CBN modulated the endocannabinoid system in human skin cells by increasing CB1 and TRPV1 receptor expression, altered endocannabinoid metabolism, and reduced pro-inflammatory cytokines while boosting anti-inflammatory ones, with the key anti-inflammatory effect mediated through TRPV1.
People interested in CBN for skin conditions, and researchers studying minor cannabinoids.
CBN reduced itch-associated IL-31 through a specific TRPV1 receptor mechanism
What the researchers found
CBN increased CB1 gene expression and TRPV1 protein expression and function in keratinocytes. It modulated anandamide and 2-AG metabolism. In inflamed cells, CBN reduced pro-inflammatory IL-8, IL-12, and IL-31 while increasing anti-inflammatory IL-10. The reduction of IL-31 was specifically mediated by TRPV1. CBN also modulated GSK3-beta through the MAPK signaling pathway.
Why it matters
CBN is gaining consumer interest as a cannabis minor cannabinoid, but its mechanisms are poorly understood. This study reveals a specific pathway (TRPV1-mediated IL-31 reduction) through which CBN exerts anti-inflammatory effects on skin, providing scientific support for its potential in dermatological applications.
The numbers in context
CBN increased CB1 gene expression, TRPV1 protein expression, and activities of NAPE-PLD, FAAH, and MAGL. In inflamed cells: reduced IL-8, IL-12, IL-31; increased IL-10. IL-31 reduction specifically mediated by TRPV1. GSK3-beta modulated in MAPK pathway.
How the study worked
Human keratinocytes (HaCaT cells) were treated with CBN in both normal and LPS-inflamed conditions. Researchers measured expression and function of cannabinoid receptors (CB1, CB2) and TRPV1, endocannabinoid metabolic enzyme activities (NAPE-PLD, FAAH, MAGL), cytokine release (IL-8, IL-10, IL-12, IL-31), and MAPK signaling pathway components.
What this study cannot tell us
In vitro study using an immortalized cell line (HaCaT), which may not fully represent in vivo skin biology. Single cannabinoid tested in isolation, whereas real cannabis products contain multiple compounds. Concentrations used may not reflect achievable tissue levels from topical application.
How to read the evidence
In vitro study with detailed mechanistic analysis in a human cell line, but lacking in vivo validation.
When this study was published
Published in 2025.
The bigger picture
IL-31 is a key itch-inducing cytokine in inflammatory skin conditions like eczema and atopic dermatitis. The finding that CBN reduces IL-31 through TRPV1 provides a specific mechanistic rationale for CBN in anti-itch skincare products, moving beyond general "anti-inflammatory" claims.
Questions still open
- Does topical CBN achieve sufficient concentrations in human skin to produce these effects? Would CBN be effective for itch-dominant skin conditions like atopic dermatitis? How does CBN compare to CBD for skin inflammation?
Common questions
What is CBN?
What is TRPV1?
Read the original research
Cannabinol modulates the endocannabinoid system and shows TRPV1-mediated anti-inflammatory properties in human keratinocytes.
BioFactors (Oxford, England), 51(1), e2122
Citation
Di Meo, Camilla; Tortolani, Daniel; Standoli, Sara; Ciaramellano, Francesca; Angelucci, Beatrice Clotilde; Tisi, Annamaria; Kadhim, Salam; Hsu, Eric; Rapino, Cinzia; Maccarrone, Mauro. (2025). Cannabinol modulates the endocannabinoid system and shows TRPV1-mediated anti-inflammatory properties in human keratinocytes.. BioFactors (Oxford, England), 51(1), e2122. https://doi.org/10.1002/biof.2122
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