Communications Biology volume 4, Article number: 7 (2021 ) Cite this article
Antimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.
Bacteria have become increasingly resistant to antibiotics, leading to the United States (US) Centers for Disease Control and Prevention (CDC) stating in a 2019 report that we need to “stop referring to a coming post-antibiotic era—it’s already here”1. This “post-antibiotic era” means that millions of people who are at increased risk of infection due to surgery, cancer care, organ transplant, kidney dialysis or chronic conditions such as diabetes face a potentially untreatable illness. Unfortunately, the unfavorable economics of antibiotic development2,3,4 means that almost all major pharmaceutical companies have abandoned antibiotic research and placed smaller biotech companies in a precarious financial position, leaving few new therapeutics in the clinical pipeline5,6,7. This is particularly true for Gram-negative infections, where there have essentially been no novel molecular classes discovered and approved for clinical use since the 1960’s, but we also need better Gram-positive therapies, as resistant Gram-positive infections still cause substantial mortality1.