The enthusiasm surrounding glucagon-like peptide-1 receptor agonists (GLP-1RAs) has moved beyond diabetes and obesity. Scientists are now investigating whether drugs such as semaglutide and tirzepatide could help treat addiction by reducing cravings and altering the brain circuits involved in reward.
There is a biological rationale for this idea. GLP-1 receptors are present in brain regions involved in reward, motivation, learning, and behavior. Early research suggests that GLP-1RAs may influence some of the same pathways implicated in addictive behavior.
But addiction is more than a biological process. It also has psychological and social dimensions. People may use substances or engage in compulsive behaviors to cope with trauma, loneliness, shame, anxiety, stress, or difficult environments. Recovery can therefore require more than suppressing a craving: it can involve developing new coping mechanisms, rebuilding relationships, changing one’s environment, and learning to live without the behavior that once served a psychological function.
That raises a question that has received less attention amid the excitement over GLP-1 drugs: if a medication reduces the biological urge to use a substance, does that necessarily mean it has treated the addiction? Or has it simply created an opportunity for the person to begin addressing the deeper psychological and social factors underlying the behavior?
There are also unresolved questions about the long-term effects of manipulating neural pathways involved not only in reward and craving, but also in motivation, pleasure, and affect. While current regulatory assessments and randomized trials have not established a causal link between GLP-1RAs and serious psychiatric harms, observational and pharmacovigilance studies have generated signals that warrant further investigation.
A long-running debate
That tension is reflected in a long-running debate over the role of willpower and personal agency in addiction. If addiction is driven largely by changes in brain circuitry, then framing recovery in terms of choice, discipline, or self-control can seem simplistic. But clinicians who work with people in recovery argue that acknowledging addiction’s biological basis does not eliminate the need for personal agency or the psychological work of recovery.
“It is not a matter of willpower or discipline” has become the rallying cry of advocates of prescribing glucagon-like peptide receptor agonists (GLP-1RAs) for addiction. The argument is that these drugs act on the neurobiology of hunger, satiety, cravings, and reward—processes that may operate beyond deliberate self-control.
But Brook McKenzie does not quite agree with this notion. The licensed chemical dependency counselor who has spent over a decade with families and individuals struggling with substance use disorder is convinced that willpower and discipline have a role to play in recovery. The counselor believes the real question isn’t whether willpower or discipline matter, but what they can accomplish. While he notes that these human traits are essential, he adds that “it is not all that is required, but they could open the door to recovery.”
Dr. Lauren Grawert, a double board-certified addiction psychiatrist, similarly argues that recovery requires repeated acts of commitment and accountability.
“It takes discipline and willpower to repeat many of the same challenging decisions: attending therapy sessions, adhering to the medication regimen as ordered by their doctor, avoiding risky behaviors, mending damaged relationships and practicing coping mechanisms to avoid giving into cravings. These types of decision-making require commitment and accountability. There is a need for a middle ground to exist in addiction treatment.”
The debate over willpower, however, is only one part of a larger disagreement about how addiction should be understood. If addiction is viewed primarily through a biological lens, it follows that changing the brain’s reward circuitry could be seen as a powerful way to treat it. But research on addiction has long suggested that biology is only part of the story.
The biological rationale: Why GLP-1s are being studied for addiction
It is not surprising that GLP-1RAs are being investigated for use in addiction. Over the years, this class of medication’s therapeutic use has expanded beyond its initial indication for diabetes to areas such as obesity, renal disease, and cardiovascular disease.
GLP-1 receptors are abundant in the body and are expressed in the kidney, lungs, heart, pancreatic cells, gastrointestinal tract, and the brain. Their presence in the brain has attracted particular interest because addiction involves neural systems responsible for reward, motivation, and behavior.
One of the pharmacological drivers of the research into novel treatments for addiction is the limitations that have been observed with conventional treatments. Pharmacological approaches such as opioid antagonists, dopamine reuptake inhibitors, and nicotinic partial agonists target only specific neurotransmitter pathways involved in reinforcement and craving. However, important gaps in long-term treatment response and relapse prevention remain, highlighting the need to investigate approaches that may address the complex interplay of neurobiological, behavioral, and metabolic processes involved in addiction.
