# Understanding Fetal Exposure to Cannabinoids Through In Vitro and In Vivo Studies

> **NIH NIH P01** · UNIVERSITY OF WASHINGTON · 2022 · $448,111

## Abstract

Marijuana (cannabis) use by pregnant women in the US is increasing. Yet, we do not know if this use is safe 
for the fetus. A recent comprehensive literature review by the National Academy of Sciences, Engineering and 
Medicine found substantial evidence of an association between marijuana use during pregnancy and lower birth 
weight, but only limited evidence of other health problems related to prenatal, perinatal or neonatal outcomes of 
marijuana use during pregnancy. However, they noted a number of limitations of the reviewed studies such as 
reliance on self-reporting to ascertain marijuana exposure, the varying potency, dosage and timing of marijuana 
exposure, limited statistical power to detect many outcomes, and marijuana exposure confounded by the use of 
other substances namely tobacco and alcohol. To understand fetal safety of marijuana use during pregnancy, 
animal studies were conducted and showed that fetal exposure to Δ9-tetrahydrocannabinol (THC), the most 
abundant and psychoactive cannabinoid, caused lower birth weight, increased fetal resorption and even in utero 
deaths in animals. THC also inhibits human placental trophoblast proliferation and differentiation. However, most 
of the animal and in vitro studies were conducted with high THC doses or concentrations that cannot be used or 
observed in humans and therefore the data obtained cannot be used to predict human toxicity. Also, fetal 
plasma/tissue THC concentrations, after maternal marijuana use, are unknown. 
 Given the limitations of human observational, animal and in vitro studies, alternative approaches to determine 
fetal exposure and risks of marijuana use during pregnancy need to be explored. The overall goals of this P01 are 
to predict maternal-fetal exposure to THC and its psychoactive metabolite 11-OH-THC through innovative in vitro 
and in vivo studies integrated through maternal-fetal-Physiologically Based Pharmacokinetic (m-f-PBPK) 
modeling and simulations (M & S) and conduct exploratory studies that will inform fetal neurotoxicity of THC/11- 
OH-THC that could result in long-term sequelae. To achieve these goals, it is imperative that we first understand 
factors that determine fetal exposure to THC/11-OH-THC, the focus of this project (Project 1). Based on literature 
data and our preliminary studies, we hypothesize that placental P-gp, BCRP and CYP1A1 work in tandem to 
modulate fetal exposure to THC/11-OH-THC. To test this hypothesis, Project 1 will characterize THC/11-OH- 
THC metabolism and transport in relevant maternal organs (intestine and liver), placenta and fetal tissues. To 
verify if efflux transporters in the placenta are involved in trans-placental transfer of THC/11-OH-THC, we will also 
perform ex vivo human placental perfusion and in vivo maternal/fetal pharmacokinetic studies in mouse models. 
 These studies address a critical gap in our understanding of THC/11-OH-THC metabolism and transport 
clearances in humans and will provide data...

## Key facts

- **NIH application ID:** 10463603
- **Project number:** 5P01DA032507-09
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** QINGCHENG MAO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $448,111
- **Award type:** 5
- **Project period:** 2013-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463603

## Citation

> US National Institutes of Health, RePORTER application 10463603, Understanding Fetal Exposure to Cannabinoids Through In Vitro and In Vivo Studies (5P01DA032507-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463603. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*