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Similar to research with other recreational drugs, studies on the effects of cannabis use by pregnant women have encompassed pregnancy outcome as well as potential changes in brain function and behavior in the exposed offspring as they grow and develop. Reviews and meta-analyses of these studies have reported a significant association between maternal cannabis use and increased risk for maternal anemia, low birthweight of the infant, smaller head circumference at birth (which indicates reduced brain size and predicts lower IQ later in life), increased risk of preterm birth, and greater likelihood that the newborn will require placement in the neonatal intensive care unit. In some analyses, these effects continued to be statistically significant even when the data were controlled for maternal tobacco use, which itself is a major cause of intrauterine growth restriction (Calvigioni et al., 2014; Gunn et al., 2016). On the other hand, the analysis by Conner and coworkers (2016) found that the growth-impairing effects of cannabis use were no longer present when the data were adjusted for tobacco use and other confounding variables. Assuming that cannabis use does contribute to growth restriction in utero, this effect may be related at least partly to activation of placental CB1 receptors and resulting decreases in nutrient and oxygen availability to the fetus (Jaques et al., 2014).
Other research has examined the relationship between prenatal cannabis exposure and offspring behavior during infancy, childhood, adolescence, and adulthood. For example, a recent study compared a group of marijuana-exposed infants to a non-exposed control group for developmental milestones every 3 months from 6 months to 24 months of age (Alvarez et al., 2018). The marijuana-exposed infants showed delays in fine motor skills and social behavior at 15 and 18 months of age. Several reviews have additionally reported adverse effects of prenatal marijuana exposure on various measures of cognitive function, with the specific effect depending on the age at testing and the type of cognitive function assessed by the researchers (Calvigioni et al., 2014; Jaques et al., 2014; Roncero et al., 2020; Nashed et al., 2021). Other studies found associations between prenatal marijuana exposure and increased symptoms of depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) in adolescence and/or adulthood. Lastly, research focused on addiction vulnerability found that compared to controls, offspring of marijuana-using women showed earlier use of marijuana and cigarettes during adolescence, had greater frequencies of marijuana and cigarette use, and were at heightened risk for cannabis use disorder (CUD) (Sonon et al., 2016; Dodge et al., 2019).
Clinical studies of prenatal drug exposure are limited by several potential confounding factors, including but not limited to polysubstance use (especially cigarette smoking by pregnant marijuana users), the lack of prenatal care that is often present in pregnant substance users, differences in socioeconomic status between marijuana-using and non-using women, and wide variability in doses and patterns of drug (in this case marijuana) use. Because of their ability to circumvent these confounds, studies using laboratory rats and mice have played a critical role in helping discern the effects of prenatal cannabinoid exposure on subsequent brain and behavioral functioning. Such studies, which typically involve repeated treatment of dams with either THC or a synthetic cannabinoid agonist such as WIN 55,121-2, have found numerous treatment effects on motor function, learning and memory, anxiety, social behaviors, and drug-seeking behavior, as well as significant changes in several different neurotransmitter systems (Hurd et al., 2019; Pinky et al., 2019; Navarrete et al., 2020). A visual summary of some of the reported effects of prenatal cannabinoid exposure from both human and animal studies is shown in Figure 1. It is evident from the figure that some effects are similar across human and animal studies, whereas others are not. Note that neurochemical changes discovered in the animal research have often not yet been studied in humans, usually because of technical limitations. On the other hand, discrepancies in behavioral outcomes between the animal and human studies could be explained by a number of reasons, including inadequate validation of a particular animal test to model the targeted human behavior (e.g., when a behavioral effect has been observed in human but not animal studies), lack of statistical power and/or the presence of uncontrolled confounding factors (e.g., when a behavioral effect has been observed in animal but not human studies), or poor modeling of cannabinoid exposure in the animal study (choices of dose, frequency of administration, etc. that fail to correspond properly to the cannabis-using population of women being investigated). These complexities are not unique to the prenatal marijuana literature but come into play in all prenatal drug studies.
Despite the fact that we are far from having a complete picture of the possible neurodevelopmental effects of prenatal cannabinoid exposure, there is sufficient evidence to indicate that maternal cannabis use during pregnancy and possibly also while nursing poses a risk for her infant. Accordingly, the American College of Obstetricians and Gynecologists (2017) recommends that women who are pregnant, contemplating pregnancy, or breastfeeding should be discouraged from any cannabis use. Ordean and Kim (2020) additionally recommended that if a nursing mother finds it impossible to abstain from marijuana smoking, she should at least avoid breastfeeding her infant until at least 1 hour after marijuana use. Based on THC pharmacokinetics, this practice should minimize the infant’s exposure to the breast milk that contains the highest THC concentration.
