|Year : 2020 | Volume
| Issue : 2 | Page : 101-104
A Review on Exploring the Antibacterial Activity of Cannabinoids with Respect to Biofilm Formation
Amit Agrawal1, Ankita Gupta2
1 Department of Pediatrics, Gandhi Medical College and Hamidia Hospital, Bhopal, Madhya Pradesh, India
2 Department of Public Health Dentistry, Rishiraj College of Dental Sciences, Bhopal, Madhya Pradesh, India
|Date of Submission||30-Apr-2020|
|Date of Decision||11-May-2020|
|Date of Acceptance||11-Aug-2020|
|Date of Web Publication||12-Jan-2021|
Dr. Ankita Gupta
Department of Public Health Dentistry, Rishiraj College of Dental Sciences, Bhopal, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Cannabis sativa L is a useful plant as it presents many interesting properties due to its rich metabolic profile such as anti-biofilm and bactericidal action. The metabolite of C. sativa (Cannabinoid) is very potent in treating infectious diseases of bacterial origin. This antibacterial activity is mainly due to the presence of several Cannabinoids like Tetrahydrocannabinol (Δ-8-THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and cannabichromene (CBC). Various studies done in the past have proved that the cannabinoids are active against various Gram-positive and Gram-negative bacteria but there are no published literature related to the effect of cannabinoids on the formation of biofilm. Hence, the present review was conducted with an aim to explore the antibacterial effectiveness of cannabinoid and also its effect on the formation of biofilm.
Keywords: Antibacterial, Biofilm, Cannabis sativa, Infections
|How to cite this article:|
Agrawal A, Gupta A. A Review on Exploring the Antibacterial Activity of Cannabinoids with Respect to Biofilm Formation. J Integr Health Sci 2020;8:101-4
|How to cite this URL:|
Agrawal A, Gupta A. A Review on Exploring the Antibacterial Activity of Cannabinoids with Respect to Biofilm Formation. J Integr Health Sci [serial online] 2020 [cited 2021 Apr 12];8:101-4. Available from: https://www.jihs.in/text.asp?2020/8/2/101/306722
| Introduction|| |
Biofilm is the most abundant state in which microbes are found in nature. It is a cluster of micro-organisms in which they adhere to each other either on a living or non-living surfaces within a self-produced matrix of an extracellular polymeric substance consisting of polysaccharides, proteins, and nucleic acids. The credit for discovering biofilm goes to a Dutch researcher, Antoni van Leeuwenhoek who observed for the first time 'animalcule' on surfaces of a tooth by using a simple microscope. In 1978, this 'animalcule' was termed as 'biofilm'. Mature biofilms cannot be penetrated by most antibacterial agents and, thus, represent a major cause of various chronic infections that are resistant to antibiotics and hence, considered infectious in nature. According to the National Institutes of Health (NIH), about 65% of all microbial infections, and 80% of all chronic infections are associated with biofilms. Since biofilm contains thousands of bacteria, there is an urgent to discover antibacterial agents that can kill the bacteria or stop the growth of bacteria and also helps in preventing infections from the biofilm.
Nowadays, there is a growing interest in those antibacterial agents that can cure infections caused by biofilms forming bacteria as they are the utmost concern for medical microbiology. Antibacterial agents can be classified on the basis of their origin as of plant origin and of animal origin. Antibacterial agents of plant origin have enormous potential to treat various diseases as they have the power to mitigate infectious diseases and they lack adverse side effects that often associated with existing antimicrobial agents such as hypersensitivity, allergic reaction, and immunosuppression. Investigations done in the past have proved the effectiveness of various plant metabolites against several Gram-positive and Gram-negative microorganisms., Owing to their benefits, there is an urgent need to discover more and more antibacterial plants that can cure infectious diseases.
