The purpose of this Notice is to encourage investigators to submit grant applications to the National Institute on Drug Abuse (NIDA)to study the effects of cannabis and cannabinoid exposure on the developing brain, from pre-, peri-, and post-natal development through young adulthood in humans and using animal models.

Background

Cannabis use has been on the rise in all populations including adolescents, young adults and pregnant women. This trend parallels the decreased perceived risk of harm from cannabis in all age groups, and the relaxed local laws and policies regarding cannabis use. In recent years, various formulations of cannabinoids, including two of its most prominent cannabis plant components: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested as treatments for a range of conditions without evidence of their beneficial or adverse effects, especially on the developing brain. Meanwhile, growing evidence in humans and animals has implicated cannabis and cannabinoids in adverse psychiatric, cognitive, and behavioral consequences in both children and adults.

Some studies suggest that in utero cannabinoid exposure significantly impacts fetal brain development, causing neurological impairments, abnormal dopaminergic transmission, hyperactivity, and poor cognitive function in children. In animal models, early exposure to cannabinoids leads to developmental disorders, dysregulation of repressive epigenetic markers that affect brain morphogenesis, neuronal and glial alterations, and impaired axonal pathfinding and synaptic plasticity. Beyond early development, many animal studies have also shown that developmental cannabinoid exposure has harmful behavioral consequences, such as increased impulsivity, anxiety, abnormal fear extinction and altered reward sensitivity in later life.

More research is needed to replicate and extend these findings on the effects of cannabinoid use during various stages of brain development. It is especially important to identify the cellular and molecular mechanisms associated with the endo- and exogeneous cannabinoid exposure during different developmental stages. Elucidating the mechanisms by which cannabinoids affect development both in animals and/or humans is a goal of this notice.

Research Objectives

The following should be studied in the context of non-adult periods of development, e.g. fetal, neonatal, childhood and adolescent development. Research areas of interest for this noticeinclude, but are not limited to:

• Understand how and when the endocannabinoid system emerges and the roles it plays during brain development, and its subsequent impact on cognition and behavior
• Identify the timing when the brain is, or specific brain regions are, most vulnerable to the insult and/or injury by cannabis and cannabinoids
• Determine how cannabinoids affect various aspects of cellular and molecular events affecting neural proliferation, migration, differentiation, axonal pathfinding, and synapse formation and plasticity
• Determine how other abused substances (i.e., tobacco, opioids, and stimulants) interact with cannabinoids and exacerbate cannabinoid effects with long term consequences
• Determine whether and how early cannabinoid exposures affect sex and gender specifications of the developing brain

Application and Submission Information

This notice applies to due dates on or after June 5, 2020 and subsequent receipt dates through September 8, 2023.

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-19-091: NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required
• PA-19-052: NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed
• PA-19-092: NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required
• 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)

All 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-20-039 (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 contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Da-Yu Wu, PhD
Division of Neuroscience and Behavior
National Institute on Drug Abuse (NIDA)
Telephone: (301)435-4649
Email: wudy@nida.nih.gov

Ann L. Anderson, MD, MPH
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5916
aa135m@nih.gov

Naimah Weinberg, M.D.
Div. of Epidemiology, Services & Prevention Research
National Institute on Drug Abuse/NIH
Telephone:(301) 402-1908
Email: nw46w@nih.gov