GLP-1 Drugs: The Latest Breakthrough in Treating Alcohol and Opioid Addiction?

A potential revolutionary trifecta of weight loss and type 2 diabetes treatments, glucagon-like peptide-1 receptor agonists have been garnering much attention lately. Not only may they help with nonalcoholic fatty liver disease and cardiovascular disease, but early research indicates they could potentially even treat Alzheimer’s disease and addiction. A true medical milestone if proven successful.

Glucagon-like peptide-1 (GLP-1) is a remarkable hormone; it plays an important role in providing a fullness sensation after meals, helps maintain healthy blood sugar levels, and can be mimicked by GLP-1 agonists – making these treatments highly effective in managing diabetes and obesity.

Michael Glickman, an obesity medicine specialist at Revolution Medicine, Health & Fitness, has seen remarkable transformations in those who received treatments involving soundwave technology. Not only have these treatments been successful in reducing cravings for food and promoting weight loss, but many of Glickman’s patients have reported a decrease in their desire to drink or smoke as well. It seems that the same soundwave technology which aids in curbing unhealthy eating habits may also be capable of helping those suffering from addictive disorders.

Negating the Reward

Consuming drugs not only brings about a variety of pharmacological effects but also produces reward signals in the brain. According to a 2019 review in Physiological Reviews, these effects are mainly attributed to dopamine signaling in the nucleus accumbens – the brain’s pleasure centre – thus provoking an intense craving for more.

Patricia “Sue” Grigson, an addiction researcher at Pennsylvania State University, has discovered promising preclinical evidence that GLP-1 agonists can act as a substitute for dopamine in the primary reward center. This breakthrough has exciting implications for those struggling with addiction.

Patients’ reports indicate that GLP-1 may be inhibiting the pleasure response across the board – throwing light on the complex interplay of dopamine and the brain involved in the pleasure response and addiction. As Dr. Glickman put it, “I think there are so many interplays in the brain that are involved with the dopamine pleasure response, and addiction falls into that.”

Grigson explains that there are three main paths to relapse: re-exposure to cues related to the drug and drug use, re-exposure to the drug after a period of abstinence, and stress. Targeting the GLP-1 receptor, though, may provide a different approach to tackling drug dependence. It may work by decreasing someone’s sensitivity and response to substance-associated cues and potentially lead to long-term sobriety.

Lorenzo Leggio, a physician-scientist at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA), emphasizes the crucial role of GLP-1 and its receptor in individuals with a penchant for over-indulging in food and alcohol. According to Leggio, GLP-1 and its receptor are important for keeping overeating and alcohol abuse in check.

Dr. Heber has uncovered a startling correlation between overeating and alcoholic binging: the same neural system is to blame for both. His research has indicated that drugs targeting GLP-1 can help to correct the underlying imbalances, enabling users to break unhealthy cycles of overindulgence. In other words, by supplying a “dose” of GLP-1, one can work to restore balance to the body’s pathological GLP-1 system.

Leggio’s team is venturing into uncharted territory as they investigate the potential link between GLP-1 and AUD. To that end, they have conducted several studies, with one in particular measuring the GLP-1 levels in the blood of AUD patients.

Leggio discovered that GLP-1 levels drop after consuming alcohol, suggesting that it may work through a similar pathway to food in impacting glucose regulation. He comments, “What we saw was that . . . after drinking alcohol, GLP-1 was going down.”

Semaglutide, the main ingredient in Novo Nordisk’s GLP-1 receptor agonists Wegovy, Ozempic and Rybelsus, may be a promising new medication for alcohol use disorder (AUD) according to recent research published in JCI Insight. The paper showed that semaglutide reduces alcohol consumption and binge-like drinking in rodents, offering exciting new evidence in the quest to find effective treatments for AUD. Dr. Leggio, one of the authors of the paper, commented that this preclinical evidence supports the growing body of research into semaglutide’s efficacy in treating AUD.

Neurobiologists agree that the molecule GLP-1 has an important role to play in AUD, or Alcohol Use Disorder, but the question remains: will this be true for humans, too? Such preclinical findings have yet to be fully explored.

In the Clinic

A groundbreaking study conducted in 2022 by researchers at the Psychiatric Centre Copenhagen suggests that AstraZeneca’s GLP-1 receptor agonist, exenatide, could be integral in the treatment of Alcohol Use Disorder (AUD). 127 people with AUD were randomly assigned to receive either the medication or a placebo, in addition to standard cognitive-behavioral therapy, over the course of26 weeks. The results from this study could prove to be monumental in helping to treat AUD and could revolutionize the way we approach alcohol addiction treatment.

Surprisingly, exenatide, a diabetes medication, not only reduced alcohol cue reactivity in the ventral striatum and septal area—areas of the brain that play an important role in reward pathways—but also significantly decreased heavy drinking days and total alcohol intake in an exploratory analysis of obese patients. Though it did not significantly lower the number of heavy drinking days compared with placebo in the overall population, this discovery provides an encouraging direction for further research into the use of exenatide in treating alcohol addiction.

With a study of semaglutide in people with AUD currently undergoing review by the Institutional Review Boards (IRB), Dr. Leggio is at the brink of uncovering the answer to an intriguing question. He anticipates a decision over the outcome to come “very soon”, as this research could provide a revolutionary insight into the management of alcohol use disorders.

NIAAA and the University of North Carolina at Chapel Hill have united to conduct a Phase II trial exploring the potential of semaglutide to help smokers with AUD. This research is based on preclinical data that suggests GLP-1 can have a positive and powerful effect on both the craving and consumption of nicotine and alcohol. The trial outline is available on for anyone interested in learning more.

This October, the team at Penn State under the leadership of Dr. Grigson will be unveiling their findings on the efficacy of liraglutide, a GLP-1 analog, as a potential treatment for opioid use disorder in patients enrolled at the Caron Treatment Centers. This study marks an exciting advancement in the fight against opioid addiction.

Grigson’s lab has suggested that addiction involves an actual physical need for a drug, inspiring a new research effort to explore whether GLP-1 drugs might reduce the disruptive effects of sudden withdrawal. In an upcoming study, Grigson and her team have demonstrated that GLP-1 agonists can in fact block signs of conditioned withdrawal, suggesting that these drugs may tackle the profound physiological dependence on the drug. As Grigson commented, these findings are a strong indication of the potential of GLP-1 agonists in reducing the intensity of withdrawal symptoms.

It’s an incredibly thrilling period for the space, with several leading clinical researchers exploring the exciting potential of this promising target and conducting exploratory studies. As Prof. Leggio phrased it, “It’s a very, very exciting time!”

Still Early Days

Research on GLP-1 agonists for addiction has been met with mixed results, with a recent 2021 study finding that low-dose exenatide failed to significantly alter cocaine self-administration in those with cocaine use disorder. Though the study could not produce a definitive conclusion, it did highlight the importance of chronic pre-treatment when attempting to assess efficacy of drugs in CUD.

Dr. Miriam Grigson affirmed that a single dose of the GLP-1 drugs could have affected the study findings, and further noted that the participants had no inclination toward kicking their cocaine habit. She remarked that when it comes to the effects of these drugs, “the seeking is where you get the big effect,” meaning that the impulse to search out and take the drug is much more affected than the action of actually taking it.

GLP-1 drugs may revolutionize diabetes management, but Dr. Grigson cautions they are not a magic bullet. “No drug is going to be a panacea,” she said. “But it is an additional weapon in our arsenal to treat certain patients and is something to be welcomed with open arms.”

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