Researchers at the Yale School of Medicine have uncovered significant structural and functional changes in specific brain regions of individuals with opioid use disorder (OUD). The findings, published today in Radiology, a journal of the Radiological Society of North America (RSNA), provide new insights into the brain’s response to opioid addiction.
Opioids, a class of drugs that includes synthetic substances like fentanyl, prescription painkillers such as oxycodone, and illegal narcotics like heroin, are known for their high potential for misuse. Opioid use remains a leading cause of drug overdoses in the United States.
According to the National Institute on Drug Abuse, approximately 2.5 million adults in the U.S. were affected by opioid use disorder in 2021. The Centers for Disease Control and Prevention’s National Center for Health Statistics reported an estimated 81,083 opioid-related overdose deaths in 2023 alone.
The study, led by Dr. Mehta and her team, analyzed data from the National Institutes of Health-funded Collaboration Linking Opioid Use Disorder and Sleep Study (CLOUDS). The researchers compared individuals with opioid use disorder who were receiving methadone treatment to a control group of healthy individuals. The data, which includes both structural and functional MRI (fMRI) scans, was collected between February 2021 and May 2023.
Resting state fMRI, a technique that measures brain activity by tracking changes in blood flow, allows researchers to observe brain connectivity during periods of rest. This technique is particularly useful for studying the brain’s default networks, the areas of the brain that remain active when a person is not focused on any particular task.
The study analyzed structural MRI data from 103 participants with opioid use disorder and 105 healthy controls, as well as resting state fMRI data from 74 individuals with OUD and 100 controls. All participants with OUD were stabilized with medication (methadone) for less than 24 weeks at the time of the study. The median age of participants with opioid use disorder was 37, with 40% identifying as women. In the control group, the median age was 27, with 55% identifying as women.
The research team found notable differences in brain structure and function between the two groups. Specifically, individuals with opioid use disorder exhibited smaller volumes in the thalamus and right medial temporal lobe, regions dense with opioid receptors, compared to healthy controls. In contrast, the cerebellum and brainstem were larger in volume in individuals with OUD. Furthermore, these brain regions showed increased functional connectivity in those with opioid use disorder, indicating heightened interaction between neural networks.
“We observed widespread increases in global connectivity in individuals with opioid use disorder,” Dr. Mehta explained. “Our goal is to understand the underlying causes of these alterations and explore how they might inform new treatment strategies.”
The study also highlighted significant sex differences in brain structure. Women with opioid use disorder showed reduced volume in the medial prefrontal cortex compared to their male counterparts. The medial prefrontal cortex plays a key role in executive functions, decision-making, and regulation of emotions, and it is often implicated in various mental health conditions.
“We found that patterns of alteration in the medial prefrontal cortex differed between men and women in the opioid use disorder group,” Dr. Mehta said. “This underscores the need for neuroimaging studies of opioid use disorder to consider sex differences.”
Dr. Mehta emphasized that these findings pave the way for future studies to explore the behavioral implications of these brain alterations. Specifically, researchers aim to determine whether these structural and functional changes are permanent and how they might relate to recovery outcomes for individuals with opioid use disorder.
“Our long-term goal is to link these brain alterations to clinical outcomes,” Dr. Mehta said. “Understanding how the brain is affected by opioid addiction could help guide the development of targeted treatments and interventions.”
This study offers new insights into the complex relationship between opioid use disorder and the brain, providing valuable information for future research aimed at improving treatment strategies for individuals affected by addiction.
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