Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1R01HL150836-01
Sleep, opiate withdrawal and the N/OFQ - NOP system New Strategies to Prevent and Treat Opioid Addiction Sleep Dysfunction as a Core Feature of Opioid Use Disorder and Recovery NHLBI SRI International KILDUFF, THOMAS S (contact); BRUCHAS, MICHAEL R Menlo Par, CA 2019
NOFO Title: HEAL Initiative: Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder (OUD) and Response to Medication Assisted Treatment (MAT) (R01 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-19-028
Summary:

The widespread misuse of opioids has underscored the need to develop nonaddicting pain medications. Chronic pain is a major factor contributing to insomnia, and sleep disruption due to chronic pain causes patients to seek relief, exacerbating the drive for prescription opioids. In opioid use disorder, withdrawal from opiates induces insomnia, posing an additional challenge for successful abstinence. This study aims to determine whether treatment of opioid withdrawal-induced insomnia with nociceptin/orphanin FQ receptor (NOPR) agonists will mitigate the drive for opiate use. A major component of the arousal/withdrawal circuitries resides in the locus coeruleus (LC), which expresses MOPRs. The study will determine whether and how the NOPR system engages LC circuits to reduce arousal and insomnia-related phenotypes and assess the hypotheses that 1) the NOPR system is a component of the endogenous sleep/wake regulatory system and 2) NOPR agonists can act as therapeutic interventions to reduce opiate use.

1UF1MH121944-01
The Whole Health Study: Collaborative Care for OUD and Mental Health Conditions New Strategies to Prevent and Treat Opioid Addiction Optimizing Care for People with Opioid Use Disorder and Mental Health Conditions NIMH UNIVERSITY OF PENNSYLVANIA MANDELL, DAVID S (contact); BOGNER, HILLARY R; KAMPMAN, KYLE MATTHEW Philadelphia, PA 2019
NOFO Title: HEAL Initiative: Effectiveness Trials to Optimize, Implement, Scale, and Sustain the Collaborative Care Model for Individuals with Opioid Use Disorders and Mental Health Conditions (U01 Clinical Trial Required)
NOFO Number: RFA-MH-19-525
Summary:

This study will refine and test a collaborative care model for patients with opioid use disorder (OUD) and major depression, post-traumatic stress disorder, or an anxiety disorder in primary care. The primary aims of the study are: (1) prototype and test elements of the research team’s collaborative care models; (2) conduct a randomized study of three collaborative care conditions to determine which is most effective in improving outcomes for people with OUD and mental health conditions: Augmented Usual Care, Collaborative Care, or Collaborative Care + Social Worker; (3) measure clinician and organizational-level factors associated with implementation to increase success; (4) conduct a cost evaluation of each collaborative care model; and (5) work with smaller and rural practices to develop and test effective strategies to manage OUD. Successful completion of this study will provide evidence regarding the elements of integrated collaborative care required to maximize outcomes for individuals with OUD and psychiatric disorders.

3UG1DA013035-17S7
Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy New Strategies to Prevent and Treat Opioid Addiction Optimizing the Duration, Retention, and Discontinuation of Medication Treatment for Opioid Use Disorder NIDA New York University School of Medicine ROTROSEN, JOHN P New York, NY 2019
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

This study will (1) test pharmacologic and behavioral strategies to improve OUD pharmacotherapy treatment retention and to improve outcomes among patients who have been successfully stabilized on OUD medications and want to stop medication and (2) identify predictors of successful outcome and develop a stage model of relapse risk.

