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) Sort ascending | Year Awarded |
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1UG3DA050322-01
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Preclinical and clinical evaluation of the NMDA modulator NYX-783 for OUD | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Yale University | DiLeone, Ralph | New Haven, CT | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: This study will conduct preclinical and clinical assessments of the NMDA modulator NYX-783 for treatment of opioid drug-seeking and relapse to opioid use disorder (OUD). NYX-783, a novel small molecule being developed by Aptinyx, has shown evidence of safety/tolerability in Phase 1 studies and is currently in Phase 2 trials for post-traumatic stress disorder. This project will test the safety, tolerability, and pharmacokinetics (PK) of NYX-718 in morphine-maintained patients in residential settings and then conduct a combined inpatient (safety/tolerability/PK) / outpatient (preliminary efficacy) study testing NYX-783’s effects on opioid use and relapse, stress/cue reactivity, craving, and quality of life in OUD subjects maintained on standard extended release naltrexone over a 10-week period. Successful completion of these studies will set the stage for larger scale Phase 2/3 studies of efficacy in OUD that will ultimately be required for FDA approval of NYX-783 for the treatment of drug-seeking and relapse in OUD. |
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1R01DA047094-01A1
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Guanfacine Target Engagement and Validation to Improve Substance Use Outcomes in Women | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | YALE UNIVERSITY | Sinha, Rajita | New Haven, CT | 2019 |
NOFO Title: NIH Research Project Grant (Parent R01 Clinical Trial Required)
NOFO Number: PA-18-345 Summary: There are currently no FDA-approved treatments for cocaine use disorder (CUD) or co-occurring substance use disorder. High relapse rates pose a major obstacle to treatment, and this is due in part to the way that high drug cravings reduce individuals’ cognitive flexibility in situations where they are stressed or exposed to drug-related cues. These effects appear to be stronger in women with CUD than in men. Building on preliminary data that a drug called Guanfacine reverses these effects in women, but not in men, this 3-year pilot clinical study will test whether Guanfacine will reduce cocaine use and increase abstinence and will use laboratory challenges to determine whether it reduces cravings and enhances cognitive flexibility in stressful or drug-cue-related situations. |
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1UG3DA048371-01
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Development of Next-generation Pharmacotherapy 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 | ASTRAEA THERAPEUTICS, LLC | ZAVERI, NURULAIN T | Mountain View, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Although effective, current pharmacotherapies for opioid use disorder (OUD) present serious limitations. For example, methadone, a mu opioid receptor (MOP) full agonist, has significant abuse liability and causes withdrawal after chronic use, while buprenorphine (Bup), an MOP partial agonist and kappa opioid receptor (KOP) antagonist, produces limited respiratory depression and is less effective than methadone in reducing drug use, craving, and relapse. To address the limitation of currently available MATs, this project uses a phased plan that will fast-track the IND development of a next-generation medication for OUD based on small-molecule compounds targeting the nociception opioid receptor (NOP)—with no misuse or dependence liability—that have shown promising efficacy in reducing oxycodone intake in rhesus monkeys trained to self-administer, with efficacies similar to that of buprenorphine. The project’s ultimate goal is to file an IND application for an NOP agonist as a promising new approach to treat illicit and prescription OUD that may offer an alternative to buprenorphine. |
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1UG3DA059285-01
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Development of Cebranopadol, a Potent Dual MOP/NOP Agonist, for the Treatment of Opioid Use Disorder (OUD) | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | PARK THERAPEUTICS, INC. | GRIECO, JOSEPH (contact); GREENWALD, MARK K; CICCOCIOPPO, ROBERTO | Morristown, NJ | 2023 |
NOFO Title: Development of Medications to Prevent and Treat Opioid and/or Stimulant Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional)
NOFO Number: PAR-22-200 Summary: There is an urgent need for improved medications to treat OUD. This project will test cebranopadol, a novel synthetic medication that interacts in a new way with the human opioid system as a safe and potentially effective alternative treatment for OUD. The research will test the safety and efficacy of cebranopadol in preclinical and clinical studies, toward guiding future research to support potential approval of this medication by the U.S. Food and Drug Administration. |
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3UH3DA047714-04S1
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Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory 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 | WEST VIRGINIA UNIVERSITY | REZAI, ALI R | Morgantown, WV | 2023 |
NOFO Title: Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory Opioid Use Disorder
