v
Search
Advanced Search

Publications > Journals > Journal of Exploratory Research in Pharmacology > Article Full Text

  • Review Article
  • OPEN ACCESS

Potential Applications of Cannabis Plant Extracts and Phytochemicals as Natural Antimicrobials

  • Hebah M.S. AL Ubeed1,* ,
  • Asgar Farahnaky1,
  • Emma L. Beckett2,3,
  • Momena Khandaker4 and
  • Christopher J. Pillidge1
 Author information
Journal of Exploratory Research in Pharmacology   2023;8(2):121-130

doi: 10.14218/JERP.2022.00062

Abstract

Cannabis has a long history of use in treating human diseases, but scientific research on its properties has only recently gained momentum. The increasing prevalence of antibiotic resistance in human and animal pathogens has sparked renewed interest in exploring alternative antimicrobial therapies from Cannabis and other plant sources. There is also potential for Cannabis extracts or purified cannabinoids to be applied in novel medical contexts. Industrial hemp extracts may find applications in food manufacturing, veterinary purposes, and microbial control in cleaners and sanitizers. This review highlights the latest discoveries regarding Cannabis plant extracts and phytochemicals as potent antimicrobial agents against various microorganisms, including Gram-positive and Gram-negative bacteria. More importantly, the challenges of using cannabinoids as effective and affordable natural antimicrobial agents are reviewed. While antimicrobial and other applications of Cannabis extracts and phytochemicals appear promising, concerns about possible toxic side effects exist. Therefore, future research should focus on addressing the safety of these compounds, evaluating their in vivo activity, and understanding structural changes that influence their pharmacokinetic properties. Standardized tests will be crucial for facilitating valid inter-laboratory comparisons. The review article also discusses future research directions aimed at developing novel broad-spectrum antibiotics based on Cannabis.

Keywords

Cannabis, Antibacterial, Antifungal, Antiviral, Natural phytochemicals, Medicinal Cannabis extract

Introduction

Cannabis sativa L. or marijuana, is a flowering plant that has been used for millennia for food, drugs (both legal and illegal), textile (hemp), and religious purposes.1 Selective breeding has resulted in numerous C. sativa strains (cultivars) with different properties. For example, hemp strains are fibrous and low in cannabinoids, while medicinal strains are highly flowering and contain both phytonutrients and phytochemicals.2–4 Bioactive compounds can be extracted from oils or as aqueous phases from seeds, flowers, leaves, and stems using traditional techniques such as cold-pressing and solvent extraction or by contemporary procedures like ultrasound.5 Supercritical fluid extraction with carbon dioxide (SFE-CO2) is another technology used in industry to extract phytochemical compounds.6,7 This is no different from other plant products, which have been historically used as rich sources of natural products for human health.8

Potential therapeutic applications and bioactive mechanisms of crude Cannabis extracts and purified compounds derived from C. sativa have been investigated in various pharmacological scenarios, including their use as anti-convulsive, analgesic, anti-anxiety, and anti-emetic therapeutic drugs.9 While much research has centered around the psychoactive properties of cannabinoids,10 the antimicrobial properties of compounds extracted from C. sativa are now becoming of particular interest due to the emergence of antimicrobial resistance as a vital threat to human health globally.11 Mitigating the human and economic impacts of this problem, and more broadly, the emergence of new microbial pathogens,12 requires identifying and elucidating new antimicrobial therapies.

One possibility to combat such infections, apart from antibiotics, is to use phage-based therapies, including lysin therapy and engineered phage enzymes.13,14 Another alternative is to use plant-derived compounds or extracts with antimicrobial properties (bacterial, fungal, and viral). Among these, Cannabis extracts and (more specifically) cannabinoids show colossal promise, especially towards multi-drug resistant microorganisms like MRSA (methicillin-resistant Staphylococcus aureus), which can be very difficult to treat.15 While there is much anecdotal evidence on the efficacy of Cannabis compounds or extracts, controlled laboratory investigations of these novel antimicrobial agents, their mode of action, efficacy, and safety, together with the development of safe and approved disease treatment therapies, is certainly needed. In vitro antifungal, antibacterial, antimalarial, antileishmanial, and cytotoxic properties of C. sativa extracts and compounds have been investigated since the early 2000s.13,16–19 However, significant challenges exist in assessing the efficacy of these agents (both impure phytochemical extracts and purified compounds), determining their safety, and implementing research findings. These challenges include high variability in cannabinoid content in different C. sativa strains; also for different parts of plants and in the extraction methods;5 a lack of uniform methods for antimicrobial screening assays; diversity in microbial targets (strain variability); failure to consider the stability of extracts or the effects of additional compounds (impurities), both in cell culture experiments and animal trials. Furthermore, challenges regarding the negative perception of Cannabis, its safety and potential side effects, variable delivery methods, local and systemic effects, and synergistic effects need to be addressed.20,21