3UG1DA015815-17S7
Subthreshold Opioid Use Disorder Prevention (STOP) Trial New Strategies to Prevent and Treat Opioid Addiction Prevention of Progression to Moderate or Severe Opioid Use Disorder NIDA University of California, San Francisco SORENSEN, JAMES L San Francisco, CA 2019
NOFO Title: The National Drug Abuse Treatment Clinical Trials Network (UG1)
NOFO Number: RFA-DA-15-008
Summary:

According to SAMHSA’s 2017 National Survey on Drug Use and Health (NSDUH), 11.4 million persons in the U.S. report past-year opioid misuse; out of them, only 2.1 million individuals met criteria for an OUD. Very little is known about efficacious interventions for those who do not meet criteria for moderate/severe OUD (i.e., subthreshold OUD). The prevalence of subthreshold OUD in primary care settings is 5 percent to 10 percent, with higher rates (21 percent to 29 percent) among those receiving prescribed opioids. Although they are at high risk of developing moderate/severe OUD and/or dying from an overdose, little or no empirical evidence exists for pragmatic prevention interventions that can be adopted at integrated general medical settings. To study the efficacy of prevention interventions to arrest the progression from risky opioid use, researchers will test the efficacy of a STOP intervention in primary care settings. STOP adopts an early intervention approach, based on a collaborative care model to prevent progression to moderate/severe OUD, and consists of a practice-embedded nurse care manager who provides patient education and supports the primary care provider (PCP) in engaging, monitoring and guiding patients who have risky opioid use; brief advice delivered to patients by their PCP; and phone counseling of patients by behavioral health providers to motivate and support behavior change. Researchers will determine whether STOP reduces risky opioid use and examine the impact of STOP on progression to moderate/severe OUD, overdose risk behavior and overdose events in adults with risky use of illicit or prescription opioids.

75N95019D00013-0-759501900097-1
Subthreshold Opioid Use Disorder Prevention (STOP) Trial New Strategies to Prevent and Treat Opioid Addiction Prevention of Progression to Moderate or Severe Opioid Use Disorder NIDA Emmes Corportation VanVeldhuisen, Paul Rockville, MD 2019
NOFO Number:
Summary:

According to SAMHSA’s 2017 National Survey on Drug Use and Health (NSDUH), 11.4 million persons in the U.S. report past-year opioid misuse; out of them, only 2.1 million individuals met criteria for an OUD. Very little is known about efficacious interventions for those who do not meet criteria for moderate/severe OUD (i.e., subthreshold OUD). The prevalence of subthreshold OUD in primary care settings is 5 percent to 10 percent, with higher rates (21 percent to 29 percent) among those receiving prescribed opioids. Although they are at high risk of developing moderate/severe OUD and/or dying from an overdose, little or no empirical evidence exists for pragmatic prevention interventions that can be adopted at integrated general medical settings. To study the efficacy of prevention interventions to arrest the progression from risky opioid use, researchers will test the efficacy of a STOP intervention in primary care settings. STOP adopts an early intervention approach, based on a collaborative care model to prevent progression to moderate/severe OUD, and consists of a practice-embedded nurse care manager who provides patient education and supports the primary care provider (PCP) in engaging, monitoring and guiding patients who have risky opioid use; brief advice delivered to patients by their PCP; and phone counseling of patients by behavioral health providers to motivate and support behavior change. Researchers will determine whether STOP reduces risky opioid use and examine the impact of STOP on progression to moderate/severe OUD, overdose risk behavior and overdose events in adults with risky use of illicit or prescription opioids.

1UG3DA050252-01
Does Treating Young Persons Psychopathology Prevent the Onset of Opioid and other Substance Use Disorders? New Strategies to Prevent and Treat Opioid Addiction Preventing Opioid Use Disorder NIDA Massachussetts General Hospital WILENS, TIMOTHY E (contact); YULE, AMY Boston, MA 2019
NOFO Title: HEAL Initiative: Preventing Opioid Use Disorder in Older Adolescents and Young Adults (ages 16–30) (UG3/UH3 Clinical Trial Required
NOFO Number: RFA-DA-19-035
Summary:

Despite psychopathology robustly increasing the risk for later substance use disorders (SUD), remarkably few studies have examined the impact of treating psychopathology on reducing rates of opioid use disorder (OUD), nicotine, and SUD. The main aims of this study are to implement a pragmatic set of office-based instrumentation using patient related outcome measures linked to electronic health records (EPIC) for intake and follow-up assessments to evaluate psychopathology, OUD, nicotine use disorder, and other SUDs in young people aged 16-30 years old who are receiving psychopathology treatment as part of routine outpatient clinical care. The study will also examine similar age patients with non-opioid SUD in outpatient SUD treatment settings to examine the impact of treatment in mitigating the development of OUD. Data derived from this study will help inform clinical guidelines and public health policy and provide important secondary outcomes for further work on the prevention of OUD, nicotine use disorder, and other SUDs in relation to early-onset psychopathology.

