# Pharmacology of Drugs of Abuse During Pregnancy

> **NIH NIH P01** · UNIVERSITY OF WASHINGTON · 2022 · $1,475,139

## 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. However, these animal
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. On the other hand, human data
on fetal and infant developmental outcomes due to marijuana use during pregnancy are limited, confounded by
other factors and remain controversial. Conducting a controlled clinical trial to determine if marijuana results in
negative fetal/neonatal outcomes is unethical. Therefore, alternative approaches to determine fetal outcomes
of marijuana use during pregnancy need to be explored. However, this can only be achieved when the fetal
exposure to THC and its active metabolite,11-OH-THC, has been addressed and accurately predicted. To
achieve this goal, we propose a systems pharmacology approach to begin to address this significant public
health problem and test the central hypothesis: Maternal-fetal exposure for THC/11-OH-THC during
pregnancy can be predicted through innovative in vitro and in vivo studies integrated through
maternal-fetal PBPK modeling and simulation (m-f-PBPK M & S). Fetal exposure to THC/11-OH-THC will
be dependent on their maternal disposition, placental transport/metabolism and fetal clearance. Fetal exposure
to THC/11-OH-THC will drive their fetal toxicity. Therefore, the projects of this P01 are designed to: 1)
understand fetal exposure to THC/11-OH-THC by characterizing metabolism and transport of THC/11-OH-THC
in maternal organs, placenta and fetus (Project 1); 2) predict the changes in maternal exposure to THC and its
comprehensive metabolome including 11-OH-THC, 11-nor-COOH-THC and the glucuronides, throughout
pregnancy, and the mechanistic basis for these changes (Project 2); and 3) predict and verify gestational age-
dependent placental-fetal exposure to THC/11-OH-THC through PBPK M & S by integrating the data from the
above two projects (Project 3). 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 (Project 3). Our approach uses novel and innovative tools (e.g. m-f-PBPK model, development of an
inhalational m-f-PBPK model, perfused human placenta, quantitative targeted proteomics and metabolomics)
to address a compel...

## Key facts

- **NIH application ID:** 10463599
- **Project number:** 5P01DA032507-09
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JASHVANT D Unadkat
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,475,139
- **Award type:** 5
- **Project period:** 2013-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463599

## Citation

> US National Institutes of Health, RePORTER application 10463599, Pharmacology of Drugs of Abuse During Pregnancy (5P01DA032507-09). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10463599. Licensed CC0.

---

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