Cannabidiol selectively modulates interleukin (IL)-1β and IL-6 production in toll-like receptor activated human peripheral blood monocytes

Cannabidiol (CBD) is a major non-euphoric cannabis-derived compound that has become popular in its over-thecounter use. CBD possesses low affinity for cannabinoid receptors, while the primary molecular target(s) by which it mediates biological activity remain poorly defined. Individuals commonly self-medicate using CBD products with little knowledge of its specific immunopharmacological effects on the human immune system; however, research has established primarily in rodent models that CBD possesses immune modulating properties. The objective of this study was to evaluate whether CBD modulates the innate immune response by human primary monocytes activated through toll-like receptors (TLR) 1-9. Monocytes were activated through each TLR and treated with CBD (0.5-10 mu M) for 22 h. Monocyte secretion profiles for 13 immune mediators were quantified including: IL-4, IL-2, IP-10, IL-1 beta, TNF alpha, MCP-1, IL-17a, IL-6, IL-10, IFN gamma, IL-12p70, IL-8, and TGF-beta 1. CBD treatment significantly suppressed secretion of proinflammatory cytokine IL-1 beta by monocytes activated through most TLRs, apart from TLRs 3 and 8. Additionally, CBD treatment induced significant modulation of IL-6 production by monocytes activated through most TLRs, except for TLRs 1 and 3. Most other monocyte-derived factors assayed were refractory to CBD modulation. Overall, CBD selectively altered monocyte-derived IL-1 beta and IL-6 when activated through most TLRs. This study is of particular importance as it provides a direct and comprehensive assessment of the effects of CBD on TLR-activated primary human monocytes at a time when CBD containing products are being widely used by the public.

Automated summary

This study evaluated the impact of CBD on human primary monocytes activated through Toll-like receptors (TLR). The results showed that CBD suppressed the secretion of inflammatory cytokine IL-1β by monocytes activated through most TLRs, while also significantly modulating the production of IL-6. Most other immune mediators were not affected by CBD modulation.