A recent study sheds new light on how prenatal cannabis exposure (PCE) affects offspring, with significant implications for neurodevelopment across the lifespan. The research, published in Molecular Psychiatry and led by Alexandra Noble and her team, is the first of its kind to investigate the molecular impact of PCE on DNA methylation, specifically in genes tied to brain development and neurodevelopmental disorders. By examining data from two longitudinal studies—the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK and the Christchurch Health and Development Study (CHDS) in New Zealand—this research demonstrates how cannabis use during pregnancy can lead to lasting changes in gene expression through alterations in DNA methylation.
Cannabis and Pregnancy: A Growing Concern
As cannabis legalization spreads globally, its use during pregnancy has become more prevalent, despite a lack of comprehensive understanding of its long-term effects. In the United States, the percentage of pregnant women using cannabis increased from 3.4% in 2017 to 7.0% by 2022. The rise is attributed to a perception of reduced risk due to the legalization of cannabis. However, this new study emphasizes the need for caution. The research team highlights that cannabis can cross the placental barrier, potentially affecting the developing fetus by interacting with the endocannabinoid system, a crucial regulator of brain development.Unveiling DNA Methylation Changes Across the Lifespan
The study is the first large-scale epigenome-wide association study (EWAS) of its kind, examining the DNA methylation profiles of offspring exposed to cannabis in utero at different developmental stages: birth, 7 years, 15–17 years, and 27 years. DNA methylation, an epigenetic process that can alter gene expression, is often influenced by environmental factors, including substance exposure. The researchers identified significant alterations in methylation at specific CpG sites across various time points, with genes like LZTS2, NT5E, and NPSR1 showing consistent changes.Notably, the study found that PCE affects pathways involved in neurodevelopment, neurotransmission, and neuronal structure. These molecular changes are associated with an increased risk of neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and schizophrenia. This research underscores the importance of further investigation into the molecular mechanisms driving these risks.
Key Findings: Genes and Pathways Affected by PCE
Among the most striking findings is the differential methylation of the gene TUBB2B, which is linked to cortical development, and LZTS2, associated with both neurodevelopmental delays and psychiatric disorders like depression. Changes in WAC, another gene implicated in severe intellectual disabilities, were observed during adolescence.The study also highlighted that specific genes showed methylation changes across different developmental stages, suggesting that PCE can have persistent effects on the methylome. For example, methylation changes in *NPSR1*, *NT5E*, and *CRIP2* were observed in both childhood and adolescence, pointing to long-lasting impacts on the genes responsible for brain function and cognitive development.
Implications for Public Health and Future Research
This research represents a critical step forward in understanding the long-term effects of cannabis use during pregnancy. It provides molecular evidence supporting the epidemiological link between PCE and adverse neurodevelopmental outcomes. However, the authors emphasize the need for larger cohort studies to confirm these findings and provide clearer guidelines for cannabis use during pregnancy.The study’s findings have immediate implications for public health policy, particularly in regions where cannabis is legal. Given the rising use of cannabis among pregnant women and the potential risks to offspring, there is an urgent need for more comprehensive education and counseling around prenatal cannabis use.
For more details, the full study can be accessed here (clearnet).