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Study breakdown

Prenatal THC and CBD exposure caused different brain and behavior changes in male vs female rat offspring

AnimalPreliminary evidence
The takeaway

Prenatal exposure to THC, CBD, or both produced sex-specific behavioral and brain changes in adolescent rat offspring, including altered anxiety, social cognition, and sensorimotor gating tied to disrupted endocannabinoid signaling.

Developmental neuroscience researchers; clinicians advising pregnant patients about CBD and cannabis product use.

CBD alone caused prenatal brain changes, not just THC

What the researchers found

Prenatal THC and CBD exposure (alone and combined) caused low birth weight and sex-specific changes in adolescent rats: altered anxiety, temporal order memory, social cognition, and sensorimotor gating. These behavioral changes were linked to treatment- and sex-specific neuronal and gene expression abnormalities in the prefrontal cortex and ventral hippocampus, with dysregulated endocannabinoid system signaling and excitatory/inhibitory balance.

Why it matters

Most prenatal cannabis research focuses on THC alone. This study examined THC, CBD, and their combination separately, revealing that CBD is not necessarily benign during pregnancy and that male and female brains respond differently to prenatal cannabinoid exposure.

The numbers in context

Both THC and CBD exposure were associated with low birth weight. Sex-specific changes were observed across multiple behavioral domains. Gene transcription and neuronal activity differences were detected in two brain regions central to emotional and cognitive development.

How the study worked

Preclinical rat model with prenatal exposure to THC, CBD, or THC+CBD. Offspring assessed at adolescence using behavioral tests, electrophysiology, and RT-qPCR in prefrontal cortex and ventral hippocampus.

What this study cannot tell us

Rat model with direct cannabinoid administration; does not replicate human cannabis use patterns. Doses may not correspond to human exposure levels. Effects measured at adolescence only.

How to read the evidence

Controlled preclinical study with multiple outcome measures. Animal model limits direct human applicability.

When this study was published

2024 study

The bigger picture

The finding that CBD alone caused neurodevelopmental effects challenges the common perception that CBD is harmless. The sex-specific patterns may help explain why males and females show different psychiatric vulnerability after prenatal cannabis exposure.

Questions still open

  • Do the sex-specific effects persist into adulthood? At what developmental stage is the fetal brain most vulnerable to cannabinoid exposure?

Common questions

Is CBD safe during pregnancy?
This rat study suggests CBD is not necessarily benign during pregnancy, as it caused brain and behavioral changes in offspring. Human data on prenatal CBD safety is limited.
Why did males and females respond differently?
The endocannabinoid system develops differently in male and female brains. Prenatal cannabinoid exposure may interact with sex hormones or sex-specific developmental timelines to produce different effects.

Read the original research

Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus.

Neurobiology of disease, 199, 106588

Citation

DeVuono, Marieka V; Nashed, Mina G; Sarikahya, Mohammed H; Kocsis, Andrea; Lee, Kendrick; Vanin, Sebastian R; Hudson, Roger; Lonnee, Eryn P; Rushlow, Walter J; Hardy, Daniel B; Laviolette, Steven R. (2024). Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus.. Neurobiology of disease, 199, 106588. https://doi.org/10.1016/j.nbd.2024.106588

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