Effect of In-Utero Cannabinoid Exposure on Foetal Growth and Placental Efficiency
DOI:
https://doi.org/10.30442/ahr.1103-04-291Keywords:
Cannabinoids, Foetal growth, Placental health, Prenatal exposure, Tetrahydrocannabinol (THC)Abstract
Background: Cannabis sativa. L. contains over 550 components, including cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD), which affect the endocannabinoid system and influence human neurodevelopment and physiological functions. Although it has therapeutic potential, cannabis use during pregnancy can disrupt foetal development, especially in the brain and placenta.
Objective: To examine the prenatal exposure to THC and CBD on foetal growth and placental health using a Wistar rat model.
Methods: A total of 24 female rats were divided into four groups; each received orally 150mg/kg/day of THC, CBD, or a combination (CBD and THC) at 150 mg/kg/day. The control received only water and feed. The early-phase administration of cannabinoids occurred from day 6 to 19.
Results: There were substantial reductions in foetal weight. The mean weight was 3.78g in the control group. The THC-exposed group showed a 36% reduction (2.41g), the CBD-exposed group had a 41% reduction (2.22g), and the combined THC/CBD group had a decrease of 3.51g. Significant alterations in placental morphological architecture were observed. The THC and CBD exposure groups exhibited pronounced structural distortions and increased trophoblast degeneration, respectively, whereas the combined exposure showed milder placental changes. The foetal-to-placental weight ratio was significantly reduced in all cannabis-exposed groups.
Conclusion: This study shows prenatal THC and CBD harm foetal growth and placental health. THC caused the most severe effects of reduced foetal weight and placental changes. Therefore, public health initiatives should be intensified to alert pregnant women regarding the risks of using cannabis.
References
1. Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M. Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol 2018;227:300–315. https://doi.org/10.1016/j.jep.2018.09.004.
2. Rock EM, Parker LA. Constituents of Cannabis Sativa. In: Murillo-Rodriguez E, Pandi-Perumal SR, Monti JM, editors. Cannabinoids and Neuropsychiatric Disorders [Internet]. Cham: Springer International Publishing; 2021. p. 1–13. (Advances in Experimental Medicine and Biology; vol. 1264). DOI:10.1007/978-3-030-57369-0_1
3. Wishart DS, Hiebert-Giesbrecht M, Inchehborouni G, Cao X, Guo AC, LeVatte MA. Chemical Composition of Commercial Cannabis. J Agric Food Chem 2024;72:14099. https:..doi.org/10.1021/acs.jafc.3c06616.
4. Navarrete F, García-Gutiérrez MS, Gasparyan A, Austrich-Olivares A, Femenía T, Manzanares J. Cannabis Use in Pregnant and Breastfeeding Women: Behavioral and Neurobiological Consequences. Front Psychiatry 2020;11:586447. https://doi.org/10.3389/fpsyt.2020.586447.
5. Thompson A, Koren G, McGowan J. Cannabis use during pregnancy: A review of the literature. J Matern Fetal Neonatal Med 2019;32:2027-2034. https://doi.org/10.1080/14767058.2018.1441853.
6. Mark K, McCaffrey D, Larkins A. Prenatal cannabis exposure: Potential implications for child development and behavior. Child Dev Perspect 2017;11:42-48. https://doi.org/10.1111/cdep.12202.
7. Singh T, Bhandari S, Kaur S. The impact of prenatal cannabis exposure on fetal and neonatal outcomes: A systematic review. Neurotoxicology 2020;78:106849. https://doi.org/10.1016/j.ntt.2020.106849.
8. Kroon E, Kuhns L, Hoch E, Cousijn J. Heavy cannabis use, dependence and the brain: a clinical perspective. Addiction 2020;115:559–572. https://doi.org/10.1111/add.14776.
9. De Camargo RW, De Novais Júnior LR, Da Silva LM, Meneguzzo V, Daros GC, Da Silva MG. Implications of the endocannabinoid system and the therapeutic action of cannabinoids in autism spectrum disorder: A literature review. Pharmacol Biochem Behav 2022;221:173492.
10. Montgomery L, Dixon S, Mantey DS. Racial and Ethnic Differences in Cannabis Use and Cannabis Use Disorder: Implications for Researchers. Curr Addict Rep 2022;9:14. https://doi.org/10.1007/s40429-021-00404-5
11. Mulligan MK, Hamre KM. Influence of prenatal cannabinoid exposure on early development and beyond. Adv Drug Alcohol Res 2023;3:10981. https://doi.org/10.3389/adar.2023.10981.
12. Cameron LD, Fleszar-Pavlović SE, Yepez M, Manzo RD, Brown PM. Beliefs about marijuana use during pregnancy and breastfeeding held by residents of a Latino-majority, rural region of California. J Behav Med 2022;45:544–557. https://doi.org/10.1007/s10865-022-00299-1.
