# Impact of maternal marijuana use on epigenetic regulation of offspring neurodevelopment

> **NIH NIH DP1** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $525,000

## Abstract

PROJECT SUMMARY
 Marijuana is now the most commonly used illicit drug in pregnancy. The main psychoactive compound of
marijuana, delta-9-tetrahydrocannabinol (THC), can access and bind to cannabinoid receptors in the placenta
and fetal brain. Preliminary data suggest that prenatal cannabinoid exposure results in epigenetic changes in
the placenta and brains of exposed offspring. This is concerning because the placenta plays a key role in fetal
growth and development by mediating fetal nutrition, oxygenation, inflammatory signaling, and transmission of
maternal environmental exposures. Compromises to placental function can adversely affect brain development.
Epigenetic responses to maternal marijuana use likely result in molecular alterations in gene regulation of
offspring developmental trajectories towards neurodevelopmental morbidity, including addiction, autism
spectrum disorder, attention deficit hyperactivity disorder, and cognitive disabilities. Specifically, prenatal THC
exposure is known to alter reward processing, by histone modification of ventral striatal dopaminergic signaling,
affecting addiction vulnerability. However, a mechanistic link between maternal THC use and its impact on
offspring epigenetic regulation of neurodevelopment is impeded by the lack of in vivo longitudinal assessment
secondary to the limitations of current imaging capabilities and feasibility of tissue sampling. We propose to
address this problem by defining a trajectory of perturbed epigenetic regulation following in utero THC exposure
across fetal and early childhood brain and behavioral development. To this end, we will employ three innovative
and complementary approaches using our novel, non-human primate model of chronic maternal THC use: 1)
first-in-kind, longitudinal in vivo imaging of placental and fetal epigenetic regulation and development, 2)
extensive postnatal assessment of infant cognition and behavior, and 3) sophisticated tissue studies confirming
the role of epigenetic modifications in the imaging and behavioral studies. In summary, our study will interrogate
the previously inaccessible mechanistic links underlying the impact of maternal marijuana use on fetal origins of
health, disease and addiction risk. The successful completion of our study will result in 1) new insights into the
impact of maternal THC use on the developing fetal and infant brain, 2) the impact of THC-induced epigenetic
alterations on trajectories of offspring neurodevelopment and behavioral regulation 3) the creation of a
comprehensive, longitudinal in vivo map of offspring epigenetic regulation of neurodevelopment from fetal life to
early childhood, and 4) characterization of ex vivo epigenetic and transcriptomic assessments that can be used
as a reference for other drugs of abuse and environmental exposures. This study has the potential for immediate
translational impact, given the high prevalence of prenatal and postnatal marijuana use and limited data on
longer-term off...

## Key facts

- **NIH application ID:** 10908441
- **Project number:** 5DP1DA056493-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jamie Lo
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $525,000
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908441

## Citation

> US National Institutes of Health, RePORTER application 10908441, Impact of maternal marijuana use on epigenetic regulation of offspring neurodevelopment (5DP1DA056493-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10908441. Licensed CC0.

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