NIH NIDA Notice of Special Interest: Effects of Cannabis Use and Cannabinoids on the Developing Brain

NIH Notice Number: NOT-DA-20-039

The full notice is available at the following link: https://grants.nih.gov/grants/guide/notice-files/NOT-DA-20-039.html

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
The full notice is available at the following link: https://grants.nih.gov/grants/guide/notice-files/NOT-DA-20-039.html
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