NOFO Number: PA-20-272 Summary: Novel treatments for opioid use disorder are critically needed as the addiction and overdose crises continue. Neuromodulation is a promising supplemental treatment to standard care. The overarching project seeks to evaluate low-intensity focused ultrasound that targets the nucleus accumbens, a primary component of the brain’s reward neurocircuitry. This supplement will expand the number of participants in part of the study and will increase the project’s overall impact consistent with the original objectives and aims of the parent grant. |
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5UG3DA047714-02
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Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory 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 | WEST VIRGINIA UNIVERSITY | Rezai, Ali R | Morgantown, WV | 2019 |
NOFO Title: Device-Based Treatments for Substance Use Disorders (UG3/UH3, Clinical Trial Optional)
NOFO Number: PAR-18-494 |
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1R01DA056675-01
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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. |
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1UG3DA048386-01
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Vaccines for fentanyl and its derivatives: A strategy to reduce illicit use and overdose | 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 | PRAVETONI, MARCO | Minneapolis, MN | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: The United States has seen dramatic increases in fatal overdoses due to heroin, counterfeit prescription drugs, and cocaine adulterated with fentanyl or fentanyl-like analogs. Current medications may not be sufficient to address the opioid overdose epidemic. As a complementary strategy, the researchers plan to develop vaccines against fentanyl and fentanyl-like compounds to reduce their abuse liability and the growing incidence of fatal overdoses. This research team has already developed vaccines against heroin and oxycodone that stimulate the production of antibodies effective in reducing opioid distribution to the brain, opioid-induced behaviors, and opioid-induced respiratory depression and have identified a promising fentanyl vaccine candidate cued up for optimization. Successful completion of an anti-fentanyl vaccine development project could offer a long-lasting, safe, and cost-effective intervention complementary to medication-assisted treatment (MAT) and may reduce overdoses in opioid users as well as protect people in professions (e.g., law enforcement, airport security, postal workers) at risk of accidental exposure to fentanyl and fentanyl analogs. |
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1UG3DA048508-01
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Combined tDCS and Cognitive Training for the Treatment of Opioid Addiction | 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 | Lim, Kelvin | Minneapolis, MN | 2019 |
NOFO Title: Device-Based Treatments for Substance Use Disorders (UG3/UH3, Clinical Trial Optional)
NOFO Number: PAR-18-494 |
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1RF1DA050571-01A1
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Reversing opioid-induced hypoxemia with novel thiol-based drugs without compromising analgesia in goats | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | MEDICAL COLLEGE OF WISCONSIN | HODGES, MATTHEW ROBERT; FORSTER, HUBERT V | Milwaukee, WI | 2022 |
NOFO Number: PA-19-056
Summary: Opioid overdoses result from reduced oxygen in the bloodstream. Although the opioid blocker naloxone can reverse the immediate harmful effects of opioids, it also has limitations. It does not last very long, blocks pain relief, and may induce withdrawal. This project will characterize and test the effectiveness of a novel, potent, and long-lasting respiratory stimulant. The study will use a freely behaving, large animal model with physiology similar to humans. |
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1UG3DA054799-01
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Development of Lofexidine as a First-line Non-Opioid Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | USWM, LLC | GULLO, KRISTEN LEANN | Louisville, KY | 2021 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092 Summary: The nation’s opioid epidemic remains a public health emergency, marked by high rates of opioid use and misuse among adults and a correlated rising incidence of neonatal opioid withdrawal syndrome (NOWS) in infants exposed to opioids before they are born. There are currently no pharmacotherapies approved by the Food and Drug Administration (FDA) for the treatment of NOWS. This research will complete manufacturing and clinical trial activities to evaluate and support FDA approval of a pediatric-appropriate formulation of lofexidine, a non-opioid medication approved for mitigation of opioid withdrawal symptoms in adults, as a first line-therapy in NOWS patients through two clinical trials to (1) identify an optimal dosing regimen of lofexidine for treatment of NOWS, and (2) evaluate the risks and benefits of its use in improving withdrawal symptoms, limiting infant exposure to other off-label narcotic medications and shortening the infant’s overall stay in the hospital. |
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1R21DA056740-01
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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. |
