About the Authors
Caitlyn Bradford, PharmD, BCPPS, is an assistant clinical professor at the Philadelphia College of Pharmacy at Saint Joseph’s University in Pennsylvania.
Maura Cantwell is a class of 2025 PharmD candidate at the Philadelphia College of Pharmacy at Saint Joseph’s University in Pennsylvania.
Gia Ho is a class of 2025 PharmD candidate at the Philadelphia College of Pharmacy at Saint Joseph’s University in Pennsylvania.
Rena Cuneo is a class of 2025 PharmD candidate at the Philadelphia College of Pharmacy at Saint Joseph’s University in Pennsylvania.
Danielle Alm, PharmD, BCPS, BCPPS, is a clinical associate professor at the Philadelphia College of Pharmacy at Saint Joseph’s University in Pennsylvania.
Cannabis use has increased over the past few years among the American population, and pregnant individuals are no exception. However, the use of cannabis in pregnant individuals has the potential to impact fetal development. In a study conducted by Young-Wolff et al, roughly 20% of the 279,457 pregnant women aged 24 or older studying in California between 2009 and 2016 tested positive for cannabis on a routine drug screen at a prenatal care appointment. The percentage of younger pregnant women using cannabis started at around 12.5% in 2009 and gradually increased to about 22% throughout the 7 years the study was conducted.1 During this period, the use of cannabis in pregnant women aged 25 to 34 years remained relatively stagnant, likely due to cannabis use being most prevalent in women aged 18 to 25 years.2
However, Young-Wolff et al explain that self-reporting of cannabis use during pregnancy is also neither accurate nor reliable, as only 29.2% of the 54.9% of women who tested positive on drug screens reported their cannabis use. There are a variety of reasons why pregnant women may choose not to disclose their cannabis use, but one notable reason may be the stigma associated with substance use of any kind during pregnancy. However, it is important to address this stigma, specifically in relation to cannabis use, as cannabis can impact the health of neonates.
The impact of cannabis on neonates can be attributed to the variety of chemicals it contains, with the primary components being tetrahydrocannabinol (THC) and cannabidiol (CBD). Since the 1990s, the potency of THC found in forms of nonmedical cannabis has increased from approximately 4% to more than 15%.3
The chemical structure of THC is similar to a chemical in the brain called anandamide. This similar structure allows THC to be recognized by the brain and alter brain communication.4 THC, a psychoactive chemical, binds to our endogenous cannabinoid receptors, influencing areas of the brain that affect coordination, concentration, thinking, memory, and pleasure.4-6
CBD, on the other hand, is a nonpsychoactive chemical found in cannabis.7 Medical formulations of CBD are not intended to contain THC. CBD alone is often well-tolerated by individuals but induces adverse effects such as dry mouth, drowsiness, changes in alertness, gastrointestinal distress, and changes in mood (eg, irritability and agitation).8 The purity and dosage of CBD products are often unreliable, as many products contain lower amounts of CBD than indicated, or they potentially contain THC.8,9
One of the first steps to establish safety and toxicity limits of cannabis use in the general population—and specifically within the pregnant population—is stricter regulations with clear labeling of doses and ingredients. Similarly, long-term studies are needed to evaluate the lasting effects of in-utero cannabis exposure and whether there is a dose-dependent relationship with potential toxicities.
The main concern about cannabis use during pregnancy is that the chemicals in cannabis, such as THC, can pass to the baby through the placenta. A 2015 study published in Frontiers of Human Neuroscience scanned the brains of babies exposed to cannabis in utero, looking specifically at the caudate, insula, amygdala, and other regions of the brain.10 These scans found that the neonates exposed to cannabis in utero had altered connectivity between certain areas of the brain compared with neonates who were not exposed. These alterations in brain function connectivity could contribute to deficits in the child’s motor-spatial activity, attention, integration and coordination, and social-emotional stability.10 Further, this is not the only study to raise concerns about the use of cannabis during pregnancy, as other studies have suggested similar warning signs of function and behavior in children exposed to cannabis in utero.11,12
Future Neurology published an article discussing the manifestations that cannabis use can have on a person in each stage of life after exposure to cannabis in utero.11 In neonates, it was noted that a decrease in the dopamine receptor levels in the brain and a reduction in birth weight may occur. In early development, there have been observations of a reduction in verbal reasoning scores and short-term memory, as well as an increase in aggression, anxiety, and depression. Additionally, there have been links between prenatal cannabis exposure and impaired executive functions, such as impulse control, visual memory, and attention throughout the school year. There are also reports of young children experiencing an increase in impulsivity, inattention, and hyperactivity, which are all symptoms found in children with attention-deficit/hyperactivity disorder.11 In adolescents, an increase in depressive symptoms, delinquency, and antisocial behavior, and a reduction in abstract reasoning were found.13,14 Even into adulthood, there are implications of an increased likelihood of drug-seeking behavior and a reduction of visuospatial memory in those exposed to cannabis in utero.11 These articles do not include a specific statistical analysis of risk but rather emphasize the life-long possible risks associated with cannabis use in pregnant women (Table 111). Additional human studies are needed to determine the definitive impact cannabis can have on this specific population.