The alternative system of medicine is being used for more than thousands of years in the medical and dental field because of their antimicrobial activity, biocompatibility, anti-inflammatory properties, easy availability, cost-effectiveness, increased shelf life, and lack of microbial resistance., One such plant with enormous therapeutic potential is Cannabis sativa. The metabolite of C. sativa (Cannabinoid) is very potent in treating infectious diseases of bacterial origin and also has an important role in altering the biofilm composition. The present review was conducted with an aim to assess the antibacterial effectiveness of cannabinoid and its effect on biofilm formation. To the best of our knowledge, this is the first review to be conducted on such a vital topic.
| Biofilm- A Hub of Infections|| |
Almost all (99.9%) micro-organisms have the ability to form biofilm on a wide range of surfaces. Biofilms are an association of micro-organisms residing in a matrix of extracellular polymeric substances (EPS) which is produced by microbes only. EPS is made up of water (97%) and other substances such as extracellular polysaccharides, (1-2%), DNA, RNA (less than 1-2%), and proteins (less than 1-2%). Channels in the biofilm allow for water, air, and nutrients to get to all parts of the structure. The extracellular polymer layer of biofilms is protective in nature and plays a critical role in antibiotic resistance by restricting the diffusion of antibiotics to the biofilm-producing cells. Also, the bacterial cells growing within the biofilm secrete different surface molecules and virulence factors that enhance the pathogenicity of the bacteria by 100 times.,
Due to their power of antibiotic resistance, the biofilm-producing microorganisms have become a public health concern. The diseases which are caused by these bacteria are infections, such as pneumonia, fibrosis, osteomyelitis, periodontitis, and many more. Apart from this, they further been identified in most indwelling medical device infections such as medical implants, urinary catheters, etc., and also in biliary tract infections, periodontitis, ophthalmic infections.
Biofilm caused by bacteria can be removed by antibacterial substances but the commonly used synthetic antibacterial substances constitute several undesirable adverse effects. Hence owing to the side effects associated with these commercial antibiotics, a search should be initiated for an alternative system of medicine having antibacterial potential and at the same time should be safe and economical. In the present review, we have focused on C. sativa plant and its metabolites. Also, we have tried to explore the antibacterial effectiveness of C. sativa against several diseases including diseases related to the formation of biofilm.
| Cannabis sativa and its Metabolites|| |
Cannabis sativa L is a very interesting, dioecious, annual, and herbaceous plant that belongs to the family Cannabinaceae. The origin of the plant is thought to be from Central Asia and it is one of the oldest psychoactive plants known to man. The plant contains several active compounds of which some are primary metabolites consisting of amino acids, fatty acids, and steroids while others are secondary metabolites known as cannabinoids.
Cannabinoids are actually secondary metabolites of cannabis. The chemical composition of cannabinoids is made of 21 carbon compounds. They are produced by the small glands present on the surface of the plant and act on the cellular cannabinoids receptors. These cannabinoids are responsible for the plant's peculiar pharmacological effects. Approximately, more than 100 types of cannabinoids are produced by the plant.
Cannabinoids are divided into three groups on the basis of their source: endogenous or endocannabinoids (that are produced in the bodies of humans and animals), synthetic (that are produced in the laboratory), and phytocannabinoids (that occur uniquely in the cannabis plant). Some examples of cannabinoids are Tetrahydrocannabinol (Δ-8-THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and cannabichromene (CBC), and many more. The structure of active compounds of these metabolites is shown in [Figure 1]. Among these, THC and CBD are the most studied cannabinoid that has attracted the people across the world due to its psychoactive properties.
| The Antibacterial Nature of Cannabinoids|| |
The number of studies published on exploring the antibacterial nature of C. sativa are less as compared to other plant-derived phytochemicals, probably due to the drug abuse nature of Marijuana which is used as a recreational drug but in spite of that, the antibacterial properties of the plant should be explored.
A few studies done in the past have proved that preparations of this plant have good antibacterial properties.,,,,,,,,, Langezaal CR et al. identified cannabidiol as a component of hemp oil which is found effective against Gram-positive bacteria and yeast. Nissen et al. also assessed the antibacterial action of cannabis but not in the form of extract. They tested the action of essential oils obtained from the three hemp varieties of low-THC against Gram-positive Clostridium species with MIC of 2.83 ± 0.24 μg/ml, Enterococcus species (MIC = 2.56 ± 0.65 μg/ml) and Gram-negative Pseudomonas species with MIC of 3.71 ± 0.58 μg/ml, Pectobacterium species (MIC = 3.12 ± 0.73 μg/ml) bacteria and found a strong inhibitory action of the oil.
