Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
5U24DA055325-02 The HEALthy Brain and Child Development National Consortium Administrative Core Enhanced Outcomes for Infants and Children Exposed to Opioids HEALthy Brain and Child Development Study (HBCD) NIDA UNIVERSITY OF CALIFORNIA, SAN DIEGO CHAMBERS, CHRISTINA (contact); NELSON, CHARLES ALEXANDER La Jolla, CA 2023
NOFO Title: Notice of Special Interest (NOSI): HEAL Initiative: Biospecimen Collection in Pregnancy
NOFO Number: NOT-DA-23-005
Summary:

Opioid use during pregnancy is associated with adverse outcomes for pregnant individuals and offspring. The mechanisms through which these outcomes arise and the consequences of prenatal opioid exposure on child health and development remain largely unexplored. The HEALthy Brain and Child Development (HBCD) Study is a nationwide longitudinal prospective study of early child development that will assess a broad spectrum of biological, behavioral, social, and health factors among 7,500 pregnant women and their children from pregnancy to mid-childhood. This supplement will expand the biospecimen collection of the HBCD protocol at the University of North Carolina at Chapel Hill to include delivery specimens (placenta, cord tissue, and cord blood). This will provide an unprecedented resource-generating opportunity for the larger scientific community to comprehensively evaluate mechanisms that mediate the connection between substance use during pregnancy and adverse neonatal, infant, and/or maternal health outcomes and inform innovative preventive strategies.
5R24DA051988-02 Advancing the science on recovery community centers to support persons treated with medications for opioid use disorder Translation of Research to Practice for the Treatment of Opioid Addiction Recovery Research Networks NIDA MASSACHUSETTS GENERAL HOSPITAL KELLY, JOHN F. Boston, MA 2021
NOFO Title: 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-20-014
Summary:

Individuals with opioid use disorder tend to be more in need of additional services; feel more isolated and marginalized; have less available resources such as education, training, employment, and housing opportunities (collectively known as “recovery capital”); and report lower quality of life than those with other substance use disorders. Recovery Community Centers (RCCs) are designed specifically to help grow recovery capital and enhance remission and quality of life. Preliminary evidence suggests RCCs are particularly valuable for people with opioid use disorder, but little is known about their clinical and public health benefits and cost-effectiveness. This project will organize activities on a national level to enhance research on RCCs. It builds on existing professional and academic resources, including an established recovery dissemination platform (i.e., the Recovery Research Institute).
5R24DA051973-02 Studies to Advance Recovery Supports (STARS) in Central Appalachia Translation of Research to Practice for the Treatment of Opioid Addiction Recovery Research Networks NIDA EAST TENNESSEE STATE UNIVERSITY PACK, ROBERT P Johnson City, Tennessee 2021
NOFO Title: 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-20-014
Summary:

Central Appalachia has been devastated by opioid use disorder and overdose deaths for decades. Treatment access is improving across that region, yet few individuals successfully remain on treatment with medications for opioid use disorder (MOUD). Peer recovery support services can be highly effective in improving treatment outcomes and recovery, but there is limited evidence of how they can be implemented and used most effectively, particularly for individuals receiving MOUD. This project will create the Studies To Advance Recovery Supports (STARS) Network that aims to expand the infrastructure necessary to implement and evaluate peer recovery support services for these individuals. It will build research capacities at universities and health partners, enroll MOUD clinics and peer recovery support professionals, and promote data harmonization across network partners.
5R24DA051950-02 Building a Lasting Foundation to Advance Actionable Research on Recovery Support Services for High Risk Individuals with Opioid Use Disorder: The Initiative for Justice and Emerging Adult Populations Translation of Research to Practice for the Treatment of Opioid Addiction Recovery Research Networks NIDA OREGON SOCIAL LEARNING CENTER, INC. SHEIDOW, ASHLI J Eugene, OR 2021
NOFO Title: Building a Lasting Foundation to Advance Actionable Research on Recovery Support Services for High Risk Individuals with Opioid Use Disorder: The Initiative for Justice and Emerging Adult Populations
NOFO Number: RFA-DA-20-014
Summary:

