Background: Infections caused by drug-resistant Gram-positive bacteria affect millions of people and cause tens of thousands of deaths in North America alone. New antimicrobial agents are urgently needed, particularly novel structural classes with new mechanisms of action that can overcome resistant strains. Cannabidiol, the main non-psychoactive component of cannabis, has found increasing attention for a range of medical conditions, including epilepsy and inflammation. Here, we assess the antimicrobial activity of synthetically-produced cannabidiol, free from isolation-dependent impurities that may confound biological testing results obtained with plant extracts.
Material/methods: Cannabidiol was tested in a suite of standard antimicrobial assays, starting with broth microdilution assays against a range of aerobic and anaerobic Gram positive bacteria. Time-kill, resistance induction, and biofilm disruption experiments were also conducted, along with in vitro assessment of activity against bacteria on pig skin, and in vivo testing of activity against MRSA in several murine models. Mode of action studies were also conducted.
Results: Cannabidiol was remarkably effective at killing a range of Gram-positive (but not Gram-negative) bacteria in vitro, with broth microdilution MICs similar to clinical antibiotics such as vancomycin and daptomycin. Notably, activity was retained against-resistant strains of S. aureus (MRSA, VISA, VRSA), Streptococcus pneumoniae (MDR) and E. faecalis (VRE). Cannabidiol was bactericidal, showed low levels of propensity to induce resistance, and was active against MRSA biofilms. Efficacy varied in in vivo models, with topical treatments showing promise.
Conclusions: Cannabidiol possesses surprisingly effective activity as an antibiotic, comparable to widely used antibiotics for Gram positive infections such as vancomycin and daptomycin, but with retention of activity against bacteria that have become resistant to these drugs. Given cannabidiol’s documented anti-inflammatory effects and extensive safety data in humans, it is a promising new antibiotic. The combination of inherent antimicrobial activity and potential to reduce damage caused by the inflammatory response to infections is particularly attractive.