Funded Projects

Explore our currently funded projects. You may search with all three fields, then focus your results by applying any of the dropdown filters. After customizing your search, you may download results and even save your specific search for later.

Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1R61DA057675-01
Using System Dynamics Modeling to Foster Real-Time Connections to Care Cross-Cutting Research Translating Data 2 Action to Prevent Overdose NIDA YALE UNIVERSITY HECKMANN, REBEKAH (contact); S SABOUNCHI, NASIM New Haven, CT 2022
NOFO Title: HEAL Initiative: HEAL Data2Action Innovation Projects (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-DA-22-051
Summary:

First responders prevent many overdose deaths by providing life-saving resuscitation and giving naloxone to reverse an opioid overdose. This project will use a modeling approach to assess the impact of Good Samaritan Laws that protect people from certain criminal penalties if they call 911 to save an overdose victim by giving naloxone on overdose mortality. This research will develop and test a novel, scalable, telehealth platform that can be used at the time of an opioid overdose to link patients with access to medication for opioid use disorder, harm reduction services, and recovery support. The research will be informed by patient-outcome data.

1U01DA056240-01
IND-Enabling Program for a Long-Acting Anti-Methamphetamine Monoclonal Antibody for Treating Methamphetamine Use Disorder Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA INTERVEXION THERAPEUTICS, LLC STEVENS, MISTY WARD Little Rock, AR 2022
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01)
NOFO Number: PAR-19-327
Summary:

There are currently no medications approved by the U.S. Food and Drug Administration to treat methamphetamine use disorder, even though risky patterns of methamphetamine use and overdose deaths have increased in recent years. Research using animal models shows that immune molecules that latch onto methamphetamine (anti-methamphetamine antibodies) show promise in blocking the effects of the drug. This project aims to identify a long-acting monoclonal antibody targeted to methamphetamine and conduct development and safety studies to prepare for future testing of the antibody treatment in humans.

1R01DA057443-01
Peer-Delivered, Behavioral Activation Intervention to Improve Polysubstance Use and Retention in Mobile Telemedicine OUD Treatment in an Underserved, Rural Area Translation of Research to Practice for the Treatment of Opioid Addiction Improving Delivery of Healthcare Services for Polysubstance Use NIDA UNIVERSITY OF MARYLAND, COLLEGE PARK MAGIDSON, JESSICA F (contact); KATTAKUZHY, SARAH M College Park, MD 2022
NOFO Title: HEAL Initiative: Understanding Polysubstance Use and Improving Service Delivery to Address Polysubstance Use (R01 Clinical Trial Optional)
NOFO Number: DA22-047
Summary:

Polysubstance use, especially use of both opioids and stimulants, is compounding the already devastating effects of the opioid crisis in underserved rural areas. This project builds on a previously established treatment model for opioid use disorder that uses telehealth and mobile treatment units, which seeks to engage people in activities they enjoy, to help them avoid negative behaviors such as drug use. This research will evaluate the effectiveness of a behavioral treatment approach delivered by peer recovery support specialists in rural areas and using mobile treatment units. The project will measure the intervention’s effect on treatment retention and polysubstance use – as well as evaluate the intervention’s feasibility, acceptability, adoption, and economic value.

1R34DA057604-01
Planning Grant for a Multi-Site Trial to Examine the Effectiveness of Recovery Community Centers Serving Black Communities to Support Persons Using Medications for Opioid Use Disorder Translation of Research to Practice for the Treatment of Opioid Addiction Recovery Research Networks NIDA Massachusetts General Hospital HOEPPNER, BETTINA B (contact); KELLY, JOHN F Boston, MA 2022
NOFO Title: HEAL Initiative: Planning Grants for Efficacy or Effectiveness Trials of Recovery Support Services for Individuals Treated with Medications for Opioid Use Disorder (R34 Clinical Trial Optional)
NOFO Number: RFA-DA-22-034
Summary:

People who take medications for opioid use disorder as part of their recovery pathway need to take these medications for extended periods of time to reduce risk of overdose. Recovery community centers, which provide a range of recovery-oriented and peer-delivered services in a welcoming environment, may be an important asset for these individuals. This project joins two recovery community centers that serve Black communities with an academic research team to inform the design of a rigorous, large-scale clinical trial to determine if clinical referral to recovery community centers improves long-term recovery outcomes.

