“Non-psychotropic Cannabis sativa L. chemotypes have gained increasing interest due to their diverse profiles of bioactive compounds. While cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), are known for their biological effects, the role of other cannabinoids such cannabichromene (CBC) remains underexplored as for chemotype V, which lacks in cannabinoids but is characterized by other minor phytochemicals.
This study aimed to evaluate the individual and combined contributions of cannabinoids and non-cannabinoid phenolics to the antioxidant, antimicrobial, and anti-inflammatory properties of extracts derived from four C. sativa chemotypes, including a cannabinoid-free variant as a comparison.
Ethanolic extracts were obtained from four hemp chemotypes: CBD-rich (CS1), CBG-rich (CS2), CBC-rich (CS3), and cannabinoid-free (CS4). Phytochemical profiling was conducted using UHPLC-HRMS. Antioxidant properties were assessed via DPPH, ABTS, and FRAP assays. Antimicrobial activity was tested against Gram-positive and Gram-negative bacteria through MIC, MBC, and time-kill assays. Anti-inflammatory activity was evaluated in LPS-stimulated RAW 264.7 macrophages via gene expression analysis of pro- and anti-inflammatory mediators (IL1b, IL6, Cox2, IL10, IL1Ra).
Phytochemical analysis confirmed the chemotype-specific profiles, with CS3 showing the highest levels of canniprene and the early discovered 5-methoxy-dihydrodenbinobin. Antioxidant assays revealed that cannabinoids were the main contributors to radical scavenging capacity, though CS3 exhibited additional ferric ion reducing power likely due to non-cannabinoid phenolics. Antibacterial activity was confined to Gram-positive bacteria, where CS1 showed the highest efficacy, and CS4 showed no activity, highlighting the critical role of cannabinoids. All extracts reduced LPS-induced Il1b, Il6, and Cox2 gene expression, but only cannabinoid-rich extracts upregulated the anti-inflammatory cytokines IL10 and IL1Ra, indicating a cannabinoid-dependent effect.
Both cannabinoids and non-cannabinoid phenolics contribute to the biological activity of Cannabis sativa extracts, with cannabinoids playing a central role in antimicrobial responses and stronger anti-inflammatory effect as a pure cannabinoid or as an extract. From this point of view, the cannabinoid-free chemotype V could be a valuable functional control for isolating the effects of cannabinoids, reinforcing the need for integrative analyses in evaluating the therapeutic potential of cannabis-derived formulations.”
“In this study, we provided a phytochemical characterization and biological activity of non-psychoactive Cannabis sativa L. extracts from III, IV, V and the emerging CBC chemotype. The phytochemical profile confirmed the distinct percentage of cannabinoid and non-cannabinoid composition of each chemotype, with the CS3 sample exhibiting the highest levels of canniprene and 5-methoxy-dihydrodenbinobin. Antioxidant assays demonstrated that cannabinoids significantly contribute to the radical scavenging capacity of the extracts, with an additional support from non-cannabinoid phenolics as testified by the CS4. Antimicrobial assays showed that only the cannabinoid-containing extracts exhibited potent bactericidal activity against Gram-positive pathogens, including drug-resistant MRSA, while the cannabinoid-free extract lacked such activity. Furthermore, all extracts, including the cannabinoid-free one, were able to suppress LPS-induced pro-inflammatory gene expression in macrophages. However, only the cannabinoid-rich extracts promoted the anti-inflammatory cytokines IL-10 and IL-1Ra, underscoring a cannabinoid-dependent immunomodulatory effect.
Taken together, these results highlight the importance of cannabinoid in the biological properties of Cannabis sativa with a contribution apported by non-cannabinoid phenolic compounds. Moreover, the anti-inflammatory, antimicrobial, and antioxidant effects observed with both pure cannabinoids and cannabinoid-containing extracts support their potential use in topical formulation for the treatment of chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis. These conditions are often exacerbated by skin dysbiosis and colonization by Gram-positive bacteria like Staphylococcus aureus, which contribute to skin barrier dysfunction and amplify immune dysregulation (Zhang et al. 2025). Therefore, while the cannabinoid-free chemotype V serves as a valuable control for dissecting the specific contributions of individual cannabinoids within CS extracts, our findings pave the way for future investigations into the therapeutic potential of selected cannabis-derived products—particularly in the context of antimicrobial resistance and inflammatory diseases associated with dysbiosis.”
https://pubmed.ncbi.nlm.nih.gov/41121423/
https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00336-1