Sleep, Circadian Rhythms, and Substance Use Disorders

Post Date: September 10, 2025

Expiration Date: September 10, 2026

The purpose of this topic is to delineate the biological mechanisms that underlie the relationship between sleep/circadian rhythms and substance use disorders (SUDs). These studies will: a) offer insights into the fundamental mechanistic processes that link SUDs to disorders of sleep/circadian rhythms and vice versa, b) identify sleep/circadian-based markers for managing risks associated with developing SUDs and/or predicting relapse or recovery, and c) identify novel therapeutic targets.  

Background

SUDs and disorders of sleep/circadian rhythms are intricately interconnected. Sleep dysregulation including insufficient sleep duration, altered sleep architecture, poor sleep quality and/or irregular circadian rhythmicity is prevalent in >75% of individuals with SUDs and represents a major challenge to recovery. Conversely, acute and chronic exposure to addictive substances disrupts sleep and circadian rhythmicity. The substantial overlap between neuronal systems and processes involved in SUDs and sleep/circadian rhythms likely underlies these interactions. However, this has not been systematically investigated at a mechanistic level and the regulation of sleep/circadian rhythms has not been integrated with the neurobiology of SUD mechanisms and risk factors. 

There are several brain regions and neurotransmitter substrates that regulate arousal, sleep/circadian rhythms, as well as motivation and reward. Various neuronal systems regulate arousal and sleep while also having known roles in reward-related behaviors. These include the locus coeruleus noradrenergic neurons, serotonergic neurons in the raphe, basal forebrain cholinergic neurons, midbrain dopaminergic neurons, hypothalamic hypocretin (orexin) -ergic neurons, the endocannabinoid and histaminergic systems and their projections. However, little is known about how cells, molecules, neurotransmitters, receptors within these brain regions and their associated circuits mechanistically intersect to cause a bidirectional interaction between sleep/circadian rhythms and SUDs. Studies that determine the directionality and mechanisms of sleep/circadian rhythms and SUD interactions are needed to understand fundamental processes that link SUD and sleep/circadian dysregulation, identify sleep/circadian-based predictors for SUD prevention or relapse, and to identify targets for improved therapy. 

The goal of this topic is to encourage basic and pre-clinical research projects that explore the mechanisms that drive the interrelationship between sleep and/or circadian rhythms and SUDs. Applicants may propose research projects using behavioral, cognitive, cellular, circuit, genetic, molecular, imaging, pharmacological, and/or computational approaches.