Cannabis contains over 500 different compounds, including cannabinoids, terpenoids, and flavonoids. Cannabidiol (CBD) is a non-psychoactive constituent, whereas beta-caryophyllene (BCP) is one of most the well-known terpenoids of Cannabis sativa. In recent years, there has been an emerging idea that the beneficial activities of these compounds are greater when they are combined. The aim of this study was to evaluate the anti-inflammatory effect of CBD and BCP using the in vitro model of lipopolysaccharide (LPS)-stimulated human keratinocytes (HaCaT) cells. The vitality of the cells was quantified using LDH and MTT assays. The levels of the following pro-inflammatory proteins and genes were quantified: IL-1β, COX-2, and phospho-NF-κB p65 (p-p65) through Western blotting (WB) and interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) through quantitative real-time polymerase chain reaction (RT-qPCR). When present in the incubation medium, CBD and BCP reduced the increased levels of pro-inflammatory proteins (IL-1β, COX-2, and p-NF-kB) induced by LPS. The anti-inflammatory effects of CBD were blocked by a PPARγ antagonist, whereas a CB2 antagonist was able to revert the effects of BCP. Selected concentrations of CBD and BCP were able to revert the increases in the expression of pro-inflammatory genes (IL-1β, IL-6, and TNFα), and these effects were significant when the drugs were used in combination. Our results suggest that CBD and BCP work in concert to produce a major anti-inflammatory effect with good safety profiles.

Background/Objectives: Anxiety, agitation, and mood disturbances are increasingly common among children and adolescents. Given the limitations of conventional pharmacological treatments in the pediatric population, particularly for subthreshold or mild conditions, interest in complementary approaches such as phytotherapy is growing. This review aims to critically evaluate the clinical evidence supporting the use of herbal medicines and botanical food supplements for mental health symptoms in youths and to explore the pharmacological basis of their activity. Methods: A systematic search was conducted across main databases for clinical trials involving herbal products for psychologically related symptoms in children and adolescents. Eligible studies included those using registered herbal medicines, as well as authorized food supplements, that evaluated behavioral or cognitive outcomes. In addition, bioinformatic analyses were performed on selected phytocompounds to predict their molecular targets. Results: Twenty-nine clinical trials were identified, including eighteen targeting pathological conditions (notably attention deficit/hyperactivity disorder (ADHD), anxiety, and depression) and eleven addressing borderline symptoms such as nervous agitation, restlessness, or sleep disturbances. Herbal products showing clinical promise include Bacopa monnieri (L.) Wettst., Crocus sativus L., Ginkgo biloba L., Hypericum perforatum L., Lavandula angustifolia Mill., Melissa officinalis L., Panax ginseng C.A. Meyer, Passiflora incarnata L., Pinus pinaster Aiton, Valeriana officinalis L., and Withania somnifera (L.) Dunal. Bioinformatic predictions revealed polypharmacological activity profiles involving neuroinflammatory, neuroprotective, and neurotransmitter-related pathways. Conclusions: This review highlights both the potential and the current limitations of herbal products in pediatric mental health care. Evidence supports their use for selected indications, provided that standardized preparations and clinical oversight are ensured. Further research is essential, particularly to inform dosing, safety, and integrative care strategies.