Maternal edible THC consumption alters offspring neurodevelopment and emotional behavior in rhesus macaques.

D'Mello R.; Shorey-Kendrick L.; Karpf J.; Chan C.; Grafe M.; Edenfield R.; Graham J.; Hagen O.; Manuzak J.; Burwitz B. et al. · Neurobiology of disease · 2026

**Background & Methods** This translational study used rhesus macaques to investigate the effects of chronic prenatal THC exposure on offspring neurodevelopment and behavior. Animals were divided into control and THC-exposed groups, with both receiving daily edibles (placebo or THC) from pre-conception through pregnancy and the postnatal period. Comprehensive assessments included longitudinal MRI imaging during gestation and infancy, postnatal behavioral testing (motor and emotional), and molecular analyses at 6 months of age including histology, immunohistochemistry, whole genome bisulfite sequencing (WGBS), and bulk RNA-sequencing. **Key Findings** • **White matter alterations**: THC-exposed infants demonstrated increased fractional anisotropy in the corpus callosum and centrum semiovale, indicating microstructural white matter changes, though no significant differences in regional brain volumes were observed. • **Behavioral abnormalities**: THC-exposed infants exhibited increased vocalizations and decreased independence during behavioral testing, consistent with signs of increased stress and anxiety. • **Molecular and epigenetic changes**: WGBS identified differentially methylated regions (DMRs) in the cerebellum and prefrontal cortex associated with THC exposure, annotated to genes involved in synaptic organization and brain development. RNA-sequencing confirmed differential expression of genes related to axon development and glutamatergic synapse function, with expression levels correlating with methylation patterns. **Dosage & Administration** Not reported. The abstract specifies daily edible administration pre-conception through pregnancy and postnatally but does not provide specific THC doses or concentrations. **Safety & Adverse Effects** Not reported beyond the neurodevelopmental and behavioral alterations documented as study outcomes. **Evidence Quality** This is a translational animal study providing mechanistic evidence for prenatal THC effects but with inherent limitations regarding human applicability. The rhesus macaque model offers advantages in translating findings to primate neurobiology, but behavioral and neuroimaging findings in non-human primates may not directly parallel human development. The study lacks information on effect sizes, statistical power analysis, and specific dosing comparisons to human exposure scenarios. As a 2026 publication, this represents recent evidence, though the mechanism-focused design limits direct clinical extrapolation. The combination of structural imaging, behavioral assessment, and multi-level molecular analyses (epigenetic and transcriptomic) strengthens mechanistic understanding but does not constitute human clinical trial evidence.

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