Funded Projects

Project # Project Title Research Focus Area Research Program Administering IC(s) Institution(s) Investigator(s) Location(s) Year Awarded
1UG3DA056247-01
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
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA 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.

1UG3DA053094-01A1
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
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA 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.

1U01DA057846-01
Transdermal Rotigotine as Adjunct to Behavioral Therapy for 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 VIRGINIA COMMONWEALTH UNIVERSITY BJORK, JAMES M; ARIAS, ALBERT JOSEPH Richmond, VA 2022
FOA Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01)
FOA Number: PAR-19-327
Summary:

Currently no medications are approved by the U.S. Food and Drug Administration to treat cocaine use disorder, which compromises cognitive function associated with achieving goals such as working memory, the ability to update information, and mental flexibility. This project will test whether  stimulating dopamine activity in the brain with the drug rotigotine (approved to treat Parkinson’s disease) is effective for treating cocaine use disorder. Past research has also shown that rotigotine can improve nerve cell and cognitive function in Alzheimer’s disease. This project will conduct a clinical trial to test whether treatment with rotigotine combined with cognitive behavioral therapy can reduce cocaine use in people with cocaine use disorder.

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

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

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

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

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

1UG3DA057853-01
Naltrexone Transdermal Patch - An Accessible, Patient-Focused Option to Treat OUD Relapse Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA LIBERO PHARMA LIMITED GARDINER, ANDREW Edinburgh, United Kingdom 2022
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3)
FOA Number: PAR-20-092​
Summary:

Naltrexone is the only medication approved by the U.S. Food and Drug Administration to prevent relapse from opioid use disorder. This medication remains underused because it must be injected into muscle by a nurse and is relatively expensive. This project will develop and test a novel naltrexone skin patch that is easier to use, more comfortable, and inexpensive.

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

1R01DA056660-01
Target Specificity of Tabernanthalog Treatment in Opioid Use Disorder Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of Colorado, Denver PETERS, JAMIE; HEINSBROEK, JASPER Denver, Colorado 2022
FOA Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
FOA 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.

1R21DA056637-01
KCa2 Channel Activators 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 University of California, Davis WULFF, HEIKE Davis, CA 2022
FOA Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R21 Clinical Trial Not Allowed)
FOA Number: RFA-DA-22-032
Summary:

Safe and effective options are urgently needed to prevent and treat opioid use disorder and polysubstance use disorders. Previous research in humans and animals suggests that activating the calcium-activated potassium channel KCa2.2 is a promising therapeutic approach for treating substance use disorders and associated health conditions. This project will perform a virtual high-throughput screen using novel machine learning approaches to discover new molecules that interact with the KCa2.2 channel. The newly discovered molecules help develop novel drugs for the treatment of opioid use disorder and associated health conditions.

1R01DA056658-01
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
FOA Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
FOA 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. 

1UG3DA054785-01A1
Development of Specific Mu Opioid Receptor Antagonists to Reverse the Acute and Chronic Toxicity of Fentanyls 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 ZHANG, YAN Richmond, Virginia 2022
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: PAR-20-092
Summary:

Fentanyl and its analogs are synthetic opioids that are 100 to 10,000 times more potent than morphine. Overdose from these opioids is extremely dangerous due to their ultra-potency and longer half-life than naloxone, the front-line treatment for fentanyl overdose. This research study will develop novel mu opioid receptor antagonists that bind to the same receptor as the opioid drugs and specifically counteract fentanyl and its analogs, thereby reversing the drugs’ acute toxicity more effectively and with fewer side effects than current treatments. The researchers will characterize novel fentanyl derivatives, identify promising compounds, and pursue preclinical development of these compounds as novel reversal agents against the acute toxicity of fentanyl. The goal is to file an Investigational New Drug application with the U.S. Food and Drug Administration.

1R01DA056608-01
Endocannabinoid Targeting for Opioid Induced Respiratory Depression Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of Arizona MILNES, TALLY MARIE; VANDERAH, TODD W Tucson, Arizona 2022
FOA Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
FOA Number: RFA-DA-22-031
Summary:

This research project will investigate the cannabinoid receptor 2 protein (CB2R) as a novel therapeutic target for opioid-induced respiratory depression caused by fentanyl, oxycodone, and heroin. This study will shed light on how the endocannabinoid system in the brainstem works to control breathing under normal conditions and during opioid-induced respiratory depression. The research aims to determine whether activation of the CB2R with a brain-penetrant CB2R-binding molecule is safe and clinically useful for treating opioid overdose prevention and reversal. This research will pave the way for discovering new medications that activate CB2R to reduce opioid-related deaths.

