Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1R61NS126026-01A1
Antagonists of CRMP2 Phosphorylation for Chemotherapy-Induced Peripheral Neuropathy Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF ARIZONA KHANNA, RAJESH Tucson, Arizona 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

A more thorough understanding of neuropathic pain is critical for developing new target-specific medications. Researchers know that peripheral nerve injury changes various cell processes that affect two ion channels linked with chronic pain. Preliminary studies indicate that molecular changes known as phosphorylation to the collapsin response mediator protein 2 (CRMP2), one of five intracellular phosphoproteins, promotes abnormal excitability in the brain region that contributes to neuropathic pain. This project aims to develop small molecule inhibitors of CRMP2 phosphorylation as potential therapeutics for pain.
1R01DA056660-01
Target Specificity of Tabernanthalog Treatment in 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 University of Colorado, Denver PETERS, JAMIE (contact); HEINSBROEK, JASPER Denver, Colorado 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:

Currently available treatments for opioid use disorder (OUD) are insufficient for many patients. Novel compounds that can promote alterations in brain connections (i.e., neural plasticity) possess enormous potential for improving substance use disorder (SUD) treatments. Psychedelic compounds induce neural plasticity and can elicit long-lasting, beneficial impacts on a wide variety of SUDs. However, these compounds have significant side effects, including hallucinations and cardiotoxicity. Researchers have developed a novel, synthetic derivative of the psychedelic ibogaine, called tabernanthalog, that does not have these side effects. This compound has demonstrated both short- and long-term therapeutic effects in a preclinical model of OUD. This research study will determine the molecular and neural mechanisms through which tabernanthalog affects opioid seeking. It will also evaluate whether the effects are specific to opioids and do not alter response to natural rewards and will examine the efficacy of tabernanthalog in a preclinical model of comorbid opioid and alcohol use disorder.
1R43HD107727-01A1
Novel Approach to Personalize and Monitor Therapeutic Training At Home in Chronic Pelvic Pain Management Cross-Cutting Research Small Business Programs NICHD Hillmed, Inc. DIAS, NICHOLAS Katy, TX 2022
NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 – Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-011
Summary:

Chronic pelvic pain is a debilitating condition that negatively affects the social and sexual quality of life for up to 20% of American women. Pelvic floor muscle (PFM) pain is caused by many factors, as well as by incorrect posture and excessive sensitization of the peripheral nervous system. This project will introduce a prototype of the Chronic Pelvic Pain (CPP) HomeTrainer that monitors, quantitatively and in real time, both PFM activation capacity and muscle interactions between the PFM and hip/trunk muscles and adapts the PFM training to the user’s needs in their own home. The proposed CPP HomeTrainer offers biofeedback to aid myofascial physical therapy and movement pattern training by tailoring the protocol to specifically correct interactions between the PFM and problematic hip/trunk muscles.
1U19NS130617-01
Harvard PRECISION Human Pain Center Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS BRIGHAM AND WOMEN'S HOSPITAL RENTHAL, WILLIAM RUSSELL (contact); WOOLF, CLIFFORD J Boston, MA 2022
NOFO Title: HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes and Cells (U19 Clinical Trial Not Allowed)
NOFO Number: NS22-018
Summary:

This project will use state-of-the-art technologies to analyze individual cells to characterize how human pain receptors communicate pain between the human dorsal root ganglia and the brain – including how the signals vary across diverse populations. This research will generate useful, high-quality human data about pain for further analysis and re-use by other scientific teams, toward identifying and prioritizing novel therapeutic targets for pain.
3RM1DA055301-01S1
Integrative Treatment for Achieving Holistic Recovery from Comorbid Chronic Pain and Opioid Use Disorder Cross-Cutting Research Training the Next Generation of Researchers in HEAL NIDA UNIVERSITY OF NEW MEXICO WITKIEWITZ, KATIE A; PEARSON, MATTHEW RYAN Albuquerque, NM 2022
NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107; PA-21-071
Summary:

Few integrated treatments are available that simultaneously address the fundamental causes of chronic pain and opioid misuse/opioid use disorder and focus on well-being among individuals with chronic pain and opioid misuse/opioid use disorder. This research will inform development of patient-centered interventions that increase quality of life and engagement in valued activities, are culturally appropriate for use by diverse patient populations, and reduce stigma related to chronic pain and opioid misuse/opioid use disorder. The results of this project will be used to inform future research focused on developing mobile health treatments for individuals with chronic pain and opioid use disorder, and for developing culturally appropriate treatments for chronic pain and opioid use disorder in Hispanic/Latino individuals.
1R61AT012421-01
Integrative Training Program for Pediatric Sickle Cell Pain Clinical Research in Pain Management Advancing Health Equity in Pain Management NCCIH EMORY UNIVERSITY SIL, SOUMITRI Atlanta, GA 2022
NOFO Title: HEAL Initiative: Advancing Health Equity in Pain and Comorbidities (R61/R33 Clinical Trial Required)
NOFO Number: RFA-NS-22-037
Summary:

