CBD and Caryophyllene combined reduce inflammation markers better than each alone

Cannabis and Hemp plants typically contain many terpenes in addition to many cannabinoids. Beta-Caryophyllene (BCP) is a major terpene found in most of them, and CBD is the dominant cannabinoid in hemp.

Published in the journal Pharmaceuticals (Basel) in April 2024, this study focused on dermatological anti-inflammatory effects of CBD and/or beta-caryophyllene in vitro in a model of human skin inflammation. In vitro studies are especially relevant to skin conditions since they are also "topically" applied to a specific area of concern.

Keratinocytes are cells in the outer layer of human skin and "play multiple essential roles for skin function and repair". The cellular models used in this study were LPS-stimulated (lipopolysaccharide) human Keratinocyte (HaCaT) cells, which express a functional ECS (endocannabinoid system) as is found in human skin.

Their results:

Our results showed that both CBD and BCP were able to reverse the LPS pro-inflammatory activity.

Our data showed that the combination of CBD and BCP induced a superior anti-inflammatory effect compared to the administration of the single compound. 

at the concentrations of 0.001, 0.01, and 0.1 µM, CBD induced a significant reduction in the expression levels of COX-2 and Il-1β, and 0.1 µM of CBD induced a significant reduction in p-NF-kB. On the other hand, the 1 µM CBD did not reduce the pro-inflammatory effect of LPS. 

the 1, 10, and 50 μM concentrations of BCP induced a significant reduction in p-NF-kB levels; in addition, the 1 and 10 µM concentrations induced a significant reduction in COX-2 and Il-1β levels.


They found that once the CBD (alone) concentration got too high, its anti-inflammatory effects were reduced. However, much lower concentrations had a significant anti-inflammatory effect. 

The concentration of BCP was much higher than that of CBD in the combined CBD+BCP experiments. The ratios of CBD:BCP used were 1:10 and 1:100. For reference, a hemp plant will typically have a CBD:BCP ratio around 10:1 to 20:1.

The authors concluded:

Our data suggest that the topical use of a combination of CBD and BCP should be efficacious for treating skin inflammation and/or other inflammatory disorders.

The combination of CBD and BCP allows us to use lower doses of the single components to obtain anti-inflammatory effects, reducing the potential adverse effects associated with the use of higher concentrations. 


The full text article is here at PubMed Central.



Mazzantini C, El Bourji Z, Parisio C, Davolio PL, Cocchi A, Pellegrini-Giampietro DE, Landucci E. Anti-Inflammatory Properties of Cannabidiol and Beta-Caryophyllene Alone or Combined in an In Vitro Inflammation Model. Pharmaceuticals (Basel). 2024 Apr 7;17(4):467. doi: 10.3390/ph17040467. PMID: 38675427; PMCID: PMC11055086.