1R21DA049861-01
Impact of SB 273 on West Virginia Patients, Providers and Overall Prescription Rates of Opioid Medications New Strategies to Prevent and Treat Opioid Addiction Preventing Opioid Use Disorder NIDA West Virginia University Cara Sedney; Treah Haggerty Morgantown, WV 2019
NOFO Title: Mechanism for Time-Sensitive Drug Abuse Research (R21 Clinical Trial Optional)
NOFO Number: PAR-19-064
Summary:

In 2018, new opiate prescribing limits (SB 273) were implemented across West Virginia to combat the opiate misuse epidemic. This study will utilize quantitative and qualitative measures to determine the effect of the recent opiate prescription laws in West Virginia, how a change in policy affects the opiate misuse epidemic, and how communities may apply this knowledge more broadly. The research team will: 1) collaborate with the West Virginia Board of Pharmacy to ascertain changes in opiate prescribing habits before and after the start of SB 273 using an interrupted time series methodology, and 2) achieve broad and deep understanding of how SB 273 has affected prescribing practices and experiences amongst primary care physicians, specialists (pan physicians, surgeons, emergency room physicians, etc.), and patients who currently or previously utilized opiate medications.

1R01HL150566-01
Arousal circuitry and opiate-associated memories New Strategies to Prevent and Treat Opioid Addiction Sleep Dysfunction as a Core Feature of Opioid Use Disorder and Recovery NHLBI Stanford University DE LECEA, LUIS (contact); CHEN, XIAOKE Stanford, CA 2019
NOFO Title: HEAL Initiative: Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder (OUD) and Response to Medication Assisted Treatment (MAT) (R01 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-19-028
Summary:

Repetitive drug use forms powerful memories associating drug-evoked experiences with its proximal environmental cues. Memories are major obstacles for successfully treating addiction, since even after a prolonged period of abstinence, reexposure to such cues often triggers craving that promotes relapse. A polysynaptic pathway from the paraventricular nucleus of the thalamus (PVT) to the lateral hypothalamus (LH) has been shown to play a role in the maintenance of the opioid-associated memories. Hypocretin (Hcrt) neurons in the LH strongly innervate the PVT, required for maintaining wakefulness and involved in drug seeking. These factors may link sleep disorders in opioid addicts with their long-lasting drug-associated memories. This study will (1) determine whether Hcrt neurons in the LH are the major target; (2) examine whether manipulating the LH (Hcrt)-PVT pathway can effectively prevent relapse; and (3) test whether sleep intervention could be an effective strategy to prevent relapse.

3UH3AT009293-03S1
OPTIMIZATION OF SPINAL MANIPULATIVE THERAPY (SMT) PROTOCOLS New Strategies to Prevent and Treat Opioid Addiction NCCIH University of Utah FRITZ, JULIE M Salt Lake City, UT 2018
NOFO Title: Innovation Award for Mechanistic Studies to Optimize Mind and Body Interventions in NCCIH High Priority Research Topics (R33)
NOFO Number: RFA-AT-16-006
Summary:

Low back pain (LBP) is a common and costly condition. Spinal manipulative therapy (SMT) is a common mind-body intervention for individuals with LBP. Studies that have supported SMT have generally found relatively small treatment effects. The prior work of this research team has identified two mechanisms explaining the therapeutic effects of SMT: a reduction in spinal stiffness and improved activation of the lumbar multifidus muscle. Our research team has also developed accurate, non-invasive methods to measure these effects and their response to SMT. Our overall goal is to optimize SMT treatment protocols for patients with LBP. In this project, we will use innovative methodology to efficiently evaluate the effects of various individual treatment components toward an overall effect. Results of this project will provide optimized SMT protocols that will be ready for application in future randomized controlled trials examining the efficacy and effectiveness of SMT.