This review will describe the potential uses of agents found in medicinal Cannabis extracts as antimicrobials, the current knowledge on their mechanism of action, the challenges around phytochemicals’ stability and bioavailability, optimized extraction protocols, and isolation of active antibiotic compounds. Also, the prospect of using new formulations containing ‘old’ antibiotics combined with therapeutic plant compounds to provide a synergistic killing effect is noted. Such combined treatments could more effectively kill or inhibit antibiotic-resistant bacteria causing local and systemic infections.

New classes of potent antimicrobial agents

It has been known for decades that Cannabis plant extracts can be effective antimicrobial agents.22,23 More than 525 phytochemicals have been extracted and isolated in C. sativa.24–26 The most important classes of Cannabis phytochemicals are the C21 terpenes, phenolics, and cannabinoids. The respective antimicrobial properties of these compounds will be discussed in this report.

There are many benefits for isolated cannabinoids, including antifungal, antibacterial, antimalarial, antileishmanial, and cytotoxic properties.26 Active cannabinoids like CBG,27,28 CBN, CBC,29 and psychoactive cannabinoids delta-9-trans-tetrahydrocannabinol (Δ9-THC)17 (summarized in Table 1 and Fig. 1) and their precursors have a high level of antimicrobial activity.16,26,30,31 Synthesis of cannabinoids is complex; essentially, they are derived from cannabigerolic acid (CBGA), which is the precursor of olivetol acid (OLA) and geranyl pyrophosphate (GPP), and is induced by the prenyltransferase geranyl pyrophosphate: olivetolategeranyltransferase (GOT).32 There are some examples of co-enzymes involvement like tetrahydrocannabinolic acid synthase (THCAS), cannabidiolic acid synthase (CBDAS), or cannabichromeneacid synthase (CBCAS). With the assistance of the co-enzyme, CBGA is finally converted to tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabichromenic acid (CBCA). Then, oxidation of THCA occurs to produce cannabinolic acid (CBNA) in the buds.33,34 Cannabinoids Δ9-THC, CBD, CBG, CBC, and CBN displayed anti-staphylococcal activity with even greater antibiotic effect than traditional antibiotics like norfloxacin, erythromycin, tetracycline, and oxacillin.3 CBG exhibits antibacterial activities against Streptococcus mutans (S.mutans).35,36

Table 1

Cannabinoids from Cannabis sativa L. with antimicrobial activity

Active compoundOrganismMode of actionReferences
CBDS. aureus; B. subtilisCBD is more active than CBDA due to exchanged positions of the one hydroxyl group and lipophilic side chain.3,89,100
Hepatitis C virusCBD interacts with the CB2 receptor and stimulates apoptosis in thymocytes and splenocytes, then inhibiting the proliferation of T-cells and macrophages as such mechanism cause to indirectly slows the pathogenic process of the HBV virus.
SARS-CoV-2CBD additive or synergic effect with terpene control viral replication or clonal stable conformations with the binding of the transmembrane protease serine 2 (SARS-CoV-2) and angiotensin-converting enzyme-2 (ACE2).
CBGMycobacterium; Leishmania donovani; S. mutans; S. sanguis; S. sobrinus; S. salivarius; MRSACBG alters membrane structures of treated bacteria and disorders of the cytoplasm activity.70
CBCS.aureus; B.Subtils; C. albicans; Mycobacterium smegmatis; Saccharomyces cerevisiae; Trichophyton mentagrophytesThe activity of CBC due to bearing the lipophilic side chain and one hydroxyl group in exchanged positions displayed similarly potent activity.3,74
CBNAnti-MRSA; antileishmanial; Plasmodium falciparumDecreased or increased esterification or methylation of the carboxylic acid moieties were detrimental to the activity and additional hydroxy function in the lipophilic side chain.3,76
Δ9-THCS. aureus, Streptococcus pyogenes, Streptococcus. milleri, Enterococcus faecalis, E. coli, Salmonella typhi, Proteus vulgaris, MRSADecreased or increased esterification or methylation of the carboxylic acid moieties were detrimental to the activity.3,16

ACE-2, Angiotensin-converting enzyme-2; CBD, Cannabidiol; CBDA, Cannabidiol acid; CBG, Cannabigerol; CBN, Cannabinol; MRSA, Methicillin-resistant Staphylococcus aureus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Δ9-THC, Delta-9-trans-Tetrahydrocannabinol.