1R01DA057556-01
Disrupting Social Determinants of Health to Improve Substance Use and Mental Health Outcomes for Parents in Rural Regions New Strategies to Prevent and Treat Opioid Addiction Preventing Opioid Use Disorder NIDA OREGON SOCIAL LEARNING CENTER, INC. SALDANA, LISA Eugene, OR 2022
NOFO Title: NIH HEAL Initiative: Preventing Opioid Misuse and Co-Occurring Conditions by Intervening on Social Determinants (R01 Clinical Trials Optional)
NOFO Number: RFA-DA-22-036
Summary:

Social determinants of health are individual and environmental factors that affect health, the ability to function, and quality of life. This project will study the impact of the family-focused Families Actively Improving Relationships (FAIR) prevention intervention currently offered in rural Oregon counties to parents experiencing substance use and mental health challenges. Through the FAIR program, participants receive substance use treatment services; mental health treatment services; parent management training; and support to access employment, housing, education or to mitigate exposure to violence and discrimination. This research will examine how the FAIR intervention affects substance use and societal determinants of health, toward informing payors and decision makers about the cost and value of FAIR prevention services in rural communities.

1R34DA057639-01
Leveraging Parents and Peer Recovery Supports to Increase Recovery Capital in Emerging Adults with Polysubstance Use: Feasibility, Acceptability, and Scaling Up of Launch Translation of Research to Practice for the Treatment of Opioid Addiction Improving Delivery of Healthcare Services for Polysubstance Use NIDA CHESTNUT HEALTH SYSTEMS DRAZDOWSKI, TESS K Eugene, OR 2022
NOFO Title: HEAL Initiative: Pilot & Feasibility Trials to Improve Prevention and Treatment Service Delivery for Polysubstance Use (R34 Clinical Trial Optional)
NOFO Number: DA22-048
Summary:

Young adults (18 to 26) with a substance use problem have the highest rates of polysubstance use among all age groups. At the same time, individuals in this age group (especially in rural areas) are generally lacking in recovery capital: resources to help them recover from substance use, such as vocational or educational skills. This project will assess the feasibility and acceptability of “Launch,” which uses parental and peer recovery support to increase recovery capital for young adults with polysubstance use. The intervention will use coaching as well as contingency management, a treatment approach in which individuals receive tangible rewards as incentives for desired behaviors such as abstinence. If successful, the findings will inform a future large-scale trial assessing the effectiveness of this approach.

3R24DA051946-01S1
CoARS Administrative Supplement Translation of Research to Practice for the Treatment of Opioid Addiction Recovery Research Networks NIDA PARTNERSHIP TO END ADDICTION HOGUE, AARON New York, NY 2022
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent admin Supp Clinical Trial Optional)
NOFO Number: PA-20-272
Summary:

The science of recovery support services for individuals choosing to take medications for opioid use disorder as part of their recovery pathway is gaining momentum and will benefit from a dedicated, sustainable cross-project research infrastructure. This project enhances research in the existing Consortium on Addiction Recovery Research Science. This effort coordinates varied research and training efforts across recovery support research projects, amplifies communication and dissemination channels for their activities, and is organizing the first national meetings on addiction recovery support services science.

1UG3DA057850-01
Development of a Monoclonal Antibody to Reverse Overdose from Fentanyl and Its Analogs: From Manufacturing to Clinical Trials Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA UNIVERSITY OF WASHINGTON PRAVETONI, MARCO; COMER, SANDRA D Seattle, WA 2022
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3)
NOFO Number: PAR-20-092​
Summary:

The widespread availability of fentanyl and other potent synthetic opioids has dramatically increased opioid-related fatal overdoses. This project will develop and manufacture immune molecules (monoclonal antibodies) to reverse and treat overdose from fentanyl by keeping it out of the brain. This research will advance promising results in animal studies (preventing and reversing fentanyl- and carfentanil-induced breathing problems and irregular heartbeat) to clinical testing in people with opioid use disorder and others at high risk of opioid overdose from accidental or deliberate exposure to fentanyl and fentanyl-like drugs.

1R01DA057673-01
The Short and Long-Term Dynamics of Opioid/Stimulant Use: Mixed Methods to Inform Overdose Prevention and Treatment Related to Polysubstance Use Translation of Research to Practice for the Treatment of Opioid Addiction Improving Delivery of Healthcare Services for Polysubstance Use NIDA JOHNS HOPKINS UNIVERSITY GENBERG, BECKY LYNN (contact); GERMAN, DANIELLE Baltimore, MD 2022
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.