Emerging adults (ages 16-25) involved with public systems and individuals involved with the justice system (including emerging adults) are at the highest risk for problems stemming from opioid use disorder. Emerging adults report the highest rates of drug use, including opiates, and those involved with public systems are more likely to have poor outcomes. For adults of all ages, opioid use increases the likelihood of justice system involvement. Peer recovery support services and recovery residences are growing nationally and may benefit these two groups tremendously, but research on them is limited. This project will establish the Initiative for Justice and Emerging Adult Populations to advance recovery support services research through a partnership between researchers, people in recovery from these two populations, recovery support service providers, and payors.
5R01NS104295-03 Cellular and Molecular Role of CXCR4 signaling in Painful Diabetic Neuropathy Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS Northwestern University MENICHELLA, DANIELA M Evanston, IL 2019
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Neuropathic pain is a debilitating affliction present in 26% of diabetic patients, with substantial impact on the quality of life. Despite this significant impact and prevalence, current therapies for painful diabetic neuropathy (PDN) are only partially effective, and the molecular mechanisms underlying neuropathic pain in diabetes are not well understood. Our long-term goal is to elucidate the molecular mechanisms responsible for PDN in order to provide targets for the development of therapeutic agents. Our objective is to identify the molecular cascade linking CXCR4/SDF-1 chemokine signaling to DRG nociceptor hyper-excitability, neuropathic pain, and small fiber degeneration. Our aims will determine: 1) the ion-channel current profile of the nociceptor hyper-excitable state produced by CXCR4/SDF-1 signaling in PDN; 2) the gene expression profile of the nociceptor hyper-excitable state produced by CXCR4/SDF-1 signaling in PDN; and 3) the specific features of nociceptor mitochondrial dysfunction produced by CXCR4/SDF-1 signaling in PDN.
5R01NS102432-02 AIBP and regulation of neuropathic pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS Univ. of Calif., U.C. San Diego Miller, Yury La Jolla, CA 2018
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Persistent pain states arising from inflammatory conditions, such as in arthritis, diabetes, HIV, and chemotherapy, exhibit a common feature in the release of damage-associated molecular pattern molecules, which can activate toll-like receptor-4 (TLR4). Previous studies suggest that TLR4 is critical in mediating the transition from acute to persistent pain. TLR4 as well as other inflammatory receptors localize to lipid raft microdomains on the plasma membrane. We have found that the secreted apoA-I binding protein (AIBP) accelerates cholesterol removal, disrupts lipid rafts, prevents TLR4 dimerization, and inhibits microglia inflammatory responses. We propose that AIBP targets cholesterol removal to lipid rafts harboring activated TLR4. The aims of this proposal are to: 1) determine whether AIBP targets lipid rafts harboring activated TLR4; 2) test whether AIBP reduces glial activation and neuroinflammation in mouse models of neuropathic pain; and 3) identify the origin and function of endogenous AIBP in the spinal cord.
5R01NS097880-02 Regulation of neuropathic pain by exercise: effects on nociceptor plasticity and inflammation Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS DREXEL UNIVERSITY DETLOFF, MEGAN R Philadelphia, PA 2018
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Spinal cord injury (SCI) impairs sensory transmission leading to chronic, debilitating neuropathic pain. While our understanding of the molecular basis underlying the development of chronic pain has improved, the available therapeutics provide limited relief. In the lab, we have shown the timing of exercise is critical to meaningful sensory recovery. Early administration of a sustained locomotor exercise program in spinal cord–injured rats prevents the development of neuropathic pain, while delaying similar locomotor training until pain was established was ineffective at ameliorating it. The time elapsed since the injury occurred also indicates the degree of inflammation in the dorsal horn. We have previously shown that chronic SCI and the development of neuropathic pain correspond with robust increases in microglial activation and the levels of pro-inflammatory cytokines. This proposal seeks to lengthen the therapeutic window where rehabilitative exercise can successfully suppress neuropathic pain by pharmacologically reducing inflammation in dorsal root ganglia.
5R01NS094461-04 Clustering of individual and diverse ion channels together into complexes, and their functional coupling, mediated by A-kinase anchoring protein 79/150 in neurons Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANTONIO SHAPIRO, MARK S San Antonio, TX 2018
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Multi-protein complexes have emerged as a mechanism for spatiotemporal specificity and efficiency in the function and regulation of cellular signals. Many ion channels are clustered either with the receptors that modulate them or with other ion channels whose activities are linked. Often, the clustering is mediated by scaffolding proteins, such as AKAP79/150. We will probe complexes containing AKAP79/150 and three different channels critical to nervous function: KCNQ/Kv7, TRPV1, and CaV1.2. We will use"super-resolution" STORM imaging of primary sensory neurons and heterologously expressed tissue-culture cells, in which individual complexes can be visualized at 10–20 nm resolution with visible light. We hypothesize that AKAP79/150 brings several of these channels together to enable functional coupling, which we will examine by patch-clamp electrophysiology of the neurons. Since all three of these channels bind to AKAP79/150, we hypothesize that they co-assemble into complexes in neurons and that they are dynamically regulated by other cellular signals.
5R01DE027454-02 Modeling temporomandibular joint disorders pain: role of transient receptor potential ion channels Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDCR Duke University Chen, Yong Durham, NC 2019
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Masticatory and spontaneous pain associated with temporomandibular joint disorders (TMJD) is a significant contributor to orofacial pain, and current treatments for TMJD pain are unsatisfactory. Pain-related transient receptor potential (TRP) channels, expressed by trigeminal ganglion (TG) sensory neurons, have been implicated in both acute and chronic pain and represent possible targets for anti-pain strategies. Using bite force metrics, we found TMJ inflammation-induced masticatory pain to be significantly, but not fully, reversed in Trpv4 knockout mice, suggesting the residual pain might be mediated by other pain-TRPs. Our gene expression studies demonstrated that TRPV1 and TRPA1 were up-regulated in the TG in response to TMJ inflammation in a Trpv4-dependent manner. We hypothesize that TRPV1 and TRPA1, like TRPV4, contribute to TMJ pain. Our specific aims will examine the contribution of TRPV1, TRPV4, and TRPA1 to pathogenesis of TMJD pathologic pain including assessment of the role of neurogenic inflammation.
