Published: 02/11/2026 | Author: Eric Owens

Appalachia has a complex and changing opioid crisis. One of the biggest challenges is that fentanyl is more frequently found in drugs like methamphetamine, raising the risk of accidental opioid overdose.

Adding to the problem, many people buying methamphetamine are often not aware that they’re getting a dangerous, and often deadly, combination of Fentanyl and meth. 

A research team at East Tennessee State University (ETSU), headed by Dr. Brooke Schmeichel, is using $2.5 million in grant funding from the National Institutes of Health to study how these two drugs interact. One aspect of their research is how the combination affects the brain. 

The Challenge of Polysubstance Use in Opioid Addiction

Taking multiple drugs together, also called polysubstance use, creates major challenges in treating opioid addiction, especially when fentanyl is involved.

Addiction treatment professionals know how to help a person navigate substance use disorder recovery because they can usually predict how a person will respond to detox and inpatient treatment. That’s because they understand how various single substances affect the brain.

When someone uses fentanyl and methamphetamine together, the brain’s response is different than when it’s dealing with only one substance.  The combination disrupts hypocretin, a brain chemical responsible for alertness and stress management.

The brain on these two drugs reacts strongly to stress and negative emotions, two things commonly experienced during opioid withdrawal. 

The result is that withdrawal can feel much more intense. It’s a recipe for relapse, but Dr. Schmeichel hopes to find a solution.

How Hypocretin Blockers Could Help Opioid Recovery

One challenge of addiction treatment is access to medications that work in tough situations. Many people struggling with opioid use disorder have to wait years for the development of effective medications.  

ETSU’s research team is testing approved medications used to treat insomnia. These medications block hypocretin receptors. The team is exploring whether they can also help manage withdrawal symptoms and help with relapse prevention.

Dr. Schmeichel says the team’s mission is to “get more pharmacological tools into the hands of clinicians to help individuals struggling with substance use disorders.”

Being able to use already approved medications means people could see results sooner. This is critical in areas like Appalachia, where the opioid crisis is urgent, and having better treatment options could save lives. 

Working With Providers in Appalachia

The ETSU team isn’t studying some faceless population. Their work is closely connected to the needs of people living in Appalachia, right where the Tennessee university is located.

They have close partnerships with local addiction treatment providers, which helps ensure their research is relevant to the communities most affected by polysubstance use in Appalachia. 

Both patient and provider experiences shape the team’s research. By using feedback from both Dr. Brooke Schmeichel and the ETSU research team are helping build tools that clinicians can use right now to support recovery.

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