1R24DA057659-01
Peer Recovery Innovation Network (PRIN) Translation of Research to Practice for the Treatment of Opioid Addiction Recovery Research Networks NIDA University of Texas Health Science Center at San Antonio POTTER, JENNIFER SHARPE (contact); ASHFORD, ROBERT San Antonio, TX 2022
NOFO Title: HEAL Initiative: Research Networks for the Study of Recovery Support Services for Persons Treated with Medications for Opioid Use Disorder (R24 Clinical Trial Optional)
NOFO Number: RFA-DA-22-043
Summary:

About 23 million Americans identify as being in recovery from opioid and other substance use disorders. While recovery support services are an established best practice to support people in recovery, there is little scientific evidence to support the efficacy and implementation of peer recovery support services, training approaches, and delivery models. Recovery support services are particularly lacking in the U.S. Southwest and for individuals who choose to take medications for opioid use disorder as part of their recovery pathway. This project will establish the Peer Recovery Innovation Network to address research gaps. This research will incorporate input from people with lived experience in all stages of the recovery process – toward helping to set the research agenda and conducting the research, as well as enhancing infrastructure for peer recovery support services research.

1U01DA057862-01
Development of PPL-138, a Novel Mixed NOP/Mu Partial Agonist for Treatment of Cocaine Use Disorder Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA PHOENIX PHARMALABS, INC. TOLL, LAWRENCE R; LEVIN, FRANCES RUDNICK; LEVY, DANIEL Woodscross, UT 2022
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01)
NOFO Number: PAR-19-327
Summary:

Currently no medications are approved by the U.S. Food and Drug Administration for psychostimulant (cocaine and methamphetamine) use disorder. This project will develop a novel opioid molecule (PPL-138) that blocks cocaine and methamphetamine self-administration in animal models and that lacks rewarding properties that could lead to addiction. This research will conduct manufacturing and safety studies to prepare for Phase 1 clinical trials to determine safety in human patients.

1R01DA057631-01
Motivational Interviewing and Mindfulness-Oriented Recovery Enhancement for Tobacco Dependence and Other Drug Use in Methadone Treatment Translation of Research to Practice for the Treatment of Opioid Addiction Improving Delivery of Healthcare Services for Polysubstance Use NIDA RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL COOPERMAN, NINA (contact); GARLAND, ERIC LEE Piscataway, NJ 2022
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.

1R34DA057627-01
Peer Recovery Support Services for Individuals in Recovery Residences on MOUD Translation of Research to Practice for the Treatment of Opioid Addiction Recovery Research Networks NIDA MARYLAND TREATMENT CENTERS, INC. FISHMAN, MARC (contact); WENZEL, KEVIN R Baltimore, MD 2022
NOFO Title: HEAL Initiative: Planning Grants for Efficacy or Effectiveness Trials of Recovery Support Services for Individuals Treated with Medications for Opioid Use Disorder (R34 Clinical Trial Optional)
NOFO Number: RFA-DA-22-034
Summary:

Patients choosing treatment with medications for opioid use disorder as part of their recovery pathway often have difficulties staying on these medications for extended periods of time. Currently, no established evidence-based interventions are available to help. This project will leverage the impact of two widely used recovery support services: peer recovery support services and recovery housing. Delivered by community-based peers with lived recovery experience, the intervention will include assertive outreach, which encourages people in recovery between episodes of care to continue treatment and return to care after treatment dropout and/or resumed opioid use. This research will also examine whether these services can enhance benefits offered by the supportive recovery housing living environment.

1R21TR004333-01
Discovery of Novel Openers of the Understudied Human Drug Target Kir6.1 Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCATS NEW YORK UNIVERSITY SCHOOL OF MEDICINE CARDOZO, TIMOTHY J New York, NY 2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

Routine treatment of pain with prescription opioid medications may evolve into opioid use disorder, addiction, and potentially overdose. New, non-opioid molecular targets for pain are needed as a key element of responding to the opioid and overdose crisis. Ion channels are molecular gateways that convert electrical signals into physiological responses, and many have been implicated in transmitting pain signals. The ion channel Kir6.1/KCNJ8 has been linked to the control of postoperative and cancer pain. Studies in animal models show that low levels of this ion channel are evident after an injury. This research will identify compounds that can open the Kir6.1/KCNJ8 channel as potential treatment strategy for pain.

1R21NS130417-01
The Role of Lysosomal Mechano-Sensitive Ion Channel in Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS INDIANA UNIVERSITY PURDUE AT INDIANAPOLIS TAN, ZHIYONG Indianapolis, IN 2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

Chronic pain severely reduces the quality of life and ability to work for millions of Americans. Because misuse of opioids for chronic pain treatment contributes to opioid addiction and opioid overdose, there is an urgent need to study novel non-opioid mechanisms, targets, and treatment strategies for chronic pain. Many ion channels control the flow of electrical signals in peripheral sensory neurons and are thus key targets for understanding and treating chronic pain. This project will conduct detailed studies to identify major ion channel-related molecular activities, targets, and treatment strategies for chronic pain. In particular, this research will explore the role of a specific ion channel (lysosomal mechanosensitive ion channel, orTmem63A) in neuropathic pain resulting from nerve injury.

