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 Sort descending | Research Focus Area | Research Program | Administering IC | Institution(s) | Investigator(s) | Location(s) | Year Awarded |
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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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1UG3DA048768-01A1
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Novel LAAM formulations to treat 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 | Virginia Commonwealth University | Xu, Qingguo | Richmond, VA | 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: Levo-alpha-acetylmethadol (LAAM) offers numerous behavioral and clinical advantages for select opioid use disorder (OUD) patients who do not respond to standard treatment. While LAAM was withdrawn from the market despite being approved for OUD treatment, this project seeks to develop novel, patentable, convenient dosage forms of LAAM, including novel LAAM oral dosage formulations and novel buccal film formulations of LAAM. Morphology, mechanical property, drug release kinetics, and stability of the oral dosage and buccal film formulations will be characterized to determine the instant release or steady release of LAAM, respectively. The two lead LAAM formulations with adequate release and stability profiles will be chosen through optimization studies both in vitro and in vivo. A human pharmacokinetic/pharmacodynamic study will then be carried out on the two selected formulations. |
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1UG3DA048775-01
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Novel nanovaccines against 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 | VIRGINIA POLYTECHNIC INST AND ST UNIV | ZHANG, CHENMING M; PRAVETONI, MARCO | Blacksburg, VA | 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: Opioid use disorders (OUD) are a national public health emergency with more than 115 fatal overdoses occurring each day in the U.S. and an economic burden of more than $78 billion a year. Several medications are available for treating OUD, but their access is limited and efficacy is often sub-optimal. It is thus urgent to develop new, affordable strategies for the effective treatment of OUD. Immunopharmacotherapy has emerged as a promising treatment approach against OUD that relies on the induction of drug-specific antibodies to neutralize circulating drug molecules and reduce or cancel their effects. Several groups have attempted to apply this strategy with mixed results, suggesting that novel immunization platforms must be tested to further improve vaccine efficacy against OUD. This project will fabricate novel nanoparticle-based vaccines against OUD that are likely to boost their immunogenicity and lead to a more robust and effective immune response against the target opioid. The broad impact of this project resides in the rational design of nanoparticle-based vaccines that are safe and effective against opioids. This novel nanoparticle-based immunization strategy can be applied to the development of next-generation vaccines against a range of OUD and other substance use disorders. |
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1UG3DA049598-01
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Novel Therapeutics for Opioid Use Disorder in the Acute Overdose and Maintenance Settings | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Epiodyne, Inc. | Schmidt, William | San Francisco, 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: Opioid use disorder (OUD) and opioid overdose (OD) are major health issues. Breathing can be restored after OD by naloxone, but its short half-life can require multiple administrations to reverse OD, and OD symptoms may return after initial reversal if illicit opioids are still present after the effects of naloxone have worn off. Additionally, while the standard treatment of OUD with buprenorphine and methadone reduces relapse and mortality, access and adoption are limited by dosage forms, metabolic liabilities, and potential for misuse and diversion. This study seeks to develop chemically novel, potent mu-opioid receptor (MOR) antagonists and low- and mid-efficacy partial agonists. Current lead counts can outcompete opioid overdoses in preclinical models with a longer half-life, a key naloxone liability for treating OD. The potent, low-efficacy partial agonists add a low opioid tone, diminishing the aversive effects of pure antagonists. These, and the mid-efficacy partial agonists, are leads to maintenance therapeutics for OUD. |
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1R03DA046011-01A1
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Opioid sparing potential of light-induced analgesia: a pilot trial of a novel, non-pharmacological treatment for pain | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | DUKE UNIVERSITY | Gulur, Padma | Durham, NC | 2019 |
NOFO Title: NIDA Small Research Grant Program (R03 Clinical Trial Required)
NOFO Number: PA-18-634 Summary: Exposure to opioid analgesics during medical care is a key driver of the opioid epidemic. Such exposures are widespread. Yet opioids remain essential first-line agents in treating pain, and it remains vital that pain be appropriately managed. Non-opioid pain treatments help to resolve the opioid/pain conflict. This project will examine the opioid-sparing and pain-relieving potential of a novel, non-pharmacological treatment for pain, using the effects of green light exposure to reduce pain and thereby reduce the quantity of opioids needed for pain relief. |
