Delta-9-Tetrahydrocannabinol (THC) Alleviates Inflammation by Modulating Immune Responses in LPS-Induced Murine Inflammation Mode

In this study, we integrated transcriptomic, cellular, and in vivo approaches to investigate how THC regulates lipopolysaccharide (LPS) induced inflammation. Using human THP-1 monocytic cells, we found that THC independently induces a stress-adaptive transcriptional program upregulating genes associated with the unfolded protein response (UPR) and autophagy pathways while robustly suppressing LPS-induced Type-I interferon stimulated genes (ISGs) and pro-inflammatory cytokines such as IL-1β and TNF-α.

These results were corroborated in primary human monocytes, where THC significantly reduced the expression of activation markers CD80, CD83, and CD209. In a murine model of systemic inflammation, chronic THC exposure attenuated the activation of splenic myeloid and T cells. Notably, RNA-seq analysis of brain tissue revealed that THC dampened neuroinflammatory gene expression while promoting pathways linked to neurogenesis and synaptic plasticity.