New research published in the European Journal of Pharmacology found that THC and CBD—especially when combined in equal parts—can significantly reduce inflammation in human immune cells triggered by toll-like receptors 7 and 8 (TLR7/8), key components of the body’s response to viral RNA.
Conducted by scientists at the University of Dublin, the study explored how these cannabinoids—both found in approved medications like Sativex and Epidiolex—impact immune signaling linked to neuroinflammation and autoimmune disease. Researchers used THP-1-derived macrophages and peripheral blood mononuclear cells (PBMCs) from healthy individuals, stimulating them with a TLR7/8 agonist to mimic viral infection.
Activation of TLR7/8 prompted a strong inflammatory response, including increased production of TNFα, CXCL10, and type I interferons, as well as activation of NF-κB, p38 MAPK, and IRF7 transcription. However, when CBD and THC were administered—either alone or in a 1:1 ratio similar to Sativex—the inflammatory response was notably reduced.
The 1:1 THC-CBD combination was most effective, suggesting a potential therapeutic role for these cannabinoids in regulating immune responses to viral or autoimmune triggers. The researchers concluded that phytocannabinoids may serve as immunomodulatory agents by targeting endosomal toll-like receptors to suppress harmful inflammation.
The study’s full abstract can be found below:
Cannabinoid regulation of endosomal signalling via innate immune toll-like receptors (TLRs) is understudied. Endosomal cell signalling via TLR7 and TLR8 governs cellular responses to infection with viral and bacterial single-stranded RNA. TLR7/8 activation is associated with neuroinflammation, with inappropriate activation of TLR7/8 linked to the propagation of autoimmune disease. Following activation, TLR7 and TLR8 control the cellular production of cytokines, chemokines and type I interferons (IFNs). In this study we focused on two clinically relevant plant-derived (phyto) cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), given that cannabinoid-based therapeutics containing these compounds are currently available in the form of sativex® (nabiximols) and epidiolex®. The study aim was to determine the anti-inflammatory effects of CBD and THC, when delivered in isolation and in a sativex-like combination (1:1), on TLR7/8-induced inflammation in immune cells. We employed the use of CL075 (3M-002), a thiazoloquinolone derivative that acts as an agonist of both TLR7 and TLR8. Using THP-1-derived macrophages and primary peripheral blood mononuclear cells (PBMCs) from healthy control subjects, we demonstrate that TLR7/8 activation promoted the time- and concentration-dependent production of the chemokine CXCL10, cytokine TNFα and type I IFNs in both macrophages and PBMCs. TLR7/8 activation promoted nuclear factor (NF)-κB activation, p38 MAPK phosphorylation and the transcription of interferon regulator factor 7 (IRF7). We assessed the anti-inflammatory effects of CBD and THC, when delivered alone and in a 1:1 combination, on CL075-stimulated inflammatory mediator production in macrophages/PBMCs. Data presented herein indicate that CBD and THC, particularly when delivered in a 1:1 combination, can act as TLR7/8 immunomodulatory drugs to dampen inflammation in macrophages and PBMCs. This study provides evidence that phytocannabinoids target TLR7/8-induced viral signalling on endosomal compartments to control inflammation in immune cells.
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