Recent development of plant-derived and synthetic cannabinoids as novel antimicrobial agents

Antimicrobial resistance remains a critical global health threat, driving the urgent need for novel therapeutic agents. Cannabinoids, bioactive secondary metabolites derived from Cannabis sativa, have gained attention for their promising antimicrobial properties. This review presents the latest advances in the antimicrobial properties of cannabinoids, emphasizing their activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and selected Gram-negative bacteria. We summarize their antibacterial and antifungal effects, along with insights into structure-activity relationships that reveal the critical roles of functional groups such as the resorcinol moiety and alkyl side chain. Mechanistic studies suggest that membrane disruption, metabolic interference, and reactive oxygen species generation contribute to their antimicrobial action. Moreover, we summarize the synergistic potential of cannabinoids when used in combination with conventional antibiotics, highlighting both promising outcomes and notable limitations. Despite these advances, challenges such as poor solubility, limited in vivo data, and regulatory barriers persist. Addressing these gaps through focused medicinal chemistry and translational research will be essential to harness the full potential of cannabinoids as next-generation antimicrobial agents.