In all the published studies related to C. sativa,,,,,,,, the inhibitory action was found against S. aureus which implies that C. sativa can be used as a substitute of antibiotics for the treatment of various S. aureus-related diseases which is also a major contributor in the formation of biofilm but unfortunately, we could not get any study related to the effect of cannabinoids on the biofilm formation. According to Appendino G et al., cannabinoids are known for their antibacterial property against various Gram-positive and Gram-negative bacteria including methicillin-resistant Staphylococcus aureus (MRSA) strain by the cannabinoids like CBD, CBC, CBG, CBN, and THC. Wasim K et al. explored the inhibitory action of cannabis extract against various Gram-positive and Gram-negative bacteria (Bacillus subtilis, Bacillus pumilus, Staphylococcus aureus, Micrococcus flavus, Proteus vulgaris, and Bordetella bronchioseptica) as well as compared the efficacy of the extract with the antibiotic Celphalexin and found 250 times superior inhibitory potential of cannabis extract in comparison to the antibiotic. Ali et al. concluded that C. sativa was found to be active against S. aureus and E. coli with MIC of 25 μg/ml each while the MIC for P aeruginosa was 50 μg/ml. These results were similar to the findings of Novak et al. Naveed M et al. tested the antibacterial efficacy of C. sativa extract against S. aureus, E. coli, P. aeruginosa, E. faecalis, Kleibsella, and S. typhi and found that the extract showed strong antibacterial activity with S. aureus (zone of inhibition = 24.1mm), E. coli (zone of inhibition = 22.2mm), E. faecalis (zone of inhibition = 18.1mm) and P. aeruginosa (zone of inhibition = 10.3mm) and for the rest of the strains, the extract was inactive. Sarmadyan H et al. found determined the antimicrobial effects of cannabis extract against the bacteria isolated from the nosocomial infections and found that the antibacterial action was highest for Gram-positive cocci S. aureus with 14mm zone of inhibition, moderate for the Enterobacteriaceae family (10mm zone of inhibition) but the Gram-negatives were resistant. The MIC of cannabis extract was highest for Acinetobacter baumannii (more than 1000 μg/ml), followed by K. pneumonia (100 μg/ml) and lowest for S. aureus (25 μg/ml). Antibacterial activity of THC and CBD was also demonstrated by Klingeren BV and Ham MT. They concluded that THC and CBD both are bacteriostatic as well as bactericidal and Gram-negative bacteria are resistant to both of them. The MIC of THC and CBD was highest for Proteus vulgaris, S. typhi, E. coli (>100 μg/ml each), followed by S. aureus (2-5 μg/ml) and lowest for Streptococcus milleri (2 μg/ml). Feldman M et al. investigated the antimicrobial activity of the endocannabinoid (EC) anandamide (AEA) and the endocannabinoid-like (EC-like), arachidonoyl serine (AraS) against MRSA bacteria. They found that the total biofilm inhibition of MRSA strains CI and 33592 was detected at a dose of 32 μg/ml AEA, which is more than 8-fold lower than its MIC against these strains. AraS demonstrated minimal biofilm inhibitory concentration (MBIC) 32 μg/ml for all strains. Hence, they concluded that these compounds have natural defense power against MRSA or other pathogenic bacterial strains and also can be used in place of antibiotics. In contrast, Borchardt et al. found that the antibacterial action of the extract was only against the S. aureus species, whereas, other studies found the antibacterial action against other bacteria also.
Gal IE et al. showed that cannabidiolic acid is also antibacterially active. The first evidence of interference of bacterial signal-transduction systems by a synthetic cannabinoid HU-210 was given by Soni D et al. in their study. They concluded that the synthetic cannabinoid HU-210 has an inhibitory effect on QS and QS-dependent properties, such as bioluminescence, biofilm formation and swimming motility of V. harveyi, without affecting its growth.
Apart from the medical field, Singh P et al. demonstrated the usefulness of C. sativa in the bionanotechnology field by using gold and silver nanoparticles. They found that the nanoparticles exhibited MIC values of 6.25 and 5 μg/mL and minimum bactericidal concentration values of 12.5 and 25 μg/mL against P. aeruginosa and E. coli, respectively.