1R01DA056646-01
Ghrelin Deacylase as a Treatment for Opioid Polysubstance Abuse Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of Kentucky Research Foundation ZHAN, CHANG-GUO (contact); ZHENG, FANG Lexington, KY 2022
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031
Summary:

There is an urgent need for novel substance use disorder treatments aimed at treating polysubstance use disorders, such as opioid and methamphetamine co-use. One promising new target is the peptide ghrelin, which recent studies have implicated in drug- and reward-relevant behaviors. This research project will investigate the recently identified enzyme, ghrelin deacylase, that affects the activity of ghrelin to attenuate the rewarding and reinforcing effects of fentanyl and heroin in combination with methamphetamine. The researchers will also design and test new, long-acting forms of ghrelin deacylase that may be potential therapeutic candidates for the treatment of polysubstance use disorders.

R41DA055405-01
Virtual Reality Facilitation of Recovery from Opioid Use Disorder Cross-Cutting Research Small Business Programs NIDA Relate XR LLC OBERLIN, BRANDON G (contact); NELSON, ANDREW Indianapolis, IN 2022
NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-020
Summary:

Relapse is common in people with opioid use disorder, and recovery attempts often fail within 6 months. This research project will test a novel virtual reality intervention to improve recovery outcomes for people recovering from opioid use disorder. By increasing future orientation and delay-of-reward behavior with a precision medicine personalized experience, the intervention is designed to enhance advantageous decision-making and increase positive future outcomes. The results of this study will provide critical data for creating a commercially viable software product for facilitating relapse prevention and improving opioid use disorder recovery outcomes.

1R01DA056828-01
Brain-Penetrant GPR88 Agonists as Novel Therapeutics for Opioid Abuse Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Sanford Burnham Prebys Medical Discovery Institute SMITH, LAYTON HARRIS; KENNY, PAUL J La Jolla, CA 2022
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031
Summary:

Opioid dependence is a leading cause of premature illness and death. Previous research suggests that a protein called G-protein coupled receptor (GPR88) controls many addiction-relevant behavioral and physiological actions of opioids. This research study will validate GPR88 as a drug target for opioid use disorder as well as develop novel, brain-penetrant GPR88-binding molecules with properties optimized for treating opioid dependence. This research is an initial step toward the goal of developing GPR88-binding molecules as novel therapeutics to facilitate abstinence in people dependent on opioids.

R44DA053845-01A1
Fast-track: Scalable Digital Delivery of Evidence-Based Training for Addiction Professionals to Maximize Treatment Admission and Retention Rates of Opioid Use Disorder in Affected Families Cross-Cutting Research Small Business Programs NIDA Public Health Management Corporation; We the Village, Inc MACKY, JANE Philadelphia, PA; New York, NY 2022
NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Effective medication-based treatment could prevent overdose deaths and help individuals recover from opioid use disorder, but only a fraction of those in need access treatment or receive a medication approved by the U.S. Food and Drug Administration. One way to improve people’s choice to seek and stay in treatment is to improve training for addiction treatment counselors beyond current methods that rely on brief online or in-person workshops. The goal of this research project is to develop and evaluate the technical feasibility and commercial viability of a scalable digital program to train behavioral addiction professionals in Community Reinforcement and Family Training (CRAFT), an evidence-based approach to increase treatment entry, using ongoing counselor training with feedback and coaching.

1R01DA057120-01
Characterization, Optimization, and Development of Dual mGlu2/3 Positive Allosteric Modulators for Opioid Use Disorder Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Sanford Burnham Prebys Medical Discovery Institute COSFORD, NICHOLAS DAVID; VELICELEBI, GONUL La Jolla, CA 2022
NOFO Title: Strategic Alliances for Medications Development to Treat Substance Use Disorders (R01Clinical Trial Optional)
NOFO Number: PAR-19-318
Summary:

Given recent increases in co-use of opioids and methamphetamine, there is a dire need for novel treatment strategies that prevent relapse to drug use in both opioid use disorder (OUD) and methamphetamine use disorder (MUD). The localization of certain receptors for the neurotransmitter glutamate—metabotropic glutamate receptor subtypes 2 and 3 (mGlu2/3)—and the mechanism through which they transmit signals, strongly suggest that activation of both of these receptors will effectively treat multiple symptoms that contribute to relapse, such as responsiveness to drug cues, physical withdrawal symptoms, neuroinflammation, and sleep disturbances. This project seeks to evaluate molecules that can activate mGlu2/3 receptors without binding to the same site as glutamate (i.e., positive allosteric modulators) as a novel pharmacological treatment for preventing relapse to OUD. The research also will examine the potential of such modulators for treating MUD.