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1U01DA056240-01
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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. |
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1R01DA056646-01
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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. |
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1R01DA056828-01
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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. |
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1UG3DA050316-01
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Development of SBI-553, an allosteric modulator of NTR1, for the treatment of substance use disorders | 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 | Pinkerton, Anthony | La Jolla, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Addiction to opioids is related to the physiology of the brain’s dopamine-based reward system. As a modulator of dopaminergic systems, the neurotensin 1 receptor (NTR1) should be a molecular target for treating addictive disorders; however, few non-peptide brain penetrant neurotensin modulators have been identified, and orthosteric NTR1 ligands display side effects that have limited their clinical development. This group discovered a series of brain-penetrant NTR1 modulators, including a lead compound SBI-553, with a unique mechanism of action at NTR1. SBI-553 is an orally available, brain penetrant ?-arrestin biased allosteric modulator of NTR1, which shows efficacy in a range of addiction models and circumvents the clinically limiting side effects. While potentially high risk, the activity of SBI-553 has been validated in vitro and in vivo, and the initial safety profiling indicates no issues that would preclude further development. This study will develop SBI-553 as a treatment for opioid use disorder. |
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1R01DA057120-01
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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. |
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1R01DA056658-01
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Transcriptomic Single-Cell Profiling in Breathing-Specific Parabrachial Mu-Opioid Receptor Neurons | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Salk Institute for Biological Sciences | HAN, SUNG | 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: Opioids can be effective analgesics but can also be fatal due to opioid-induced respiratory depression after overdose. This project will use cutting-edge molecular, physiological, behavioral, and imaging techniques to better understand and distinguish opioid-induced respiratory depression and opioid-mediated analgesia. Nerve cell-specific, single-cell transcriptomic analysis will be used to identify functional markers expressed in nerve cells that play a specific role in opioid-induced respiratory depression, but not opioid analgesia. This research study will help to identify novel therapeutic targets that could selectively rescue opioid-induced respiratory depression while maintaining the beneficial pain-relieving effects of opioids. |
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1UG3DA050923-01
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AMPA Antagonism: A Novel Pharmacology for Launching Recovery from Opioid Addiction | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS | Chambers, Robert | Indianapolis, IN | 2020 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: The excruciating multiday experience of opioid withdrawal syndrome (OWS), is exacerbated by the opioid antagonist drugs naloxone and naltrexone. This industry-academia collaboration will explore the potential of the glutamate AMPA receptor antagonist Tezampanel (TZP). Animal studies have shown reduced hyperactivity in brain circuits involved in OWS, without relying on direct stimulation or antagonism of the opioid system ,and has already been delivered to over 500 human subjects and found to be safe for a potential migraine indication. This proposal will build up the evidence needed to apply for and conduct open label and blinded placebo-controlled human trials of TZP safety and efficacy for OWS. If successful, this project will allow planning for a pivotal registration trial for TZP for OWS, and as a transitional treatment to long-term recovery on naltrexone and help us stem the tide of the opioid crisis. |
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1R01DA056673-01
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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. |
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1UG3DA050325-01
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Use of a GLP-1 Agonist to Treat Opioid Use Disorder in Rats and Man | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Pennsylvania State University Hershey Medical Center | Grigson, Patricia | Hershey, PA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: High relapse rates among people with opioid use disorder (OUD) indicate that addiction involves appetitive pathways. Peripheral stimulation of the glucagon-like peptide-1 receptor (GLP-1R) “satiety” pathway could reduce heroin seeking and taking. Pretreatment with a GLP-1R agonist reduces heroin taking, seeking, and drug-induced reinstatement in rats. This project tests whether GLP-1R agonists can reduce relapse in humans with OUD. A pilot study will be conducted to determine whether once-daily treatment with the shorter acting GLP-1R agonist, liraglutide, can safely and effectively reduce cravings among OUD patients. Animal models will be used to test the efficacy and safety of a longer-acting GLP-1R agonist, semaglutide, and then a clinical trial will be conducted to test whether semaglutide will reduce relapse and use in animal models. If successful, the study will show that treatment with GLP-1R agonists can safely and effectively reduce opioid craving, seeking, and relapse. |
