Researchers Look at Different Treatments for Opioid Use Disorder

Amir Levine, MD

As the opioid epidemic rages on, researchers are hoping to discover how different patients can benefit from different treatment regimens.

A team, led by Amir Levine, MD, Columbia University, evaluated plasma-derived extracellular vesicle signatures and how they differ in patients who responded to 2 pharmacologically contrasting treatments for opioid use disorder—the µOR agonist methadone, and the µOR antagonist naltrexone—in a proof of concept study.

Opioid use disorder is a driving force behind drug overdoses in the US, resulting in the deaths of approximately 47,000 people in the US in 2018 alone. An increase in the use of fentanyl analogues in the heroin drug supply are putting users at a greater risk of overdoses than during previous years.

In addition, admissions to treatment programs for opioid use disorder have nearly doubled since 2006, while relapse rates continue to be high. There has been attempts to get the opioid epidemic on the right track to reduce usage and overdose rates.

However, while it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes.

In the study, the researchers obtained blood samples from patients with blood samples from patients with opioid use disorder who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n = 5) and naltrexone (n = 5). The study also included healthy controls (n = 5). Extracellular vesicles were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs).

The researcher then analyzed extracellular vesicles for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry and determined extra vesicle miRNA cargo was determined by RNA sequencing.

The researchers found 1 lipid class and 6 miRNAs that differed significantly between the naltrexone group and the methadone and control groups. In addition, the researchers found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups when compared to the control groups.

“Naltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment,” the authors wrote. “It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.”

The study, “Discovering Non-invasive Biomarkers Predictive of Opioid Use Disorder Treatment Response,” was published online by NEI.