As the overdose crisis continues to evolve across Appalachia, researchers at East Tennessee State University are diving into the complex science of polysubstance use to find new ways to break the cycle of addiction.
Dr. Brooke Schmeichel, an investigator at ETSU, was recently awarded two major grants from the National Institutes of Health totaling more than $2.5 million. The funding supports her team’s mission to understand how methamphetamine and fentanyl interact within the brain to drive uncontrollable use.
In the Appalachian region, fentanyl has become a widespread contaminant, often appearing in drugs like methamphetamine, whether the user knows it or not. Schmeichel’s research tackles this problem head-on by acknowledging that the spiking of the drug supply has changed the clinical reality for patients.
“Fentanyl has become a widespread contaminant in the U.S. drug supply and is often used, knowingly or unknowingly, alongside methamphetamine,” Schmeichel said. “By uncovering the neurobiological mechanisms of fentanyl and methamphetamine co-use, we aim to better understand the disease of addiction.”
A key focus of the research is the role of hypocretin, a brain chemical that regulates wakefulness and stress. Under normal conditions, hypocretin helps the brain respond to challenges and maintain balance. However, research suggests that drugs such as fentanyl and methamphetamine can disrupt this system, particularly during drug withdrawal.
This disruption appears to worsen the stress and negative emotional states that many people experience when they stop using the drugs. These negative feelings can strongly drive the urge to use again, contributing to craving and relapse risk.
“Withdrawal and negative emotions can be a powerful driver of persistent drug taking despite many consequences of continued drug use,” Schmeichel explained. “Restoring balance to the brain’s stress systems is an important part of treating substance use disorders.”
To address this, one of the most novel aspects of Schmeichel’s work is the goal of repurposing existing medications to treat addiction and withdrawal. Rather than waiting years for a new medication to be developed and approved, the team is testing FDA-approved hypocretin receptor blockers, currently prescribed for insomnia, to restore balance in stress-related brain systems disrupted by substance use.
“The current proposal includes preclinical studies aimed to better understand how hypocretin signaling contributes to withdrawal-related brain changes,” Schmeichel said. “Ultimately, we hope to get more pharmacological tools into the hands of clinicians to help individuals struggling with substance use disorders.”
The Schmeichel Lab’s work is guided by a clear goal: helping research findings translate into real benefits for people in our community. By keeping close ties with the clinical world, the team ensures its science meets the actual needs of those in the Appalachian region.
“We want the experiences of patients and clinicians to guide our research,” Schmeichel said.
Jargon Buster
Polysubstance Use: Using multiple drugs at once, often unintentionally, when one is spiked with another.
Preclinical Studies: Laboratory research used to understand (brain) changes before moving to human clinical trials.
