GLP-1 Agonists & Addiction: Emerging Research

People taking semaglutide for weight loss or diabetes have been saying something unexpected for years now: they don't just want less food — they want less alcohol, fewer cigarettes, and in some cases, less of whatever substance they'd been struggling with. What started as scattered anecdotes from patients and doctors has turned into one of the most active areas of addiction research in decades.

The idea that a diabetes drug could reshape how the brain processes reward might sound far-fetched. But the science is catching up to the patient reports, and the early results are striking. GLP-1 receptors don't just live in the gut and pancreas. They sit right in the middle of the brain's reward circuitry — and activating them appears to turn down the volume on cravings across the board.

What Are GLP-1 Receptor Agonists?
GLP-1 Receptors in the Brain's Reward System
How GLP-1 Agonists May Reduce Addictive Behavior
Preclinical Evidence: What Animal Studies Show
Clinical Trials: From Anecdotes to Data
Real-World Evidence from Patient Registries
What Patients on Semaglutide Are Reporting
Ongoing and Upcoming Clinical Trials
Limitations and Open Questions
FAQ
The Bottom Line
References

What Are GLP-1 Receptor Agonists? {#what-are-glp-1-receptor-agonists}

GLP-1 (glucagon-like peptide-1) is a hormone your gut produces after eating. It tells your pancreas to release insulin, slows stomach emptying, and signals fullness to your brain. GLP-1 receptor agonists — drugs like semaglutide (Ozempic, Wegovy), liraglutide (Saxenda), tirzepatide (Mounjaro), and exenatide (Byetta) — mimic this natural hormone but last much longer in the body.

These medications were developed for type 2 diabetes and obesity. They work, and they work well. But researchers began noticing something they weren't designed to do: patients were spontaneously reducing their alcohol intake, smoking less, and reporting fewer compulsive behaviors.

The reason may come down to where GLP-1 receptors exist in the brain — and what happens when you activate them.

GLP-1 Receptors in the Brain's Reward System {#glp-1-receptors-in-the-brains-reward-system}

GLP-1 receptors aren't limited to the pancreas and gut. They're found throughout the central nervous system, including in regions that control motivation, pleasure, and reward-seeking behavior. The three most important areas for understanding addiction are:

The ventral tegmental area (VTA) — This small cluster of neurons near the base of the brain is the origin point for dopamine signaling in the reward pathway. It's where "wanting" begins at a neurochemical level.

The nucleus accumbens (NAc) — Downstream from the VTA, this region processes reward signals. It's heavily involved in reinforcing behaviors that feel good, from eating to substance use.

The prefrontal cortex — The brain's decision-making center, involved in impulse control and weighing consequences against immediate gratification.

GLP-1-producing neurons in the nucleus tractus solitarius (NTS) — a brainstem region that processes gut signals — project directly to both the VTA and nucleus accumbens (Alhadeff et al., Journal of Neuroscience, 2012). This means the gut-brain GLP-1 system has a direct line to your reward circuitry.

Single-nuclei transcriptomics studies have confirmed that GLP-1 receptors in the VTA sit primarily on GABA neurons — the brain's main inhibitory cells (Schmidt et al., Science Advances, 2024). This detail matters for understanding the mechanism.

How GLP-1 Agonists May Reduce Addictive Behavior {#how-glp-1-agonists-may-reduce-addictive-behavior}

The proposed mechanism works like this:

GLP-1 receptor activation on VTA GABA neurons — When a GLP-1 agonist binds to receptors on GABA interneurons in the VTA, those inhibitory neurons become more active.
Increased inhibition of dopamine neurons — More active GABA neurons suppress the firing of nearby dopamine neurons that project to the nucleus accumbens.
Reduced dopamine release in the nucleus accumbens — With less dopamine reaching the NAc, the reward signal from substances (or food, or other compulsive behaviors) is blunted.
Dampened reward-seeking behavior — The subjective experience: "I just didn't want it anymore."

In vivo fiber photometry studies — which measure neural activity in real time in living animals — confirmed this sequence. Systemic GLP-1 receptor agonist administration increased VTA GABA neuron activity, decreased VTA dopamine neuron activity, and reduced cocaine-evoked dopamine release in the nucleus accumbens (Schmidt et al., Science Advances, 2024).

There's more going on beyond simple dopamine suppression. GLP-1 receptor activation also appears to:

Reduce glutamatergic tone in the NAc, further dampening reward signaling
Modulate neuroinflammatory pathways — exenatide normalized cocaine-induced NF-kB activity in the NAc (PMC, 2025)
Engage additional brainstem relay circuits — GLP-1 receptors in the laterodorsal tegmental nucleus (LDTg) also inhibit VTA dopamine neurons, providing a second pathway for reducing drug-seeking (Molecular Psychiatry, 2021)

The picture that's forming is multi-layered: GLP-1 agonists don't just flip one switch. They turn down reward signaling through several interconnected pathways.