Figure 1 Visual summary of selected effects of prenatal cannabinoid exposure based on rodent and human studies Outcomes of rodent (rats or mice) studies are shown on the upper part of the figure, whereas outcomes of human studies are shown on the lower part of the figure. Results are separated by the developmental period when the assessment was performed. Arrows shown on the upper left of the figure indicate whether a particular outcome variable was increased, decreased, or altered in the cannabinoid-exposed group compared to controls. The designation “altered” means that the variable is changed in a complex way that cannot be summarized as simply “increased” or “decreased.” (After Scheyer et al., 2019.)
References
Alvarez, A. V. G., Rubin, D., Pina, P., and Velasquez, M. S. (2018). Neurodevelopmental outcomes and prenatal exposure to marijuana. Pediatrics, 142 (1 Meeting Abstract), 787. doi: 10.1542/peds.142.1_MeetingAbstract.787.
American College of Obstetricians and Gynecologists. (2017). Marijuana use during pregnancy and lactation. Committee Opinion No. 722. Obstet. Gynecol., 130, e205–e209.
Calvigioni, D., Hurd, Y. L., Harkany, T., and Keimpema, E. (2014). Neuronal substrates and functional consequences of prenatal cannabis exposure. Eur. Child Adolesc. Psychiatry, 23, 931–941.
Conner, S. N., Bedell, V., Lipsey, K., Macones, G. A., Cahill, A. G., and Tuuli, M. G. (2016). Maternal marijuana use and adverse neonatal outcomes: A systematic review and meta-analysis. Obstet. Gynecol., 128, 713–723.
Dodge, N. C., Jacobson, J. L., and Jacobson, S. W. (2019). Effects of fetal substance exposure on offspring substance use. Pediatr. Clin. North Am., 66, 1149–1161.
Gunn, J. K., Rosales, C. B., Center, K. E., Nuñez, A., Gibson, S. J., Christ, C., and Ehiri, J. E. (2016). Prenatal exposure to cannabis and maternal and child health outcomes: A systematic review and meta-analysis. BMJ Open, 6, e009986. doi: 10.1136/bmjopen-2015-009986.
Hurd, Y. L., Manzoni, O. J., Pletnikov, M. V., Lee, F. S., Bhattacharyya, S., and Melis, M. (2019). Cannabis and the developing brain: Insights into its long-lasting effects. J. Neurosci., 39, 8250–8258.
Jaques, S. C., Kingsbury, A., Henshcke, P., Chomchai, C., Clews, S., Falconer, J., et al. (2014). Cannabis, the pregnant woman and her child: Weeding out the myths. J. Perinatol., 34, 417–424.
Nashed, M. G., Hardy, D. B., and Laviolette, S. R. (2021). Prenatal cannabinoid exposure: Emerging evidence of physiological and neuropsychiatric abnormalities. Front. Psychiatry, 11, 624275. doi: 10.3389/fpsyt.2020.624275.
Navarrete, F., García-Gutiérrez, M. S., Gasparyan, A., Austrich-Olivares, A., Femenía, T., and Manzanares, J. (2020). Cannabis use in pregnant and breastfeeding women: Behavioral and neurobiological consequences. Front. Psychiatry, 11, 586447. doi: 10.3389/fpsyt.2020.586447.
Ordean, A., and Kim, G. (2020). Cannabis use during lactation: Literature review and clinical recommendations. J. Obstet. Gynaecol Can., 42, 1248–1253.
Pinky, P. D., Bloemer, J., Smith, W. D., Moore, T., Hong, H., Suppiramaniam, V., and Reed, M. N. (2019). Prenatal cannabinoid exposure and altered neurotransmission. Neuropharmacology, 149, 181–194.
Roncero, C., Valriberas-Herrero, I., Mezzatesta-Gava, M., Villegas, J. L., Aguilar, L., and Grau-López, L. (2020). Cannabis use during pregnancy and its relationship with fetal developmental outcomes and psychiatric disorders. A systematic review. Reprod. Health, 17(1), 25. doi: 10.1186/s12978-020-0880-9.
Scheyer, A. (2019). Prenatal exposure to cannabis affects the developing brain. The Scientist, 33(1), 36–41.
Sonon, K., Richardson, G. A., Cornelius, J., Kim, K. H., and Day, N. L. (2016). Developmental pathways from prenatal marijuana exposure to Cannabis Use Disorder in young adulthood. Neurotoxicol. Teratol., 58, 46–52.