Another major motivation for developing novel treatments for addiction is the high rate of relapse seen with conventional therapies. Current pharmacological treatments are highly effective for many people and work by relieving withdrawal symptoms, reducing cravings, or blocking the rewarding effects of addictive substances. However, addiction is driven by many neurobiological processes, including reward, stress, learning, memory, and executive control, and no existing medication fully addresses all of these mechanisms.
GLP-1 receptor agonists offer a different therapeutic approach. Rather than acting on a single receptor system associated with a specific substance, these drugs appear to influence multiple brain circuits involved in addiction through the gut-brain axis and the mesocorticolimbic reward system. The gut-brain axis is a bidirectional communication network linking the gastrointestinal tract and the central nervous system. It plays a key role in regulating reward processing, motivation, and feeding behavior. Signals from the gut are transmitted to the brain primarily via the vagus nerve, where they are integrated in the nucleus tractus solitarii (NTS), a part of the brain rich in GLP-1-producing neurons and GLP-1 receptors. From the NTS, these signals are relayed to downstream brain regions involved in appetite regulation, energy homeostasis, and behavior.
On the other hand, the mesocorticolimbic system comprises a network of brain parts such as the ventral tegmental area(VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC). These parts play a key role in mediating reward, reinforcement learning, and compulsive drug-seeking. GLP-1RAs are expressed across this circuitry, where their activation modulates dopaminergic, glutamatergic, and GABAergic neurotransmission.
This biological rationale helps explain why researchers are interested in GLP-1RAs. But it does not answer a different question: what happens to the psychological and social dimensions of recovery when treatment focuses primarily on reducing biological urges?
The psychological components of recovery
Before U.S. Army personnel departed Vietnam for home in September 1971, they underwent urine drug screening amid growing concerns that many servicemen had become addicted to heroin during the war. Of the approximately 13,760 enlisted soldiers returning to the United States that month, around 1,400 tested positive for drugs such as opiates, amphetamines, or barbiturates. These screenings laid the foundation for what would become one of the most influential studies on addiction and recovery.
To carry out the study, Lee N. Robins and his colleagues divided the returning soldiers into two groups. The first was a “general” sample of 470 men randomly selected to represent all Army enlisted men returning from Vietnam. The second consisted of 495 men whose urine had tested positive for opiates when they left Vietnam, making them a drug-positive group at higher risk of continued drug use. The researchers attempted to locate and interview participants in both groups after their return to the United States.
Among the 470 men in the general sample, the researchers found that hard-drug use before Vietnam had been uncommon, and less than 1% had ever been addicted to narcotics. During their service in Vietnam, however, nearly half reported using narcotics, and about one-fifth developed physical or psychological dependence. After returning to the United States, about 10% reported some experience with opiates during the following 8 to 12 months, but less than 1% showed signs of opiate dependence.
The findings were different among the 495 men in the drug-positive group. About three-quarters reported that they had been addicted to narcotics while in Vietnam. Yet after returning home, only about one-third reported any experience with opiates, and 7% showed signs of dependence. Many shifted from heroin to other drugs, including amphetamines and barbiturates.
Put together, the results showed a striking decline in heroin use and dependence after the soldiers returned to the United States, even among men who had been using opiates heavily in Vietnam.
The results suggested that environmental change contributed significantly to recovery from addiction. The researchers posited that the decrease in drug intake after Vietnam may be a function of a decline in the drug epidemic in the United States, the men getting old, or the effect of the extraordinary ease of obtaining such drugs in Vietnam. However, they also pointed to the fact that environmental change alone was not responsible for recovery. Other factors such as family support, reduced drug availability, lower heroin purity, higher cost, and the end of wartime stress likely played a role as well.
Robins’ findings underscore an often overlooked factor in addiction treatment: the environment’s influence on both initiation and recovery. This doesn’t diminish the important biological contributions to the disorder, but defining addiction solely through a biological lens is misleading. That nuance helps explain why some critics remain skeptical about positioning GLP-1 receptor agonists as a primary treatment for addiction.