Preclinical Evidence: What Animal Studies Show {#preclinical-evidence-what-animal-studies-show}

The animal data is extensive and remarkably consistent across substances. A major 2024 systematic review identified 35 preclinical studies examining GLP-1 receptor agonists and addictive behaviors (Frontiers in Pharmacology, 2025).

Alcohol

GLP-1 receptor agonists reduced voluntary alcohol consumption in rodent models, prevented relapse after a period of abstinence, and blunted stress-induced alcohol seeking. Brain imaging showed reduced dopamine release and less activation in reward centers.

Cocaine

Chemogenetic activation of GLP-1-producing NTS neurons that project to the VTA suppressed drug seeking in cocaine-experienced rats. Cocaine use itself was found to decrease plasma GLP-1 levels, suggesting that cocaine may disrupt the brain's natural GLP-1 signaling — and that restoring it with an agonist could counteract cravings (Science Advances, 2024).

Opioids

Several GLP-1 receptor agonists reduced self-administration of heroin, fentanyl, and oxycodone in rodent models. They also reduced reinstatement of drug seeking — the animal equivalent of relapse (Frontiers in Pharmacology, 2025).

Nicotine

Preclinical studies showed that GLP-1 agonists reduced nicotine self-administration, and this finding has now been partially supported by human trial data showing reduced cigarette consumption.

The consistency across drug classes matters. If GLP-1 agonists only worked for one substance, the mechanism might be substance-specific. The fact that they appear to work across alcohol, stimulants, opioids, and nicotine points to a shared reward-pathway mechanism — one that operates at the level of how the brain assigns value to rewarding experiences, rather than at the level of any single drug's pharmacology.

Clinical Trials: From Anecdotes to Data {#clinical-trials-from-anecdotes-to-data}

The UNC Semaglutide-AUD Trial (2025)

The first completed randomized controlled trial of semaglutide for alcohol use disorder (AUD) was led by Christian Hendershot, PhD, at the University of North Carolina School of Medicine. Published in JAMA Psychiatry (2025), this phase 2 trial randomized 48 adults with AUD to receive either semaglutide (starting at 0.25 mg/week, titrated to 1.0 mg) or placebo over 9 weeks.

Key findings:

Semaglutide significantly reduced weekly alcohol craving compared to placebo
Average drinks per drinking day decreased in the semaglutide group
In the final month of treatment, about 40% of semaglutide patients reported zero heavy drinking days, compared to 20% on placebo
Semaglutide did not significantly change the number of drinking vs. abstinent days overall
The drug was well tolerated, with 96% of medication-group participants completing the study
Side effects were typical GLP-1 effects: decreased appetite, GI symptoms, headache

What stood out to the researchers was the magnitude of the effects on craving and heavy drinking — potentially greater than what's typically seen with existing AUD medications, even at the lowest clinical doses of semaglutide.

Semaglutide and Smoking (2024-2025)

Nicotine addiction affects roughly 30 million Americans, and existing cessation therapies (nicotine replacement, varenicline, bupropion) have relapse rates above 60% within a year. A randomized, placebo-controlled trial with 46 smokers found that semaglutide (2.4 mg weekly for 12 weeks) led to measurable reductions in daily cigarette consumption, verified by self-report and carbon monoxide validation (Psychiatrist.com, 2025). The treatment was well-tolerated and not associated with serious adverse events. In the UNC AUD trial, a subgroup of participants who smoked also showed greater reductions in cigarettes per day with semaglutide — a finding that suggests the anti-craving effect spans multiple substances simultaneously, even when the study wasn't designed to test smoking outcomes.

Cannabis Use Disorder

A retrospective cohort study published in Molecular Psychiatry (2024) found an association between semaglutide use and reduced incidence and relapse of cannabis use disorder in real-world populations.

Real-World Evidence from Patient Registries {#real-world-evidence-from-patient-registries}

While randomized trials are the gold standard, several large registry-based studies have provided supporting evidence:

38,454-patient cohort study — Use of GLP-1 receptor agonists was associated with a 54% lower risk for an alcohol-related event compared to DPP-4 inhibitors (HR 0.46; 95% CI, 0.24-0.86) (Diabetes, Obesity and Metabolism, 2025).

227,866-patient observational study — In individuals with AUD, semaglutide and liraglutide were linked to a lower risk of alcohol-related hospitalization than existing AUD medications including acamprosate, disulfiram, and naltrexone (Endocrine Society, 2025).