Antimicrobial activity of cannabinoids like cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), and delta-8-tetrahydrocannabinol (Δ<sup>8</sup>-THC).
Fig. 1  Antimicrobial activity of cannabinoids like cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), and delta-8-tetrahydrocannabinol (Δ8-THC).

Both compounds Δ9-THC and CBD showed significant antibacterial activity towards S. aureus, Streptococcus pyogenes (S. pyogenes), Streptococcus milleri (S. milleri), Enterococcus faecalis (E. faecalis), E. coli, Salmonella typhi, and Proteus vulgaris.37 Farha, et al.37 further described the antibacterial activity of specific cannabinoids CBC, CBCA, CBD, CBDV, CBDA, CBDVA, CBG, CBGA, CBN, CBL, THC, Δ8-THC, exo-tetrahydrocannabinol (exo-THC), Δ9-tetrahydrocannabinolic acid-A (THCAA), THCV, (±) 11-nor-9-carboxy-Δ9 – THC, and (±) 11-hydroxy-Δ9-THC against MRSA to inhibit its ability to form biofilms and stationary phase cells’ resistance to antibiotics. CBD also showed potent activity against various MRSA strains.38 A detailed paper on the antimicrobial activity of CBD, including mechanistic mode-of-action studies, was later provided by Blaskovich et al.17 They showed that cannabidiol has a superior effect against biofilms. This cannabinoid could potentially treat Gram-negative bacteria infections, including Neisseria gonorrhoeae and Gram-positive bacterial infections. CBD was also shown to be a bigger inhibitor of membrane vesicle emission from E. coli (strain VCS257) compared to S. aureus. Whenever CBD was used in combination with selected antibiotics, it caused higher inhibition action against Gram-negative bacteria.39 Similar to terpenes, cannabinoids show synergistic effects with antibiotics. Grassi et al.40 demonstrated that when cannabinoids were combined with polymyxin B, there was an effective inhibition against Gram-negative bacteria.

Apart from cannabinoids, geranyl pyrophosphate is the precursor in synthesizing the terpenoids, leading to the creation of monoterpenoids in secretory cell plastids.41 For instance, volatile oil fractions incorporate monoterpenoids (C10)42 or sesquiterpenoids and triterpenoids in the cytoplasm.43,44 Sesquiterpenes (C15) are major compounds in hemp extracts.42 After harvest, Cannabis buds must be dried to remove the carboxylic acid functional group to extract high-purity CBD, CBC, and CBG. Then, oxidization of THC yields delta-8-tetrahydrocannabinol (Δ8-THC, the main psychoactive compound) and CBN.26,45,46

Many factors affect the quality and consistency of these antibacterial extracts, including environmental and climatic conditions for the growth of leaves, flowers, and seeds. Also, Muscarà et al.47 studied two standardized hexane extracts for their phytonutrients and antibiotic activities. The first extract consisted of cannabidivarinic acid (CBDVA) and tetrahydrocannabivarinic acid (THCVA). The second extract contained cannabidivarin (CBDV) and tetrahydrocannabivarin (THCV) from a new Chinese C.sativa variety and other non-psychoactive strains. Both extracts showed extraordinary antioxidant activity and antimicrobial and antifungal properties against clinical strains of MRSA and other microorganisms.28 Various methods have been applied to extract and isolate these and other antimicrobial agents, such as solvent extraction, physical methods, and supercritical fluid extraction, giving different results.5,6

Other Cannabis compounds with antimicrobial activity include terpenoids. These form a large percentage of essential oils.48–51 Some 120 terpenoids have been found in marijuana and hemp,52 but relatively few terpenes have been isolated, purified, and tested.53 Hemp seed oil was also effective in controlling spoilage of food and phytopathogenic microorganisms.16,54 An in vitro or cell culture study by Nostro et al.55 considered a range of plant extracts, potentially inhibiting biofilms in food. They found that extracts were effective against S. aureus, including MRSA strains, Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). Another study focused on linalool and α-Phellandrene, which were investigated due to their very low toxicity and ease of use and were registered as a potential new therapeutic.47,56 Another type of active compound extracted from Cannabis seeds are the flavonoids, also effective against bacteria and yeast.57