When Robins asked the soldiers whether they had personally known heroin or opium users before Vietnam, 91% knew none, yet 43% eventually used narcotics in Vietnam. The finding highlights once more the important role that the environment can play in shaping addictive behavior. McKenzie explains it this way: “I think there is a tendency to assume that if we can change the brain’s reward system, we’ve solved addiction—I’m not convinced that’s the right framework”.
The licensed therapist believes that the reward pathway matters, but argues that it is one piece of a much larger picture that includes trauma, loneliness, shame, relationships, habits, identity, and environment.
“Recovery isn’t simply the absence of an urge. It’s the presence of new ways to live,” McKenzie added. He explained that if a medication reduces cravings but a person never develops healthier coping skills, relationships, purpose, or accountability, “we’ve treated an important symptom without fully addressing the life that existed around it.”
Therefore, the question is not whether GLP-1RAs might have a role in addiction treatment, but how large that role should be and what other components of recovery must accompany it.
Why GLP-1 drugs might hinder psychosocial recovery
From a psychological perspective, Wildaliz Caro, PhD, believes that treating addiction is more than suppressing cravings. The medical contributor at the Healing Center Cherry Hill, a drug and alcohol rehabilitation center, says treatment must also address what people do with the emotions, thoughts, and circumstances that have contributed to their addictive behaviors. “The primary purpose of most addictions is to serve a psychological function,” Caro explained.
Addictive substances or behaviors can provide temporary relief from distress, distract from anxiety, block memories of trauma, provide comfort, or create a sense of escape. “Reducing the desire to consume a particular substance doesn’t mean removing the need that was being met by consuming that substance,” Caro said.
The licensed clinical psychologist believes this distinction is particularly important when addiction is viewed through a trauma-informed lens. For people who have used drugs, alcohol or other compulsive behaviors to manage overwhelming emotions, reducing the urge to use may be beneficial, but it could also bring long-unaddressed feelings to the surface.
“I would not view this as a failure on behalf of the medication,” Caro said. “Instead, I would view it as a reason to incorporate psychotherapy into the treatment plan, rather than expecting that reducing urges alone will lead to complete recovery.”
Melanie Johnson’s experience with binge eating also points to a deeper question about what may drive compulsive behavior in the first place and why the use of GLP-1RAs might not fully address the issue of addiction. Johnson was diagnosed with binge eating disorder but was initially prescribed Zepbound for obesity and sleep apnea. When asked whether GLP-1 treatment helped her binge eating disorder, she said the effect was almost immediate: “It decreased the food noise, regulated my appetite.”
This happened within a couple of days, she said, and she became more intentional about the type of food she ate and her portion sizes. Before Zepbound, she said, “I was so out of control.”
Her experience seems to align with what some individuals report on forums such as Reddit. Personal accounts from people taking GLP-1RAs for diabetes and obesity describe drinking less, losing interest in alcohol, experiencing fewer cravings or becoming abstinent, and eating less.
“Even if all these effects are attributed to GLP-1RAs, we don’t yet know whether they’ll rebound after discontinuation,” said Phil Smyth, a behavioral health executive at Milestone Treatment Center.
Johnson’s story, however, also illustrates why reducing a behavior may not be the same thing as understanding it. She grew up in America in the 1980s, when she described the prevailing messaging around food and weight as “unhealthy,” much of it coming from both parents and society. Such messages made her think she was fat when, in reality, her weight was normal. As she put it, “gaining weight was a self-fulfilling prophecy.” She said childhood trauma and her need to be in control also contributed.
Her account is a reminder that loss of control over a behavior does not necessarily tell us what is driving it. And that distinction matters when considering GLP-1RAs as potential treatments for addiction.
Even if these drugs can dampen cravings or reduce the urge to engage in addictive behavior, they may not address the psychological, emotional, and environmental factors that helped sustain the behavior in the first place.
The concern is not limited to what researchers and clinicians say about GLP-1RAs. The way these drugs are discussed in the media can also shape how the public understands addiction and what recovery is supposed to look like.
