Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity
Abstract Prenatal cannabis use is associated with neurodevelopmental deficits, likely due to exposure to the psychoactive cannabinoid, (-)-Δ9-tetrahydrocannabinol, and its active metabolite, (±)-11-OH-Δ9-tetrahydrocannabinol. To determine causality, preclinical studies mimicking human fetal cannabin...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55863-5 |
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| author | Aditya R. Kumar Lyndsey S. Benson Erica M. Wymore Jocelyn E. Phipers Jennifer C. Dempsey Lucinda A. Cort Jashvant D. Unadkat |
| author_facet | Aditya R. Kumar Lyndsey S. Benson Erica M. Wymore Jocelyn E. Phipers Jennifer C. Dempsey Lucinda A. Cort Jashvant D. Unadkat |
| author_sort | Aditya R. Kumar |
| collection | DOAJ |
| description | Abstract Prenatal cannabis use is associated with neurodevelopmental deficits, likely due to exposure to the psychoactive cannabinoid, (-)-Δ9-tetrahydrocannabinol, and its active metabolite, (±)-11-OH-Δ9-tetrahydrocannabinol. To determine causality, preclinical studies mimicking human fetal cannabinoid exposure must be conducted. Here we show cannabinoid concentrations across gestation in maternal plasma and paired fetal tissues in trimester 1 and 2 and maternal plasma and fetal umbilical venous plasma in trimester 3. The mean ± SD trimester 1 and 2 (-)-Δ9-tetrahydrocannabinol fetal brain/maternal plasma is 0.50 ± 0.18 (n = 3), 0.45 ± 0.28 (n = 14), respectively; trimester 3 (-)-Δ9-tetrahydrocannabinol umbilical venous plasma/maternal plasma is 0.35 ± 0.13 (n = 18). To predict fetal cannabinoid exposure at different prenatal cannabis doses (oral or inhaled), we used a verified maternal-fetal physiologically based pharmacokinetic model. At an inhalational and oral dose of 10 mg (-)-Δ9-tetrahydrocannabinol, the model-predicted average fetal brain steady-state (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol concentrations, at gestational week 15, are 3.7/7.0 nM and 0.73/8.9 nM, respectively. Our maternal-fetal physiologically based pharmacokinetic model can guide future studies to inform risks associated with prenatal cannabis use. |
| format | Article |
| id | doaj-art-03d73f21aa6c4778914543e788afa53b |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-03d73f21aa6c4778914543e788afa53b2025-01-19T12:32:17ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-025-55863-5Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicityAditya R. Kumar0Lyndsey S. Benson1Erica M. Wymore2Jocelyn E. Phipers3Jennifer C. Dempsey4Lucinda A. Cort5Jashvant D. Unadkat6Department of Pharmaceutics, University of Washington School of PharmacyDepartment of Obstetrics and Gynecology, University of Washington School of MedicineDepartment of Pediatrics, University of Colorado School of MedicineDepartment of Pediatrics, University of Colorado School of MedicineDepartment of Pediatrics, University of Washington School of MedicineDepartment of Pediatrics, University of Washington School of MedicineDepartment of Pharmaceutics, University of Washington School of PharmacyAbstract Prenatal cannabis use is associated with neurodevelopmental deficits, likely due to exposure to the psychoactive cannabinoid, (-)-Δ9-tetrahydrocannabinol, and its active metabolite, (±)-11-OH-Δ9-tetrahydrocannabinol. To determine causality, preclinical studies mimicking human fetal cannabinoid exposure must be conducted. Here we show cannabinoid concentrations across gestation in maternal plasma and paired fetal tissues in trimester 1 and 2 and maternal plasma and fetal umbilical venous plasma in trimester 3. The mean ± SD trimester 1 and 2 (-)-Δ9-tetrahydrocannabinol fetal brain/maternal plasma is 0.50 ± 0.18 (n = 3), 0.45 ± 0.28 (n = 14), respectively; trimester 3 (-)-Δ9-tetrahydrocannabinol umbilical venous plasma/maternal plasma is 0.35 ± 0.13 (n = 18). To predict fetal cannabinoid exposure at different prenatal cannabis doses (oral or inhaled), we used a verified maternal-fetal physiologically based pharmacokinetic model. At an inhalational and oral dose of 10 mg (-)-Δ9-tetrahydrocannabinol, the model-predicted average fetal brain steady-state (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol concentrations, at gestational week 15, are 3.7/7.0 nM and 0.73/8.9 nM, respectively. Our maternal-fetal physiologically based pharmacokinetic model can guide future studies to inform risks associated with prenatal cannabis use.https://doi.org/10.1038/s41467-025-55863-5 |
| spellingShingle | Aditya R. Kumar Lyndsey S. Benson Erica M. Wymore Jocelyn E. Phipers Jennifer C. Dempsey Lucinda A. Cort Jashvant D. Unadkat Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity Nature Communications |
| title | Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity |
| title_full | Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity |
| title_fullStr | Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity |
| title_full_unstemmed | Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity |
| title_short | Quantification and prediction of human fetal (-)-Δ9-tetrahydrocannabinol/(±)-11-OH-Δ9-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity |
| title_sort | quantification and prediction of human fetal δ9 tetrahydrocannabinol 11 oh δ9 tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity |
| url | https://doi.org/10.1038/s41467-025-55863-5 |
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