0Natural ingredients in cannabis may provide a solution to the global antibiotic resistance crisis. A recent study, published in bioRxiv preprint, has identified a chemical in cannabis that kills a range of antibiotic-resistant superbugs.
Antibiotics are drugs that prevent and cure bacterial infections, saving millions of lives all around the world. However, these medicines are under severe threat with the emergence of several types of antibiotic-resistant bacteria that have evolved to overcome the effects of our most effective drugs.
Stagnation of new antibiotic development by the pharmaceutical industry due to complicated regulations and low financial gains is resulting in the antibiotic resistance crisis, which is seen as one of the biggest global threat alongside climate change.
The new research shows that antibacterial activity of ‘cannabinoids’ (chemicals in cannabis) is effective against several groups of bacteria. McMaster University microbiologists, Dr Maya Farha and Dr Omar El-Halfawy co-authored the study.
“In the last 30 years, researchers have only discovered one new class of antibacterial drugs, so we’re always thinking of new approaches to discover the next antibiotic,” said Farha.
The research says that cannabinoids represent an attractive area for the search of potential new antibiotic drugs, and scientists hope that their discovery sparks further antimicrobial investigations into cannabinoids.
Researchers have known for decades that cannabinoids show antibacterial properties. For example, cannabis extracts have been used as antiseptics in some parts of the world since the 1950s. “Cannabinoids represent an attractive, yet previously untapped source for antimicrobial development. The drug properties of cannabinoids are favourable in humans, and this makes them a good starting point to search for new antibiotics,” Farha said.
Farha, El-Halfawy and their McMaster University colleagues tested 18 different cannabinoids and related molecules against several antibiotic-resistant superbugs. Tested bacteria included the gram-positive bacteria, MRSA (methicillin-resistant Staphylococcus aureus), and gram-negative bacteria, E. coli (Escherichia coli). Scientists found that ‘cannabigerol’ or CBG, a class of cannabinoids, showed the most promise as an antibacterial agent in the mouse model organism.
“We collected several antibiotic-resistant bacteria from patients at local hospitals intending to see if any cannabinoids could kill these bacteria. When we started our experiments, we immediately knew that CBG has an extraordinary broad-range antibacterial activity against several groups of bacteria. Notably, CBG still killed bacteria that are resistant to other conventional antibiotics,” said El-Halfawy.
CBG is non-psychoactive and non-sedative, which is ideal for potential antibiotic development for use in animals or humans. “Unlike cannabinoids like THC, you can’t get high on CBG. These properties make CBG an ideal candidate for further investigation. We saw that CBG cured MRSA-infected mice, while not showing any toxic side-effects on the animals,” El-Halfawy said.
Researchers found that, within 30 minutes of treatment, CBG stopped bacterial growth and killed the MRSA bacteria, which is tolerant to current antibiotics, such as gentamicin, ciprofloxacin and vancomycin. In addition to testing CBG on the gram-positive MRSA bacterium, scientists also tested CBG against the most problematic gram-negative bacteria. (Tested gram-negative bacteria were: E. coli; Acinetobacter baumannii; Pseudomonas aeruginosa; and Klebsiella pneumoniae.)
Many antibiotics aren’t effective against gram-negative bacteria like E. coli, because they don’t allow the antibiotic to enter inside the bacterium cell. Similarly, CBG alone couldn’t kill E.coli. But when used in combination with another antibiotic (polymyxin B) — which makes E. coli membrane more penetrable — CBG enters inside the E. coli cell, and kills the bacterium.
In fact, researchers found that — when used in combination with polymyxin B — CBG killed all four gram-negative bacteria. The combination of antibiotic therapy is gaining popularity in medicine and could be a vital tool against antibiotic resistance.
Scientists also found that MRSA couldn’t develop resistance against CBG. This is remarkable given that MRSA is already resistant against several available antibiotics. Farha said: “We know how to derive antibiotic-resistant bacteria under laboratory conditions, but despite several attempts and experimental setups, we were unable to develop bacteria that are resistant to CBG.”
Most common antibiotics have a specific target in bacteria, which makes it easier for bacteria to acquire antibiotic resistance. However, CBG targets random sites of the bacterial membrane, without which bacteria die. Therefore, it’s difficult for bacteria to develop resistance against CBG.
“We grew bacteria under low CBG amount for 15-days, and still they couldn’t develop resistance to CBG. Whereas, under the same conditions, the common antibiotic, rifampicin, would lose its antibacterial activity by about a 100-fold,” Farha said.
Scientists hope that they can further investigate the potential of CBG to be developed into a commercial antibiotic. El-Halfawy said: “We showed that CBG promises to be a good lead compound for antibiotic development. Our study can be used to further design and test novel molecules aiming to improve the drug’s potency and efficiency against antibiotic-resistant bacteria.
“However, there are a few hurdles to clear before it’s available as a commercial antibiotic. First, it’s vital to test CBG’s safety rigorously; it’ll then go through pre-clinical development phases and clinical trials. This process can take between five to ten years or longer. So, it’s difficult to predict exactly how long it’ll be before doctors prescribe CBG to treat bacterial infections.”
Read the full bioRxiv preprint article: “Uncovering the hidden antibiotic potential of Cannabis” https://www.biorxiv.org/content/10.1101/833392v3
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