1R21AT010106-01
PSYCHOSOCIAL PAIN MANAGEMENT TO IMPROVE OPIOID USE DISORDER TREATMENT OUTCOMES New Strategies to Prevent and Treat Opioid Addiction Behavioral Research to Improve Medication-Based Treatment NCCIH University of Michigan, Ann Arbor ILGEN, MARK A. ANN ARBOR, MI 2018
NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
Summary:

Many individuals who receive medication-assisted therapy (MAT) leave treatment early and continue to struggle with opioid use disorder (OUD), often within the context of poorly managed comorbid chronic pain. Psychosocial interventions for pain have been effective in patients with chronic pain and substance use disorders, but these interventions have not been examined in the OUD population receiving MAT. This study proposes to refine and adapt a psychosocial pain management intervention (PPMI) delivered by telephone for patients with OUD receiving MAT and then to conduct a randomized controlled trial of the intervention in patients receiving MAT to improve adherence and pain- and substance-related outcomes. The intervention uses elements of cognitive behavioral pain management interventions adapted specifically for patients with OUD receiving MAT. The new intervention will be compared to an enhanced usual care condition (EUC) in 100 patients.

1UG3DA050234-01
Community Randomized Trial in the Cherokee Nation: CONNECT and CMCA for Preventing Drug Misuse among Older Adolescents New Strategies to Prevent and Treat Opioid Addiction Preventing Opioid Use Disorder NIDA Emory University KOMRO, KELLI ANN (contact); LIVINGSTON, MELVIN D Atlanta, GA 2019
NOFO Title: HEAL Initiative: Preventing Opioid Use Disorder in Older Adolescents and Young Adults (ages 16–30) (UG3/UH3 Clinical Trial Required
NOFO Number: RFA-DA-19-035
Summary:

The national public health opioid crisis has disproportionately burdened rural white populations and American Indian populations. To address this crisis, the Cherokee Nation and Emory University public health scientists will carry out an opioid prevention trial to be conducted in at-risk rural communities in the Cherokee Nation (in northeast Oklahoma) with populations of white and American Indian adolescents and young adults. The study will expand and integrate two established intervention approaches, consisting of community organizing and universal school-based brief intervention and referral to further enhance their effects in preventing and reducing opioid misuse. These interventions, called CMCA and CONNECT, were originally designed to target adolescent alcohol use, but showed significant beneficial effects on use of other drugs, including prescription drug misuse. The expanded, integrated interventions will be tested in a community-randomized trial with the goal of new systems for sustained implementation within existing structures of the Cherokee Nation.

3U01AA021691-08S1
NATIONAL CONSORTIUM ON ALCOHOL AND NEURODEVELOPMENT IN ADOLESCENCE: OHSU New Strategies to Prevent and Treat Opioid Addiction Preventing Opioid Use Disorder NIAAA Oregon Health & Science University NAGEL, BONNIE J Portland, OR 2019
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
3UG1DA013035-18S6
Subthreshold Opioid Use Disorder Prevention (STOP) Trial New Strategies to Prevent and Treat Opioid Addiction Prevention of Progression to Moderate or Severe Opioid Use Disorder NIDA New York University School of Medicine ROTROSEN, JOHN P New York, NY 2019
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

According to SAMHSA’s 2017 National Survey on Drug Use and Health (NSDUH), 11.4 million persons in the U.S. report past-year opioid misuse; out of them, only 2.1 million individuals met criteria for an OUD. Very little is known about efficacious interventions for those who do not meet criteria for moderate/severe OUD (i.e., subthreshold OUD). The prevalence of subthreshold OUD in primary care settings is 5 percent to 10 percent, with higher rates (21 percent to 29 percent) among those receiving prescribed opioids. Although they are at high risk of developing moderate/severe OUD and/or dying from an overdose, little or no empirical evidence exists for pragmatic prevention interventions that can be adopted at integrated general medical settings. To study the efficacy of prevention interventions to arrest the progression from risky opioid use, researchers will test the efficacy of a STOP intervention in primary care settings. STOP adopts an early intervention approach, based on a collaborative care model to prevent progression to moderate/severe OUD, and consists of a practice-embedded nurse care manager who provides patient education and supports the primary care provider (PCP) in engaging, monitoring and guiding patients who have risky opioid use; brief advice delivered to patients by their PCP; and phone counseling of patients by behavioral health providers to motivate and support behavior change. Researchers will determine whether STOP reduces risky opioid use and examine the impact of STOP on progression to moderate/severe OUD, overdose risk behavior and overdose events in adults with risky use of illicit or prescription opioids.

