Maternal edible THC consumption alters offspring neurodevelopment and emotional behavior in rhesus macaques.
Rahul J D'Mello, Lyndsey E Shorey-Kendrick, Joshua A Karpf, Chi Ngai Chan, Marjorie R Grafe, R Clayton Edenfield, Jason A Graham, Olivia L Hagen, Jennifer A Manuzak, Benjamin J Burwitz, Jason C Hedges, Eliot R Spindel, Kathleen A Grant, Christopher D Kroenke, Elinor L Sullivan, Jamie O Lo
Neurobiology of Disease October 6, 2026 DOI: 10.1016/j.nbd.2026.107640 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Translational animal study (rhesus macaque model) Peer reviewed |
|---|---|
| Population | Rhesus macaque infants and their mothers, divided into control and THC-exposed groups |
| Interventions | Delta-9-tetrahydrocannabinol (THC) edible |
| Duration | Daily edible from pre-conception through pregnancy and postnatally; brain tissue collected at 6 months of age |
| Measures | MRI (volumetric and microstructural), behavioral testing (motor and emotional assessments), histology, immunohistochemistry (IHC), whole genome bisulfite sequencing (WGBS), bulk RNA-sequencing |
| Topics | Cannabis |
| Keywords | Behavior Brain Neurodevelopment Pregnancy |
| Key points | Chronic prenatal edible THC exposure in rhesus macaques was associated with higher fractional anisotropy in the corpus callosum and centrum semiovale, no significant regional brain volume differences, increased vocalizations and decreased independence in infants, and differentially methylated regions and gene expression changes related to synaptic organization, axon development, and glutamatergic synapses. |
Abstract
Prenatal cannabis exposure is associated with adverse offspring outcomes including altered neurodevelopment. However, there is insufficient evidence to establish a direct association. We sought to determine the impact of chronic prenatal delta-9-tetrahydrocannabinol (THC) exposure on offspring neurodevelopment and emotional behavior in a translational rhesus macaque model. Animals were divided into two groups, control and THC-exposed, with both groups receiving a daily edible (placebo or THC) pre-conception, throughout pregnancy, and postnatally. MRI was performed longitudinally across gestation and infancy to assess volumetric and microstructural brain development. Serial behavioral testing, including motor and emotional assessments, was performed postnatally. At 6 months of age, brain tissue was collected for histology, immunohistochemistry (IHC), whole genome bisulfite sequencing (WGBS), and bulk RNA-sequencing. Analysis of the MRI images showed white matter changes with higher fractional anisotropy in the corpus callosum (CC) and centrum semiovale in THC-exposed infants. However, there were no significant differences in regional brain volumes. Behavioral testing demonstrated that THC-exposed infants displayed increased vocalizations and decreased independence. WGBS identified differentially methylated regions (DMRs) associated with THC exposure in the cerebellum and prefrontal cortex, annotated to genes involved in synaptic organization and brain development. RNA-sequencing confirmed differential expression of genes related to axon development and glutamatergic synapse, with expression correlating with methylation levels. Chronic prenatal edible THC exposure in the rhesus macaque was associated with changes in white matter development, effects on infant behavior with signs of increased stress and anxiety, and brain DNA methylation and expression of genes involved in neurodevelopment. NIH, March of Dimes, Silver Family Innovation.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 3
- Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in the Mesolimbic Circuitry. eNeuro 2022
- Cannabis and synaptic reprogramming of the developing brain. Nature Reviews Neuroscience July 2021
- Perinatal delta-9-tetrahydrocannabinol exposure disrupts social and open field behavior in adult male rats. Neurotoxicology and Teratology 2008