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Study breakdown

Prenatal THC exposure disrupted spatial memory in adolescent male rats more than females

Animal StudyModerate evidence
The takeaway

Adolescent rats exposed to THC prenatally showed sex-specific spatial memory impairments, with males more severely affected and showing reduced inhibitory interneurons in the hippocampus.

People interested in prenatal cannabis exposure and its potential effects on brain development.

Males lost inhibitory interneurons; females gained them

What the researchers found

Prenatal THC exposure caused sex-specific disruption in spatial memory retrieval and flexibility. Males showed decreased density of CCK-positive basket cells (inhibitory interneurons) and increased neuroplasticity markers. Females showed delayed memory retrieval but preserved flexibility, increased CCK+BC density, and mostly preserved neuroplasticity markers.

Why it matters

This study provides biological mechanisms for why prenatal cannabis exposure might affect brain development differently in males and females, specifically through disruption of the excitatory/inhibitory balance in the hippocampus.

The numbers in context

THC dose: 2 mg/kg daily. Exposure period: gestational days 5-20. Males showed decreased CCK+BC density. Females showed increased CCK+BC density. Changes in neuroligin-1 and neuroligin-3 isoforms were observed in both sexes.

How the study worked

Sprague Dawley dams received THC (2 mg/kg) or vehicle from gestational day 5-20. Adolescent offspring were tested in the Barnes Maze for spatial memory. Hippocampal tissue was analyzed for CCK+BC density, neuroplasticity gene expression, and neuroligin isoform expression.

What this study cannot tell us

Animal model using a single THC dose that may not reflect typical human prenatal exposure patterns. Rats were exposed throughout most of gestation, while human exposure patterns vary. Adolescent testing only, so long-term adult outcomes are unknown.

How to read the evidence

Well-designed animal study with multiple biological endpoints and both sexes. THC dose and exposure timing are controlled, though translation to human prenatal exposure requires caution.

When this study was published

Published in 2024 in Biomedicine & Pharmacotherapy.

The bigger picture

With prenatal cannabis exposure increasing alongside legalization, understanding sex-specific developmental effects is critical. The finding that males and females show opposite changes in inhibitory interneuron density suggests fundamentally different biological responses to prenatal THC.

Questions still open

  • Do human studies show similar sex-specific patterns in children prenatally exposed to cannabis? Are the increased CCK+BCs in females protective or a separate kind of disruption? Would lower THC doses produce similar sex-dependent effects?

Common questions

Does prenatal cannabis affect boys and girls differently?
In this rat study, prenatal THC exposure affected male offspring more severely than females. Males showed worse spatial memory and lost inhibitory brain cells, while females had milder memory effects and actually gained inhibitory brain cells.
What part of the brain was affected?
The hippocampus, which is critical for spatial memory and navigation. Specifically, the balance between excitatory and inhibitory neurons was disrupted in sex-specific ways.

Read the original research

Prenatal THC exposure drives sex-specific alterations in spatial memory and hippocampal excitatory/inhibitory balance in adolescent rats.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 181, 117699

Citation

Castelli, Valentina; Lavanco, Gianluca; Tringali, Giuseppe; D'Amico, Cesare; Feo, Salvatore; Di Bartolomeo, Martina; D'Addario, Claudio; Kuchar, Martin; Brancato, Anna; Cannizzaro, Carla. (2024). Prenatal THC exposure drives sex-specific alterations in spatial memory and hippocampal excitatory/inhibitory balance in adolescent rats.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 181, 117699. https://doi.org/10.1016/j.biopha.2024.117699

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