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

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

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

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

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

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

3UG3DA048502-01A1S2
Non-invasive vagal nerve stimulation in 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 EMORY UNIVERSITY BREMNER, JAMES DOUGLAS Atlanta, GA 2021
FOA 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)
FOA Number: NOT-NS-20-107
Summary:

This research will expand the understanding of the effects of non-invasive vagal nerve stimulation on patients with opioid use disorder by examining the relationship between nerve stimulation and treatment, respiratory physiology, withdrawal symptoms, and relapse. Additionally, these relationships will be added to existing algorithms and equipment being developed by the Inan Research Lab at the Georgia Institute of Technology. Collecting and determining the quality of conventional respiration signals, as well as collecting high-resolution impedance based respiratory measurements, will help to determine the impact of non-invasive vagal nerve stimulation on breathing and lung function in people with opioid use disorder, toward development of a profile of physiological effects of non-invasive vagal nerve stimulation during opioid withdrawal.

1UF1DA054817-01A1
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
FOA Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
FOA 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.

1UG3DA052166-01A1
CVL-354, a kappa opioid receptor antagonist for treatment of opioid use disorder, withdrawal and relapse Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA CEREVEL THERAPEUTICS, LLC IREDALE, PHILIP Cambridge, MA 2021
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: PAR-20-092
Summary:

Kappa opioid receptors (KOR) are expressed in brain areas that control reward, motivation, and anxiety. Upon opioid drug withdrawal and abstinence, dysregulated KOR signaling can result in aversive physical and affective states that are a major driver of relapse. Preclinical data have demonstrated that antagonism of KOR can reduce the physical symptoms of opioid withdrawal. Currently, the alpha 2-adrenergic agonist lofexidine is the only approved therapy for the mitigation of the physical symptoms of opioid withdrawal but it is only modestly effective and can have significant unwanted side effects. Cerevel Therapeutics has identified a novel selective KOR antagonist, CVL-354, with unique properties and good preclinical safety margins. This project will assess this drug in early human safety/pharmacokinetics and occupancy studies. Future studies will then be able to assess efficacy of this drug in acute opioid withdrawal.

1UG3DA054825-01
A novel and highly selective orexin 1 receptor antagonist for the treatment of patients with 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 ASTRAZENECA PHARMACEUTICALS INAMDAR, AMIR Wilmington, DE 2021
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: PAR-20-092
Summary:

In collaboration with Eolas Therapeutics and the NIH Blueprint Neurotherapeutics Network, AstraZeneca has developed a novel compound for treatment of opioid use disorder, AZD4041, which targets orexin 1 (OX1) receptors in the brain. In animal studies, AZD4041 reduced the motivation to consume opioids or nicotine, reduced relapse-like drug-seeking behaviors, and showed a favorable safety profile. The compound also has proven to be safe in an initial Phase 1 clinical trial in healthy human volunteers. This project will further evaluate the safety (e.g., respiratory depression profile) of AZD4041 in human volunteers, using multiple and increasing doses. Upon successful completion of these studies, the compound will be tested in a proof-of-concept efficacy study in patients with opioid use disorder. If this is successful, the compound will advance to larger Phase 2 and Phase 3 pivotal clinical trial to tests its effectiveness in the treatment of opioid use disorder.

1UG3DA053123-01
Bacteriophage virus-like particle vaccines for fentanyl and heroin 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 NEW MEXICO HEALTH SCIS CTR CHACKERIAN, BRYCE C Albuquerque, NM 2021
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: PAR-20-092
Summary:

Opioids account for nearly 70 percent of overdose deaths in the United States, with fentanyl and heroin use the most common causes. The goal of this project is to create a vaccine to elicit serum antibodies that bind and sequester the drug in the blood, preventing it from crossing the blood-brain barrier where it acts on the central nervous system. Current opioid vaccine strategies require multiple boosts and months to reach peak titers, the level of antibodies in a blood sample, and have yet to show protection against lethal overdose. In this project, researchers will use a bacteriophage virus-like particle vaccine platform to engineer and test the effectiveness of a combined vaccine to elicit high titer antibodies quickly to protect against lethal overdose from fentanyl or heroin.

1UG3DA054799-01
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
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA 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.

1UG3DA052173-01A1
Combating opioid addiction using CVL-936, a novel D3/D2 receptor antagonist Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA CEREVEL THERAPEUTICS, LLC CHAKILAM, ANANTHSRINIVAS RAO Cambridge, MA 2021
FOA Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
FOA Number: PAR-20-092
Summary:

Opioid use and addiction affects more than 2 million Americans and contribute to a large proportion of all drug overdose deaths. Current treatments for opioid use disorder (e.g., methadone and buprenorphine) are not always effective, may be misused, and can have side effects that discourage treatment continuation. Therefore, Cerevel Therapeutics is evaluating a novel compound, CVL-936, which targets brain molecules called dopamine D3 receptors. These receptors are involved in the brain’s reward and relapse pathways and are present in higher levels in people with addictions. In animal studies, the molecule reduced self-administration of nicotine and fentanyl, including in relapse situations. The project will test the safety and tolerability of CVL-936 in animals and healthy humans and will examine its effectiveness in reducing craving in people with opioid use disorder.