Glucagon-like peptide-1 (GLP-1) receptor agonists are a type of medication used to treat type 2 diabetes mellitus and obesity, often referred to as the ‘weight loss jab’. [1] They work by reducing food cravings, but they may also reduce cravings for alcohol and illicit substances. [2] Researchers are investigating the possible effect of GLP-1s on reward-related behavior and substance use. [2] They have identified that signalling in the lateral septum of the brain may influence how the brain connects reward, context, and motivated behavior. [2]
What GLP-1 drugs reveal about cravings and the brain
Studies have linked GLP-1 use to reduced consumption of alcohol and other drugs, including nicotine, cocaine, and opiates. [2] This has been attributed to GLP-1's impact on areas of the brain involved in rewards, motivation, cravings, and other impulses. [2]
There are several areas of the brain involved in the ‘reward pathways’ commonly referred to in addiction science, including the ventral tegmental area and the nucleus accumbens. [2] These pathways are largely driven by the neurotransmitter dopamine, which makes people feel pleasure and serves to reward and reinforce certain behaviors. [2]
However, dopamine only tells the brain that something feels good, but not why a craving arrives at a particular moment. Researchers also identified a lack of GLP-1 receptors in these areas, leading them to search for alternative areas of the brain that could be linked with cravings. [2] Researchers have now identified an area called the lateral septum as a suspected ‘craving center’, which has a high density of GLP-1 receptors. [2]
The lateral septum is emerging as a reward-processing hub
The lateral septum is located near the middle of the brain and is traditionally linked to emotion and stress regulation. [2] However, new research has highlighted its role in craving control and reward processing. [2][3]
The lateral septum receives signals from the hippocampus, the brain's memory and spatial-mapping center. [2][3] The lateral septum then associates environmental information from the hippocampus with the dopamine regions of the brain involved in reward. [2]
This is key for cravings, which are usually associated with a place, time, memory, or routine, rather than an abstract thought. [2] This highlights the lateral septum’s key role in cravings and forms the basis for why GLP-1s could be effective for craving control by acting on this area. [2]
How GLP-1 drugs may affect the brain’s craving circuit
Initially, GLP-1s' impact on cravings and substance use was thought to be due to their effect on the reward system of the brain. However, the low density of GLP-1 receptors in the ventral tegmental area and the nucleus accumbens forced researchers to look elsewhere. [2] By contrast, the lateral septum has a large number of GLP-1 receptors, which has drawn researchers' attention to GLP-1's effects on the craving circuit. [2]
GLP-1 drugs' traditional role in the treatment of type 2 diabetes and obesity involves reduced cravings for food. One hypothesis is that their potential role in substance use cravings involves the same neural pathways. GLP-1 receptor activation could reduce neurotransmission in the lateral septum, resulting in reduced dopamine release linked to alcohol or substance use, ultimately leading to reduced cravings. [2]
What research says about GLP-1 drugs and addiction
There is an increasing body of evidence linking GLP-1 use to reduced alcohol and illicit substance consumption. Firstly, animal studies have associated GLP-1 use with reduced intake of cocaine, amphetamines, alcohol, and nicotine. [4] This has also been linked to reduced dopamine release from the nucleus accumbens, reinforcing the potential pathway for cravings. [5]
More recent human studies have associated GLP-1 use with reduced alcohol intake, reduced opioid-seeking behavior, and reduced self-administration of opioid drugs. [6][7] GLP-1 drugs are also linked to reduced behaviors associated with relapse across several substances, including alcohol, nicotine, and cocaine. [8]
What we still don't know about GLP-1 drugs and cravings
Much of the evidence so far comes from animal studies, with a lack of large human studies to solidify the findings. The science so far suggests an association between GLP-1 drugs and reduced cravings for alcohol and illicit substances, but their effectiveness has not yet been quantified in randomized controlled trials. This would need to be established before GLP-1 could be considered as part of cravings management for individuals with substance use disorders.
Several confounding factors also need to be considered. For example, people prescribed GLP-1 medications often have more frequent contact with healthcare providers and greater ongoing engagement with medical care. This increased clinical support, rather than the medication alone, could partly influence reductions in substance use observed in some studies. [9]
What GLP-1 craving research could mean for addiction treatment
A better understanding of the lateral septum’s role in controlling cravings could lead to a meaningful shift in how addiction is understood. Current treatments often target either the dopamine pathway directly or the psychological patterns around use. However, this shared circuit for craving could lead to more targeted treatments in the future that are designed specifically to act on the lateral septum.
What this could mean for patients
Having treatments acting specifically on a shared craving circuit could reduce the stigma associated with substance use treatment. This could, in theory, make treatment more widely accessible, meaning individuals who were previously not receiving any treatment for their substance use disorder could get the help they need. However, this should not be seen as a replacement for current strategies, such as behavioral therapies, but rather an additional treatment alongside them.
While GLP-1s are not yet licensed for managing cravings in substance use, once more data on their effectiveness is available, this could be a possibility in the future. This is a growing area of knowledge, with larger studies expected soon.
Final thoughts
Currently, GLP-1 drugs are prescribed primarily for the treatment of diabetes and obesity, but emerging research indicates promising applications in other areas of health, including the treatment of substance addictions. A region of the brain called the lateral septum could provide meaningful clues for understanding and managing cravings, which could eventually lead to major breakthroughs in the treatment of addictive disorders.
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