Amid growing enthusiasm for the potential use of GLP-1RAs in addiction treatment, some headlines have framed the drugs in ways that may give readers the impression that their effectiveness is already established. Examples include:
Such headlines can reduce a complicated question to a simple narrative: addiction produces cravings, GLP-1RAs reduce cravings, therefore GLP-1RAs treat addiction. But that framing risks obscuring the other components of recovery. If public discussion focuses heavily on a drug’s ability to suppress cravings, people may come to view recovery primarily as the elimination of an unwanted biological signal rather than a process that can also involve psychotherapy, behavioral change, social support, accountability, relationships, and changes in environment.
This matters because the evidence for GLP-1RAs in addiction remains preliminary. Much of it is observational, anecdotal or at an early stage. Even where randomized evidence is emerging, studies remain relatively small in size and scope and do not yet establish the effectiveness of GLP-1RAs across different substance use disorders.
The danger, then, may not simply be that people overestimate what the drugs can do. A single-story narrative about addiction can also make the biological component appear to be the whole story. That is precisely why behavioral and psychosocial interventions remain important.
As Grawert explains, “There are instances where behavioral therapy is sufficient, especially for those with less severe cases, high levels of motivation, and a stable/positive environment.”
Behavioral therapies such as cognitive behavioral therapy (CBT), motivational approaches and contingency management can help individuals identify personal triggers, tolerate cravings, and establish new habits. She cautions, however, that this should never be viewed as a universal solution for all patients.
The broader point is not that medication and behavioral therapy should compete. Rather, addiction may require a combination of interventions tailored to the individual. A medication may help create the biological space in which recovery becomes more achievable, while psychotherapy, social support, behavioral interventions, and changes in the person’s environment may help make that recovery sustainable.
Long-term neuropsychiatric concerns
Because GLP-1RAs are being investigated for addiction treatment based on their nervous system activity, concerns have emerged about their potential long-term effects on the human psyche. Available data are limited owing to small sample sizes and short follow-up in human trials. Moreover, the same neural pathways through which GLP-1RAs may attenuate addictive behaviors—reward, motivation, and affective processing—are also involved in experiences of sexual desire, pleasure, and meaning. This raises the question of whether chronic GLP-1RA exposure could affect one’s psychological state long term. To explore this issue, we examined the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. The FAERS is a database that contains postmarketing reports of adverse drug events received from manufacturers, consumers, and healthcare professionals.
One FDA pharmacovigilance report concerns a purported link between GLP-1RA use and suicidal ideation. Although the agency’s current assessment concluded that there is no clear causal relationship, citing limited information on many reports and the potential influence of confounding factors, it cautions that a small risk cannot be excluded. This uncertainty stems from the low number of suicidal thoughts or behaviors observed in both GLP-1RAs users and comparator groups. Consequently, the FDA continues to monitor and investigate this safety signal. Similarly, a systematic review and meta-analysis involving more than 107,000 patients found no association when compared to placebo.
Contrary to the FDA conclusion and the systematic review and meta-analysis, a separate observational study by Jisu Park et al. found that GLP-1RAs, when used for weight loss, were associated with higher risks of certain psychiatric and gastrointestinal outcomes when compared with non-users. The psychiatric outcomes included depression and anxiety. This was corroborated by another study by Wei Chen et al. in which 8,240 reports of psychiatric adverse events were analyzed among individuals on GLP-1RA treatment. Findings showed a significant association between GLP-1RAs and the development of specific psychiatric adverse events.
Taken together, the evidence concerning the neuropsychiatric effects of GLP-1RAs remains inconsistent. While randomized clinical trials and regulatory assessments have not demonstrated an increased risk of psychiatric adverse events or suicidality, pharmacovigilance and observational studies have identified signals involving depression, anxiety, and other psychiatric outcomes. Differences in study design, population, follow-up duration, and potential confounding may partly explain these discrepancies. More important, relatively little is known about the consequences of prolonged pharmacological modulation of the neural circuits involved in reward, motivation, and affect. As GLP-1RAs move into investigations for addiction, understanding whether their effects on these circuits remain therapeutically selective, which will be an important area for long-term research.
How independent is the GLP-1 addiction research?