Although the long-term effects of cannabis use on children in utero are still unclear due to the lack of human trials and research, preliminary findings suggest that prenatal cannabis use may impair fetal growth and development, which could increase the risk of stillbirths.1,16 A study by Varner et al looked at the association between illicit drug use, smoking, and stillbirths. Results from the study showed that women with pregnancy potential with documented THC acid (THCA) levels had a 2-fold increase in the odds of stillbirth. THCA was the most common individual drug detected among pregnant women with stillbirth, with an odds ratio of 2.34 (95% CI, 1.13-4.81). This result indicates that pregnant women who are exposed to THCA are 2.34 times more likely to experience stillbirths than those who are not exposed to THCA.16
Small numbers of controlled substances, such ashydrocodone and morphine, also trended toward increased odds of stillbirth in another study.16 This finding is particularly significant in light of the ongoing prescription opioid misuse crisis, emphasizing the potential risks associated with these medications during pregnancy.16 However, there may be a confounding relationship between illicit drug use and stillbirth due to concomitant tobacco smoking, since those who were positive for both nicotine and substance drug use had an odds ratio for stillbirth at 3.86 (95% CI, 1.61-9.24).16 Pregnant women who use both nicotine and illicit drugs had nearly 4 times (3.86 times) the odds of experiencing stillbirth compared with those who did not use either substance.
The growing use of cannabis during pregnancy may be attributed to the increasing legalization of recreational cannabis use across the country. California and Washington were the first 2 states to legalize the use of recreational cannabis in 2012. Over the next decade, 22 additional states and 2 U.S. territories followed suit, totaling 24 states to legalize the use of cannabis for non-medical purposes. Meanwhile, 47 states permit the use of medical cannabis, as well as three U.S. territories.17 Due to the increasing number of states legalizing cannabis, the number of pregnant women using cannabis is likely to increase based on recent surveys conducted by the National Institute of Health.4,17 To change the trajectory of these growing rates, health care professionals must acknowledge the issue and recommend alternatives to cannabis that take into account clinical indications, patient-specific factors, and particular circumstances (Table 2).
It is important to note that medical cannabis use has provided some benefits in pregnancy, despite the neonatal effects that were observed. There are a variety of clinical uses of cannabis, although the FDA-approved indications are few. For instance, Epidiolex (Jazz Pharmaceuticals), which contains pure forms of CBD, is FDA-approved for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex.27-29 Additionally, dronabinol (Marinol; Solvay Pharmaceuticals), which is a synthetic form of THC, is FDA-approved for the treatment of HIV/AIDS-induced anorexia as well as chemotherapy-induced nausea and vomiting in patients who failed antiemetics.11,30 However, these FDA-approved forms of cannabis have been used off-label to help patients with various disease states, such as epilepsy, depression, anxiety, insomnia, multiple sclerosis, and pain management. Cannabis has also been used off-label to help with nausea and vomiting that pregnant women may experience during their first trimester.5 Based on a survey conducted by the American Journal of Obstetrics and Gynecology, 79% of 785 pregnant women surveyed between 2007 and 2012 reported perceiving little to no harm in the prenatal use of cannabis.31 These survey results emphasize the need for public education of both benefits and risks (Table 332).
In conclusion, the use of cannabis during pregnancy remains a contentious issue with potentially serious consequences for infants’ development. While some studies suggest the potential benefits of cannabis use for certain medical conditions, the overall consensus is to be cautious and discourage cannabis use during pregnancy. The limited research available further raises concerns as there are currently many unknowns concerning risks. Additional research is needed to further elucidate the potential short- and long-term benefits and risks of prenatal cannabis use.
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