Antibiotic-resistance and the potential rise of “superbugs” continues to loom as a grave concern for future generations. Some of the most dangerous pathogens include methicillin-resistant Staphylococcus aureus (MRSA), which can cause necrotizing fasciitis (also known as flesh-eating disease), multidrug-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus spp, multidrug-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. As traditional antibiotics become less effective against these microorganisms, the need for alternative antimicrobial agents is growing in response to this threatening dilemma.

Further, as knowledge about biofilms and their role in antibiotic-resistance continues to expand, there is a greater demand for agents that are not just dedicated to directly killing a microorganism, but reducing its virulence by sneaking in the back door – perhaps, by attacking its protective biofilm, strengthening the body’s immune defenses, or stripping away an organism’s food supply.

A multifaceted approach to eradicating dangerous organisms may be a more effective alternative, and it opens the door to the use of supportive agents as well as new antimicrobials. Then again, perhaps a unique agent that addresses all aspects of pathogen eradication does exist. At present, it seems that cannabinoids might be good candidates for this task. Newer research on the endocannabinoid system, endogenous cannabinoids, and phytocannabinoids has strayed from the traditional areas of investigation (i.e., analgesic, anti-inflammatory, and neuroprotective benefits) and presented the possibility of using cannabinoids as alternative antibiotic agents which do, indeed, employ a multifaceted approach to antimicrobial activity.

Antimicrobial Action of Endocannabinoids

A recent study published in 2018 in Scientific Reports investigated the antimicrobial activity of the primary endocannabinoid, anandamide (AEA), as well as an endocannabinoid-like compound, arachidonoyl serine (AraS), against MRSA. Both compounds produced “a strong inhibition of biofilm formation of all tested MRSA strains as well as a notable reduction of metabolic activity of pre-formed MRSA biofilms… [and] were able to modify bacterial membrane potential. Importantly, both compounds prevent biofilm formation by altering the surface of the cell without killing the bacteria.” Even though this study focuses on the power of endocannabinoids, phytocannabinoids exert their effects on the same receptors and have been shown to also fight pathogens such as MRSA.

Antimicrobial Action of Phytocannabinoids

Previous research has shown Cannabis sativa possesses various cannabinoids (including cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), Delta (9)-tetrahydrocannabinol (THC), and cannabinol (CBN)) with antimicrobial activity against several strains of MRSA. Collectively, in vitro studies have shown Cannabis sativa extract expresses antibacterial activity against Baccilus subtilus, Baccilus pumilus, Staphylococcus aureus, Micrococcus flavus, Proteus vulgaris, and Bordetella bronchioseptica, though the mechanisms of action aren’t completely understood yet.

A new in vitro study which has not yet been published, but was presented in late June 2019 at the annual meeting of the American Society for Microbiology, explored the effects of CBD on a range of aerobic and anaerobic Gram-positive bacteria, including MRSA. The results found CBD to be just as effective as vancomycin and daptomycin in killing certain strains of Staphylococcus aureus and Streptococcus pneumoniae bacteria. Not only was CBD bactericidal, but it was active against MRSA biofilms, showed little ability to induce resistance, and its potent anti-inflammatory properties reduced damage elicited by the immune system in response to infection.

Endocannabinoid System as an Immunomodulator

Strengthening the immune defenses is just as important for fighting the battle with pathogens, as focusing on the pathogens, themselves. The endocannabinoid system and its cannabinoid receptors, CB1 and CB2, are heavily involved in immunomodulation. B cells, specifically, express high levels of CB2 receptors which are important in producing antigen-specific IgM. Additionally, CB2 receptors positively regulate T-cell responses. These activities are central in the immune system’s ability to initiate the clearance of blood borne pathogens with antibody responses and protect against further infection.

As research on cannabinoids continues to develop, it is exciting to learn that these compounds may also address the vital need for antimicrobial alternatives. As stated earlier, multiple phytocannabinoids have shown antimicrobial activity and, therefore, it is important that full-spectrum cannabinoids are chosen to ensure a strong “entourage effect” and the most effective activity against harmful pathogens.