In contrast to all the above-mentioned studies, Agurell S et al. concluded that THC and CBD are poor antibacterial substances in the presence of serum as they disappear quickly from the blood. Therefore, they should not be used as therapeutics but can be used for topical preparations.
Since C. sativa is a plant with enormous therapeutic potential and there are no published literature related to the effect of cannabinoids on the formation of biofilm, more research should be conducted on this crucial topic to evaluate the efficacy, as well as toxicity of these products by conducting a few clinical trials.
| Conclusion|| |
Antibacterial agents that are commercially available in the market are expensive and have several side effects. Therefore, more and more natural products with a wide biological activity should be searched as they have immense potential in treating multidrug-resistant bacteria.
The discovery of a potent therapy from plant origin such as Cannabis sativa L. is a great advancement in the field of medicine but its use is not explored much. Hence, there is an urgent need to explore the antibacterial effectiveness of C. sativa metabolites that can satisfy the present demand.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Costerton J, Costerton JW, Stewart PS, Greenberg EP, Ali EMM, Almagboul AZI, Khogali SME, et al
. Bacterial biofilms: a common cause of persistent infections. Sci. 1999; 284: 1318-1322.
Costerton, JW, Geesey GG, Cheng GK. How bacteria stick. Sci. Am. 1978; 238:8
Jamal M, Tasneem U, Hussain T, Andle S. Bacterial Biofilm: Its Composition, Formation and Role in Human Infections. Research & Reviews: J Microbiol Biotech 2015; 4 (3): 1-13.
Iwu MW, Duncan AR, Okunji CO, editors. New antimicrobials of plant origin. ASHS Press; Alexandria, VA: 1999. pp 457–462
Dall'agnol R, Ferraz A, Bernardi AP, Albring D, Nor C, Schapoval EES, et al
. Bioassay-guided isolation of antimicrobial benzopyrans and phloroglucinol derivatives from Hypericumspecies. Phytother Res. 2005;19:291–293.
Gibbons S, Moser E, Hausmann S, Stavri M, Smith E, Clennett C. An anti-staphylococcal acylphloroglucinol from Hypericum foliosum. Phytochem. 2005;66:1472–1475.
Gupta R, Ingle NA, Kaur N, Yadav P, Ingle E, Charania Z. Ayurveda in Dentistry: A Review. J Int Oral Health. 2015; 7:141-3.
Abascal K, Yarnell E. Herbs and drug resistance. Part 2-clinical implications of research on microbial resistance to antibiotics. Altern Complem Therap. 2002; 8:284–90. doi: 10.1089/107628002760396445
Fux C, Costerton JW, Stewart PS, Stoodley P. Survival strategies of infectious biofilms. Trends Microbiol. 2005; 13: 34-40.
Lu TK, Collins JJ. Dispersing biofilms with engineered enzymatic bacteriophage. PNAS. 2007; 104:11197-11202.
Kostakioti M, Hadjifrangiskou M, Hultgren SJ. Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med. 2013;3 (4):a010306.
Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents. 2010;35 (4): 322–332.
Singh P, Singh H, Kim YJ, Mathiyalagan R, Wang C, Yang DC. Extracellular synthesis of silver and gold nanoparticles by Sporosarcina koreensis DC4 and their biological applications. Enzyme Microb Technol. 2016;86:75–83.
Singh P, Kim YJ, Singh H, Mathiyalagan R, Wang C, Yang DC. Biosynthesis of anisotropic silver nanoparticles by Bhargavaea indica and their synergistic effect with antibiotics against pathogenic microorganisms. J Nanomater. 2015;2015:10.
Yokoi N, Okada K, Sugita J, Kinoshita S. Acute conjunctivitis associated with biofilm formation on a punctal plug. Japan J Ophthalmol. 2000; 44: 559-566.
Sachindra N, Pradhan A. Marijuana Drug Abuse Clinical and Basic Aspects. The C.V. Mosby Company, Saint Louis, 1977, pp. 148-173
Iversen L. The science of marijuana. USA: Oxford University Press, 2000:4-183.
Mehmedic Z, Chandra S, Slade D, Denham H, Foster S, Patel AS, et al
. Potency Trends of Δ9-THC and Other Cannabinoids in Confiscated Cannabis Preparations From 1993 to 2008. J Forensic Sci. 2010; 55:1209.
