Funded Projects

Exercise could repair structural and functional brain changes caused by opioid use disorder (OUD) and chronic pain by increasing growth and brain-derived neurotrophic factors and promote decreased substance cravings, reduced depression and anxiety, and increased analgesic effects that improve chronic pain. The team’s previous work with Parkinson’s disease and stroke patients showed that “assisted” exercise on a stationary cycle improved motor function and increased dopamine levels. The team also developed a novel self-regulation/cognitive behavioral therapy (CBT) program that co-addresses opioid addiction and pain (STOP) and improves pain tolerance, cravings, and functional engagement in daily activities. This study will take a multiphase optimization strategy approach to refining intervention protocols, testing feasibility, and evaluating the effects of exercise and STOP as adjunctive treatments to medication-assisted treatment (MAT) in adults with an OUD and chronic pain enrolled in residential treatment programs to decrease drug cravings and pain and increase adherence to MAT.

The Planning for the HEALthy Early Development Study will contribute to the design and recommended protocol for a future large-scale, multi-site research study to prospectively examine human brain, cognitive, behavioral, social, and emotional development of children beginning prenatally through ages 9–10 and to determine the impact of maternal pre- and postnatal substance use on short- and long-term development of children. The planning study will link investigators across 6 research sites who have complementary experience and expertise in the areas that are essential to designing the study. Planning activities will be accomplished using a coordinated set of 10 working groups. By the end of the planning phase, the 6 consortium sites will have produced and tested a recommended protocol for the future multi-site study and will have established feasibility of carrying out the study protocol at each of the 6 linked sites.

Prevalence rates of opioids misuse in Los Angeles County (LA) are particularly high among individuals of childbearing age and in already-vulnerable populations including African American females. These data highlight a pressing need for a systematic study of the effects of prenatal drug exposures (PDE) in the unique sociodemographic LA County area. In this project, researchers aim to establish the feasibility for the large-scale Phase II HEALthy BCD study in the Los Angeles area with three specific aims: (1) build a broad interdisciplinary team of investigators capable of a multi-faceted study of brain and behavioral development in both typically developing and at-risk infants/children; (2) establish a set of highly executable recruitment and retention strategies for both drug-free and drug-exposed infants/children; and (3)establish comprehensive study protocols that will help address the three key research objectives of the Phase II study.

Opioid use and addiction affects more than 2 million Americans and contribute to a large proportion of all drug overdose deaths. Current treatments for opioid use disorder (e.g., methadone and buprenorphine) are not always effective, may be misused, and can have side effects that discourage treatment continuation. Therefore, Cerevel Therapeutics is evaluating a novel compound, CVL-936, which targets brain molecules called dopamine D3 receptors. These receptors are involved in the brain’s reward and relapse pathways and are present in higher levels in people with addictions. In animal studies, the molecule reduced self-administration of nicotine and fentanyl, including in relapse situations. The project will test the safety and tolerability of CVL-936 in animals and healthy humans and will examine its effectiveness in reducing craving in people with opioid use disorder.

Opioid use disorder (OUD) is a significant public health problem in the United States. Particularly troubling is the rapid evolution of an opioid epidemic within the past decade, characterized by a surge in unintentional overdose deaths involving synthetic opioids, such as fentanyl. The current standard of care for opioid overdose is reversal with opioid antagonist naloxone. Naloxone is effective at reversing overdose from prescription opioids and heroin, but less effective when combating fentanyl, due to fentanyl?s high potency. Therapeutic monoclonal antibodies (mAbs) against fentanyl could overcome this problem by specifically preventing the drug from entering the central nervous system, averting overdose and attenuating opioid-induced respiratory depression. This study will develop and design of laboratory protocols needed to establish a Good Manufacturing Practice (GMP) process, quality assurance protocol, and stability profile for a new human mAb against fentanyl. Subsequent production of current GMP material will enable Good Laboratory Practice (GLP) toxicology studies in rats and dogs and eventually a Phase I/IIa clinical trial. This material will also be used in final opioid-induced respiratory depression studies in mice and non-human primates to confirm therapeutic efficacy of final drug product. If successful, these activities will enable filing for an investigational new drug application for this mAb candidate with the FDA.

