Glucagon-like peptide (GLP-1) receptor agonists like semaglutide and liraglutide are already … More
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The buzz at this year’s American Society of Addiction Medicine (ASAM) Annual Conference was all about GLP-1 receptor agonists (GLP-1 RAs), commonly used as medications for treating obesity. Mainstream media seems to be following suit, with weight loss medication ads dominating the airwaves. In addition to their role in managing obesity and type 2 diabetes, GLP-1s have shown potential in addressing substance use disorders (SUD). Given the numerous questions surrounding safety, effectiveness, and long-term impact, ASAM invited various experts to present the latest findings on the use of GLP-1 RAs in addiction.
As a healthcare professional, even I find it challenging to keep up with the constant stream of anti-obesity medications hitting the market. Popular ones include semaglutide (Ozempic, Wegovy), liraglutide (Victoza), tirzepatide (Mounjaro, Zepbound), dulaglutide (Trulicity), and exenatide (Byetta). While these medications differ in duration, formulation, and other characteristics, they all share a common origin—the Gila monster.
Origin Story Begins with a Venomous Lizard
The Gila monster. Exendin-4, a peptide hormone structurally similar to GLP-1, was discovered in 1991 … More
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In 1991, exendin-4, a peptide hormone found in the venom of the Gila monster, was identified as structurally akin to the human hormone, glucagon-like peptide-1 (GLP-1), as explained by Joji Suzuki, MD, FACLP, director of the Division of Addiction Psychiatry at Brigham and Women’s Hospital. GLP-1s stimulate insulin release but have a very short half-life (1-2 minutes), making them unsuitable for diabetes treatment. On the other hand, the lizard hormone had a much longer half-life (~2.5 hours), prompting further research into enhancing stability, resistance to degradation, and improved binding to the GLP-1 receptor.
Since that initial discovery almost four decades ago, research and publications on GLP-1 RAs have proliferated rapidly, as indicated by data presented by Dr. Suzuki. Liraglutide entered clinical trials in 2000, with exenatide becoming the first FDA-approved GLP-1 analog in 2005. Semaglutide was FDA-approved in 2017 as an injectable treatment for type 2 diabetes under the brand name, Ozempic. In 2022, tirzepatide received approval, and GLP-1 drug sales reached $22 billion that same year.
Role in Addiction
The dopamine neurotransmitter in the brain affects mood and addiction. Activation of the GLP-1 … More
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GLP-1 receptors are abundant in the brain, particularly in the reward centers. Addictive substances such as nicotine, alcohol, and opioids exploit the brain’s reward system to induce excessive dopamine release, the ‘feel-good’ neurotransmitter. Studies have demonstrated that activating the GLP-1 receptor in the brain diminishes dopamine release caused by addictive substances like nicotine and alcohol, leading to reduced cravings and reinforcement. Researchers exploring the impact of GLP-1 agonists in addiction are optimistic.
“For the first time in a long time, we actually have the possibility for a whole new class of medications our patients [with addiction] might benefit from,” shared Dr. Suzuki. He added, “The exciting part is that GLP-1 RAs might benefit a broad range of addictive behaviors including disordered eating or behavioral addictions.”
Nicotine Addiction
Although randomized control trials (RCTs) are limited, promising preclinical data show that liraglutide reduces nicotine withdrawal-induced hyperphagia (excessive hunger) and weight gain. Furthermore, epidemiological studies have indicated that individuals with type 2 diabetes (T2D) using GLP-1 RAs were less likely to be diagnosed with nicotine misuse compared to those using other T2D medications. This patient group also had lower healthcare utilization for tobacco use disorder.
Like all medications, GLP-1 RAs come with potential side effects. Luba Yammine, PhD, associate professor of psychiatry at UTHealth Houston, cautioned the audience about common gastrointestinal symptoms such as nausea, vomiting, and diarrhea, as well as acute kidney injury. There is also an elevated risk of pancreatitis and medullary thyroid cancer.
Despite these risks, Dr. Yammine remains hopeful, especially for individuals struggling with multiple substance addictions: “A substantial proportion of people with SUD use multiple substances. Pending positive outcomes from ongoing and forthcoming RCTs, GLP-1 RA medications may become a pharmacotherapeutic approach for treating polysubstance use.”
GLP-1 acts on several organs including the pancreas, brain, and stomach, affecting insulin release, … More
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Alcohol Addiction
Among all substances, alcohol has been extensively studied in relation to GLP-1 RAs. Michael Weaver, MD, professor of psychiatry at UTHealth Houston, highlighted research indicating that GLP-1 RAs reduced alcohol consumption in alcohol-preferring vervet monkeys, a primate species. Stephanie Weiss, MD, PhD, Assistant Director for Clinical Research, Medication Development Program at NIDA, shared data from the first published clinical trial of GLP-1 RAs in alcohol use disorder: in obese patients with a BMI over 30, exenatide reduced heavy drinking days by 23.6% and decreased total alcohol intake. She also discussed ongoing NIDA-funded clinical trials, including the Semaglutide Therapy for Alcohol Reduction (STAR) study, which is currently enrolling participants.
What About Other Drug Addictions?
Research on cocaine and other drugs is limited, according to Dr. Weaver.
Research on the use of an experimental GLP-1 agonist compound has shown a potential to reduce cocaine self-administration in rats, although it is not FDA-approved. Limited data is available for opioids, with one study indicating that liraglutide (“Victoza”) may decrease heroin self-administration in rats. Experts remain cautious but optimistic, emphasizing the need for further clinical research in this area.
GLP-1 receptor agonists show promise in reducing cravings for addictive substances like … More
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Ethical Issues Regarding GLP-1 Medications
The emergence of GLP-1 RAs raises ethical concerns, including issues related to equitable access. Dr. Nancy Shenoi, an assistant professor of psychiatry at Baylor College of Medicine, highlighted disparities in obesity treatment access in low- and middle-income countries and rural areas. She also noted that only four countries provide insurance coverage for obesity treatment, including Brazil, Canada, Chile, and the U.S. Factors such as Canada’s universal healthcare system and lower diabetes medication costs improve accessibility. Additionally, the 2022 Inflation Reduction Act authorized Medicare to negotiate prices for certain expensive medications without generic alternatives, although no GLP-1 RA is currently included. Dr. Shenoi stressed the importance of considering mental health, citing studies linking liraglutide and semaglutide to suicidal ideation, self-harm, and depression.
Bottom Line
Preliminary data on the use of GLP-1 receptor agonists in addiction treatment shows promise, with potential benefits including reduced mortality, anti-inflammatory effects, and neuroprotection that could be advantageous in chronic substance use disorders associated with neuroinflammation and oxidative stress. Despite these positive findings, experts at the ASAM conference unanimously agreed on the need for more research. Dr. Suzuki emphasized the necessity for rigorous studies to establish the safety and efficacy of GLP-1 agonists, while Dr. Weaver underscored the importance of patience, as results from clinical trials may take years to materialize.
Addiction medicine experts at the 2025 ASAM Annual Conference from L to R: Stephanie Weiss, MD; Joji … More
Lipi Roy, MD, MPH
Furthermore, the importance of utilizing existing anti-addiction medications, such as methadone, buprenorphine, naltrexone, and nicotine replacement therapy, was emphasized by all presenters. Despite their proven effectiveness, these medications are underutilized, with only a fraction of individuals with opioid or alcohol use disorders receiving treatment. It is crucial to maximize the use of these life-saving medications while exploring innovative therapeutic options like GLP-1 receptor agonists.