Sickle cell disease is an inherited blood disorder affecting about 100,000 Americans and more than 20 million people worldwide. It is caused by a mutation in the gene for beta-globin that results in the characteristic sickled shape of red blood cells, life-long severe pain, and shortened lifespan. Optimal treatment of  chronic pain from the condition targets psychological factors contributing to pain, such as pain-related anxiety, fear of movement, and depression. This project will interact with patients and their families to revise and test an existing mind–body and behavioral health treatment tool to target the unique needs and preferences of people managing chronic sickle cell disease pain.
2R44DA050358-02A1
A Project to Test the Efficacy and Safety of An Innovative Treatment for Opiate Use Disorders Cross-Cutting Research Small Business Programs NIDA MINDLIGHT, LLC SCHIFFER, FREDRIC (contact); TEICHER, MARTIN H Newton, MA 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:

This project will refine an experimental non-invasive light therapy to create an effective, safe, convenient, and affordable method for treating opioid use disorder. This research will test whether a short treatment of near infra-red light administered through the skull can reduce drug use, relapse, and craving, and improve overall function in people with opioid use disorder. If effective, the findings could support a path toward commercialization of this new treatment.
1R24DA057632-01
Collaborative Hub for Emerging Adult Recovery Research (CHEARR) Translation of Research to Practice for the Treatment of Opioid Addiction Recovery Research Networks NIDA UNIVERSITY OF CONNECTICUT SCH OF MED/DNT ZAJAC, KRISTYN Farmington, CT 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:

The opioid crisis has been particularly devastating to adolescents and young adults between 16 and 25 years old. Recovery support services in community settings can help these individuals who take medications for opioid use disorder find a path to recovery. This project will develop a network of advanced researchers, recovery support specialists, adolescents and young adults in recovery, and other key community stakeholders to help rapidly advance the science of recovery support services. This research will focus in particular on continuing care services specialized for adolescents and young adults who currently take or who have taken medications for opioid use disorder.
1R01DA057686-01
Fast and Fine: NLP Methods for Near Real-Time and Fine-Grained Overdose Surveillance Cross-Cutting Research Leveraging Existing and Real-Time Opioid and Pain Management Data NIDA UNIVERSITY OF KENTUCKY KAVULURU, VENKATA NAGA RAMAKANTH Lexington, KY 2022
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:

Timely and accurate surveillance of fatal and non-fatal overdoses is necessary in light of the worsening overdose crisis, but data is rarely available in real-time. Tracking non-fatal overdoses is especially important because patients who overdose once are likely to experience additional and potentially fatal overdoses. This project aims to increase the quality and timeliness of non-fatal overdose data estimates by analyzing clinicians’ notes rather than clinical codes from emergency department and emergency medical services records. The datasets and models produced from this research will be used to build an interactive dashboard with up-to-date, county-level overdose-surveillance estimates for use by Kentucky first responders to aid in rapid allocation of resources.
1R01DA057645-01
Mobile Health Strategies to Support Longitudinal Engagement in Harm Reduction Services Translation of Research to Practice for the Treatment of Opioid Addiction Harm Reduction Approaches to Reduce Overdose Deaths NIDA UNIVERSITY OF WISCONSIN-MADISON WESTERGAARD, RYAN PATRICK (contact); SEAL, DAVID W Madison, WI 2022
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. 
1R21AG082344-01
Using Secondary Analyses to Test Novel Pathways Linking Family Stress and Pain Incidence and Persistence Among African Americans Cross-Cutting Research Leveraging Existing and Real-Time Opioid and Pain Management Data NIA UT SOUTHWESTERN MEDICAL CENTER WOODS, SARAH B Dallas, TX 2022
NOFO Title: HEAL Initiative: Secondary Analysis and Integration of Existing Data Related to Acute and Chronic Pain Development or Managementin Humans (R21 Clinical Trials Not Allowed)
NOFO Number: RFA-DE-22-011
Summary:

Chronic pain is a persistent source of disability and reduced quality of life for aging adults. Chronic pain-related outcomes are disproportionately worse for aging African Americans, who report greater pain severity and worse pain-related disability compared to White peers. A significant pain risk factor for African Americans is chronic stress (including family-related stress), which is worsened by structural inequities that affect this population. Although many African Americans identify family support as critical for pain self-management, this influence has not been studied thoroughly. This project will study how pain conditions develop and persist for aging African Americans by analyzing existing data from African American participants in two large aging studies: Midlife in the U.S. (721 participants) and the Health and Retirement Study (2,698 participants). The research aims to determine how family emotional climate affects pain risk, taking into account structural factors like discrimination, socioeconomic disparity, and the influence of various neighborhood settings.
1R61NS126029-01A1
Inhibiting RIPK1 with Necrostatin-1 for Safe and Effective Pain Treatment Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS Massachusetts General Hospital SHEN, SHIQIAN (contact); HOULE, TIMOTHY T; WANG, CHANGNING ; ZHANG, CAN MARTIN Boston, MA 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