83,825-patient obesity cohort — Semaglutide compared with other anti-obesity medications was associated with a 50-56% lower risk of both new AUD diagnoses and AUD relapse over 12 months (Nature Communications, 2024).

These are observational studies, which means they can't prove causation. But the consistency of the signal — across different populations, different comparison groups, and different research teams — is hard to ignore.

A notable contrast comes from bariatric surgery research: observational data shows that bariatric surgery patients actually have an increased risk of developing alcohol use disorder post-surgery. GLP-1 receptor agonist therapy shows the opposite pattern. This divergence supports the idea that GLP-1 agonists are doing something specific in the brain beyond just causing weight loss (ScienceDirect, 2024).

What Patients on Semaglutide Are Reporting {#what-patients-on-semaglutide-are-reporting}

The clinical data didn't emerge in a vacuum. Patient reports came first.

As prescriptions for semaglutide and similar medications surged for weight loss and diabetes, anecdotal reports of reduced alcohol use became extremely common. Patients described a sudden loss of interest in drinking — not willpower, not effort, but a genuine change in desire. The drink they used to reach for after work just didn't appeal to them anymore.

Healthcare providers noticed the same pattern. As one group of researchers put it: "Rapidly increasing prescription rates of long-acting GLP-1 agonist medicines like semaglutide have been accompanied by frequent informal reports of reduced alcohol intake and craving by patients" (UNC Health, 2025).

These reports extended beyond alcohol. Patients described reduced interest in:

Cigarettes and nicotine products
Compulsive eating behaviors (beyond the expected appetite suppression)
Gambling urges
Other repetitive, reward-driven behaviors

It's worth noting that anecdotes aren't evidence, and they carry known biases — people who notice dramatic changes are more likely to report them. But the sheer volume and consistency of these reports are what drove researchers to design the formal trials now underway.

Ongoing and Upcoming Clinical Trials {#ongoing-and-upcoming-clinical-trials}

The early-phase results have triggered a wave of larger studies:

Phase 3 trials for AUD — Multiple Phase 3 trials evaluating semaglutide specifically for alcohol use disorder are now underway. These larger studies will assess efficacy, tolerability, and safety in broader populations and over longer treatment periods (ClinicalTrials.gov NCT07218354; NCT07223983).

Post-bariatric surgery AUD prevention — Trials are examining whether semaglutide can prevent AUD in patients after bariatric surgery, a population known to be at elevated risk.

Opioid use disorder studies — Building on the strong preclinical data with heroin, fentanyl, and oxycodone, clinical trials are being designed to test GLP-1 agonists in opioid use disorder.

Multi-substance studies — Broader investigations are looking at GLP-1 agonists across different types of substance use disorders simultaneously.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA) have both signaled strong interest in this research direction. As NIH researchers wrote in Nature Medicine (2023): "GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders."

Limitations and Open Questions {#limitations-and-open-questions}

The research is promising but early. Here's what we don't know yet:

Sample sizes are small. The UNC trial randomized just 48 people. Phase 3 trials with hundreds or thousands of participants are needed before any addiction indication could be considered.

Treatment duration is short. Most studies ran for 8-12 weeks. Addiction is a chronic condition. Whether effects persist over months and years — and what happens when people stop taking the medication — remains unknown.

Optimal dosing is unclear. The UNC trial used low-dose semaglutide (up to 1 mg). The full weight-loss dose is 2.4 mg. Whether higher doses produce stronger anti-craving effects, or whether lower doses are sufficient, hasn't been determined.

Cost is a barrier. Semaglutide costs roughly $1,000-1,300 per month without insurance, and current insurance coverage is limited to diabetes and obesity indications. Even if it works for addiction, access will be a problem unless coverage expands or costs drop.

Mechanism isn't fully mapped. While the dopamine-modulation story is compelling, GLP-1 agonists likely affect multiple neurotransmitter systems. The full picture is still being assembled.

Individual variation is real. Not everyone taking semaglutide reports reduced cravings. Understanding who responds and why is an active area of investigation.

GI side effects may confound results. Nausea and reduced appetite are common side effects. It's possible that feeling unwell contributes to reduced substance use independently of direct brain effects, though craving reductions suggest a central mechanism.

The comparison to existing treatments is incomplete. We don't yet have head-to-head trials comparing semaglutide to naltrexone, acamprosate, or other established addiction medications. Registry data suggests GLP-1 agonists may perform favorably, but observational comparisons can't account for all differences between patient populations. Definitive comparison data will need to come from randomized trials designed for that purpose.

FAQ {#faq}

Is semaglutide approved to treat addiction?

