Abstract The growing perception that marijuana is safe during pregnancy has led to a marked increase in prenatal cannabis use, raising concerns about its long-term effects on brain development and cognition. This study investigated the consequences of prenatal delta-9-tetrahydrocannabinol (THC) exposure on hippocampal circuit function, synaptic plasticity, and memory in adolescent offspring using a rodent model. We found that prenatal THC exposure resulted in persistent deficits in hippocampal-dependent memory and significant disruptions in synaptic plasticity, including impaired long-term potentiation (LTP) and increased long-term depression (LTD). Electrophysiological analyses revealed reduced AMPAR-mediated synaptic transmission and a shift toward increased inhibitory signaling, suggesting an excitation/inhibition (E/I) imbalance in the hippocampus. These functional changes were accompanied by selective downregulation of postsynaptic glutamatergic proteins (GluA1, GluN2A, GluN2B, and PSD95), while presynaptic glutamate markers remained unchanged. Notably, immunohistochemical and anatomical analyses demonstrated region-specific reorganization of inhibitory networks, including altered distribution and co-localization of cannabinoid 1 receptor (CB1R) and vesicular GABA transporter (VGAT) across hippocampal subregions. Together, our results reveal that prenatal THC exposure leads to coordinated functional and structural remodeling of hippocampal circuits, producing a lasting E/I imbalance and memory impairments during adolescence. These findings highlight disrupted GABAergic signaling as a potential therapeutic target for mitigating cognitive deficits resulting from prenatal cannabis exposure.
Pinky et al. (2026) studied this question.