Acute exposure to vaporized cannabidiol remodels coding and noncoding transcriptomes in the mouse striatum

Abstract

Cannabidiol (CBD) is increasingly consumed via vaping, but its acute molecular impact on the striatum, a critical hub for motor control and reward processing that is highly sensitive to cannabinoid modulation, remains poorly understood. This study investigated differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the striatum after acute exposure to vaporized CBD. Male ICR mice (n = 5 per group) were exposed to vaporized CBD oil (50 mg) and striatal tissues were collected 24 h later. Differentially expressed mRNAs and lncRNAs were identified using total RNA sequencing and mRNA-lncRNA co-expression networks were constructed. Selected transcripts were validated using qRT-PCR and discriminative capacity was assessed by ROC analysis. CBD exposure altered the expression of 931 mRNAs and 229 lncRNAs. GO and KEGG analyses revealed bidirectional regulation of pathways involved in neural development and synaptic transmission, including both up-and downregulated genes in categories such as glutamatergic synapse. Ion transport genes (Trpm2, Tmem63a, Tmem175, Glrb) were robustly upregulated, while genes involved in excitatory synaptic structure (Dlgap2, Shisa9, Tac1) and dopaminergic-associated pathways (Drd3, Oxt) were downregulated. mRNA-lncRNA network analysis highlighted regulatory hubs including NONMMUT114016.1 and NONMMUT057055.2, and ROC analysis identified strong biomarker candidates such as Tmem175, Ptprd, NONMMUT042895.2, and NONMMUT151847.1. These findings indicate that acute CBD vaping induces widespread transcriptomic remodeling in the striatum, enhancing ion transport and inhibitory signaling while suppressing excitatory and dopaminergic pathways. This study provides the first comprehensive striatal transcriptome profiling of coding and noncoding RNAs in response to vaporized CBD.