This multi-site clinical research study will collaborate with six county jails in Illinois and medication-assisted treatment (MAT) providers to test an adapted version of an evidence-based intervention, the Recovery Management Checkups (RMC) model, which provides quarterly check-ups and assistance with treatment retention and re-linkage as indicated at the quarterly check-ups. The study will determine if tailoring the check-ups to an individual’s need for treatment leads to more efficient targeting of resources to those in need, reduces the intervention burden on those with lower need, and results in an improved overall effectiveness and cost-effectiveness of RMC.

Less than half of youth in the juvenile justice system who meet the criteria for substance use disorders (SUD) have ever received treatment, and less than one third of those received treatment while under community or correctional supervision. SUDs during adolescence can lead to significantly longer periods of substance use, more severe offending, and penetration in the justice system. The Translational Research on Interventions for Adolescents in the Legal System (TRIALS) cooperative is intended to develop and test implementation strategies and associated measures to improve the continuum of substance abuse and HIV prevention and treatment services delivered to youth under juvenile justice supervision.

The HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative model of developmental trajectories over the first 10 years of life. All sites in the HBCD-NC will carry out a common research protocol and will assemble and distribute a comprehensive research dataset to the scientific community. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. Most participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first 10 years of life. This study will be based out of the Children’s Hospital of Philadelphia and the University of Pennsylvania and will represent an urban population with a wide socioeconomic status range.

The HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative model of developmental trajectories over the first 10 years of life. All sites in the HBCD-NC will carry out a common research protocol and will assemble and distribute a comprehensive and well curated research dataset to the scientific community at large. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. Most participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first 10 years of life. The Children’s Hospital of Los Angeles study site will enroll participants from across the Greater Los Angeles region, where the prevalence of legal and illegal non-opioid drug use is high, enabling researchers to recruit from diverse, high-risk populations.

The objective of the HEALthy Brain and Child Development (HBCD) Prenatal Experiences and Longitudinal Development (PRELUDE) multi-site consortium is to characterize typical brain development from birth through childhood. All sites in this consortium will measure the influence of key biological and environmental factors on child social, cognitive, and emotional development. Researchers will assess how prenatal exposure to opioids and other substances, as well as other adverse environmental factors, affect brain development and other child health outcomes. The Cincinnati Children’s Hospital study site is in a region hit hard by the opioid crisis and has a large catchment area that includes many rural counties in Ohio, Kentucky, Indiana, and West Virginia.

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

Ohio and Kentucky have high rates of opioid-related overdose deaths in the nation. This site is a large regional perinatal center, providing clinical services for approximately 25,000 newborns each year. It also actively participates in other HEAL Initiative studies.

There is an urgent need for longer acting opioid overdose reversal medications to treat acute fentanyl intoxication and overdose. This project will develop a novel molecule (CS-1103) that sticks to fentanyl and removes it from the body. Previous research with animal models shows that CS-1103 has several features that make it attractive for a new medication. It can reverse fentanyl-induced respiratory depression, preventing another overdose; work in combination with naloxone; and appears to be safe and well-tolerated. The research will continue exploration of CS-1103 toward testing CS-1103 in human research participants.

Many people intending to take medications for opioid use disorder, including buprenorphine, as part of their recovery pathway do not stay in treatment long enough to reduce risk for overdose. These individuals also often continue to use one or more other drugs during treatment, which may further raise their overdose risk. This project will develop and conduct a preliminary test of an innovative integrated intervention that combines buprenorphine treatment with recovery coaching and online cognitive behavioral therapy. This research will assess whether the approach reduces drug use during buprenorphine treatment and helps people stay in treatment longer.