As cannabis becomes more widely legalized and socially accepted, many expecting mothers face a critical question: is cannabis safe to use during pregnancy? While public perception may lean toward safety—especially compared to alcohol or tobacco—a growing body of research is urging caution.
“Placenta is a complex tissue of fetal origin… a ‘time capsule’ of molecular signatures of in utero exposures.”
Janine LaSalle, 2021
A 2021 commentary by Dr. Janine LaSalle in PNAS explores compelling new findings that suggest maternal cannabis use during pregnancy may influence childhood anxiety, through subtle but significant changes in placental immune gene expression. In short, cannabis might be writing a biological “record” in the placenta—one that reflects in the mental health of the child years later. 
The Study: Linking Maternal Use to Child Anxiety
LaSalle’s commentary highlights the study by Rompala et al., which examined a cohort of 322 mother–child pairs in the New York metropolitan area. About 22% of the mothers self-reported cannabis use during or shortly after pregnancy. Adjusting for confounders like race, age, tobacco use, and maternal mental health, the researchers found that maternal cannabis use was significantly associated with higher anxiety in children aged 3 to 6 years.
This was measured through:
• Elevated cortisol levels in hair (a stress biomarker),
• Higher anxiety scores on behavioral assessments, and
• Lower heart rate variability, often associated with poor stress regulation.
The Placenta: A Molecular “Time Capsule”
What makes this study groundbreaking is its use of placental tissue, collected within an hour of birth and frozen for later analysis. Using RNA sequencing, researchers looked at which genes were active in the placenta and whether they differed between cannabis users and nonusers.
The answer was yes.
While individual genes didn’t reach statistical significance after corrections, groups of genes related to immune system signaling—especially type I interferon pathways and monocyte function—were downregulated in the placentas of cannabis-exposed pregnancies. These immune genes are vital for healthy placentation and early fetal development, including blood supply formation and immune response regulation.
A Systems Biology Approach: Tying Genes to Behavior
To bridge the gap between gene expression and child outcomes, the researchers used weighted gene correlation network analysis (WGCNA), a method that groups genes into co-expressed “modules.” Three modules linked to immune suppression were significantly correlated with childhood anxiety scores.
Key immune genes included:
• HLA-A, -B, and -F (adaptive immunity),
• IFI-35 (innate immune response),
• Other cytokine-related and inflammatory genes
These findings support the idea that cannabis exposure may trigger immune-related adaptations in the placenta that reverberate through development, influencing the child’s stress response system.
The Goldilocks Effect: Why Too Little Immune Activity Matters
Much of the past research on maternal immune activation (MIA) and offspring mental health has focused on excessive immune responses—like those seen with infections during pregnancy. However, this study reveals an important nuance: too little immune activation can also pose a risk.
The placenta requires finely tuned immune signaling to manage tasks like:
• Invading maternal tissue to establish nutrient exchange
• Regulating the timing of labor and delivery
• Signaling to the developing fetal brain
Disruptions to these processes—whether through excess inflammation or suppressed immunity—can affect the neurodevelopmental trajectory of the fetus, potentially increasing vulnerability to anxiety, depression, and other psychiatric conditions.
Important Caveats and Ethical Considerations
Like all early-stage human research, this study has limitations. Cannabis use was self-reported, and it was not possible to distinguish prenatal from postnatal exposure. Correlation does not equal causation, and other factors—such as home environment or maternal mental health—could play a role.
Still, the placental gene expression patterns provide a biological link that strengthens the case for a developmental pathway between maternal cannabis use and child outcomes.
LaSalle urges a non-punitive, supportive approach to research and policy. Expecting mothers should not be criminalized or stigmatized, but rather supported with accurate, science-based information and access to safe alternatives.
Why This Matters for Future Research
This study opens new pathways for understanding how maternal cannabis use may shape child development, including:
• Placental transcriptomics and epigenetics as early biomarkers
• Sex differences in response to cannabis exposure
• The potential for noninvasive prenatal tests using cell-free fetal DNA
• Development of intervention strategies before behavioral symptoms emerge
It also calls for more animal models, especially non-human primates, to clarify causal mechanisms and human relevance—especially given the unique evolution of the human placenta and brain.
