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Notice of Special Interest (NOSI): Targeting the Endocannabinoid System for Brain Health and Acute and Chronic Diseases

National Institutes of Health

This Notice of Special Interest (NOSI) encourages studies of the endocannabinoid system (ECS) and its roles in brain health and acute and chronic disease, substance use, and substance use disorder (SUD). The desired outcomes of research will be a mechanistic understanding of how cannabinoids and manipulation of the ECS can elicit both therapeutic and deleterious effects as well as the role of cannabinoids and ECS in symptom management.

Studies conducted in various biological model systems have implicated engagement of ECS in central nervous system development, neural synaptic organization, and plasticity, and in cellular responses to injury or disease. These studies have been used as a basis for supporting the therapeutic uses of cannabis. However, conflicting clinical reports suggest both positive and negative effects of cannabinoids. As a widespread modulator system that impacts the functions of various tissues and organs, alterations in the ECS (either hypo- or hyper- activation) may disrupt molecular networks that are critical for physiological stabilization. Given these conflicting views, this NOSI encourages research to explore and validate roles of the ECS under physio-normative and disease conditions, including their sequelae, and the impacts of recreational or medicinal cannabinoid use (acute and/or chronic).

The research supported by this NOSI includes, but is not limited to: 1) research to identify the causal mechanisms underlying therapeutic benefits of cannabinoids and the ECS; 2) studies utilizing pharmacological, immunological, or genetic approaches to manipulate specific elements of the ECS; 3) research to establish biological relevance and translational validity of findings using biological models (cell/tissue, biological specimens, or postmortem brain tissue from treated or untreated SUD patients); and 4) research to investigate the role of cannabinoids and the ECS in treatment-related conditions. This NOSI also encourages research examining the longitudinal effects of cannabinoid use in order to describe biological mechanisms associated with persistent ECS dysregulation. Key in this regard is the collection of data on parameters such as dose, frequency and duration of exposure.

This notice applies to due dates on or after February 5, 2023 and subsequent receipt dates through January 8, 2026.

NOT-DA-22-048