5R01DA038645-05 KOR AGONIST FUNCTIONAL SELECTIVITY IN PERIPHERAL SENSORY NEURONS Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDA UNIVERSITY OF TEXAS HLTH SCIENCE CENTER CLARKE, WILLIAM P; BERG, KELLY ANN SAN ANTONIO, TX 2019
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Functional selectivity is a term used to describe the ability of drugs to differentially regulate the activity of multiple signaling cascades coupled to the receptor. The underlying mechanism for functional selectivity is based upon the formation of ligand-specific receptor conformations that are dependent upon ligand structure. Functional selectivity has the potential to revitalize the drug discovery/development process. Ligands with high efficacy for specific signaling pathways (or specific patterns of signaling) that mediate beneficial effects, and with minimal activity at pathways that lead to adverse effects, are expected to have improved therapeutic efficacy. We propose to demonstrate that ligand efficacy for specific signaling pathways associated with antinociception can be finely tuned by structural modifications to a ligand. We propose to use U50,488 and Salvinorin-A (Sal-A) as scaffolds to develop functionally selective analogs that maintain high efficacy for signaling pathways that lead to antinociception and minimize activity toward anti-antinociceptive signaling pathways.
5R01AI132030-02 MINING REAL-TIME SOCIAL MEDIA BIG DATA TO MONITOR HIV: DEVELOPMENT AND ETHICAL ISSUES Translation of Research to Practice for the Treatment of Opioid Addiction NIAID UNIVERSITY OF CALIFORNIA LOS ANGELES YOUNG, SEAN Los Angeles, CA 2018
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Social big data analysis of publicly available user data on social media platforms is a promising approach for attaining organic observations of behavior that can monitor and predict real-world public health problems, such as HIV incidence. In preliminary research, our team identified and collected tweets suggesting HIV risk behaviors (e.g., drug use, high-risk sexual behaviors), modeled them alongside CDC statistics on HIV diagnoses, and found a significant positive relationship between HIV-related tweets and county-level HIV cases. We propose to create a single automated platform that collects social media data, identifies and labels tweets that suggest HIV-related behaviors, and predicts regional HIV incidence. We will interview staff and participants at local and regional HIV organizations to understand ethical issues associated with mining people’s data. The software developed from this application will be shared with HIV researchers and health care workers to combat the spread of HIV.
4UH3NS123964-02 Disease Modifying Analgesia with CA8 Gene Therapy Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF MIAMI SCHOOL OF MEDICINE LEVITT, ROY C Coral Gables, FL 2023
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
4R33NS114954-02 The Inflammatory Index as a Biomarker for Pain in Patients with Sickle Cell Disease Clinical Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS MEDICAL COLLEGE OF WISCONSIN BRANDOW, AMANDA M Milwaukee, WI 2023
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
4R33NS113315-02 Biomarker Signature to Predict the Persistence of Post-Traumatic Headache Clinical Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS MAYO CLINIC ARIZONA CHONG, CATHERINE DANIELA Scottsdale, AZ 2023
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
4R33NS113258-02 Multi-Omic Biomarkers for Neuropathic Pain Secondary to Chemotherapy Clinical Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS CLEVELAND CLINIC LERNER COM-CWRU ROTROFF, DANIEL (contact); FOSS, JOSEPH F; JOHNSON, KENWARD B Cleveland, OH 2023
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
4R33DA057683-02 Leveraging regulatory flexibility for methadone take-home dosing to improve retention in treatment for opioid use disorder: A stepped-wedge randomized trial to facilitate clinic level changes Cross-Cutting Research Translating Data 2 Action to Prevent Overdose NIDA NEW YORK UNIVERSITY SCHOOL OF MEDICINE NEIGHBORS, CHARLES J (contact); BAO, YUHUA; RAMSEY, KELLY S New York, NY 2023
NOFO Title: HEAL Initiative: HEAL Data2Action Innovation Projects (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-DA-22-051
4R33AT010125-02 Effect of Mindfulness Training on Opioid Use and Anxiety During Primary Care Buprenorphine Treatment Translation of Research to Practice for the Treatment of Opioid Addiction Behavioral Research to Improve Medication-Based Treatment NCCIH CAMBRIDGE HEALTH ALLIANCE SCHUMAN OLIVIER, Z Cambridge, MA 2019
NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
4R33AT010118-02 Comprehensive CBT via reSET for a Hub and Spoke MAT System of Care Translation of Research to Practice for the Treatment of Opioid Addiction Behavioral Research to Improve Medication-Based Treatment NCCIH PENNSYLVANIA STATE UNIV HERSHEY MED CTR KAWASAKI, SARAH S; CAMPBELL, AIMEE N; HOLDEN, DENISE; NUNES, EDWARD V. Hershey, PA 2019
NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
4R33AT010117-02 Mindful Moms in Recovery: Yoga-based mindfulness relapse prevention for pregnant women with opioid disorder Translation of Research to Practice for the Treatment of Opioid Addiction Behavioral Research to Improve Medication-Based Treatment NCCIH DARTMOUTH COLLEGE LORD, SARAH E Hanover, NH 2019
NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
4R33AT010109-02 Mindfulness Oriented Recovery Enhancement as an Adjunct to Methadone Treatment for Opioid Use and Chronic Pain Management Translation of Research to Practice for the Treatment of Opioid Addiction Behavioral Research to Improve Medication-Based Treatment NCCIH RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL COOPERMAN, NINA Piscataway, NJ 2019
NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
4R33AT010106-02 Psychosocial pain management to improve opioid use disorder treatment outcomes Translation of Research to Practice for the Treatment of Opioid Addiction Behavioral Research to Improve Medication-Based Treatment NCCIH University of Michigan at Ann Arbor ILGEN, MARK Ann Arbor, MI 2019
NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
3UM1NS118922-03S2 Transition from Acute to Chronic Pain After Thoracic Surgery Cross-Cutting Research Increasing Participant Diversity, Inclusion, and Engagement in HEAL Research NINDS UNIVERSITY OF MICHIGAN BRUMMETT, CHAD M; CHANG, ANDREW CHING-HUNG; CLAUW, DANIEL J; WALJEE, JENNIFER FILIP Ann Arbor, MI 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:

