Funded Projects

NOFO Title: HEAL Initiative: Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder (OUD) and Response to Medication Assisted Treatment (MAT) (R01 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-19-028
Summary:

The widespread misuse of opioids has underscored the need to develop nonaddicting pain medications. Chronic pain is a major factor contributing to insomnia, and sleep disruption due to chronic pain causes patients to seek relief, exacerbating the drive for prescription opioids. In opioid use disorder, withdrawal from opiates induces insomnia, posing an additional challenge for successful abstinence. This study aims to determine whether treatment of opioid withdrawal-induced insomnia with nociceptin/orphanin FQ receptor (NOPR) agonists will mitigate the drive for opiate use. A major component of the arousal/withdrawal circuitries resides in the locus coeruleus (LC), which expresses MOPRs. The study will determine whether and how the NOPR system engages LC circuits to reduce arousal and insomnia-related phenotypes and assess the hypotheses that 1) the NOPR system is a component of the endogenous sleep/wake regulatory system and 2) NOPR agonists can act as therapeutic interventions to reduce opiate use.

NOFO Title: HEAL Initiative: Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder (OUD) and Response to Medication Assisted Treatment (MAT) (R01 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-19-028
Summary:

Profound sleep disturbances during abstinence have long been suspected of perpetuating vulnerability to relapse of people who misuse or are addicted to opioids. An animal model has shown that long-term sleep deficiency results in a persistent state of physiological dysregulation that is expected to modify the biology of abstinence and increase relapse potential. This study seeks to discover how persistent sleep restriction during withdrawal from opioid use increases vulnerability to relapse in the animal model by testing whether persistent sleep restriction during abstinence from opioid use is sufficient to increase opioid drug seeking. The functional outcome measure will be the degree of mitigation of opioid seeking. These studies will provide a basis for novel translational approaches to target mechanisms that are demonstrated to cause increased vulnerability to relapse.

NOFO Title: Opioid Use Disorder in Pregnancy (R01)
NOFO Number: RFA-HD-18-036
Summary:

Neonatal abstinence syndrome (NAS) rates have increased since 2000. To determine multifactorial genetic, psychosocial predictors of opioid-related maternal and infant outcomes using rigorous prospective longitudinal design, innovative combinatorial pharmacogenetic approach, fetal MRI, and neonatal brain resting state functional MRI analysis, we hypothesize that a combination of maternal and infant genetic profiles, maternal psychosocial factors, maternal opioid treatment response, fetal and neonatal neurodevelopment, and NAS treatment will affect maternal and childhood outcomes with prenatal opioid exposure. The specific aims are to (1) Identify high-risk genetic profiles and psychosocial factors in pregnant women with opioid use disorder (OUD) and predisposing to poor maternal opioid maintenance treatment outcomes; (2) Determine maternal-infant genetic profiles and maternal opioid treatment factors predicting adverse fetal development, severity of NAS, and neonatal brain function; and (3) Develop predictive models for maternal opioid relapse and poor long-term neurodevelopmental outcomes in children with in utero opioid exposure.

NOFO Title: Opioid Use Disorder in Pregnancy (R01)
NOFO Number: RFA-HD-18-036
Summary:

This study will challenge current clinical approaches to managing the pregnant woman with opioid use disorder. Dosing of buprenorphine (BUP) in pregnant women is based on studies in non-pregnant subjects, which suggests that symptoms of withdrawal occur when plasma BUP concentrations are < 1ng/ml. No such data exist for pregnant women, but this is a prerequisite for defining an appropriate dosing regimen of BUP in pregnant women. We will define this threshold by monitoring women undergoing mild, medically directed withdrawal. The Clinical Opioid Withdrawal Scale score and the Finnegan score for NAS are key to defining when withdrawal occurs and thus dictate treatment in mother and baby. Neither scoring system is based on plasma BUP concentrations and thus, may not reflect true opioid withdrawal. This proposal aims to develop physiologic-based scoring systems that refine the accuracy of diagnosis and optimize treatment.

NOFO Title: HEAL Initiative: Preventing Opioid Misuse and Co-Occurring Conditions by Intervening on Social Determinants (R01 - Clinical Trials Optional)
NOFO Number: RFA-DA-23-051
Summary:

Urban neighborhood deterioration (also known as blight) can affect individual and community health. Interventions have shown positive effects on neighborhood crime, gun violence, and mental health. In Philadelphia, government and community partnerships have remediated vacant lots and abandoned buildings to improve living conditions. This project will investigate the degree to which neighborhood improvement interventions in Philadelphia affect opioid misuse and overdose risk for residents. Results from this research could inform similar public health-based policy and community-level health interventions in other cities.

