"Miracle Drug" for Weight Loss Treats Opioid Addiction?

News

“Miracle Drug” for Weight Loss Treats Opioid Addiction?

“Miracle Drug” for Weight Loss Treats Opioid Addiction?

A small randomized controlled trial testing the GLP-1 drug liraglutide against opioid addiction showed that patients using liraglutide had a 30% reduction in craving for opioid drugs. Researchers believe that larger studies are necessary.

According to the biopharmaceutical industry media STAT, a small randomized controlled trial testing the GLP-1 drug liraglutide against opioid addiction showed that patients using liraglutide had a 30% reduction in craving for opioid drugs. This effect was evident even at the lowest dose of liraglutide.

The research results were presented on the same day at the American Association for the Advancement of Science (AAAS) conference.

Liraglutide is a first-generation GLP-1 receptor agonist developed by the Danish multinational pharmaceutical company Novo Nordisk (NVO.US). It has two products: Victoza for diabetes treatment (introduced to the Chinese market in 2011, marketed as “NovoRapid”) and Saxenda for weight loss at a higher dose.

GLP-1 drugs mimic the action of the intestinal hormone GLP-1, promoting insulin release, inhibiting glucagon secretion, reducing appetite, and food intake, thereby helping to control blood sugar levels and reduce weight.

Previous studies have shown that GLP-1RA has a relieving effect on alcohol addiction and other addictive disorders, as well as on mental illnesses such as depression and anxiety. However, the mechanism of action has not yet been fully elucidated. In recent years, some scientists have been exploring the specific mechanisms of GLP-1RA related to mental disorders, proposing some hypotheses.

"Miracle Drug" for Weight Loss Treats Opioid Addiction?

Potential Th erapy for Opioid Addiction?

The aforementioned study included 20 patients with opioid use disorder, with 10 receiving liraglutide over 19 days with gradually increasing doses, and the other 10 receiving a placebo. The results showed that among patients already treated with buprenorphine for opioid addiction, those receiving liraglutide were more likely to report zero craving for opioid drugs compared to those receiving placebo. From the tenth day of the study, the effects became statistically significant due to the increasing dose of liraglutide.

In terms of safety, there were no significant differences in side effects between the two groups of patients, indicating that GLP-1 drugs are safe for patients with opioid addiction. However, the rate of gastrointestinal discomfort in patients using liraglutide was twice that of patients using a placebo, which was the main reason for patients dropping out of the trial, with only 9 patients completing the three-week trial.

Scott Bunce, a clinical psychologist at Pennsylvania State University and one of the lead researchers of the study, suggested that combining liraglutide with buprenorphine could alleviate some safety issues, and using a low dose of liraglutide might also reduce side effects.

The study was conducted at the Caron Treatment Center in the United States and was funded by the National Institute on Drug Abuse and liraglutide developer Novo Nordisk. The two researchers, Bunce and Patricia “Sue” Grigson, a behavioral neuroscientist at the Penn State College of Medicine in Hershey, believe that GLP-1 could be a potential alternative or adjunct to existing drug addiction therapies.

The United States is a major user of opioid drugs. The Food and Drug Administration (FDA) has approved three drugs for the treatment of opioid addiction: methadone, buprenorphine, and naltrexone. However, a recent study by the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH) estimated that only 20% of patients used these drugs.

Heath Schmidt, a neuropharmacologist at the University of Pennsylvania, cautioned that these preliminary results should be interpreted with caution due to the small sample size, limited diversity of participants, and relatively short duration of the trial. In addition, patients recruited from treatment facilities may not be representative because they are more likely to relapse and may be more motivated for treatment.

The high dropout rate among patients is the biggest limitation of this study, which limits the interpretation of the results and highlights potential barriers to using GLP-1 to treat drug addiction. Andrew Saxon, an addiction psychiatrist at the University of Washington, said, “Drug addiction patients are very anxious and fearful of withdrawal, and nausea is one of the earliest withdrawal symptoms.”

However, Christian Hendershot, a psychologist at the University of North Carolina at Chapel Hill UNC, believes that these data can serve as a proof of concept and pave the way for larger trials, “In many cases, craving for opioid drugs can predict relapse. The next question is whether drugs like liraglutide can suppress craving and relapse in a natural environment.”

Grigson and Bunce also emphasized the preliminary nature of their research results and the need for further studies. They plan to conduct a randomized controlled trial at three outpatient sites in the United States with 200 patients using methadone or buprenorphine, with half receiving semaglutide treatment and the other half receiving a placebo.

Semaglutide is Novo Nordisk’s second-generation GLP-1RA, with three products: Ozempic for type 2 diabetes treatment, Wegovy for weight loss, and Rybelsus, an oral tablet for type 2 diabetes that is also being explored for weight loss indications.

Mechanism of Action Needs Exploration

Previous studies in rodents and non-human primates have shown that GLP-1RA reduces alcohol and drug intake, and similar effects have been observed in preliminary human clinical trials. A review article published in the British Journal of Pharmacology in 2021 discussed possible mechanisms of action: in published reports, most researchers believe that GLP-1RA reduces alcohol and drug intake by reducing reward/enhancement.

According to the introduction, some scientists have identified neurons or brain regions that reduce alcohol intake in rodents and mice after using GLP-1RA by using genetically engineered mice lacking GLP-1 receptors in specific tissues or techniques such as optogenetic stimulation. GLP-1 receptors appear to regulate brain circuits involved in reward and addiction at multiple levels.

Some scientists have proposed that the reduction in alcohol and drug use after using GLP-1RA may be a non-specific effect. The GLP-1 system regulates food and fluid intake, and scientists have observed that the reduction in food consumption by GLP-1RA is equivalent to the reduction in alcohol intake. Reduced intake of food, alcohol, and drugs may all be related to nausea and general discomfort.

Previous studies have also shown that GLP-1RA may help alleviate depression, anxiety, and other mental illnesses. In August 2023, a team led by Professor Guo Lixin and Professor Pan Qi from the National Geriatric Medical Center of Peking Hospital conducted a meta-analysis of five randomized controlled trials and one prospective cohort study retrieved from 10 databases, including 2071 participants. The results showed a significant decrease in depression scores in adults receiving GLP-1RA treatment, suggesting that GLP-1RA may be a potential therapy for relieving depression.

The benefits of GLP-1RA reported in existing studies also include improving cognitive function and alleviating neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Some studies are exploring the mechanism of action of GLP-1RA and its activity in the brain to further reveal its relationship with mental disorders. Hypotheses proposed include: GLP-1RA acts on the dentate gyrus region of the brain (located at the gateway to the hippocampus, crucial for learning and memory functions); improved metabolic health improves mental health; weight loss reduces symptoms of related mental disorders; GLP-1 can reduce brain inflammation and protect neurons.

It is worth noting that several studies have pointed out that the research on the benefits of GLP-1RA for mental disorders is still in its early stages, with a relatively small overall number of studies, and the hypotheses regarding its mechanisms of action have not been fully demonstrated, requiring larger-scale trials and further basic research.