Rigorous and impactful clinical pain research requires participant diversity that reflects the racial/ethnic diversity of affected populations. This project will enhance patient and other community engagement, particularly of underrepresented minorities, to participate in clinical research related to the transition of acute to chronic pain.
3UM1DA049412-04S1 MassHEAL - Reducing overdose deaths by 40% (2019-2023) Cross-Cutting Research Training the Next Generation of Researchers in HEAL NIDA BOSTON MEDICAL CENTER SAMET, JEFFREY Boston, MA 2022
NOFO Title: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: PA-21-071
Summary:

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder, and overdose, gaps remain between those needing and those receiving prevention and treatment. There is a need to better understand how to make these programs and services most effective at a local level, a problem being addressed by the HEALing Communities Study. This project supports a scientist from a group underrepresented in biomedicine to continue ongoing work to test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings.
3UM1DA049412-03S2 Research Supplement to Promote Diversity in Health-Related Research under MassHEAL - Reducing overdose deaths by 40% (2019-2023) Translation of Research to Practice for the Treatment of Opioid Addiction HEALing Communities Study NIDA BOSTON MEDICAL CENTER SAMET, JEFFREY H Boston, MA 2021
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
Summary:

Understanding municipal policies that influence implementation of effective evidence-based practices (EBPs) as well as effective strategies for working with municipal groups may inform local efforts to translate EBPs. Just as important, engaging with local stakeholders may help to facilitate the long-term sustainability of EBPs. This can only occur if diverse local actors in municipal governance are thinking about health and behavioral health in the context of municipal planning and policy. Building from research related opioid use disorder and the risk environment, built environment, and zoning, this research will work to support coalition-based approach currently implemented by the HEALing Communities Study. The research aims to develop an understanding of local policies that may affect implementation of community action plans in the HEALing Communities Study Massachusetts communities.
3UH3NS116218-02S1 Novel mGlu5 Negative Allosteric Modulators as First-in-Class Non-Addictive Analgesic Therapeutic Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS Vanderbilt University ROOK, JERRI MICHELLE Nashville, TN 2022
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements. Parent Grant: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: Supplement: PA-20-272; Parent NOFO: NS-21-010
Summary:

Negative allosteric modulators (NAMs) of the metabotropic glutamate (mGlu) receptor, mGlu5, have shown promise for treatment of multiple pain conditions without the serious adverse effects and safety concerns associated with opioids. This project will develop and test a novel series of highly selective mGlu5 NAMs that are structurally unrelated to earlier failed compounds and do not form toxic byproducts as with previous mGlu5 NAMs. A lead candidate is now being characterized in several studies to assess readiness for testing in Phase I clinical studies.