Prenatal Exposure to Cannabis Found to Cause Genetic Changes in Children

The increasing use of cannabis among pregnant women in recent years has sparked a growing interest in understanding its potential impact on prenatal development. While attention has been given to the physical effects of cannabis on pregnancy, recent research has begun exploring how prenatal cannabis exposure (PCE) could cause genetic changes in children that may persist throughout their lives. Let’s explore the most recent findings on prenatal cannabis exposure.

Cannabis Use Is A Growing Concern Amongst Pregnant Women

With the legalization and decriminalization of cannabis in many parts of the world, cannabis use during pregnancy has surged, nearly doubling from 3.4% in 2017 to 7% in 2022. This trend has led to widespread public perception that cannabis may pose little risk during pregnancy, even though there remains a lack of concrete scientific evidence on the molecular impact of PCE on developing children. Cannabis can cross the placenta and interact with the fetal endocannabinoid system (ECS), which is vital for brain development along with neuron growth, synaptic plasticity, and immune regulation. This makes understanding how PCE affects children at a molecular level essential.

Key Findings from the Study

A recent epigenome-wide association study¹ aimed to address this knowledge gap by investigating DNA methylation changes in children exposed to cannabis in utero. Conducted across two long-term studies — the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) — the research tracked participants at multiple developmental stages, from birth to adolescence and even adulthood.

The study revealed DNA methylation changes linked to PCE at various stages of life: at birth, 7 years old, 15–17 years old, and 27 years old. DNA methylation, a process that regulates gene expression, was found to be altered at specific CpG sites, with key changes observed in genes related to neurodevelopment and brain structure. These alterations were associated with long-term neurodevelopmental pathways, suggesting that prenatal cannabis exposure could predispose children to cognitive and neurological challenges as they grow.

The study also compared the effects of cannabis exposure with co-exposure to tobacco, another substance known for its harmful prenatal effects. Both cannabis and tobacco were linked to DNA methylation changes, but unique methylation patterns were identified in cannabis-exposed children, strengthening the hypothesis that PCE has its own molecular signature.

These findings highlight the potential of PCE to induce long-lasting genetic changes, particularly in genes associated with brain development and cognitive function. However, while these results provide valuable insights, they also underscore the need for further clinical research in this area.

Challenges of the Study

While the study presents groundbreaking findings, several limitations must be addressed to solidify the link between prenatal cannabis exposure and genetic changes in offspring. Here are the key challenges that researchers faced:

• Small Sample Size: The study included a relatively small number of participants, particularly in the PCE group. In the CHDS cohort, only 13 individuals were identified as having prenatal cannabis exposure. Such a small sample limits the study’s ability to make broad, definitive conclusions. For more conclusive results, larger cohort studies with more participants exposed to cannabis are needed.

• Co-Exposure to Tobacco and Other Substances: Many participants who were exposed to cannabis during pregnancy were also exposed to tobacco. Tobacco is a well-known risk factor for prenatal development and has been shown to cause significant DNA methylation changes. Although researchers did their best to control for tobacco exposure in their analyses, the overlapping effects of both substances remain a confounding factor. Furthermore, the study highlighted the difficulty of achieving uniformity across studies due to significant variables beyond tobacco use, including alcohol, other drug use, sociodemographic factors, and postnatal environment. Disentangling the specific impact of cannabis from other exposures will require future studies to include larger groups where cannabis and tobacco exposure can be clearly separated.
• Environmental and External Factors: The study could not fully account for external factors that may also cause DNA methylation changes over time. As individuals age, factors such as air pollution, diet, and even stress can lead to epigenetic changes that influence gene expression. These external factors complicate the ability to isolate the effects of PCE alone. For example, short-term exposure to pollutants like heavy metals or air pollution has been shown to alter DNA methylation, which could confound the study’s findings. Studies need to consider and ideally control, to the best of their ability, these external influences when interpreting results.
• Limited Control Over Data Collection: Data on cannabis exposure were collected through self-reports from mothers, which introduces the potential for inaccuracies or underreporting. Furthermore, prenatal exposure was assessed decades ago, when understanding and tracking drug use during pregnancy were more rudimentary. Modern studies should implement more controlled and precise methods to track prenatal substance exposure to obtain more reliable data.
• Methylation Changes May Not Reflect Brain Changes: The study primarily used blood samples to analyze DNA methylation, but blood methylation patterns do not always reflect changes in brain tissue. While methylation patterns in the blood can provide clues about systemic effects, future research should aim to examine methylation changes directly in neural tissue where possible, which would offer clearer insights into the neurological impacts of PCE.

The Need for More Controlled Clinical Studies

This study provides valuable initial insights into the genetic effects of prenatal cannabis exposure, but its findings also highlight the urgent need for more rigorous and controlled research. Larger studies that isolate cannabis exposure, account for outside factors, and use more precise methods of data collection are critical to confirm and expand on these findings. Additionally, future research should aim to understand how PCE interacts with the broader context of an individual’s life, including their environment and lifestyle, which can influence DNA methylation and overall health. As cannabis use continues to rise, especially among pregnant women, providing clear, evidence-based guidance on its risks is more important than ever.

Study Reference:

^{1. Cao-Lei, L., de Rooij, S. R., King, S., Matthews, S. G., Metz, G. A. S., Roseboom, T. J., & Szyf, M. (2024). Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course. Molecular Psychiatry. https://www.nature.com/articles/s41380-024-02752-w}