A new study from researchers at Western University and Queen’s University definitively shows that regular exposure to THC, the main psychoactive ingredient in cannabis, during pregnancy has significant impact on placental and fetal development.
With more than a year since the legalization of recreational cannabis in Canada, the effects of its use during pregnancy are only now beginning to be understood.
The study, published today in Scientific Reports, uses a rat model and human placental cells to show that maternal exposure to THC during pregnancy has a measurable impact on both the development of the organs of the fetus and the gene expression that is essential to placental function.
The researchers demonstrated in a rat model that regular exposure to a low-dose of THC that mimics daily use of cannabis during pregnancy led to a reduction in birth weight of 8 per cent and decreased brain and liver growth by more than 20 per cent.
“This data supports clinical studies that suggest cannabis use during pregnancy it is associated with low birth weight babies. Clinical data is complicated because it is confounded by other factors such as socioeconomic status,” said Dan Hardy, Ph.D., Associate Professor at Western’s Schulich School of Medicine & Dentistry and co-author on the paper.
“This is the first study to definitively support the fact that THC alone has a direct impact on placental and fetal growth.”
The research team was also able to characterize how THC prevents oxygen and nutrients from crossing the placenta into the developing fetus. By studying human placental cells, the researchers found that exposure to THC caused a decrease in a glucose transporter called GLUT-1.
This indicates that the THC is preventing the placental transfer of glucose, a key nutrient, from the mother to the fetus. They also found a reduction in placental vasculature in the rat model suggesting reduced blood flow from the mother to the fetus.
The researchers say both of those factors are likely contributing to the growth restriction that they observed in the offspring.
The researchers point out that there are currently no clear guidelines from Health Canada on the use of cannabis in pregnancy and some studies have shown that up to one in five women are using cannabis during pregnancy to prevent morning sickness, for anxiety or for social reasons.
“Marjiuana has been legalized in Canada and in many states in the US, however, its use during pregnancy has not been well studied up until this point. This study is important to support clinicians in communicating the very real risks associated with cannabis use during pregnancy,” said David Natale, Ph.D., Associate Professor at Queen’s and co-author on the paper.
Public endorsement for potential benefits of the marijuana plant is at an all-time high. To date, 33 states and the District of Columbia have responded by legalizing “medical marijuana,” with 10 states also having legalized recreational use. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations and most epidemiological studies point towards harmful associations.
Yet the general population turns to this botanical while seeking self-remedies for various ailments and conditions for which other, evidence-based, treatment modalities exist.
As physicians, we have seen some of the outcomes associated with use, particularly in vulnerable populations with underlying mental health and addictive disorders, as well as adolescents and—for the purpose of this article—pregnant individuals.
The Center for Disease Control (CDC) estimates that 16.2% of pregnant women between the ages of 18 and 44 are daily users and of all illicit cannabis is the most commonly abused by this population.
Estimates also indicate that between 2009 and 2016 cannabis use among pregnant females has nearly doubled, with young age being positively correlated with use. Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies.
Aside from continuation of use if already smoking at the time of pregnancy, some take up cannabis to manage morning sickness and overall nausea and vomiting. A study was recently done in Colorado where researchers identified as pregnant women and contacted dispensaries for guidance in managing pregnancy-related symptoms. Close to 70% of dispensaries contacted recommended products to treat symptoms particularly in the vulnerable first trimester, while 36% of theme also provided reassurance of the safety profile. Very few even encouraged a discussion with the physician.
Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, and other organs, where it interferes with neurodevelopment and the endocannabinoid system. Use during the postnatal period can also lead to secretion in breast milk for extended periods (up to a week) after last use. From retrospective studies, we know prenatal cannabis ingestion has been associated with anemia in the mothers as well as low birth weights, greater risk of preterm and stillbirths, as well as increased need for neonatal intensive care unit admissions.
Although there is no phenotypic syndrome and no overt birth defects, a review of two longitudinal studies indicates the majority of the teratogenicity translates later in life, beyond the infant developmental stage. Children born to mothers who used during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits.
There is also an increased association with psychosis proneness during middle childhood.
Given that most human studies are observational and retrospective, we turn to animal studies in attempts to go beyond determinations of associations. Studies using rodent models hint at a variety of long-term neurobiological changes in a multitude of systems, particularly the neuroendocrine system, as well as the dopaminergic and glutamate neurotransmitter systems, resulting in behavioral impact later in life.
Such behavioral consequences affect mnemonic processing and drug sensitivity but also to some extent emotional behavior and the development of locomotor activity.
The bottom line
In today’s era, it is important to be mindful of the increasing cannabis potency, as well as the different formulations and administration routes (ie. vaping), especially in light of the declining perceived risk among our patients. In 2018 the American College of Obstetricians and Gynecologists (ACOG) released guidelines advising physicians to screen for cannabis use in pregnant and breastfeeding women and encourage them to quit. This is a recommendation extended to all fields of medicine.
Furthermore, we shall not overlook the impact cannabis use can have on the mother during pregnancy, a stressful time at best. Cannabis use has been associated with increased incidence of anxiety, increased risk for developing depressive disorders, increased incidence of suicidal ideations and behavior, and increased symptoms of mania and psychosis in those with bipolar and schizophrenia spectrum conditions.
[PDF] Use of cannabis has also been linked to co-ingestion of other substances and alcohol, hence best practices would hint at screening for these as well in mothers who are using cannabis.
More information: Bryony V. Natale et al, Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta, Scientific Reports (2020). DOI: 10.1038/s41598-019-57318-6