13. Andrade C. Maternal Cannabis Use During Pregnancy and Maternal and Neonatal Adverse Outcomes. J Clin Psychiatry 2024;85:57493. https://doi.org/10.4088/JCP.24f15611.
14. Avalos LA, Oberman N, Alexeeff SE, Croen LA, Davignon MN, Adams SR, et al. Early Maternal Prenatal Cannabis Use and Child Developmental Delays. JAMA Netw Open 2024;7:e2440295. https://doi.org/10.1001/jamanetworkopen.2024.40295
15. Bligard KH, Odibo AO. Fetal Growth Restriction. In: Spong CY, Lockwood CJ, editors. Queenan’s Management of High‐Risk Pregnancy [Internet]. 1st ed. Wiley; 2024; p. 392–8. https://doi.org/10.1002/9781119636540.ch44
16. Natale BV, Gustin KN, Lee K, Holloway AC, Laviolette SR, Natale DRC, et al. Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta. Sci Rep 2020;10:544. https://doi.org/10.1038/s41598-019-57318-6.
17. Sharapova SR, Phillips E, Sirocco K, Kaminski JW, Leeb RT, Rolle I. Effects of prenatal marijuana exposure on neuropsychological outcomes in children aged 1‐11 years: A systematic review. Paediatr Perinat Epidemiol 2018; 32:512–532. https://doi.org/10.1111/ppe.12505.
18. Vishnubhotla RV, Ahmad ST, Zhao Y, Radhakrishnan R. Impact of prenatal marijuana exposure on adolescent brain structural and functional connectivity and behavioural outcomes. Brain Commun 2024;6:fcae001. https://doi.org/10.1093/braincomms/fcae001
19. Boggs DL, Nguyen JD, Morgenson D, Taffe MA, Ranganathan M. Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. Neuropsychopharmacology 2018;43:142-154. https://doi.org/10.1038/npp.2017.197.
20. Galve-Roperh I, Sánchez C, Cortés ML, Fernández-Ruiz J. The endocannabinoid system in development and perinatal events. Trends Pharmacol Sci 2002;23:83-87. https://doi.org/10.1016/S0165-6147(01)01635-2.
21. Hernández ME, Rojas C, Salazar L. Cannabinoid receptors and their modulation in the placenta. Front Pharmacol 2018;9:964. https://doi.org/10.3389/fphar.2018.00964.
22. Maccarrone M, Guzman M, Macarulla T. Endocannabinoid signalling in the regulation of immune responses. J Neuroimmune Pharmacol 2015;10:212-223. https://doi.org/10.1007/s11481-015-9586-6.
23. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008;153:199-215. https://doi.org/10.1038/sj.bjp.0707442.
24. Mayrink ML de S, Villela LD, Méio MDBB, Soares FVM, de Abranches AD, Nehab SRG, et al. The trajectory of head circumference and neurodevelopment in very preterm newborns during the first two years of life: a cohort study. J Pediatr (Rio J) 2024;100:483–490. https://doi.org/10.1016/j.jped.2024.04.005.
25. Brown S. Indiana's Punitive Responses to Prenatal Marijuana Use: A Recommendation for the Indiana Legislature. Indiana Health Law Review. 2025; 22(1):125-54. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; http://www.ncbi.nlm.nih.gov/books/NBK570616/PMID: 34033378
26. Dodge P, Nadolski K, Kopkau H, Zablocki V, Forrestal K, Bailey BA. The impact of timing of in utero marijuana exposure on fetal growth. Frontiers Pediatr 2023.11:1103749. https://doi.org/10.3389/fped.2023.1103749
27. Peng S, Li C, Xie X, Zhang X, Wang D, Lu X. Divergence of Iodine and Thyroid Hormones in the Fetal and Maternal Parts of Human-Term Placenta. Biol Trace Elem Res 2020;195:27–38. https://doi.org/10.1007/s12011-019-01834-z.
28. Furukawa S, Tsuji N, Sugiyama A. Morphology and physiology of rat placenta for toxicological evaluation. J Toxicol Pathol 2019;32:1-17. https://doi.org/10.1293/tox.2018-0042
29. Sarkar AA, Sabatino JA, Sugrue KF, Zohn IE. Abnormal labyrinthine zone in the Hectd1-null placenta. Placenta 2016;38:16–23. https://doi.org/10.1016/j.placenta.2015.12.002.
30. Miller GM, Smith D, Shukitt-Hale B. Effects of Housing on Rodent Behavior: Wire vs. Solid Plastic Caging. Anim. Husb Dairy Vet Sci 2020;4:1-5.
