# Effects of Early-life Cannabinoid Exposure on Prefrontal Circuitry and Cognitive Behavior across Development

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $465,460

## Abstract

PROJECT SUMMARY
 Cannabis consumption during pregnancy and lactation has reached 7-15% in pregnant women and nursing
mothers in recent years, and will likely rise due to widespread legalization. Increased availability of cannabis has
led to the public perception that it is a safe natural remedy for pregnancy-related ailments and postpartum mood
disorders. Yet, growing clinical and preclinical data suggest prenatal and perinatal cannabis exposure is
associated with long-term neurodevelopmental consequences in children, including sensorimotor, emotional,
and cognitive deficits, as well as increased risk for illicit drug use in adolescence and adulthood. The neural
mechanisms and sensitive periods underlying these long-term effects are still poorly understood, making it
challenging to provide accurate medical advice for risk assessment of cannabis use in mothers. To address this
challenge, our overall goal is to identify the developmental processes and circuit-specific mechanisms
underlying the effects of early-life cannabinoid exposure on the emergence of cognitive behaviors. We
will focus on the medial prefrontal cortex (mPFC) due to its high levels of cannabinoid receptor expression during
development, and its critical role in cognitive processing. We will assess the circuit and network effects of early-
life exposure to the two most widely used and frequently combined cannabinoids, 9-tetrahydrocannabinol (THC)
and cannabidiol (CBD), in mouse pups across development. We will test the central hypothesis that early-life
cannabinoid exposure disrupts mPFC maturation by interfering with network synchronization during a
critical developmental window, resulting in abnormal neuronal activation during cognitive behaviors in
adolescence and adulthood. We will leverage our novel longitudinal 2-photon imaging technique in developing
mice to assess the impact of THC, CBD, and THC+CBD exposure through three aims. In Aim 1, we will reveal
the spatial and temporal patterns of in vivo network activity and eCB dynamics across development and
determine critical windows during which altered eCB signaling affects these network dynamics. In Aim 2, we will
assess how early-life THC, CBD, or THC+CBD exposure impacts eCB and calcium dynamics during
development using longitudinal 2-photon imaging. We will also examine the effects of cannabinoid exposure on
synaptic connectivity and the balance between excitation and inhibition in the mPFC. In Aim 3, we will assess
the impact of early-life cannabinoid exposure on the neural correlates of cognitive behaviors in the mPFC across
adolescence and adulthood. We will also systematically assess the behavioral outcomes after early-life
cannabinoid exposure longitudinally across neonatal, adolescence and early adulthood. Together, outcomes of
this project will identify neural mechanisms underlying later-life behavioral deficits as a result of early-life
cannabinoid exposure. As such, this project is expected to have a significant ...

## Key facts

- **NIH application ID:** 10769567
- **Project number:** 1R01DA059378-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Alicia Yue Che
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $465,460
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769567

## Citation

> US National Institutes of Health, RePORTER application 10769567, Effects of Early-life Cannabinoid Exposure on Prefrontal Circuitry and Cognitive Behavior across Development (1R01DA059378-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10769567. Licensed CC0.

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