"The Antimicrobial Activities of Phytocannabinoids"

Novel antimicrobial drugs are urgently needed to counteract the increasing occurrence of bacterial resistance. 

Extracts of Cannabis sativa have been used for the treatment of several diseases since ancient times. 

It has been demonstrated that several cannabinoids show potent antimicrobial activity against primarily Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). As first in vivo efficacy has been demonstrated recently, it is time to discuss whether cannabinoids are promising antimicrobial drug candidates or overhyped intoxicants with benefits.

The worldwide spread of bacterial resistance against market antibiotics has been identified as one of the major threats to public health by scientists and healthcare authorities. Thus, new antibacterial strategies and antibacterial compounds are urgently needed to counteract the increasing occurrence of antibiotic-resistant and, especially, multidrug-resistant (MDR) pathogens, to keep the live-saving advantages toward bacterial pathogens. 

In 2017, the World Health Organization (WHO) emphasized the crucial need for antimicrobial drug development against a group of 13 different genii, families, and specific species of pathogenic bacteria.The real problem is that the vast majority of these prioritized bacterial pathogens are drug-resistant Gram-negative bacteria.

However, antimicrobial resistances are also increasing in Gram-positive bacteria and, among the high priority pathogens, the Gram-positive pathogen Staphylococcus aureus is the leading cause of both healthcare and community-associated infections worldwide, and a major cause for morbidity as well as mortality.

Stydies...

Natural products have always been a rich source for the identification of antimicrobial drug candidates, thus, researchers have started to reinvestigate long known natural product-based drugs in order to provide solutions to the current antibiotic crisis. 

Interestingly, different phytocannabinoids, which have so far mainly been associated with intoxication effects upon recreational usage and medical applications far beyond the treatment of infections, have been reported to show antibacterial activity against several Gram-positive bacterial pathogens, including MRSA.

-The application of plant material or seeds of Cannabis sativa for the preparation of early antibiotic treatments of different infections have already been reported from folk medicine at the end of the 19 th century, as described in early review articles by Kabelik

-First systematical evidence for the antimicrobial activity of constituents of Cannabis sativa was given by the Dissertation Krejci in 1950 [100]. Krejci reported a good activity of the cannabis extracts against the growth of Gram-positive bacteria, while Gram-negative bacteria were not affected. Furthermore, he prepared a salve containing 2% extracts and demonstrated its therapeutic efficacy in the treatment of skin infections with Staphylococci.

-Drobotko et al. described the occurrence of antibacterial activity in extracts from hemp in 1951, while Ferenczy et al. reported the finding of the occurrence of antibacterial activity in extracts obtained from seeds of hemp in 1956. Ferenczy et al. demonstrated the potency of the antimicrobial activity using dilutions of their extracts and observed that their activity was pH-dependent.

-The first early study on the antimicrobial activity of specific, isolated cannabinoids from Cannabis sativa were reported by Schultz and Haffner in 1958. They isolated CBDA and compared its antibacterial activity against S. aureus, Bacillus subtilis, and Escherichia coli to CBD. While CBD and CBDA show a potent antibacterial activity against the Gram-positive bacteria S. aureus and B. subtilis, an activity against the Gram-negative E. coli was not observed.

-In 1976, Klingeren  Ham published a study on the antibacterial activity of THC and CBD, in which both cannabinoids were screened for their antibacterial activity against the Gram-positive bacteria S. aureus, Streptococcus pyogenes, Streptococcus milleri and Enterococcus faecalis and the Gram-negative pathogens E. coli, Salmonella typhi and Proteus vulgaris.

Both compounds displayed significant antibacterial activity against all Gram-positive bacteria tested , but were in accordance with the results of Krejci et al. inactive against the Gram-negative ones. Furthermore, the authors proved on cultures of S. aureus that both compounds are bacteriostatic as well as bactericidal.

-In 1981, Turner and ElSohly published a report on the in vitro evaluation of antimicrobial activity of CBC-type cannabinoids against different Gram-positive bacteria and fungi including an in vivo study in rats investigating the anti-inflammatory activities.

In 1982, the same research group published an expanded study on the antibacterial and antimycotic activities of further CBC-type and CBG-type cannabinoid derivatives.CBC showed the highest activity of all tested CBC-type cannabinoids against S. aureus and B. subtilis

The authors also demonstrated that all tested CBC-type cannabinoids in this study reveal a higher anti-inflammatory activity compared to phenylbutazone or aspirin.

-Between 2008 and 2015, a consortium of researchers around Ross and ElSohly published a series of studies on the isolation and antimicrobial evaluation of novel minor cannabinoids from high potency variants of Cannabis sativa. 

In their studies, CBG exhibited selective moderate antimicrobial activity against Mycobacterium intracellulare and CBGA displayed moderate antileishmanial activity.

-In 2008, Appendino et al. reported a more focused structure–activity relationship study on the anti-staphylococcal activity of different naturally occurring cannabinoids and synthetic derivatives against a broad range of various multi-drug resistant strains of S. aureus, including EMRSA-15.

In their studies, all major cannabinoids THC, CBD, CBG, CBC, and CBN display potent anti-staphylococcal activity and in most cases, even superior, compared to the reference antibiotics norfloxacin, erythromycin, tetracycline, and oxacillin.

-In 2020, a very comprehensive study on the antimicrobial, antibiofilm and anti-persister cell activities of phytocannabinoids against MRSA was published by Brown and co-workers.

Their findings shows that show that cannabinoids exhibit antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), inhibit its ability to form biofilms, and eradicate preformed biofilms and stationary phase cells persistent to antibiotics. 

The mechanism of action of cannabigerol is through targeting the cytoplasmic membrane of Gram-positive bacteria and demonstrate in vivo efficacy of cannabigerol in a murine systemic infection model caused by MRSA. 

Also that cannabinoids are effective against Gram-negative organisms whose outer membrane is permeabilized, where CBG acts on the inner membrane.

Finally, that cannabinoids work in combination with polymyxin B against multidrug resistant Gram-negative pathogens, revealing the broad-spectrum therapeutic potential for cannabinoids.

Conclusion...

Novel antimicrobial drugs are urgently needed to counteract the growing occurrence of bacterial resistance towards market antibiotics. Phytocannabinoids, including Δ9-THC, CBN, CBD, CBC, and CBG have been demonstrated to display potent antibacterial activity against Gram-positive pathogens, in particular against highly virulent and prevalent MRSA, which are the leading cause of both healthcare and community-associated infections.

Due to their non-psychotropic and non-sedative pharmacologic properties, CBD, CBC, and espesialy CBG which acts on the inner membrane of the  Gram-negative organisms, are the most promising candidates for further investigations. CBG possess several desirable physiochemical properties as a medicinal.

Cannabinoids are truly promising antimicrobial drugs and I am convinced that they will find their way into a novel medical application as antibacterial treatment of infections and not only...

Source: https://www.ncbi.gov