Cannabis Molecule Kills Gonorrhea, MRSA and C. diff Bacteria

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Five years ago, Australians who were diagnosed with gonorrhea could take a single antibiotic treatment and rid their body of the sexually transmitted disease. Fast forward a few years and the STD is no longer treatable with one antibiotic, having developed resistance over the years. It’s the same thing that has happened to many other types of bacteria, increasing antibiotic resistance year-over-year and resulting in deadly strains, like MRSA, in which no treatment exists.

Now, Australian researchers have taken steps toward a new class of antibiotics for resistant bacteria—the first in more than 60 years. For the first time, Mark Blaskovich and colleagues have shown that synthetic cannabidiol, or CBD, can kill Neisseria gonorrhea, the bacteria responsible for gonorrhea.

In their study, published in Communications Biology, the researchers showed CBD was not only effective against gonorrhea, but additional types of Gram-negative and Gram-positive bacteria, as well. CBD showed excellent potency against four Gram-negative bacteria: N. gonorrhea (gonorrhea), Neisseria meningitides (meningitis), Moraxella catarrhalis (airway infections like bronchitis and pneumonia) and Legionella pneumophila (Legionnaires’ disease).

Meanwhile, it also showed consistent antimicrobial activity against a diverse range of more than 20 types of Gram-positive bacteria, including multiple strains of MRSA and Clostridium difficile. Consistent with previous studies, CBD was inactive against 20 species of Gram-negative bacteria, including E.coli and Klebsiella pneumoniae.

Confocal microscopy revealed that CBD was adept at penetrating and destroying biofilms, which is key to treatment as biofilms help bacteria survive antibiotic treatments.

The potential of any new antibiotic must always be weighed against the propensity for resistance to emerge. To get a look at CBD’s resistance frequency levels, Blaskovich and his team at the Centre for Superbug Solutions mimicked a two-week patient treatment in laboratory models to see how fast bacteria mutated. When tested against MRSA and multiple strains of C. acne, CBD showed very little to no induced resistance.

“Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during treatment,” Blaskovich explained.

The research team also discovered that CBD’s chemical analogs were active against tested bacteria.

“This is particularly exciting because there have been no new molecular classes of antibiotics for Gram-negative infections discovered and approved since the 1960s, and we can now consider designing new analogs of CBD within improved properties,” said Blaskovich.

Overall, the study results indicate CBD is an under-researched class of compounds, with various pathways to explore in the future.

"We think that cannabidiol kills bacteria by bursting their outer cell membranes, but we don't know yet exactly how it does that, and need to do further research,” said Blaskovich.

Further studies are also needed to ascertain whether there are specific pathways targeted by CBD, and whether CBD can be altered to provide systemic activity. During their study, the team’s evaluation of CBD’s systemic antimicrobial activity in an immunocompromised mouse model proved unsuccessful. But, initial evidence has the scientists hypothesizing that CBD’s physicochemical properties can be modified.

“Variations were seen in the structure-activity relationship against MRSA and N. gonorrhoeae, meaning there is potential to develop a N. gonorrhoeae targeting agent that is not only selective over other Gram-negative bacteria, but also over Gram-positive bacteria,” the researchers conclude in their paper.  “Narrow spectrum antibiotics are increasingly recognized as an important advancement in antibiotic technology, with the ability to spare the natural microbiome by not killing beneficial commensal bacteria. This could potentially provide a substantial advantage for cannabidiol derivatives over other classes of antimicrobial compounds.”

As research continues, Botanix, a clinical stage pharma company, collaborated with the Australian scientists to progress a topical CBD formulation into clinical trials for decolonization of MRSA before surgery. The Phase 2a clinical results are expected early this year.

Photo: Bacteria growing in the shape of the synthetic cannabidiol molecule. Credit: Institute for Molecular Bioscience, University of Queensland