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1R61HL156240-01
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Treatment of Fentanyl Overdose-Induced Respiratory Failure by Low-Dose Dexmedetomidine | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NHLBI | PENNSYLVANIA STATE UNIV HERSHEY MED CTR | HAOUZI, PHILIPPE A | Hershey, PA | 2020 |
NOFO Title: HEAL Initiative: Pharmacotherapies to Reverse Opioid Overdose Induced Respiratory Depression without Central Opioid Withdrawal (Target Validation and Candidate Therapeutic Development (R61/R33 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-20-031 |
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1UG3DA050317-01
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Targeting the Ghrelin System for Novel Opioid Use Disorder Therapeutics | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | The University of Texas Medical Branch at Galveston | Cunningham, Kathryn | Galveston, TX | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: To address the need for novel therapeutics for opioid use disorder (OUD), this research group identified ghrelin as an endogenous regulator of the mesocorticostriatal circuit, which contributes to the enhanced motivational attributes of addictive drugs and drug-associated cues. Ghrelin binds to the growth hormone secretagogue receptor 1? (GHS1?R) to transduce several physiological and behavioral processes, including the reward-related effects of opioid agonists. Systemic administration of a GHS1?R antagonist/inverse agonist dose-dependently attenuated self-administration of the addictive opioid analgesic oxycodone as well as oxycodone-seeking. This project proposes to employ a suite of validated rodent OUD models to define the preclinical profile for PF5190457, a selective GHS1?R antagonist/inverse agonist. PF5190457’s abuse liability, ability to suppress withdrawal and relapse-like behaviors, drug metabolism and pharmacokinetics, and brain penetrability in rats will be assessed. Phase 1 clinical studies in non–treatment seeking OUD participants will follow to assess the safety and tolerability of PF5190457. |
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1UG3DA052282-01
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NOP Receptor Antagonist for OUD Pharmacotherapy | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | UNIVERSITY OF TEXAS MED BR GALVESTON | Cunningham, Kathryn | Galveston, TX | 2020 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Medication-based treatment for opioid use disorder OUD aids in reducing mortality, opioid withdrawal, intake and opioid-seeking behaviors, however there is a clear need to increase the armamentarium of therapeutics for OUD. The ?non-classical? NOcicePtin receptor (NOPr) binds the endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ) and is a promising target based on the evidence for its function in the regulation of the rewarding and motivational effects of opioids and alcohol. This study plans to assess the ability of the novel and selective NOPr antagonist BTRX-246040 to block oxycodone intake without abuse liability, and to suppress oxycodone withdrawal and relapse-like behaviors in rats. The study will also determine Drug Metabolism and Pharmacokinetics interactions (DMPK) between oxycodone and BTRX-246040 and brain penetrability in male and female rats. If successful, these preclinical studies will be followed by a Phase 1 clinical trial in non-treatment seeking OUD participants. These investigations will advance the prospects of validating a novel medication for OUD. |
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1UG3DA048745-01A1
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Nalmefene Long-Acting Injectable (AP007) for the Treatment of 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 | Emergent Product Development Gaithersburg Inc. | Barry, John | Gaithersburg, MD | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002 Summary: Although medications are available to treat opioid use disorder (OUD), adherence with treatment programs remains a problem. Nalmefene is an opioid receptor antagonist that was previously approved for treatment of opioid overdose–induced respiratory depression that has a longer duration of action than naloxone. AP007 is a unique formulation of nalmefene-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles that when injected intramuscularly continually releases an effective dose of nalmefene and thus reduces opioid cravings in OUD patients. This group is developing AP007 and will have a lead formulation selected based on in vitro release kinetics data and in vivo pharmacokinetics data in rats. The objectives of the project are to determine safety and efficacy of AP007 in a swine opioid use/withdrawal model, preliminary safety in a first-in-human Phase 1 study, and preliminary efficacy in a Phase 2a multidose study. These results will be used to develop Phase 2 human and Phase 3 clinical studies. |