Nogueira-Filho GR, Todescan S, Shah A, Rosa BT, Tunes Uda R, Cesar Neto JB. Impact of Cannabis sativa (marijuana) smokes on alveolar bone loss: A histometric study in rats. J Periodontol 2011;82 (11) 1602–7.
Gonçalves J, Rosado T, Soares S, Simão AY, Caramelo D, Luís A, et al
. Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination. Med (Basel). 2019; 6 (1): 31.
Langezaal CR, Chandra A, Scheffer JJC. Antimicrobial Screening of Essential Oils and Extracts of Some Humulus lupulus L. Cultivars. Pharm World Sci. 1992; 14 (6):353-356.
Nissen L, Zatta A, Stefanini I, Grandi S, Sgorbati B, Biavati B, et al
. Characterization and antimicrobial activity of essential oils of industrial hemp varieties (Cannabis sativa L.). Fitoterapia 2010; 81: 413–419.
Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M, Smith E, Rahman M. Antibacterial Cannabinoids from Cannabis sativa: A Structure-Activity Study. J. Nat. Prod. 2008; 71: 1427–1430.
Wasim K, Haq IU, Ashraf M. Antimicrobial Studies of the Leaf of Cannabis sativa L. Pak J Pharm Sci 1995; 8:22- 38.
Ali EM, Almagboul AZ, Khogali SM, Ali EMM, Almagboul AZI, Khogali SME, Gergeir UMA. et al
. Antimicrobial Activity of Cannabis sativa L. Chin Med. 2012;3 (1):61.
Novak J, Zitterl-Eglseer K, Deans SG, Franz CM. Essential Oils of Different Cultivars of Cannabis sativa L. and their Antimicrobial Activity. Flavour Fragr J. 2001;16 (4): 259-262.
Naveed M, Khan TA, Ali I, Hassan A, Ali H, Ud Din Z, et al
. In vitro
antibacterial activity of Cannabis sativa leaf extracts to some selective pathogenic bacterial strains. Int J Biosci 2014; 4 (4): 65-70.
Sarmadyan H, Solhi H, Hajimir T, Najarian-Araghi N, Ghaznavi-Rad E. Determination of the Antimicrobial Effects of Hydro-Alcoholic Extract of Cannabis Sativa on Multiple Drug Resistant Bacteria Isolated from Nosocomial Infections. Iranian J Toxic 2014; 7 (23): 967-72.
Klingeren BV, Ham MT. Antibacterial activity of A9-tetrahydrocannabinol and cannabidiol. Anton Leeuw Int J G. 1976; 42: 9-12
Feldman M, Smoum R, Mechoulam R, Steinberg R. Antimicrobial potential of endocannabinoid and endocannabinoid-like compounds against methicillin-resistant Staphylococcus aureus. Sci Reports. 2018; 8:17696.
Borchardt JL, Wyse DL, Sheaffer CC, Kauppi KL, Fulcher RG, Ehlke NJ, et al
. Antimicrobial Activity of Native and Naturalized Plants of Minnesota and Wisconsin,” J Med Plant Res. 2008; 2 (5): 98-110.
Gal IE, Vayda O, Bekes I. Investigation of certain properties of cannabidiolic acid from the aspect of food preservation. (In Hungarian). elmiszervizsgalati Kozlem. 1976;4:208-216.
Soni D, Smoum R, Breuer A, Mechoulam R, Steinberg D. Effect of the synthetic cannabinoid HU-210 on quorum sensing and on the production of quorum sensing-mediated virulence factors by Vibrio harveyi. BMC Microbiol. 2015; 15:159
Singh P, Pandit S, Garnæs J, Tunjic S, Mokkapati V, Sultan A, et al
. Green synthesis of gold and silver nanoparticles from Cannabis sativa (industrial hemp) and their capacity for biofilm inhibition. I J Nanomedicine 2018;13:3571–3591
Agurell S, Nilsson M, Oulsson A, Sandberg F. On the metabolism of tritium-labelled Al-tetrahydrocannabinol in the rabbit. Biochem. Pharmacol. 1970; 19:1333-1339