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1UG3DA048353-01
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Opioid use disorders: UF Pharmacy medications discovery and development | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | UNIVERSITY OF FLORIDA | MCMAHON, LANCE R; MCCURDY, CHRISTOPHER R | Gainesville, FL | 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: Opioids have been significantly over-prescribed and are associated with numerous deaths, resulting in the nation’s current opioid crisis. The FDA recently approved the ?2 adrenergic agonist lofexidine as a non-addictive, non-opioid treatment for opioid use disorder (OUD), but there is a continued, urgent need to develop additional pharmacological alternatives to address both pain and OUD. The psychoactive, natural product, Mitragyna speciosa (kratom), has triggered significant interest in this space because Mitragynine, its main alkaloid, can interact with both mu opioid and ?2 receptors, offering a totally new approach for treating OUD. This project involves the synthesis and research of a series of Mitragynine analogs to better understand the pharmacological mechanisms that underlie Mitragynine’s opioid and adrenergic activities. If successful, this project will result in templates for the design of novel opioid receptor ligands. This advance would greatly improve the knowledge of interactions of these structurally novel compounds with opioid receptors and facilitate the development of these ligands as treatments for OUD. |
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1U01DA058541-01
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PDE7 Inhibitor for the 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 | OMEROS CORPORATION | GAITANARIS, GEORGE | Seattle, WA | 2023 |
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327 Summary: Currently there are no effective treatments approved by the U.S. Food and Drug Administration for cocaine use disorder. This project will explore the use of a novel class of small molecules that selectively block the molecule phosphodiesterase 7 (PDE7). Past research suggests that the PDE7 class of compounds helps restore normal functions of the dopamine reward system altered by chronic exposure to cocaine. This research will use both preclinical and clinical research studies to develop and test a PDE7 blocker, toward development of the first oral treatment for cocaine use disorder. |
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1UG3DA047682-01
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PF614 MPAR Abuse Deterrent opioid prodrug with overdose protection: Pre-Clinical Development and Phase 1 Clinical Trial | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | ENSYSCE BIOSCIENCES, INC. | KIRKPATRICK, LYNN | San Diego, 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: Several abuse-deterrent opioid products (primarily formulations) are currently marketed or in clinical development, but they fall short of being resistant to abuse. Rather than abuse-deterrent formulations, this project, in partnership with Ensyce Biosciences, has created two complementary, novel technologies that control the release of known opioids. One technology delivers prodrugs — drugs that are not active until they have been exposed to the right conditions within the body, at which point they are gradually converted into active drugs, making them difficult to tamper with and reducing the potential for misuse. Another technology makes it so that taking increasing numbers of pills inhibits the process of converting prodrug into active drug, reducing the potential for overdose. This project aims to refine the development of these two technologies and work to combine them, and to translate promising animal results into human use. |
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5UG3DA047682-02
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PF614 MPAR Abuse Deterrent opioid prodrug with overdose protection: Pre-Clinical Development and Phase 1 Clinical Trial | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | ENSYSCE BIOSCIENCES, INC. | Kirkpatrick,Lynn | San Diego, CA | 2019 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: DA19-002 |
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1UG3DA056247-01
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Phase 1 and 2 Studies of Sublingual Dexmedetomidine, an Alpha 2 Adrenergic Agonist, for Treating Opioid Withdrawal | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | NEW YORK STATE PSYCHIATRIC INSTITUTE dba RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC | LEVIN, FRANCES RUDNICK | New York, NY | 2022 |
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: Withdrawal symptoms associated with current opioid use disorder treatments, such as naltrexone or buprenorphine, can be serious obstacles to successful treatment. This project aims to develop a U.S. Food and Drug Administration-approved sedative medication (dexmedetomidine) as an under-the-tongue film to treat opioid withdrawal symptoms at doses that have minimal ill effects on blood pressure and heart rate. This research will compare the safety and efficacy of dexmedetomidine to lofexidine, which is currently approved to treat opioid withdrawal. |
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3UG3DA047711-02S1
