# Molecular underpinnings of the developmental Effects of Cannabis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $843,067

## Abstract

The cannabis sociopolitical landscape has dramatically shifted in recent years leading to the decriminalization,
medicalization, and legalization of cannabis use, which has contributed to the reduced risk perception of its harm.
This transformational time, however, has health implications particularly for vulnerable populations related to
neurodevelopment since cannabis is commonly used by pregnant women and women of childbearing age.
Accumulating evidence from our long-standing research has clearly demonstrated that prenatal exposure to D9-
tetrahydrocannabinol (THC), the major psychoactive component of cannabis, has long-term effects on behaviors
— relevant to reward, motivation, negative affect and decision-making, and molecular disturbances linked to
synaptic plasticity with profound epigenetic dysregulation that are exacerbated by stress. We have also identified
specific epigenetic modifications linked to synaptic plasticity and behaviors associated with the protracted effects
of developmental THC exposure. Recent results have highlighted the immune system as relevant to
developmental cannabis/THC since preliminary gene expression analysis of the placenta from women who used
cannabis during pregnancy revealed marked reorganization of the immune transcriptome that correlated with
later childhood behavior. Immune-related genes were also altered in mesocorticolimbic structures of adult rats
with developmental THC exposure, which enhances the correlation between immune- and synaptic-related
genes. To gain neurobiological and mechanistic insights, we will conduct integrative and translational studies
(human and rat models) to: (1) Determine the impact of prenatal cannabis/THC exposure on immune-related
disturbances (placenta and brain); (2) Delineate molecular networks within distinct mesocorticolimbic cell
populations through high resolution single-cell strategies altered by developmental cannabis/THC exposure
relevant to immune function; and (3) Identify early biological disturbances (sustained into adulthood) predictive
of long-term effects on brain and causally mediate behavior due to prenatal cannabis/THC exposure. The
translational knowledge gained and the human and rodent databases generated from this project will significantly
advance our understanding of psychopathology risk that often has its genesis during development.

## Key facts

- **NIH application ID:** 10849765
- **Project number:** 5R01DA055434-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** YASMIN L. HURD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $843,067
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10849765

## Citation

> US National Institutes of Health, RePORTER application 10849765, Molecular underpinnings of the developmental Effects of Cannabis (5R01DA055434-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10849765. Licensed CC0.

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