No. As of early 2026, no GLP-1 receptor agonist is approved by the FDA for any addiction or substance use disorder. Semaglutide is approved only for type 2 diabetes (Ozempic) and chronic weight management (Wegovy). Using it for addiction would be off-label. Phase 3 clinical trials are underway, but FDA approval for an addiction indication — if it comes — is likely years away.

Which substances do GLP-1 agonists appear to affect?

Based on current preclinical and clinical evidence, GLP-1 agonists have shown effects on alcohol, nicotine, cocaine, opioids (heroin, fentanyl, oxycodone), and cannabis. There are also anecdotal reports involving gambling and other compulsive behaviors. The broad range of affected substances suggests a shared mechanism involving the brain's reward circuitry rather than substance-specific effects.

How does this compare to existing addiction medications?

Current FDA-approved medications for AUD include naltrexone, acamprosate, and disulfiram. For opioid use disorder, methadone, buprenorphine, and naltrexone are standard. The early data on semaglutide, while from small trials, suggests craving reductions that may be comparable to or greater than existing medications. The once-weekly dosing is also a practical advantage, as adherence is a major challenge in addiction treatment.

Do you have to be overweight for GLP-1 agonists to affect cravings?

The current evidence doesn't suggest that weight is the key factor. The UNC trial participants were not selected for obesity. The mechanism appears to involve direct effects on brain reward circuits rather than weight-loss-mediated changes. However, more research is needed to understand whether BMI, metabolic status, or other factors influence the anti-craving response.

Are there risks to using semaglutide for addiction?

The known side effects of semaglutide include nausea, vomiting, diarrhea, and decreased appetite. More serious but rare risks include pancreatitis and gallbladder problems. For people with active substance use disorders, the interaction between GLP-1 agonists and substance use patterns hasn't been thoroughly studied. This is exactly why controlled clinical trials are necessary before any clinical recommendations can be made.

The Bottom Line {#the-bottom-line}

The connection between GLP-1 receptor agonists and reduced addictive behavior is one of the most unexpected findings in recent pharmacology. The biology makes sense — GLP-1 receptors sit directly in the brain's reward pathways, and activating them dampens dopamine-driven craving. Animal studies show consistent effects across alcohol, cocaine, opioids, and nicotine. The first randomized trial in humans showed that even low-dose semaglutide reduced alcohol craving. Large real-world datasets show lower rates of alcohol-related problems in GLP-1 agonist users.

But we're still in the early chapters of this story. The trials are small, the follow-up is short, and Phase 3 results are years away. No one should take semaglutide specifically for addiction outside of a clinical trial. And existing, proven addiction treatments shouldn't be abandoned in favor of a promising but unproven approach.

What the research does tell us is that the relationship between metabolism, gut hormones, and reward is far more intertwined than anyone expected. The same system that regulates how your body responds to food also helps regulate how your brain responds to drugs, alcohol, and other rewards. Understanding that connection — regardless of where it leads therapeutically — is reshaping how we think about addiction at a biological level.

If the Phase 3 trials confirm what the early data suggests, we may look back on this period as the moment when a class of metabolic drugs accidentally opened a new chapter in addiction medicine. But that story is still being written, and the responsible thing to do is wait for the data before drawing conclusions.

References {#references}

Schmidt HD, et al. An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking. Science Advances. 2024. Link
Hendershot CS, et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2025;82(4):395-405. Link
Wang W, et al. Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Nature Communications. 2024. Link
Scheen AJ. Glucagon-like peptide-1 receptor agonists and alcohol use disorders: an emerging unexpected beneficial effect. Diabetes, Obesity and Metabolism. 2025. Link
Klausen MK, et al. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. British Journal of Pharmacology. 2022. Link
GLP-1 receptor signaling in the laterodorsal tegmental nucleus attenuates cocaine seeking by activating GABAergic circuits that project to the VTA. Molecular Psychiatry. 2021. Link
Potential role of glucagon-like peptide-1 (GLP-1) receptor agonists in substance use disorder: a systematic review of randomized trials. Drug and Alcohol Dependence. 2024. Link
The potential role of GLP-1 receptor agonists in substance use disorders — a systematic review. Frontiers in Pharmacology. 2025. Link
Mechanisms of GLP-1 in modulating craving and addiction: neurobiological and translational insights. Medical Sciences. 2025. Link
GLP-1 therapeutics and their emerging role in alcohol and substance use disorders: an endocrinology primer. PMC. 2025. Link
Alhadeff AL, et al. GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake. Journal of Neuroscience. 2012. Link
GLP-1 analogues in the neurobiology of addiction: translational insights and therapeutic perspectives. PMC. 2025. Link

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