fell by more than half in animals treated with tirzepatide. The drug also prevented relapse-like drinking. After a period without alcohol, the animals did not increase their drinking; instead, it decreased compared with earlier levels.
“We observed clear and robust reductions in long-term alcohol consumption, binge-like drinking, and relapse-like drinking in both male and female animals. What makes this study particularly compelling is that it also provides new insight into how this class of drugs may influence the brain’s reward system,” says Christian Edvardsson, a doctoral student in pharmacology at the Sahlgrenska Academy, University of Gothenburg.
Blunting alcohol’s effects
Tirzepatide, the first medication to act as a dual agonist at receptors for the satiety hormones GIP and GLP-1, is approved for the treatment of type 2 diabetes and is widely used in clinical practice. Because its safety profile has been extensively studied, this may facilitate future research into its potential role in alcohol use disorder.
In the study, the researchers found that tirzepatide attenuated alcohol-induced effects on dopamine, a key neurotransmitter in the brain’s reward system that contributes to alcohol’s reinforcing properties. The effect appears to be mediated, at least in part, through the lateral septum, a brain region linked to motivation, reward, and relapse in both animals and humans.
The findings offer a possible neurobiological explanation for earlier observations that similar medications can reduce alcohol consumption and craving.
In the lateral septum, the researchers also identified changes in histone-related proteins that influence whether genes are switched on or off. Alterations in these proteins have previously been associated with substance use and addiction. However, the study does not show that these changes in themselves cause the reduction in alcohol consumption. Rather, the results suggest that they may form part of the biological mechanisms affected by tirzepatide.
Future treatment options
The study was conducted by researchers at the University of Gothenburg in collaboration with colleagues at the Medical University of South Carolina. It combined intake and behavioral tests with measurements of neurotransmitter levels in the brain and molecular analyses.
“This is not yet a new treatment for alcohol use disorder. But the findings reinforce the view that drugs targeting these neural systems may be relevant to investigate further as potential treatment options,” says Elisabet Jerlhag Holm, Professor of Pharmacology at the Sahlgrenska Academy, University of Gothenburg.
Key Questions Answered:
A: It’s a massive lead, but not a cure yet. While the animal data is “robust,” human trials are needed to confirm the effect. However, because Mounjaro is already FDA-approved for diabetes and weight loss, its safety profile is well-known, which could speed up its approval for alcohol use disorder.
A: Addiction and appetite share the same “reward” hardware in the brain. By quieting the hormones that make you crave food, these drugs also seem to quiet the dopamine-driven urge to drink.
A: Not necessarily. It just makes the brain less interested in the reward. The study showed that the “relapse-like” behavior—the desperate urge to drink after being sober—was effectively switched off.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuropharmacology and AUD research news
Author: Peter Larsson
Source: University of Gothenburg
Contact: Peter Larsson – University of Gothenburg
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Tirzepatide reduces alcohol drinking and relapse-like behaviours in rodents” by Christian E. Edvardsson, Louise Adermark, Sam Gottlieb, Safana Alfreji, Thaynnam A. Emous, Yomna Gouda, Annika Thorsell, Milica Vujičić, Cajsa Aranäs, Anna Benrick, Ingrid Wernstedt Asterholm, Marcelo F. Lopez, Howard C. Becker, and Elisabet Jerlhag. eBioMedicine
DOI:10.1016/j.ebiom.2025.106119
Abstract
Tirzepatide reduces alcohol drinking and relapse-like behaviours in rodents
Background
Alcohol use disorder (AUD) remains a major public health problem, with few effective medications currently available. However, peptides of the gut-brain axis appear to offer promising therapeutic targets for AUD as they influence the mesolimbic reward circuitry.
Methods
Here, we examined the effects of tirzepatide, a long-acting dual glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist approved for diabetes and obesity, using behavioural assays (locomotor activity and conditioned place preference), alcohol intake paradigms (intermittent access two-bottle choice, drinking in the dark and the alcohol deprivation effect), and molecular analyses (microdialysis, electrophysiology and proteomics) in rodents.
Findings
First, tirzepatide effectively attenuated the rewarding properties of alcohol, measured through locomotor stimulation, conditioned place preference, and accumbal dopamine release (P < 0.001). Subsequently, this GLP-1R/GIPR agonist dose-dependently reduced voluntary alcohol consumption (P < 0.001), prevented binge (P < 0.01) and relapse-like drinking (P < 0.001), and maintained efficacy during repeated administration (P < 0.001).
Finally, tirzepatide induced sustained synaptic depression in the lateral septum (P < 0.05) and further altered histone regulatory proteins in this region (P < 0.05), suggesting a potential neural substrate for its effects. Moreover, the GLP-1R/GIPR agonist affected metabolic parameters including body weight (P < 0.001), adipose tissue mass (P < 0.01), hepatic triglycerides (P < 0.01) and circulating pro-inflammatory cytokines (P < 0.05).
Interpretation
Together, our findings suggest tirzepatide modulates alcohol-related behaviours through reward-related mechanisms while also affecting physiological consequences associated with long-term alcohol use. Given tirzepatide’s established clinical use and the consistency of effects observed here, these results support further investigation for treating AUD and associated complications.
