Prenatal THC Exposure Affected Mouse Offspring Differently Based on Their Inborn Temperament | Research

The takeaway

Prenatal THC exposure increased anxiety in naturally dominant mouse offspring while decreasing anxiety and increasing sociability in naturally submissive offspring, suggesting individual temperament shapes how prenatal cannabis exposure affects behavior.

Researchers studying prenatal substance exposure and anyone interested in how genetic individuality shapes drug responses.

Opposite behavioral effects based on inborn temperament

What the researchers found

In selectively bred dominant mice, prenatal THC exposure reduced body weight and increased anxiety-like behaviors. In submissive mice, THC exposure enhanced sociability and reduced anxiety. Brain analysis revealed temperament-specific changes in endocannabinoid and dopamine system genes, with FAAH expression notably downregulated in submissive offspring's prefrontal cortex and hippocampus.

Why it matters

This is the first study to show that the behavioral effects of prenatal THC depend on pre-existing temperament. The finding that THC exposure could either increase or decrease anxiety depending on the individual's baseline stress vulnerability has significant implications for understanding variable outcomes in human prenatal cannabis exposure.

The numbers in context

THC dose: 20 mg/kg on gestation days 13, 15, 17. Body weight reductions measured at postnatal days 7 and 30. FAAH downregulated in prefrontal cortex and hippocampus of submissive PTE offspring at PND 7 and 30. Changes also seen in CB1, CB2, D1, D2, and D5 receptor expression.

How the study worked

Pregnant dominant and submissive mice (generation 54 of selective breeding) received THC (20 mg/kg IP) on gestation days 13, 15, and 17. Offspring were tested for anxiety, social behavior, and body weight. Brain mRNA expression of endocannabinoid system (CB1, CB2, FAAH) and dopaminergic system (D1, D2, D5) genes was analyzed at postnatal days 7 and 30.

What this study cannot tell us

The mouse lines are selectively bred for extreme temperament traits that may not correspond to normal human variation. The THC dose (20 mg/kg) is relatively high. The specific behavioral tests may not translate directly to human outcomes. Only male offspring were tested.

How to read the evidence

Novel animal model using selectively bred mice provides unique insight into temperament-dependent effects, but extreme phenotypes and high THC doses limit direct human translation.

When this study was published

Published in 2025.

The bigger picture

Human studies of prenatal cannabis exposure show highly variable outcomes. This animal model suggests that individual genetic temperament may explain much of that variability. Stress-vulnerable individuals may actually respond differently to prenatal THC than stress-resilient ones, complicating simple warnings about cannabis use during pregnancy.

Questions still open

Could human genetic variation in stress vulnerability predict which children are most affected by prenatal cannabis exposure? Would lower THC doses produce similar temperament-dependent effects?

Common questions

Does this mean prenatal cannabis is safe for some people?

No. The study shows that effects depend on temperament, but both dominant and submissive offspring showed significant changes. Even the "positive" effects in submissive mice (reduced anxiety) may reflect abnormal neurodevelopment rather than genuine benefit.

What is FAAH and why does its downregulation matter?

FAAH is the enzyme that breaks down anandamide, the brain's main endocannabinoid. Downregulation means more anandamide remains active, which could alter brain development during critical periods.

Read the original research

Personality-based intergenerational effects of prenatal THC exposure in an inherited mouse model of social dominance and submissiveness.

Scientific reports, 15(1), 30624

View on PubMed ↗Publisher’s paper ↗

Citation

Mari, Mohamed; Bagaev, Anastasia; Sur, Debpali; Rocha, Beatriz G S; Begmatova, Dilorom; Zemliana, Natalia; Bowirrat, Abdalla; Blum, Kenneth; Thanos, Panayotis K; Kogan, Natalya M; Pinhasov, Albert. (2025). Personality-based intergenerational effects of prenatal THC exposure in an inherited mouse model of social dominance and submissiveness.. Scientific reports, 15(1), 30624. https://doi.org/10.1038/s41598-025-15528-1