One of the most prominent medical developments in recent years has been the emergence of a class of drugs called glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The best known of these drugs is Ozempic, a diabetes drug that is often prescribed for off-label use as a weight loss aid. A new one study published in the magazine Addiction on October 16 will investigate whether GLP-1 RAs can be effective treatments for substance use disorders (SUDs).
Researchers looked at 100 million anonymized medical records Real-World Data from Oracle Cernera large database with anonymized medical data. The data covered the period January 2014 – which, as the study notes, “coincided with the initial approval of many GLP-1 RA drugs by the US Food and Drug Administration” – to September 2022. The researchers identified data from people with diagnosed addictions – specifically opioid use disorder (OUD) and alcohol use disorder (AUD) – who also happened to be taking a GLP-1 RA for diabetes or weight loss. They then compared the rates of ‘serious outcomes’ – opioid overdoses and acute alcohol intoxications, respectively – with the rates among people in the data set who had OUD or AUD, but not taking a GLP-1 RA. The results appear promising: the rate of opioid overdoses was 40% lower in those taking a GLP-1 RA than in those not taking either of these medications, while the rate of acute alcohol intoxication was 50% lower.
Dr. Fares Qeadan, the paper’s lead author, explains Popular science that opioids and alcohol were chosen for the study because “both… interact with reward pathways in the brain that GLP-1 receptor agonists (RAs) are known to affect, consistent with the hypothesized mechanism of action of these drugs.”
This supposed mode of action involves the brain’s reward pathways, which when activated provide a feeling of pleasure and satisfaction, encouraging a person to repeat the behavior that caused these feelings. “Preliminary research suggests that GLP-1 RAs modulate dopamine in reward pathways,” Qeadan explains. In other words, these drugs appear to work by suppressing the activation of these pathways. This reduces both the urge to perform the behavior in question (the craving) and the feelings of satisfaction that come from fulfilling such an urge.
The trade-off is that in some patients not only are certain behaviors modulated by Ozempic; some patients report what Qeadan calls “a general decrease in pleasure.” In some people, this can worsen symptoms of conditions such as depression anhedonia– a general inability to find joy or pleasure in life – is already a symptom.
There is significant comorbidity between substance use disorders and mental health problems, and as a result Qaedan says that “monitoring mental health outcomes and considering additional psychological support is critical if GLP-1 RAs are to be used for addiction problems, especially in populations at risk for mood disorders. -related side effects.” He also suggests it will be “special”. [important] to understand whether the drugs can selectively dampen drug-related reward without affecting other positive experiences.”
More generally, one of the ongoing questions in addiction problems is how to strike a balance between treating the addiction itself and treating the underlying causes of drug use. Existing treatments for OUD specifically involve switching patients from dangerous short-acting opiates such as diamorphine (heroin) and fentanyl to methadone or buprenorphine, allowing users to slowly wean themselves off opioids while also receiving counseling and psychotherapy.
“Many people with addiction are dealing with underlying mental health or systemic issues,” Qeadan agrees. “Drugs like GLP-1 RAs can reduce compulsion to use substances by dampening reward signals, but they do not directly address these underlying problems. [And] Unlike traditional medication-assisted treatments (MAT) such as methadone or buprenorphine, which provide a gradual taper approach and support harm reduction, GLP-1 RAs would likely be used more frequently to rapidly reduce cravings and dependency behaviors.”
This raises the question of what type of psychological support would be needed for people undergoing a relatively rapid transition from the substance to which they are addicted, and whether existing rehabilitation infrastructure would be able to provide this support. Qeadan says this is a crucial area for future research: “Going forward, research into integrating GLP-1 RAs with psychological support would be invaluable in helping to create a balanced and effective addiction treatment model, one that is both the behavioral and systemic challenges underlying addiction.”
The paper by Qeadan and his colleagues also raised a number of other important questions for future research. Because the study only looked at the frequency of serious events, it remains unclear exactly how GLP-1 RAs lead to a reduction in such events. Researchers aren’t sure whether patients taking these drugs used alcohol or opioids less often, or less heavily, or both.
It’s also unclear what impact switching from GLP-1 RAs would have on people who use them to treat addiction. Although some studies have found that most people prescribed GLP-1 RAs for off-label weight loss use were able maintain a lower weight if they stop taking the drug, other studies have found the opposite. One of the latter studies noted that the findings were “confirming.”[ed] the chronicity of obesity and suggest[ed] continued treatment is needed to maintain improvements in weight and health.” Considering that addictions are also chronic conditions, it seems important to investigate whether coming off a GLP-1 could contribute to relapse rates.
“Our study followed participants for several years,” says Qeadan. “The protective effects of GLP-1 RAs appeared consistent within this time frame. However, we do not yet have data on whether patients may require higher doses over time or how outcomes might change if they switch from GLP-1 RAs. Long-term studies would be valuable to understand whether tolerance develops or whether benefits are maintained without increasing the dose.”
This last point could be the most exciting of all. Although pharmaceutical treatments are already available for OUD and AUD, this is not the case for all medications. In fact, there are no FDA-approved treatments at all for some of the most commonly abused illegal drugs, the most prominent examples of which are cocaine and methamphetamine. Could GLP-1 RAs also be effective for addictions to these drugs?
Qeadan is cautiously optimistic: “The mechanism of GLP-1 RAs in modulating reward and craving behavior may indeed have potential for a range of addictions, potentially expanding the therapeutic applications of these drugs to other substances. [like] cocaine.” However, he warns that “further research is needed [is needed to] investigate whether GLP-1 RAs influence the reward circuits involved in stimulant addiction.”
Ultimately, this study is another first step toward diversifying the available treatment options for addiction. Qeadan says the next step will be clinical trials: “To further our understanding, randomized controlled trials specifically targeting addictions are a top priority. These studies could confirm whether GLP-1 RAs directly reduce substance use, help determine optimal dosing regimens, and establish long-term safety profiles.”
He also suggests several other areas for future research: “Neuroimaging studies would also be valuable to observe changes in the reward circuitry in real time, allowing us to see how GLP-1 RAs influence brain activity associated with craving and addiction. Furthermore, studying the effects of GLP-1 RAs on other forms of addiction, such as stimulant or nicotine dependence, could clarify the broader applicability of these medications and help guide tailored interventions.”