# PBPK prediction and verification of maternal-fetal exposure to cannabinoids

> **NIH NIH P01** · UNIVERSITY OF WASHINGTON · 2020 · $587,062

## Abstract

Use of marijuana (cannabis) among pregnant women in the US is increasing with prevalence as high as 14% 
among 12–18 year old pregnant women. The American College of Obstetrics and Gynecology recommends 
that pregnant women avoid marijuana due to evidence that it affects the fetus and may interfere with brain 
development. Studies in animals appear to support this recommendation. Although other constituents of 
marijuana cannot be discounted, the general scientific consensus is that ∆9-tetrahydrocannabinol (THC), the 
most abundant and psychoactive component in marijuana, is the likely perpetrator of the developmental 
neurotoxicity of marijuana. THC can dysregulate cannabinoid receptor 1 signaling during pregnancy and 
can result in adverse outcomes such as impaired fetal brain development, lower birth weight, increased 
fetal resorption, and even in utero deaths. THC can impact axon growth in the developing mouse fetal brain. 
Chronic exposure to THC leads to long-term behavioral deficits in male adolescent mice, akin to those 
observed in schizophrenia. However, these rodent and in vitro studies were conducted at high THC doses 
or concentrations and therefore their applicability to humans, where THC plasma concentrations are sub- 
micromolar, is unknown. For many reasons, observational clinical studies in pregnant women who use 
marijuana are not informative as to whether marijuana is safe when used during pregnancy. Due to the 
limitations of all the above approaches, we propose here a systems pharmacology approach to begin to 
address this significant public health question. Through data obtained by this project and Projects 1 & 2, we 
will predict and then verify the magnitude of maternal-placental-fetal exposure to THC and its psychoactive 
metabolite, 11-OH-THC, throughout pregnancy, after both oral and inhalational (smoking) use of marijuana. 
To do so, we will refine and extend a novel maternal-fetal Physiologically Based PharmacoKinetic (m-f-PBPK) 
model we have developed. In addition, in an exploratory manner, we will determine whether these 
cannabinoids produce any molecular signatures indicative of short or long-term developmental neurotoxicity in 
humans. Our approach uses novel and innovative tools (e.g. m-f-PBPK model, development of an 
inhalational m-f-PBPK model, quantitative targeted proteomics, transcriptomics, proteomics and 
metabolomics) to address a compelling public health question. 
1

## Key facts

- **NIH application ID:** 10009315
- **Project number:** 5P01DA032507-07
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JASHVANT D Unadkat
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $587,062
- **Award type:** 5
- **Project period:** 2013-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009315

## Citation

> US National Institutes of Health, RePORTER application 10009315, PBPK prediction and verification of maternal-fetal exposure to cannabinoids (5P01DA032507-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10009315. Licensed CC0.

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