The purpose of this noticeis to inform potential applicants to the National Institute on Drug Abuse (NIDA) about a special interest in research project applications focusing on the relationship between processes that regulate sleep/circadian rhythm and the risk, trajectory and treatment of substance use disorders. Identifying sleep/circadian mechanisms and determining the directionality of sleep and substance use disorder interactions addresses a knowledge gap and can present new opportunities for improved therapy and outcomes. Multi-disciplinary, multiple-investigator teams of researchers combining expertise in substance use disorders and mechanisms of sleep/circadian rhythms would be optimal in addressing these questions. This notice encourages studies of processes and mechanisms linking drugs of abuse and sleep/circadian rhythms. The study of other psychoactive drugs or efficacy focused clinical trials will be considered non-responsive. Likewise, descriptive studies or clinical trials solely focused on therapeutic endpoints in the absence of a mechanistic evaluation of the intervention also would be considered non-responsive.

Background

This notice invites pre-clinical and clinical research applications to elucidate sleep and circadian mechanisms contributing to substance use disorder (SUD). Sleep dysregulation including insufficient sleep duration, altered sleep architecture, poor sleep quality and irregular circadian rhythms is prevalent in >75% of individuals with SUD and represents a challenge to recovery. Conversely, acute and chronic exposure to drugs of abuse affect sleep and circadian rhythm. The substantial overlap between neuronal systems and processes involved in SUD and sleep likely underlies these interactions . However, this has not been systematically investigated at a mechanistic level and the regulation of sleep and circadian rhythms has not been fully integrated with the neurobiology of SUD mechanisms and risk factors. Mechanistic studies to determine the directionality of sleep and SUD interactions are needed to understand fundamental processes linking SUD and sleep dysregulation, and to identify new targets for prevention and improved therapy. This could optimally be achieved by interdisciplinary teams combining expertise in the mechanisms of sleep and circadian rhythms and the neurobiology of SUD.

Applications need to test mechanistic hypothesis and can use behavioral, pharmacological, genetic or other experimental models of sleep and circadian dysregulation and SUD. Studies are needed to discover how sleep dysregulation, regulation, untreated sleep disorders, and altered circadian rhythms factor into the neurobiological and pharmacological substrate changes underlying addiction, dependence, withdrawal, relapse and recovery, including reward/reinforcement, risk taking behavior/mood regulation, autonomic regulation/integration, pain perception, and signaling in neuropharmacological pathways relevant to substance abuse. An array of approaches, including in vivo, in vitro, genomic, imaging, pharmacologic, computational or other strategies may be proposed to study behavioral, physiological, molecular, genetic and pharmacological mechanisms coupling sleep and SUD. Applications need include an explicit justification of the potential application to SUD. Descriptive studies and studies evaluating the efficacy of one or more therapeutic interventions without a rigorous mechanistic study design would not be responsive for this notice.

Research Objectives

Examples of approaches that are encouraged include, but are not limited to those listed below:

• Elucidate neurobiological mechanisms through which sleep deficiency or circadian disruption modifies reward, affect, executive function, pain, and other processes that can contribute to susceptibility to SUD.
• Identify mechanisms by which sleep deficiency or circadian disruption modifies the trajectory of SUD including initiation, maintenance, withdrawal, abstinence, relapse and the course of recovery.
• Examine the underlying mechanisms by which of drugs of abuse induce sleep or circadian dysregulation.
• Examine behavioral and pharmacological mechanisms to improve sleep dysregulation in the context of SUD
• Determine whether sleep architecture changes can be used as biomarkers of SUD severity and recovery.
• Examine circadian-dependent pharmacological mechanisms contributing to drug tolerance, withdrawal, and MAT response (e.g. do the effects of drugs of abuse vary depending of time of day of administration?).

Application and Submission Information

This notice applies to due dates on or after June 5, 2020 and subsequent receipt dates through September 8, 2022.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

• PA-19-056: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-19-055: NIH Research Project Grant (Parent R01 Clinical Trial Required)
• PA-19-052: NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)
• PA-19-053: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PA-19-054: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
• PAR-18-918: Imaging - Science Track Award for Research Transition (I/START) (R03) (Clinical Trial Optional)
• PAR-18-437: Cutting-Edge Basic Research Awards (CEBRA) (R21) (Clinical Trial Optional)
• PAR-19-310: Behavioral Science Track Award for Rapid Transition (B/Start) (R03) (Clinical Trial Optional)
• PA-19-130: NIH Pathway to Independence Award (Parent K99/R00 - Independent Clinical Trial Not Allowed)
• PAR-20-035: Integrative Research on Polysubstance Abuse and Disorder (R61/R33) (Clinical Trial Optional)
• PAR-19-282: Exploratory Clinical Neuroscience Research on Substance Use Disorders (R61/R33) (Clinical Trial Optional)

ll instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-DA--20-021"-without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed funding opportunity announcements.

Scientific/Research Contact(s)

Sunila Nair, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: (301) 827-6832
Email: sunila.nair@nih.gov