Our Projects

Opioids and the Brain

NCWR researchers are looking into the intricate world of opioid addiction to understand how it affects the brain. Our focus is on individual brain cells and groups of brain cells that are known as”brain cell networks,” or “circuits”. These networks reside in specific regions of the brain and play a vital role in why people become addicted to opioids.

To uncover the mysteries of this process, we’re employing cutting-edge technologies One example, known as “miniscopes,” are tiny, powerful microscopes that allow us to peer into the activities of these brain cells while they are being exposed to various substances of abuse. The results of these experiments are providing profound insights into how opioids impact the brain. 

Our goal is to use the knowledge gained from these studies to help make more informed decisions when developing medications and treatments for individuals facing OUD. By better understanding how the brain changes in response to opioid exposure, we  can make more informed decisions in the development of medications for the treatment of OUD.

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Pain Relief and Better Options for Your Gastrointestinal Health

Opioids are a front-line therapy for certain types of pain, but they also cause unwanted side effects, including inhibition of gastrointestinal (GI) transit and constipation. This effect is known to alter the “gut microbiome” (the bacteria that exist in the GI) and aid digestion and the permeability of the GI lining. These changes allow bacterial toxins to leak from the GI into the bloodstream and ultimately into the brain where they are linked to other diseases including Alzheimer’s disease and dementia. The NCWR is at the forefront of researching alternatives to opioids for pain management that minimize the risks associated with classical opioid drugs including problem-causing alterations of the gut microbiome. We are designing a new generation of drug candidates and testing them in various model systems including animal models to accelerate the discovery and translation into clinical practice.

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Safer Pain Management Options to Help Prevent Overdose

At the National Center for Wellness and Recovery we’re working on a project to make painkillers safer. One big problem with opioids, which are often used for pain relief, is that they can slow down your breathing a lot, which can be dangerous and even deadly. Research has shown that opioid-induced respiratory depression (to stop breathing) is essentially the cause of all opioid overdoses. We’re creating new molecules that maintain opioid-strength pain relief, but minimize the effect on breathing rate. Success here would help reduce overdose deaths caused by classical opioid drugs. 

Our research is all about understanding how these new painkillers affect your breathing and what’s happening in your brain when you take them. We’re comparing them to traditional opioids, like morphine, which can be risky for your breathing. Our goal is to create pain relief medicines that work well for pain but won’t slow down or stop your breathing, keeping you safer when you need pain relief.

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The Intersection of Pain, Substance Use Disorder and Sleep

The NCWR has teamed up with the University of Arizona (U of A) for an innovative research project aimed at finding better ways to relieve pain without causing unwanted side effects like breathing problems, stomach issues or intolerance. The main goal here is to develop drugs that can reduce pain while reducing negative responses in our bodies.

Opioid addiction is believed to progress through distinct phases. It begins with the pleasurable feelings associated with drug use, followed by a second phase driven by stress and avoiding negative  reinforcement, such as withdrawal symptoms and cravings when the drug is not used. These changes in the brain push individuals to seek relief through continued drug use and can result in relapse. Stress-related brain circuits also have other consequences, such as increased alertness and difficulties with sleep. This means that sleep and pain are closely linked, creating a cycle that can worsen chronic pain.

Our research partnership with the University of Arizona includes a study to design and evaluate new molecules to study three key aspects: pain, sleep and euphoria. Our goal is to discover a molecule that has the ideal balance of effectively managing Opioid Use Disorder (OUD) by negating the withdrawal and craving, while simultaneously minimizing sleep disturbances and the risk of relapse.

In this partnership, the National Center for Wellness and Recovery will focus on designing and synthesizing the molecules, while the University of Arizona will carry out testing using cells and animals. We are combining our synergistic expertise to conduct research that neither party could efficiently accomplish on its own. If our research is successful, we aim to advance at least one of these new molecules into clinical development within five years.

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New Treatments to Help with Medication-Assisted Treatment

The NCWR is actively pursuing clinical trials that explore new medications for use in treating various substance use disorders including opioid use disorder. The strategy includes both pharmacological and non-pharmacological approaches.T his work is important because there are currently very limited options for SUD treatment, and in some cases, there are no pharmacological treatments.

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Fentanyl Overdose Reversal Agents

According to the Centers for Disease Control and Prevention, the drug-related overdose death rate in the United States since January 2019 has increased from more than 67,000 to more than 109,000 in January 2023. Most of those deaths are related to fentanyl, a very powerful opioid. There is an urgent medical need for a very powerful and long-lasting medicine to overcome the fentanyl overdose crisis. Naloxone (Narcan) is the most widely used opioid overdose medication, known to be useful for reversing overdoses cause by any opioid such as heroin and fentanyl. However, because of its very high potency and its duration of action, fentanyl poses unique challenges for Narcan, often requiring the need for more than one Narcan dose to rescue the patient. In some situations, the supply of Narcan at the scene of a rescue might be insufficient to successfully reverse the overdose.

The NCWR joined forces with the University of Arizona (U of A) in an exciting endeavor aimed at developing a groundbreaking class of fentanyl reversal agents with an extended duration of action and high potency.

This collaboration addresses an urgent need in our efforts to combat fentanyl overdose on the front-lines of the crisis.The process involves the development of NCWR molecules, which are then rigorously tested in animals at the University of Arizona. Ultimately, this project offers hope for a more efficient and effective means of preventing Fentanyl overdoses and hopefully will address the recent combinations of fentanyl and xylazine.