Substance abuse sufferers may have a promising new lead when it comes to possible treatments. 

A new study conducted by researchers at the National Institutes of Health (NIH) suggests that the brain’s salience network could be a possible target for future treatment in individuals with substance abuse disorder. 

The study was led by researchers who work for the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), both of which operate within the NIH, and was published in Nature Communications. 

The study suggests that the brain’s salience network, a group of brain pathways that work together, is shown to react when a drug is administered intravenously, but not orally. This adds further credibility to the idea that drugs are more addictive when they enter the brain quickly, such as through injection and smoking. 

Peter Manza, PhD, research fellow at the NIAAA and lead author of the study explains that when the study began, they were simply studying how the brain reacted to intravenous vs. orally administered drugs. “We looked at where brain activity changed when the dopamine increases happened across the entire brain and this network is the one that popped up as being specifically responsive to the fast dopamine increases.” 

The study suggests that the brain’s salience network, a group of brain pathways that work together, is shown to react when a drug is administered intravenously, but not orally.

He explains that “the motivation for the work goes back a long time. It goes back to this idea that the faster a drug enters your brain, the more addictive it is.” Scientists aren’t sure why, often questioning why a drug can be safe for use orally but “when you take that same exact pill and crush it up and snort it or cook it down into a liquid and inject it, that same exact dose now becomes extremely rewarding and addictive.” 

The study observed twenty healthy individuals over the course of three sessions. Each day, patients received either a dose of methylphenidate, also known as Ritalin (a drug used to treat attention deficit hyperactivity disorder) or a placebo dose. 

“The motivation for the work goes back a long time.”

Peter Manza, PhD

PET imaging, or positron emission tomography scan, is a test that can help to reveal the metabolic or biochemical function of body tissue or organs. Functional magnetic resonance imaging (fMRI) measures small changes in blood flow that occur within brain activity. Both of these methods were used during the study conducted by the NIH. 

On the first day of the study, participants received an oral dose of Ritolin. The dose was large and would be considered a standard dose for treating a severe case of ADHD. 

On the second day, participants received an intravenous injection of Ritolin. This dose was slightly different, due to the fact that it was being injected and was previously found to produce the same levels of dopamine as the larger oral dose. 

On the third day, participants of the study received a placebo dose using both methods. Additionally, a placebo dose was administered each day to ensure that the study was unbiased and not influenced by the patients. The placebo dose was administered in a different manner each day. 

“They actually got two doses each day. They got the active oral Ritolin dose and then a placebo I.V., or they got the reverse, they got the placebo oral dose and the active intravenous dose. And on the third session they got double placebo, and this was a double-blind study, which means that neither the participant nor the study team knew on any given day what medication each person was receiving.” 

Researchers then looked at the differences in dopamine levels and brain activity by monitoring with PET imaging and fMRI imaging. Simultaneously, participants reported their experiences relating to the euphoric feelings they felt in response to either the drug or placebo. 

Through fMRI scanning, researchers observed several interesting things. Two regions of the brain, the dorsal anterior cingulate cortex and the insula, were activated after the drug was injected. These are part of the salience network. Neither were activated, however, after the same drug was administered orally. This was consistent in all twenty research participants. 

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Manza went on to explain that researchers have seen other shocking things when it comes to the salience network. He went on to detail how patients with addictions who have suffered strokes that hit the salience network or parts of the brain connecting to it can “spontaneously lose their addiction.” 

Researchers are not entirely sure how or why this occurs, but hope to find answers through the course of further research.

The possibility of a potential new treatment avenue for substance abuse issues has caused a lot of newfound hope within the community. A man who has watched a loved one struggle with addiction for years explains that “every person’s situation is different and in extreme cases it [a treatment stemmed from the new research] may help someone on their journey beat the addiction early on, but they still have to deal with the root cause.”

The man, who would prefer to remain anonymous, goes on to explain that a treatment directly targeting the urge to use substances could possibly benefit addicts, but that they “wouldn’t want to have to rely on another substance for life in order to feel normal.”

“They [addicts] still have to deal with the root cause.”

Loved one affected by substance abuse

Although the study has opened doors for more research to further explore possible treatments for substance abuse that target the salience network, it is simply a starting point. Manza points out that the study, which took five years to complete, was exploratory and not created to search for any new treatments. 

The team at the NIH wanted to understand how the brain works in response to different methods of drug administration, not why it reacts in certain ways.

The study was relatively small, meaning that it cannot be used to form any large-scale conclusions regarding treatments alone. It has, however, sparked the inspiration of several new clinical research studies, which are currently in the beginning of their planning stages. 

The study was published on November 8 2023 and is a promising start that is leading to more research being conducted.