3UG1DA015815-18S5
Subthreshold Opioid Use Disorder Prevention (STOP); which will test the efficacy of a primary care Subthreshold Opioid Use Disorder Prevention (STOP) New Strategies to Prevent and Treat Opioid Addiction Prevention of Progression to Moderate or Severe Opioid Use Disorder NIDA UNIVERSITY OF CALIFORNIA, SAN FRANCISCO SORENSEN, JAMES L.; KORTHUIS, PHILIP TODD San Francisco, CA 2019
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

According to SAMHSA’s 2017 National Survey on Drug Use and Health (NSDUH), 11.4 million persons in the U.S. report past-year opioid misuse; out of them, only 2.1 million individuals met criteria for an OUD. Very little is known about efficacious interventions for those who do not meet criteria for moderate/severe OUD (i.e., subthreshold OUD). The prevalence of subthreshold OUD in primary care settings is 5 percent to 10 percent, with higher rates (21 percent to 29 percent) among those receiving prescribed opioids. Although they are at high risk of developing moderate/severe OUD and/or dying from an overdose, little or no empirical evidence exists for pragmatic prevention interventions that can be adopted at integrated general medical settings. To study the efficacy of prevention interventions to arrest the progression from risky opioid use, researchers will test the efficacy of a STOP intervention in primary care settings. STOP adopts an early intervention approach, based on a collaborative care model to prevent progression to moderate/severe OUD, and consists of a practice-embedded nurse care manager who provides patient education and supports the primary care provider (PCP) in engaging, monitoring and guiding patients who have risky opioid use; brief advice delivered to patients by their PCP; and phone counseling of patients by behavioral health providers to motivate and support behavior change. Researchers will determine whether STOP reduces risky opioid use and examine the impact of STOP on progression to moderate/severe OUD, overdose risk behavior and overdose events in adults with risky use of illicit or prescription opioids.

1UF1MH121954-01
Improving Access and Treatment for Co-occurring Opioid Use Disorders and Mental Illness New Strategies to Prevent and Treat Opioid Addiction Optimizing Care for People with Opioid Use Disorder and Mental Health Conditions NIMH RAND CORPORATION WATKINS, KATHERINE E (contact); KOMAROMY, MIRIAM Santa Monica, CA 2019
NOFO Title: HEAL Initiative: Effectiveness Trials to Optimize, Implement, Scale, and Sustain the Collaborative Care Model for Individuals with Opioid Use Disorders and Mental Health Conditions (U01 Clinical Trial Required)
NOFO Number: RFA-MH-19-525
Summary:

In 2015–2016, there were over 2 million adults with an opioid use disorder (OUD); 62% had a co-occurring mental illness and 24% had a co-occurring serious mental illness. Despite the effectiveness of treatment, many individuals never receive it, and when treatment is provided, quality is low. This is a critical treatment gap in a vulnerable and stigmatized population. Collaborative care (CC) aims to address these gaps by improving access, quality, and outcomes in primary care patients with common mental health conditions. However, CC has never been tested with co-occurring disorders (COD). In the team’s CC model for COD (CC-COD), the CC team includes a behavioral health psychotherapist, medications for OUD, pharmacotherapy for depression and post-traumatic stress disorder (PTSD), motivational interviewing (MI), problem-solving therapy, and Seeking Safety. A multisite, randomized pragmatic trial will be conducted to adapt, harmonize, and then test whether CC-COD improves access, quality, and outcomes for patients with comorbid OUD and depression and/or PTSD.