What Impact Does Prenatal Cannabis Exposure Have on Neurodevelopment? — BrainPost | Easy-to-read summaries of the latest neuroscience publications

Patterns of cannabis use during pregnancy

Cannabis is increasingly viewed as safe and natural, especially as it is increasingly legalized for recreational use in countries around the world and in the U.S. (Barbosa-Leiker 2022). This could, in part, explain why use during pregnancy is on the rise. Between 2009 and 2016, rates of cannabis use were assessed in 318,085 pregnant people with both self-report and urine toxicology, finding an increase from cannabis use in ~4% of pregnancies in 2009 to ~7% in 2016 (Young-Wolff, 2017). The authors also found estimates made via self-report were lower than those using toxicology, suggesting stigma against cannabis use during pregnancy may reduce the accuracy of reporting.

There are many reasons why pregnant people may use cannabis. Firstly, some may use cannabis recreationally before conception and continue use until they realize that they are pregnant. Second, some pregnant people may have a substance use disorder and may have difficulty quitting cannabis, especially if they use several substances and are already quitting a “harder” drug, like opioids (Meinhofer, 2022). Finally, some pregnant people self-medicate with cannabis to reduce the symptoms of morning sickness, or mood symptoms, such as anxiety (Westfall. 2006). In this final case, some pregnant people use cannabis because they think it is a safer alternative to prescribed pharmaceuticals, such as selective serotonin reuptake inhibitors (Chang, 2019). Overall, it is most common for pregnant people to use cannabis during the first trimester of pregnancy, with rates falling in the second trimester, and reducing further in the third (Einarson, 2013).

One gap in the literature, however, is how much and what kinds of cannabis pregnant people are using. In most studies, the amount of cannabis use is estimated as frequency (e.g., once per week, more than once per week, or not at all). Additionally, there are several major cannabinoids in cannabis, including the main psychoactive component, delta-9-tetrahydrocannabinol (THC), and the main non-psychoactive component, cannabidiol (CBD). Cannabis can also be consumed through a variety of methods, and while smoking or vaping cannabis is still the most common, pregnant people may decide to consume it more frequently orally to avoid the negative impact of smoking on their babies (Spindle, 2019). Without knowing what preparations of cannabis pregnant people are using, it is difficult to understand how much cannabis the developing fetuses are exposed to. For example, a pregnant person who smokes a lot of high-THC cannabis once a week will have a baby with a very different exposure profile than if a pregnant person consumes high-CBD edibles every other day.

What does human research say?

Because of the rising rates of cannabis use during pregnancy, understanding the impact on babies and children is essential, especially regarding their neurodevelopment. Unlike other drugs such as nicotine, alcohol, or opioids, prenatal cannabis exposure has not been associated with increased rates of miscarriage or child death. Nor has an association been found with physical malformations or birth defects (Orsolini, 2017; Fergusson, 2002). There is, however, some evidence for preterm birth following prenatal cannabis exposure, which is linked with developmental challenges in babies and children (Duko, 2022). One of the most robust findings following prenatal cannabis exposure is low birth weight in babies when compared to others at the same gestational age (Gray, 2010).

Several studies have examined behavior in infants, children, and teenagers following prenatal exposure to cannabis. There is some evidence for an increased risk of neurodevelopmental disorders, such as Autism Spectrum Disorders, at 18 months, and increased symptoms of psychosis in children (Corsi, 2020; Fine, 2019), however, these studies are far from conclusive. There is also evidence to suggest poorer educational and occupational achievements in children and young adults respectively following prenatal cannabis exposure (Goldschmidt, 2004; Goldschmidt, 2016). Finally, mood disorders have also been implicated, with children showing evidence of anxiety and increased cortisol levels (Rompala, 2021).

There are several challenges to assessing the impact of prenatal cannabis exposure in humans. Pregnant people who use cannabis often use other drugs, such as nicotine, as well, making it difficult to estimate the effects of the two drugs independently. Along with other drugs, other factors may be difficult to control for, such as socioeconomic status, or maternal age. Additionally, there is still a stigma surrounding cannabis use during pregnancy, so, when surveyed, some people do not report, or under-report their cannabis use. Next, as mentioned before, cannabis can be prepared and administered through a variety of methods making it difficult for both pregnant people and researchers to estimate dosage. Finally, to study the effects of prenatal cannabis exposure in teenagers or young adults, either cannabis use during pregnancy must be estimated long into the past, or studies must be conducted over decades, as they wait for participants to age. To address these limitations efficiently, animal models are used to investigate the impact of prenatal cannabis exposure.

What does animal research say?

Many of the results from human studies have been replicated in nonhuman animals. There is evidence of both low birth weight, as well as early onset of labor in rodent models (Wang, 2008; Benevenuto, 2017; Roeder, 2024). Anxiety-like behavior was also observed in newborn and adolescent rats (Trezza, 2008). Psychotic symptoms cannot be measured in nonhuman animals, however, some have examined sensorimotor gating (the process of filtering out unimportant sensory information), impairments that are associated with psychotic disorders in humans. There is minimal evidence of impairments to sensorimotor gating in rodent models, with one study finding effects only in males and another study finding no differences (Lallai, 2022; Bortolato, 2006). In contrast, impairments have been identified in short-term memory, perhaps associated with the worsened performance in school observed in human children (Lallai, 2022; Drazanova, 2019).

Nonhuman animal studies also provide a means to assess effects on a cellular level. One study using post-mortem assessments found reduced CB1 receptors (the main cannabinoid receptor in the brain) and miswired neurons following prenatal cannabis exposure (Tortoriello, 2014). Similar findings were observed in a mouse model with genetically increased native cannabinoids in the brain, suggesting networks of neuronal connections in the brain may be changed in their connectivity following prenatal cannabis exposure (Alpar, 2014).

While nonhuman animals do allow for experimental control of cannabis exposure, there are still limits to these models. Again, cannabis can be administered either by injection, orally, or through vaporization, with differences in cannabis metabolism associated with each route. Furthermore, many of these studies examine a single time point, which prevents an understanding of how cannabis may affect development over time. Finally, some of these studies still only consider male animals, making it impossible to understand the impact on females. This is especially important because there is ample evidence of a sex-dependent effect (Tirado-Muñoz, 2020).

What does the future hold?

Our understanding of cannabis use during pregnancy and its impact has increased greatly over the past two decades, nevertheless, it is still difficult for clinicians to advise patients regarding its potential harms. Laboratory researchers seek to design studies that best model cannabis use in humans. To do so, they would benefit from more precise information on how and how much cannabis pregnant people use. In turn, clinicians and researchers with human subjects could benefit from experiments in nonhuman animals that examine rodents across the lifespan, identifying key time points for study in humans. In time these parallel research streams may clarify the potential harms of prenatal cannabis use.

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