Timing matters: modeling the effects of gestational cannabis exposure on social behavior and microglia in the developing amygdala.
Aidan L Pham, Ashley E Marquardt, Kristen R Montgomery, Karina N Sobota, Margaret M McCarthy, Jonathan W VanRyzin
Neuropsychopharmacology October 2025 DOI: 10.1038/s41386-025-02173-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rodents exposed to THC either postnatally or prenatally |
| Intervention | delta-9-tetrahydrocannabinol (THC) |
| Topics | Cannabis |
| Key findings | Postnatal THC exposure caused sex-specific changes in microglial phagocytosis during development and in juvenile social behavior, whereas prenatal THC exposure caused inverse changes in phagocytosis and social behavior. The authors argue that THC's effects on the developing brain differ depending on the gestational timing of exposure. |
Abstract
Cannabis is the most frequently used illicit drug during pregnancy, with use steadily increasing in the United States as legalization and decriminalization expand to more states. Many pregnant individuals use cannabis to reduce adverse symptoms of pregnancy, considering it to be less harmful than other pharmaceuticals or alcohol. The primary psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), is a partial agonist of the candidate receptors of the endocannabinoid (eCB) system cannabinoid receptor 1 (CB1R) and 2 (CB2R). However, whether it perturbs neural development of the fetus is poorly understood. Previously we have shown that androgen mediated eCB tone in the developing amygdala promotes microglial phagocytosis of newborn astrocytes which has enduring consequences on the neural circuits regulating sex differences in social behavior. Microglia are the resident immune cells of the brain and express both CB1R and CB2R, making them likely targets of modulation by THC. It is also plausible that exposure to THC at differing gestational timepoints can result in distinct outcomes, as is the case with alcohol exposure. To model human cannabis use during either late or early pregnancy, we exposed rodents to THC either directly during the early postnatal period via intraperitoneal (IP) injection or in utero during the prenatal period via dam subcutaneous (SC) injection respectively. Here we show that postnatal THC exposure results in sex specific changes in microglial phagocytosis during development as well as social behavior during the juvenile period. Interestingly prenatal exposure to THC resulted in inverse changes to phagocytosis and social behavior. These findings highlight the differential effects of THC exposure across gestation.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 3
- Prenatal Δ9-Tetrahydrocannabinol Exposure in Males Leads to Motivational Disturbances Related to Striatal Epigenetic Dysregulation. Biological Psychiatry July 15, 2022
- Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats. Scientific Reports December 14, 2021
- Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone Nature Neuroscience September 11, 2019