Treating Addiction With Immunotherapy Research Links Alcohol Use and the Immune System

Alcohol addiction continues to be a major public health issue, and new research is beginning to challenge how scientists understand its biological roots. A recent interdisciplinary study from Brigham Young University explores a surprising connection between alcohol use, brain reward pathways, and the immune system, opening the door to potential future treatments based on immunotherapy rather than traditional brain-only approaches.

According to a 2024 U.S. national survey, alcohol misuse remains widespread. The survey found that 11.8% of males and 7.6% of females aged 12 and older met the diagnostic criteria for Alcohol Use Disorder (AUD) in 2023. These individuals struggled to stop or control their drinking despite experiencing serious health, social, or relationship consequences. While factors such as genetics, mental health conditions, and social environment are known to influence addiction risk, the biological mechanisms behind alcohol dependence are still not fully understood.

At present, there are only three FDA-approved medications designed to reduce alcohol cravings. All of them treat addiction primarily as a brain-based disorder, targeting neurotransmitters involved in reward and impulse control. The new BYU study takes a different approach by examining whether the immune system plays an active role in shaping how alcohol affects the brain.

The research was conducted by a collaborative team of four professors and 13 students from three departments across BYU’s College of Life Sciences and the College of Family, Home, and Social Sciences. Their findings were published in the peer-reviewed journal Brain, Behavior, and Immunity, a publication known for research at the intersection of neuroscience and immunology.

Although neuroimmune research has grown rapidly over the past decade, this study is among the first to directly investigate whether alcohol consumption involves immune-mediated mechanisms. The researchers focused on how immune cells might interact with the brain’s reward circuitry, particularly systems involving dopamine and GABA, two neurotransmitters central to addiction biology.

The brain’s reward system contains two major pathways. One pathway directly increases dopamine levels, producing feelings of pleasure and reinforcement. The other pathway involves GABA, a neurotransmitter that acts as a braking system by inhibiting dopamine release. Alcohol does not directly increase dopamine by stimulating dopamine-producing neurons. Instead, it works indirectly by reducing GABA activity, which removes inhibition and allows dopamine levels to rise.

Because of this indirect mechanism, the research team chose to explore whether immune system components influence the GABA-mediated pathway, thereby shaping alcohol’s rewarding effects. Their attention centered on CD5, a protein found on certain white blood cells that plays a role in immune regulation.

To investigate this connection, the researchers used male and female mice that were genetically modified so that the CD5 protein was disabled, a process known as a genetic knockout. All animals were bred, housed, and handled in strict compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, ensuring ethical and standardized experimental conditions.

Over a three-week period, both normal mice and CD5-knockout mice were given access to food, water, and alcohol. One of the most striking findings was that CD5-knockout mice drank significantly less alcohol, even though they consumed the same amount of water as the control group. This suggested that the reduced alcohol intake was not due to general appetite changes or dehydration but was specific to alcohol reward.

To understand what was happening inside the brain, the researchers conducted electrical recordings from key reward-related regions. These recordings revealed functional changes in dopamine and GABA neurons in mice lacking CD5. In addition, the knockout mice showed decreased sensitivity to alcohol’s sedative effects, including reduced impairment in posture and motor control.

Importantly, when blood alcohol levels were measured, researchers found no difference in how alcohol was metabolized between normal mice and CD5-knockout mice. This ruled out faster alcohol breakdown as an explanation for reduced drinking. Instead, the findings point to altered brain reward signaling influenced by immune system changes.

In simple terms, the mice without CD5 experienced less reward from alcohol, making them less motivated to consume it. While the researchers emphasized that the exact biological mechanism is still not fully mapped, the results strongly suggest that immune signaling can influence how rewarding alcohol feels.

This insight has major implications. If scientists can identify the precise pathway linking immune cells, CD5, and reward circuitry, it may become possible to develop immunotherapy-based treatments that reduce alcohol cravings. Such treatments would not rely solely on altering brain chemistry but would instead modulate immune responses to make alcohol less reinforcing.

The study’s first author, now a professor at the Noorda College of Osteopathic Medicine, described the research as part of a broader effort to better understand how the brain and body interact in substance use disorders. Addiction, he noted, remains one of the most difficult sets of disorders to treat, and progress depends on expanding biological understanding beyond traditional frameworks.

Why the Immune System Matters in Addiction Research

The idea that the immune system could influence addiction may sound surprising, but it is increasingly supported by scientific evidence. Alcohol is known to trigger inflammatory responses, alter immune cell behavior, and disrupt communication between the immune system and the brain. Chronic alcohol use has been linked to elevated inflammatory markers, which can affect mood, cognition, and reward sensitivity.

Immune molecules such as cytokines can cross or signal through the blood-brain barrier, influencing neural activity. Over time, these immune-brain interactions may contribute to craving, tolerance, withdrawal symptoms, and relapse risk. The BYU study adds to this growing body of research by identifying a specific immune protein that appears to shape alcohol reward at a neural level.

How This Research Fits Into Current AUD Treatments

Current medications for AUD help some individuals but are far from universally effective. Many people relapse or discontinue treatment due to side effects or limited benefits. The possibility of immune-targeted therapies introduces an entirely new treatment category, potentially allowing clinicians to combine brain-based and immune-based approaches for better outcomes.

While this research is still in the early, preclinical stage, it provides a valuable proof of concept. It shows that manipulating immune components can alter alcohol-seeking behavior without affecting alcohol metabolism or general health behaviors. That distinction is critical for future drug development.

Looking Ahead

The researchers are clear that immunotherapy for alcohol addiction is not imminent, but the study lays important groundwork. Future research will need to identify the precise signaling pathways involved, test whether similar effects occur in humans, and determine how immune modulation could be safely applied in clinical settings.

What is clear is that addiction science is moving toward a more integrated view of the body, one that recognizes the deep connections between the immune system and the brain. Studies like this suggest that the next generation of addiction treatments may look very different from those used today.

Research paper: https://doi.org/10.1016/j.bbi.2025.106151