NOFO Title: HEAL Initiative: Multilevel Interventions to Reduce Harm and Improve Quality of Life for Patients on Long Term Opioid Therapy (MIRHIQL) (R01 Clinical Trial Required)
NOFO Number: RFA-DA-23-041
Summary:

Decreasing opioid dosing faster than advised by clinical recommendations often leaves chronic pain unaddressed and may increase the risk of overdose and suicide compared to continuing long-term opioid treatment. This project will compare a patient-centered tapering protocol with or without MORE in primary care offices in New Jersey and Utah. The MORE approach integrates training in mindfulness, reappraisal, and savoring to alter behavior away from valuation of drug rewards and toward natural rewards. This research will also identify practices to use MORE in primary care settings.

NOFO Title: HEAL Initiative: Data and Methods to Address Urgent Needs to Stem the Opioid Epidemic (R01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-044
Summary:

Effective responses to the highly dynamic overdose crisis require accurate and timely information about the timing and location of drug overdoses, which is currently reported mainly through death certificates that take time to become available and thus limit life-saving responses. This project will comprehensively evaluate, optimize, and assess barriers and facilitators to adoption of a surveillance tool developed by the New York City Office of the Chief Medical Examiner. The tool uses data routinely collected during death investigations to predict in near real-time whether a death was due to an unintentional drug overdose. The findings will inform drug overdose mortality surveillance efforts in other states.

NOFO Title: HEAL Initiative: Understanding Polysubstance Use and Improving Service Delivery to Address Polysubstance Use (R01 Clinical Trial Optional)
NOFO Number: DA22-047
Summary:

Use of both opioids and stimulants is increasing, but little is known about how polysubstance use evolves over time and how it influences overdose risk. This project will use data from two groups at high risk for overdose: i) participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study who inject drugs and ii)  participants in the new Stimulant Opioid Non-Injection Cohort (SONIC) study. This research will identify drug use patterns and their association with treatment and overdose over time – toward informing overdose prevention efforts and interventions to improve the U.S. opioid crisis.

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-DA-22-046
Summary:

Despite substantial increases in overdose deaths among people who use methamphetamine, little is known about how to effectively provide harm reduction services to these individuals. This project will combine and test two harm reduction interventions for people who use methamphetamine. First, peer recovery support specialists will help identify personal harm reduction goals. The project will also test the value of incentives toward achieving these goals (a strategy known as contingency management).

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-DA-22-046
Summary:

Access to harm reduction services are often limited in rural areas. Secondary distribution is a potentially promising strategy for rural areas that involves people sharing harm reduction supplies such as naloxone or fentanyl test strips with other people who use drugs that do not come into contact with harm reduction service providers. This project aims to examine drug use and use of harm reduction services among people in rural communities, as well as highlight factors that make people more or less likely to use secondary distribution approaches.

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-DA-22-046
Summary:

Harm reduction supplies include fentanyl test strips that allow people who use drugs to identify whether the substance(s) they plan to take contain fentanyl and sterile syringes that help to prevent the spread of infectious diseases among people who inject drugs. One potential way to increase access to harm reduction supplies is mail delivery. This project will describe state-level policies that deter the use of mail-based delivery of harm reduction services, examine characteristics of people who use mail-based harm reduction services, and assess individual preferences related to mail-based harm reduction services.

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-DA-22-046
Summary:

Research is needed to better understand how to make life-saving harm reduction services more accessible to populations that are hard to reach. This project will identify the physical and psychological factors that make harm reduction services most effective. The findings will then be used to inform the development, implementation, and testing of an innovative strategy consisting of several internet- and smartphone-based tools designed to improve access to harm reduction services for people who are hard to reach. 

NOFO Title: HEAL Initiative: Understanding Polysubstance Use and Improving Service Delivery to Address Polysubstance Use (R01 Clinical Trial Optional)
NOFO Number: DA22-047
Summary:

Although approximately 80% of people with opioid use disorder smoke cigarettes, tobacco use is rarely addressed in treatment of opioid use disorder. Moreover, smoking cessation interventions that are effective in the general population have been minimally effective among people with opioid use disorder. This project will integrate into methadone treatment programs the Mindfulness-Oriented Recovery Enhancement intervention and motivational interviewing to address use of tobacco and other drugs. This research will determine the value of this intervention compared to attending a support group or receiving motivational interviewing. The project will also examine use of tobacco, opioids, and other drugs, and whether people begin treatment. The research will also study implementation barriers and facilitators to the mindfulness-based approach as well as strategies to enhance its adoption into clinical practice.