Since researchers first hypothesized that GLP-1RAs might reduce addiction-related cravings, pharmaceutical companies, independent researchers, and government-funded bodies have all become involved in testing the hypothesis.
The SEMALCO study is an example of how, even when a study is not directly funded by industry, the influence of pharmaceutical money often remains. The study was an investigator-initiated trial, funded in part by the Mental Health Services of Copenhagen. In the study, 108 Danish patients were investigated in a 26-week, randomized, placebo-controlled, double-blind clinical trial in an effort to determine if semaglutide would reduce alcohol intake among those with alcohol use disorder and comorbid obesity. The results showed that semaglutide was associated with a reduction in heavy drinking days compared with placebo.
While there was public funding for the study, funding also came from the Novo Nordisk Foundation and Novavi Foundation, two foundations funded by Norvo Nordisk, the pharmaceutical company that markets semaglutide under the names of Ozempic and Wegovy. In addition, some of the investigators on this study, such as Anders Fink-Jensen, had received an unrestricted Novo Nordisk grant for a different study and served on a Novo Nordisk randomized controlled trial advisory panel. Another investigator, Thomas Vilsboll, disclosed advisory/speaker/consulting relationships with both Novo Nordisk and Eli Lilly, which is the other major pharmaceutical company with a GLP-1 product.
However, there is important research being done that is free of such industry influence. A study by the US Department of Veterans Affairs is an example of this. This was a large, prospective observational study involving 606,434 US veterans that investigated whether the initiation of GLP-1RA is linked to lower rates of new alcohol, cannabis, cocaine, nicotine, opioid, and other substance use disorders in people without prior substance use disorders, and to fewer substance use disorder-related adverse clinical outcomes in people who already have a substance use disorder. Among 606,434 US veterans with type 2 diabetes, participants were followed up for up to three years and split into two protocols. Protocol 1 included 524,817 people starting GLP-1RA or sodium-glucose co-transporter 2 (SGLT-2) inhibitors, while protocol 2 included 81,617 such initiators.
Their findings suggested that GLP-1RA use was linked to a lower risk of new substance use disorders and fewer adverse outcomes in people who already had one, suggesting possible roles in both prevention and treatment. The researchers declared that there was no financial relationship between the funders and any organization that may have a financial interest in the submitted work, and no relationships or activities that may have influenced the submitted work within the three-year period of the research.
What would success actually look like?
For Patricia Freebery, a psychotherapist with more than 20 years of experience, specializing in addiction, trauma and emotion-focused somatic therapy, the question of what constitutes successful treatment is just as important as whether a drug would reduce cravings. Recovery in her view, is not just the absence of cravings or substance use, but the restoration of someone’s ability to live a meaningful and self-directed life.
“A successful treatment would result in a return to my authentic self,” she said, describing recovery as being “fully present in mind, body, and spirit,” and connected to oneself, family, and community. It would involve self-agency and accountability, with a person’s behaviors and intentions aligned rather than aligning with external people or substances to maintain emotional and chemical sobriety.
She also described recovery in practical and relational terms: being physically responsive to one’s body, becoming competent in adulthood, and becoming emotionally capable of engaging with others with “curious compassion, clarity, and confidence.” It means being able to tolerate uncertainty, resist becoming consumed by obsessive thoughts, experience joy and creativity, and remain connected to the present.
Ultimately, Freebery said, recovery should leave a person able to honestly say, “I am free”—not merely free from the substance or behavior, but capable of fully appreciating and engaging with their life.
Conclusion
Perhaps this is the central question that should accompany the excitement surrounding GLP-1 drugs and addiction: if we can reduce the urge, have we necessarily treated the addiction?
The answer may not be either medication or the human dimensions of recovery. It may be both. GLP-1RAs could eventually become another useful tool in the treatment of addiction. But their success should ultimately be measured by more than how effectively they suppress a craving.
A successful treatment may also need to help people regain agency, rebuild relationships, develop healthier ways of coping, address the psychological functions that addictive behaviors once served, and return to a meaningful life.
That is why the question surrounding GLP-1RAs is not simply whether they can change the brain. They may be able to. The harder question is whether changing the brain is enough to change the life around it.
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