Cannabinoids’ antimicrobial activity is one of their most pronounced features and keeps finding applications in major aspects of our lives, often giving conventional methods a run for their money.
In that spirit, scientists investigated how cannabinoids stack up against Methicillin-resistant Staphylococcus aureus (MRSA), a widespread and notoriously resistant bacteria that causes infections.  In fact, the researchers point out that MRSA is resistant to all known β-lactam antibiotics.
“Worse yet, resistance to vancomycin, linezolid and daptomycin has already been reported in MRSA clinical strains, compromising the therapeutic alternatives for life-threatening MRSA infections.”
The in vitro study explored a wide range of commercially available cannabinoids including cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), and tetrahydrocannabinol (THC), in addition to carboxylic precursors (cannabidiolic acid [CBDA], cannabichromenic acid [CBCA], etc.), analogues (e.g., tetrahydrocannabivarin [THCV]), and other synthetic isomers.
The researchers demonstrated cannabinoid efficacy in both inhibiting MRSA’s ability to form new biofilms and destroying already formed ones. Biofilms are formed when bacteria adhere to surfaces. MRSA biofilms are known for high antibiotic resistance.
From the top contenders, CBG took the lead, with as little as 0.5 μg/ml inhibiting biofilm formation by 50%. Furthermore, at 4 μg/ml, CBG eradicated pre-formed biofilm.
Other cannabinoids demonstrated efficacy with minimum inhibitory concentrations (MICs) of 2 μg/ml. These included CBD, CBN, CBCA, and THC. Neutral cannabinoids were more potent compared to acidic forms or analogues.
But eradicating MRSA’s biofilm isn’t enough to put a definitive end to the devastating bacteria. “Another challenge in the treatment of MRSA infections is the formation of non-growing, dormant ‘persister’ subpopulations that exhibit high levels of tolerance to antibiotic,” the researchers explain.
CBG was the most effective cannabinoid on this front as well. It took a higher concentration with eradication starting at 5 μg/ml. Within 30 minutes, CBG reduced “a population of ~108 144 CFU/ml MRSA persisters to below the detection threshold.” (CFU = colony forming units)
The researchers hypothesized that CBG acts on the cytoplasmic membrane of MRSA bacterium. These results added fuel to the scientists’ curiosity, prompting them to investigate how CBG acts on E. coli, being that it is Gram-negative, as opposed to MRSA, which is Gram-positive. They found that CBG’s activity against E. coli is tied to damaging the bacteria’s inner membrane, which is akin to the cytoplasmic membrane of MRSA. However, this only happened once the outer membrane, which CBG did not affect, had been rendered permeable. CBG only acted in the presence of the outer membrane disruptor polymyxin B, a testament to their synergy.
“We employed conventional checkerboard assays to determine the interaction and potency of CBG and polymyxin B when used concurrently against various multi-drug resistant clinical isolates. In all cases, synergy was evident, suggesting the potential for combination therapy of the 276 cannabinoids with polymyxin B against Gram-negative bacteria.” 
The overall findings regarding cannabinoids’ efficacy against MRSA and E. coli are powerful. CBG stealing the show might be somewhat of a surprise, especially to those less familiar with the cannabinoid’s quietly mounting momentum in the scientific community. We might have to get used to seeing CBG in the spotlight.
- Farha M, et al. Uncovering the hidden antibiotic potential of Cannabis. ACS Infect Dis. 2020;6(3):338-346. Journal Impact Factor = 4.614; Times Cited = 6 (Semantic Scholar)
Image Credits: sbtlneet / Pixabay