Using the immune system to combat addiction

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Using the immune system to combat addiction
According to new research, harnessing specific proteins that the immune system produces may lead to improved treatments for addiction, which is a notoriously difficult condition to treat.
Lab test vial
New research pits the immune system against addictive behavior.

In 2011, at least 20 million people in the United States had an addiction, excluding tobacco.

An estimated 100 people per day die from drug overdose, a figure that has tripled in the past 2 decades.

Addiction is a complex topic, involving interplay between neuroscience, psychology, and sociology.

Though multifaceted, at a base level, dopamine and the brain’s reward system are the primary drivers of addictive behavior.

Over the years, our understanding has grown stronger, but finding ways to prevent the process is still out of reach.

As such, researchers are looking at innovative targets and exploring how other bodily systems might influence addictive behavior.

Addiction and the immune system

One researcher involved in this endeavor is Erin Calipari, an assistant professor of pharmacology at the Vanderbilt Center for Addiction Research in Nashville, TN. In particular, she is interested in the potential role of the immune system.

The exact mechanisms involved in the immune system’s interactions with the brain are still being picked apart, but it is becoming more and more clear that they might be important for a range of conditions.

Calipari’s most recent work, the results of which are now published in The Journal of Neuroscience, investigates specific immune peptides that can moderate circuits in the brain.

The protein they were interested in is granulocyte colony stimulating factor (G-CSF). It is a cytokine — a protein that the immune system produces that can affect changes in other cells — and is known to influence motivation and decision-making.

G-CSF has a number of roles, such as promoting neuronal growth and preventing cell death in the brain and spinal cord. It has also been shown to play a protective role in strokes and influence learning and memory.

Previous work by Calipari and team showed that by manipulating G-CSF levels, they could alter motivation for cocaine without changing motivation toward other rewards.

From this, they concluded that G-CSF might be useful in understanding — and perhaps even intervening in — addiction.

G-CSF under the microscope

In the new study, they wanted to delve deeper into the interaction between G-CSF, dopamine, and the addiction response. According to Calipari, they found that they “could target these immune peptides and change the cravings that male mice and rats had for food and sugar.”

Just a short treatment with G-CSF altered an animal’s motivation response and improved cognitive flexibility in a learning task.

It seems that this change in behavior was mediated, at least in part, by increased dopamine release in the nucleus accumbens, which is a part of the brain known to be important in reward and reinforcement.

Previously, scientists have investigated inflammation in the brain as a potential cause of conditions such as depression, Alzheimer’s, and schizophrenia. G-CSF, however, is one of the few examples of a pro-inflammatory molecule being investigated for its potential health benefits.

There is unlikely to ever be a single cure for everyone with an addiction; there are simply too many varying factors involved for each individual. However, Calipari hopes that her work may help cut cravings while people who are affected by addiction work on other factors that are involved.

Now we’re looking at what we need to do before we can take this into human clinical trials. This is exciting because we see how peripheral systems such as the immune system could be influencing cravings.”

Erin Calipari

In a drive to get the new ideas to a human trial, she is working with Drew Kiraly at the Icahn School of Medicine at Mount Sinai in New York City, NY.

Because there is already a Food and Drug Administration (FDA)-approved treatment involving G-CSF, the path to clinical trials in humans could be less convoluted than it is for entirely novel interventions.

The team is also interested in individual variations in addiction risk; it has already demonstrated that females are more vulnerable to addiction.

Calipari explains her longer-term aims, saying, “We’re not going to find one treatment that fixes everything, but we can, eventually, target different aspects of addiction for individual patients.”

There is no great leap forward yet, but this new immune-addiction interaction is highly likely to attract a great deal of attention as its full significance is unpacked.

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