Recent studies have reported that neuropathic pain involves changes in the central nervous system that are linked to necroptosis (programmed necrotic cell death) and release of cellular components that create neuroinflammation. Necroptosis is a type of necrotic cell death affected by the protein receptor-interacting serine/threonine-protein kinase 1 (RIPK1 or RIP1). Preliminary studies also indicate that pain increases levels of RIPK1 in key brain regions implicated in pain processing. This project aims to further validate RIPK1 as a target for neuropathic pain using a newly developed positron emission tomography imaging approach. The work will pave the way for new brain-penetrant RIPK1 inhibitors as a safe, effective, and nonaddictive treatment approach for neuropathic pain.
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.
1R43NS125643-01
Development of an intranasal, direct to nerve treatment for headache disorders Cross-Cutting Research Small Business Programs NINDS Olfax, LLC BECKWITH, JONATHAN G (contact); COOK, JASON T Asheville, NC 2022
NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 – Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-011
Summary:

About 14% of U.S. adults report experiencing migraine symptoms within any given 3-month period, making it the second most disabling illness in the world. Nonspecific pain medications used in migraine (e.g., acetaminophen, nonsteroidal inflammatory drugs, opioids) are often not effective for severe migraine symptoms or cause significant adverse effects. A research team of migraine care specialists, device and drug developers, and clinical research specialists has created a technology for accurately delivering self-administered migraine medication to the upper nasal cavity. The technology enables development of a self-administered therapy to provide rapid pain relief without harsh and addictive side effects of existing migraine medications. This project will establish efficacy and evaluate commercial design feasibility for this treatment.
1RF1NS130481-01
Immune Modulating Therapies to Treat Complex Regional Pain Syndrome Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS DREXEL UNIVERSITY AJIT, SEENA Philadelphia, PA 2022
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

Complex regional pain syndrome is a difficult-to-treat chronic condition that causes excess and prolonged pain and inflammation after injury to an arm or leg and includes damage to skin of affected limbs. Although it is known that aberrant immune system function plays a role in this condition, the details remain unclear about how this occurs – in particular, through the adaptive immune system that relies on specialized immune cells and antibodies to protect the body from harm.  This project will study the role of certain immune cells (T cells) that circulate throughout the body or reside in bone using both rat or human bone samples from patients with complex regional pain syndrome.
3R61NS127285-01S1
Investigating the Contributions of Voltage Gated Sodium Channels to Oxaliplatin Induced Neuropathy Cross-Cutting Research Training the Next Generation of Researchers in HEAL NINDS UNIVERSITY OF CALIFORNIA AT DAVIS YAROV-YAROVOY, VLADIMIR M Davis, CA 2022
NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107; PA-21-071
Summary:

Many molecular gates known as ion channels control the flow of electrical signals to sensory neurons and are thus key mechanisms and targets for understanding and interrupting pain signals. Recent breakthroughs in structural and computational biology shave illuminated specific molecular shapes of ion channels, which permits the improved design and refinement of small, stable protein-like molecules (peptide antigens). These peptides can stimulate an immune response that can then be targeted with a bioengineered antibody to match the peptide antigen. This project will test bioengineered antibodies in a rat model of chemotherapy-induced peripheral neuropathy within a region of the rat spinal cord that transmits signals to and from the brain.
1R61CA280978-01
Culturally Adapted Mobile Treatment of Chronic Pain in Adolescent Survivors of Pediatric Bone Sarcoma Clinical Research in Pain Management Advancing Health Equity in Pain Management NCI ST. JUDE CHILDREN'S RESEARCH HOSPITAL BRINKMAN, TARA M Memphis, TN 2022
NOFO Title: HEAL Initiative: Advancing Health Equity in Pain and Comorbidities (R61/R33 Clinical Trial Required)
NOFO Number: RFA-NS-22-037
Summary:

More than half of children and adolescents diagnosed with a type of cancer called bone sarcoma experience pain that interferes with daily life. This project will adapt an evidence-based cognitive behavioral therapy mobile app for use with Black and Hispanic adolescents who disproportionately experience pain from this cancer, putting them at risk for opioid misuse. Once fully adapted, this therapy will be paired with a remotely delivered brain stimulation treatment (transcranial direct current stimulation). This research will also examine the impact of patient-reported conditions such as depression, anxiety, and sleep problems, as well as of various social determinants of health, on pain.
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.
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.
1R01DA057630-01
Predicting Fatal and Non-Fatal Overdose in Los Angeles County with Rapid Overdose Surveillance Dashboard to Target Street-Based Addiction Treatment and Harm Reduction Services Cross-Cutting Research Leveraging Existing and Real-Time Opioid and Pain Management Data NIDA UNIVERSITY OF CALIFORNIA LOS ANGELES SHOVER, CHELSEA LEIGH (contact); GOODMAN, DAVID Los Angeles, CA 2022
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 overdose prevention requires timely, location-specific data to efficiently direct resources and interventions as well as to inform healthcare policy. However, rarely is such information available, resulting in responses that are frequently too late. This project will partner with local government agencies from Los Angeles County, California, to rapidly acquire and analyze information in near real-time from multiple sources to identify overdose hotspots and determine overdose metrics. This information will be used to develop a publicly available Rapid Overdose Surveillance Los Angeles online dashboard with built-in analytics. The dashboard will help determine the scope and specifics of overdose and opioid use in Los Angeles County to help target response and guide mobile addiction treatment and harm reduction services.
1R01DA057633-01
Teaching Harm Reduction in Vulnerable Environments (THRIVE): A Peer-Led Intervention Bridging Acute Care Settings and the Discharge to the Community Translation of Research to Practice for the Treatment of Opioid Addiction Harm Reduction Approaches to Reduce Overdose Deaths NIDA UNIVERSITY OF PITTSBURGH WILSON, JACQUELINE DEANNA Pittsburgh, PA 2022
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:

People who use drugs often have other medical problems that cause them to visit an emergency department frequently. This project will develop and test an intervention aimed at reducing health risk among Black people who use drugs that visit an urban emergency department for care. The intervention will be delivered by people with lived experience of drug use and tailored to meet the unique needs of Black people who use drugs.
3U01DK123786-01S1
Randomized ESRD Trial COmparing CBT alone VERsus with buprenorphine (RECOVER) Cross-Cutting Research Increasing Participant Diversity, Inclusion, and Engagement in HEAL Research NIDDK UNIVERSITY OF WASHINGTON MEHROTRA, RAJNISH Seattle, WA 2022
NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-22-066
Summary:

Pain is a common problem for people with end-stage renal disease that receive hemodialysis. Opioid use rates in this population are almost three times that of the general U.S. population over 65, putting them at significant risk for addiction. This research is testing treatments to manage chronic pain in this patient population. This project will develop educational materials to overcome barriers to telehealth toward enhancing research participation by American Indian/Alaska Native communities.
1DP2TR004354-01
Scale Up Single-Cell Technologies to Map Pain-Associated Genes and Cells Across the Lifespan Cross-Cutting Research Training the Next Generation of Researchers in HEAL NCATS Massachusetts General Hospital SHU, JIAN Boston, MA 2022
NOFO Title: Emergency Awards: HEAL Initiative- New Innovator Award (DP2 Clinical Trial Not Allowed)
NOFO Number: RFA-tr-22-013
Summary:

Current treatments for chronic pain, including opioids, are not effective for many individuals. Much remains unknown about genes, circuits, and cells that contribute to chronic pain, including how chronic pain changes across the lifespan in certain populations, including infants, children, older people, and pregnant women. This project will develop technology to map the genes, circuits, and cells associated with pain across ages, sexes, and during pregnancy. The technologies will guide the search for new biomarkers for chronic pain diagnosis and treatments.
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.
1UG3NS128439-01
Allosteric Targeting of Cannabinoid CB1 Receptor to Develop Non-Addictive Small Molecule Analgesics Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS Texas A&M Health Science Center LU, DAI (contact); SELLEY, DANA E; TAO, FENG College Station, TX 2022
NOFO Title: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-21-010
Summary:

Overreliance on opioids to treat chronic pain has been a contributor to the increase in individuals experiencing opioid addiction. This project aims to develop an innovative treatment approach for chronic pain that targets the cannabinoid receptor 1 (CB1R) to block the sensation of pain. The approach seeks to identify molecules that interact with a different part of the CBR1 receptor than do endocannabinoids and the primary active component of cannabis, tetrahydrocannabinol. Molecules that bind to and activate CBR1 in this different way (at an “allosteric” site) may produce nerve signaling that might differ from the effects of cannabis and endocannabinoids. This redirection of signaling pathways could help eliminate the risk of adverse effects observed with natural cannabinoids and other CBR1-binding molecules. The goal of this project is to identify a CB1R allosteric molecule, conduct studies toward obtaining federal permission to develop it as a medication, and to test it in a Phase I clinical study.