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PHASE 1A/1B CLINICAL TRIALS OF MULTIVALENT OPIOID VACCINE COMPONENTS | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | NEW YORK STATE PSYCHIATRIC INSTITUTE | COMER, SANDRA D; PRAVETONI, MARCO | New York, NY | 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: Opioid use disorder (OUD) is a serious public health problem that is associated with high rates of morbidity and mortality. The proposed Phase 1a/1b studies are designed to evaluate a novel treatment strategy for OUD. Specifically, the safety, immunogenicity and preliminary efficacy of a vaccine (OXY-KLH) targeted against oxycodone (Study 1) and a vaccine (M-KLH) targeted against heroin/morphine (Study 2) will be evaluated in participants diagnosed with OUD. |
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1UG3DA047711-01
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Phase 1a/1b Clinical Trials of Multivalent Opioid Vaccine Components | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | NEW YORK STATE PSYCHIATRIC INSTITUTE | COMER, SANDRA D; PRAVETONI, MARCO | New York, NY | 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 current studies are designed to examine a novel approach to treating OUD, namely use of a vaccine (OXY-KLH) targeted against oxycodone, one of the most commonly misused prescription opioids, and a vaccine (M-KLH) targeted against heroin/morphine. The researchers will evaluate the safety, immunogenicity, and preliminary efficacy of OXY-KLH and M-KLH. Overall, the proposed studies will provide a great deal of information about the safety and potential efficacy of the vaccines in reducing the addiction liability of opioids, which will be administered in a controlled laboratory setting. If the outcomes of the proposed studies with OXY-KLH and M-KLH are favorable, development of the bivalent vaccine (OXY-KLH plus M-KLH) that will target oxycodone and heroin will proceed. The long-term goal of this research is to develop a multivalent vaccine directed against oxycodone, heroin, and other relevant opioids. |
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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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1UF1DA054817-01A1
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Preclinical Development of Novel Dual OXR/KOR Antagonists for Treatment of Substance Use Disorder | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | HAGER BIOSCIENCES, INC. | BUTERA, JOHN A | Bethlehem, PA | 2021 |
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327 Summary: Substance use disorder (SUD) is a serious public health and socioeconomic burden. In this project, researchers will develop novel drug compounds that dually target orexin receptors and kappa opioid receptors, which have both been implicated in SUD. The compounds will then be tested for effectiveness in preclinical models of SUD, including models of cocaine, methamphetamine, and fentanyl use. This research has the potential to provide highly impactful and innovative treatment options for SUD via simultaneous modulation of multiple signaling pathways. |
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1R21DA048074-01
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Prescription Opioid Formulation to Deter Extraction, Injection, Insufflation, and Smoking | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | PURDUE UNIVERSITY | Solorio, Luis | West Lafayette, IN | 2019 |
NOFO Title: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
NOFO Number: PA-18-489 Summary: This project aims to develop a novel abuse deterrent formulation (ADF) that will be uniquely designed to prevent abuse of the prescription pill. The study will focus on the development of the ADF with design aspects specifically focused on abuse through insufflation, smoking, injection, and taking multiple pills. The study will also validate the design by putting the pill through a rigorous test following the procedures outlined by the FDA Abuse-Deterrent-Opioids-Evaluation and Labeling guidelines. The study could result in the development of a novel ADF that will be resistant to a wide range of tampering, resulting in a safer formulation and pill design. |
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1U01DA051071-01A1
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Process Development, Manufacturing, and Preclinical Evaluation of a Monoclonal Antibody for Fentanyl Overdose | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | CESSATION THERAPEUTICS, LLC | Bremer, Paul T. | San Jose, CA | 2020 |
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327 Summary: Opioid use disorder (OUD) is a significant public health problem in the United States. Particularly troubling is the rapid evolution of an opioid epidemic within the past decade, characterized by a surge in unintentional overdose deaths involving synthetic opioids, such as fentanyl. The current standard of care for opioid overdose is reversal with opioid antagonist naloxone. Naloxone is effective at reversing overdose from prescription opioids and heroin, but less effective when combating fentanyl, due to fentanyl?s high potency. Therapeutic monoclonal antibodies (mAbs) against fentanyl could overcome this problem by specifically preventing the drug from entering the central nervous system, averting overdose and attenuating opioid-induced respiratory depression. This study will develop and design of laboratory protocols needed to establish a Good Manufacturing Practice (GMP) process, quality assurance protocol, and stability profile for a new human mAb against fentanyl. Subsequent production of current GMP material will enable Good Laboratory Practice (GLP) toxicology studies in rats and dogs and eventually a Phase I/IIa clinical trial. This material will also be used in final opioid-induced respiratory depression studies in mice and non-human primates to confirm therapeutic efficacy of final drug product. If successful, these activities will enable filing for an investigational new drug application for this mAb candidate with the FDA. |