1R21DA056740-01
Recruiting Active Expiration to Overcome Opioid-Induced Persistent Apnea Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of California, Los Angeles FELDMAN, JACK L Los Angeles, CA 2022
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R21 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-032
Summary:

Prescription opioids provide pain relief, but overdose can be fatal because opioids also depress breathing through opioid-induced persistent apnea, when breathing stops. This research will determine whether targeted activation of a specific, opioid-insensitive brain region that triggers exhalation can increase tolerance to fentanyl-induced apnea. The research also seeks to identify the receptors responsible for this exhalation, which could be targets for new medications that prevent the negative impact of opioids on breathing. This research lays the groundwork for more preclinical and translational studies to prevent opioid-induced persistent apnea. 

R24DA055306-01
Wake Forest IMPOWR Dissemination Education and Coordination Center (IDEA-CC) NIDA Wake Forest University Health Sciences ADAMS, MEREDITH C B Winston-Salem, NC 2022
NOFO Title: Administrative Supplements to Support Collaborations to Improve the AI/ML-Readiness of NIH-Supported Data
NOFO Number: NOT-OD-22-067
Summary:

This research is intended to create multidisciplinary team science collaborations to develop effective interventions, best models of care for delivery of services, and sustainable implementation strategies for access to quality care for complex patients with chronic pain and opioid use disorder or opioid misuse. To allow comparison and analysis of data created in nine unique clinical trials funded across four centers, common data elements (CDEs) were selected to assess all aspects of a patient’s condition and experience. The purpose of this project is to make the IMPOWR CDE data more FAIR (Findable, Accessible, Interoperable, Reusable) by building a tool that will automate the mapping/conversion of HEAL-related data to the Observational Medical Outcomes Partnership data model that allows for systematic analysis of data from different databases. Upon completion, this tool would be shared with the HEAL research community as a new resource to enable broader harmonization and secondary data analysis.

1R01DA056673-01
Targeting Tiam1-Mediated Synaptic Plasticity for the Relief of Opioid Tolerance Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Baylor College of Medicine LI, LINGYONG (contact); TOLIAS, KIMBERLY Houston, TX 2022
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031
Summary:

Chronic opioid use results in tolerance, a primary driver for opioid misuse and overdose that directly contribute to increased morbidity and mortality. Changes in neuronal connectivity known as synaptic plasticity are a key determinant of opioid tolerance, but the underlying molecular mechanisms remain unclear. Tiam1 is a protein known to control the development of nerve cells and their connections and is also involved in morphine-induced neuronal changes. This research will examine Tiam1-mediated synaptic plasticity underlying opioid tolerance and validate Tiam1 as a potential therapeutic target for prevention of tolerance development.

R41DA056239-01
Leptin Receptor Agonist as a Novel Prevention of Opioid Induced Respiratory Depression Cross-Cutting Research Small Business Programs NIDA Arrevus, Inc. KRAUS, CARL NEIL (contact); POLOTSKY, VSEVOLOD Y Raleigh, NC 2022
NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-020
Summary:

The primary cause of death associated with opioids is opioid-induced respiratory depression, and there is currently no way to prevent this condition. The goal of this research is to develop a therapy to prevent opioid-induced respiratory depression without disrupting opioids’ analgesic effects. Previous research has shown that the hormone leptin, which suppresses appetite and increases metabolic rate, also stimulates breathing. This research project in a mouse model will test if the novel, brain-penetrant leptin receptor-binding protein E1/Aca can prevent fentanyl-induced breathing failure without diminishing fentanyl’s analgesic effects.

1R01DA056675-01
Domain-Specific Inhibition of Angiotensin-Converting Enzyme as a Therapeutic Strategy for Opioid Use Disorders Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of Minnesota ROTHWELL, PATRICK (contact); MORE, SWATI S Minneapolis, MN 2022
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031
Summary:

Novel treatments for opioid use disorder are urgently needed. Previous research has shown that angiotensin-converting enzyme (ACE) can control levels and activity of natural, “endogenous,” opioids in a way that might reduce the rewarding effects of opioids like fentanyl. ACE inhibitors have been used to treat hypertension for decades, with no evidence of addiction or dependence. This research will evaluate ACE effects on endogenous opioids toward generating new, domain-specific ACE inhibitors with optimized properties for treating opioid use disorder. The research will also test the behavioral impact of these compounds in preclinical models of opioid use disorder.