Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1R01DA056660-01 Target Specificity of Tabernanthalog Treatment in Opioid Use Disorder Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA University of Colorado, Denver PETERS, JAMIE (contact); HEINSBROEK, JASPER Denver, Colorado 2022
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031
Summary:

Currently available treatments for opioid use disorder (OUD) are insufficient for many patients. Novel compounds that can promote alterations in brain connections (i.e., neural plasticity) possess enormous potential for improving substance use disorder (SUD) treatments. Psychedelic compounds induce neural plasticity and can elicit long-lasting, beneficial impacts on a wide variety of SUDs. However, these compounds have significant side effects, including hallucinations and cardiotoxicity. Researchers have developed a novel, synthetic derivative of the psychedelic ibogaine, called tabernanthalog, that does not have these side effects. This compound has demonstrated both short- and long-term therapeutic effects in a preclinical model of OUD. This research study will determine the molecular and neural mechanisms through which tabernanthalog affects opioid seeking. It will also evaluate whether the effects are specific to opioids and do not alter response to natural rewards and will examine the efficacy of tabernanthalog in a preclinical model of comorbid opioid and alcohol use disorder.
1R01DA056673-01 Targeting Tiam1-Mediated Synaptic Plasticity for the Relief of Opioid Tolerance Novel Therapeutic Options for Opioid Use Disorder and Overdose Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose NIDA Baylor College of Medicine LI, LINGYONG (contact); TOLIAS, KIMBERLY Houston, TX 2022
NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031
Summary:

Chronic opioid use results in tolerance, a primary driver for opioid misuse and overdose that directly contribute to increased morbidity and mortality. Changes in neuronal connectivity known as synaptic plasticity are a key determinant of opioid tolerance, but the underlying molecular mechanisms remain unclear. Tiam1 is a protein known to control the development of nerve cells and their connections and is also involved in morphine-induced neuronal changes. This research will examine Tiam1-mediated synaptic plasticity underlying opioid tolerance and validate Tiam1 as a potential therapeutic target for prevention of tolerance development.
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 (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. 
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
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.
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
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.