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1U01DA047713-01
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PTPRD ligands for stimulant and opiate use disorders | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | BIOMEDICAL RESEARCH INSTITUTE OF NEW MEX | Uhl, George Richard | Albuquerque, NM | 2019 |
NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 Clinical Trial Optional)
NOFO Number: PAR-18-219 Summary: There are no FDA-approved medications for stimulant use disorders, and therapies for opioid use disorders remain suboptimal in ways that are now a focus of national attention. Thus, there is a clear need to identify new targets and explore new approaches for addiction medication development. Several lines of evidence suggest that PTPRD (receptor type protein tyrosine phosphatase D) may be a promising target for development of pharmacotherapeutics to treat not only stimulant use disorders but opioid use disorders as well. This research will focus on improving existing PTPRD ligands, identifying their effects on the dopamine and opioid systems, and moving the best novel, patentable PTPRD ligands toward human studies. If successful, this project will generate novel, well-tolerated, and bioavailable PTPRD ligands that display in vitro potency, selectivity and stability, and in vivo modulation of both cocaine and opioid-mediated reward at doses that present no significant toxicity. |
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1UG3DA050271-01
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R-methadone-TAAP/MPAR: an abuse deterrent methadone prodrug with overdose protection: Pre-Clinical Development and Phase 1 Clinical Trial | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | Ensysce Biosciences, Inc. | Kirkpatrick, Lynn | San Diego, 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: Methadone is useful in the treatment of opioid dependence; however, methadone misuse and methadone-related fatalities have increased. Ensysce has created two complementary, novel technologies that can be applied to methadone. Their Trypsin Activated Abuse Protection (TAAP™) prodrugs are “enzyme-activated” to release clinically effective opioid drugs only when taken orally and exposed to the correct physiologic conditions, such as exposure to trypsin in the small bowel. Their multi-pill abuse resistance (MPAR™) feature involves in situ bioregulation of opioid delivery from the TAAP™ systems, enabling control over oral multi-dose pharmacokinetic profiles. It is envisaged that an R-methadone-TAAP™ prodrug would demonstrate similar reduced addiction liability as with other opioid-TAAP products. The objective of this proposal is to develop an R-methadone-TAAP™/MPAR™ drug through Phase 1 clinical studies and to translate R-methadone-TAAP™/MPAR™ results into humans, to ultimately reduce the misuse and oral overdose potential of methadone. |
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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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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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1R01DA056660-01
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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. |
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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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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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3UG3DA047793-01S1
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tDCS to decrease opioid relapse | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | BUTLER HOSPITAL (PROVIDENCE, RI) | Abrantes, Ana M | Providence, RI | 2019 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: Neurostimulation techniques, such as transcranial direct current stimulation (tDCS), have been used as interventions for substance use disorders. This is a supplement to the currently NIDA-funded UG3 DA047793, “tDCS to Decrease Opioid Relapse,” which will measure behavioral and brain responses following tDCS stimulation delivered during tasks that use a particular brain network involved in cognitive control, and utilizing FMRI to assess the effects. This supplement allows the researchers to add an EEG measurement to the study, to get a complete picture of how tDCS might affect the function of key brain networks in ways that could be helpful for SUDs. |
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1UG3DA053094-01A1
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The Development of Delta Opioid Receptor Agonists for the Treatment of Opioid Withdrawal Associated Behaviors | Novel Therapeutic Options for Opioid Use Disorder and Overdose | Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose | NIDA | UNIVERSITY OF ILLINOIS AT CHICAGO | PRADHAN, AMYNAH AMIR ALI | Chicago, IL | 2022 |
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: This project aims to develop a new way to stimulate the delta opioid receptor to treat withdrawal and abstinence from chronic opioid use. Withdrawal can cause pain, depression, and anxiety, which contribute to relapse. The research will test promising drug candidates in animal models with the intention of bringing at least one effective and safe compound to the final stage of drug development before human clinical trials can begin. |