31. Rashid S, Majeed LR, Nisar B, Nisar H, Bhat AA, Ganai BA. Phytomedicines: Diversity, extraction, and conservation strategies. In: Phytomedicine. Elsevier; 2021. p.1–33. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780128241097000091
32. Fiardilla, F., Warsiki, E., & Sugiarto. The experiment of activity and stability of antioxidant extracted from Senduduk (Melastoma malabathricum L) leaves at various conditions of concentration, pH values, and temperatures. IOP Conference Series: Earth Environ Sci 2020;472:012003. https://doi.org/10.1088/1755-1315/472/1/012003
33. Liu Y, Victoria J, Wood M, Staretz ME, Brettell TA. High Performance Thin-Layer Chromatography (HPTLC) data of Cannabinoids in ten mobile phase systems. Data Brief 2020;31:105955. https://doi.org/10.1016/j.dib.2020.105955
34. Chan P. Toxicity and Carcinogenicity of Δ9-Tetrahydrocannabinol in Fischer Rats and B6C3F1 Mice. Fundam Appl Toxicol 1996;30:109–117. https://doi.org/10.1006/faat.1996.0048
35. Allen S, Natale BV, Ejeckam AO, Lee K, Hardy DB, Natale DRC. Cannabidiol Exposure During Rat Pregnancy Leads to Labyrinth-Specific Vascular Defects in the Placenta and Reduced Fetal Growth. Cannabis Cannabinoid Res. 2024;9:766–780. https://doi.org/10.1089/can.2023.0166.
36. Sathasivam R, Selliah P, Sivalingarajah R, Mayorathan U, Munasinghe BM. Placental weight and its relationship with the birth weight of term infants and the body mass index of the mothers. J Int Med Res 2023;51:03000605231172895. https://doi.org/10.1177/03000605231172895.
37. Metz TD, Allshouse AA, Pinar H, Varner M, Smid MC, Hogue C. Maternal Marijuana Exposure, Feto-Placental Weight Ratio, and Placental Histology. Am J Perinatol 2022;39:546–553. https://doi.org/10.1055/s-0040-1717092.
38. Armengaud JB, Yzydorczyk C, Siddeek B, Peyter AC, Simeoni U. Intrauterine growth restriction: Clinical consequences on health and disease at adulthood. Reprod Toxicol 2021;99:168–176. https://doi.org/10.1016/j.reprotox.2020.10.005.
39. Lee K, Laviolette SR, Hardy DB. Exposure to Δ9-tetrahydrocannabinol during rat pregnancy leads to impaired cardiac dysfunction in postnatal life. Pediatr Res 2021;90:532–539. https://doi.org/10.1038/s41390-021-01511-9.
40. Vinchurkar KN, Aiyappan SK, Prem Kumar C, Shanmugam V, Singh A. Correlation of placental thickness with gestational age in second and third trimester using ultrasonography. Egypt J Radiol Nucl Med 2023;54:164. https://doi.org/10.1186/s43055-023-01112-y.
41. Vrooman LA, Xin F, Bartolomei MS. Morphological and molecular changes in the placenta: What we can learn from environmental exposures. Fertil Steril 2016;106:930–940. https://doi.org/10.1016/j.fertnstert.2016.08.016.
42. Furukawa S, Hayashi S, Usuda K, Abe M, Hagio S, Ogawa I. Toxicological Pathology in the Rat Placenta. J Toxicol Pathol. 2011;24(2):95–111. doi: 10.1293/tox.24.95
43. Mortuza A, Fahim N, Ahmed M, Mustafa A. Effects of CBD (Cannabidiol) on the physiology of Nile tilapia (Oreochromisn niloticus) as a chronic stress mitigating agent In-vivo. PLOS ONE 2023 15;18:e0290835. https://doi.org/10.1371/journal.pone.0290835
44. Shafrir E, Barash V. Placental glycogen metabolism in diabetic pregnancy. Isr J Med Sci 1991;27:449–461.
45. Akison LK, Nitert MD, Clifton VL, Moritz KM, Simmons DG. Review: Alterations in placental glycogen deposition in complicated pregnancies: Current preclinical and clinical evidence. Placenta 2017;54:52–58. https://doi.org/10.1016/j.placenta.2017.01.114.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Annals of Health Research (The Journal of the Medical and Dental Consultants Association of Nigeria, OOUTH, Sagamu, Nigeria)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The articles and other materials published in the Annals of Health Research are protected by the Nigerian Copyright laws. The journal owns the copyright over every article, scientific and intellectual materials published in it. However, the journal grants all authors, users and researchers access to the materials published in the journal with the permission to copy, use and distribute the materials contained therein only for academic, scientific and non-commercial purposes.