Another active compound class that can be extracted from Cannabis and used as an antibiotic alone or in combination with other compounds is Cannabis alkaloids. Natural alkaloids accumulate to differing extents in particular parts of the plant, such as barks, roots, and leaves.58,59 These alkaloids can be chemically modified to produce synthetic and semi-synthetic smart drugs. However, natural compounds are generally safer and cheaper than alternative synthetic compounds.60 Currently, natural alkaloids are used as a therapeutic compound for human disease and as pesticides in agriculture.61 Natural alkaloids and phenolic compounds have potential antimicrobial activity due to their ability to alter the structure of the bacterial wall.62

In summary, the most valuable compounds in Cannabis, besides cannabinoids, include its alkaloids, terpenoids, steroids, phenols, glycosides, and tannins.63

A novel mode of action

The most active compounds in C. sativa with antimicrobial potential are THC, CBD, CBG, and CBC.56,64–66 These compounds may also effectively treat psychological and physiological disorders.67,68 Medicinal Cannabis phytochemicals applied to specific medical devices were active against biofilms composed of Gram-positive and Gram-negative bacteria, and their mode of action was to alter and penetrate the bacteria cells69 are summarized in Table 1. Various methods like scanning electron microscopy, transmission electron microscopy, Nile Red membrane staining, and laurdan membrane fluidity assays have shown that CBG inhibits bacteria via alterations to the bacterial cell structure by inducing membrane hyperpolarization and decreasing the membrane fluidity.70 CBG exhibited moderate antimicrobial activity towards Mycobacterium25 and Leishmania donovani (L. donovani).3 Not only CBG but also its derivative iso-CBG-C1 showed potential activity against S. aureus and Bacillus subtilis (B. subtilis), and Mycobacterium smegmatis (M. smegmatis).27

Other studies found that CBD has a higher effect against Gram-positive bacteria than their acid form due to differences in lipophilicity.27,71,72 Studies have shown that CBD and CBG have a higher antimicrobial effect than their precursors (acidic cannabinoids or raw material before drying) due to exchanged positions of a hydroxyl group and lipophilic side chain.3

While CBD and CBG are effective against Gram-positive bacteria, Krejci et al.73 reported that both cannabinoids were inactive against Gram-negative bacteria. Moreover, compared to other natural cannabinoids and antibiotics like streptomycin, CBC has the highest activity against S. aureus and B. subtilis,74 and similar effects were confirmed with iso-CBC due to connecting with the lipophilic side chain and a hydroxyl group in interchanged positions.75 Furthermore, a cannabinol derivative CBN76,77 showed moderate anti-MRSA, antileishmanial, and anti-Plasmodium falciparum (P. falciparum) activity. However, both Δ9-THCVA and CBDVA showed lower anti-staphylococcal activity based on deleting a side chain compared to Δ9-THCV and CBDV.78,79 The primary action of CBG against MRSA is the disordering of the principal activity of the cytoplasm.37 Recent structure-function studies have helped to determine the most effective cannabinoids.80 Cannabinoids showed significant differences in antimicrobial activity due to a decrease or increase in methylation or esterification. The most active antimicrobial cannabinoids are Δ9-THC, CBN, and CBG.16,70

No significant antifungal activity has been observed yet for cannabinoids.19 However, the antiviral potential of CBD has received some attention.81–86 CBD was effective against hepatitis C virus (HCV),87–92 which causes liver inflammation.93 In contrast, CBD was ineffective against the hepatitis B virus (HBV). CBD was more efficient than sofosbuvir and had a less cytotoxic effect.94 Other research indirectly showed that CBD could effectively work and inhibit Kaposi’s sarcoma-associated herpesvirus (KSHV).95

One key research target is control of the human coronavirus (COVID-19).96–99 In a recent article, CBD in combination with terpenes showed antiviral effects against Human Coronavirus E229.100 Also, in an earlier investigation, terpenes were found to show an antiviral effect on severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1).101 However, while such compounds show promise, most of these antivirals have not been trialed on humans or undergone controlled clinical trials.102,103 According to Chatow et al.,100 the combined possibility of plant terpenes with CBD against a human coronavirus strain could be seen using a tissue cell culture model.

Although such studies are a good start, they cannot determine side effects or potential cytotoxicity as in vivo animal model studies. Recent studies showed phytochemicals have stable conformations with the binding enzyme of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has a vital role in viral replication, cloning, suppressing viral entry and activation, and down-regulating ACE2 receptor and TMPRSS2 enzyme.104–106 Further investigation on developing new vaccines or antivirals will be needed to address strain variability, i.e., target all strains of COVID-19. This needs more intensive research in the future, together with studies giving mechanistic insights into their action.

Challenges in applications of cannabinoids as an antimicrobial agent

As noted earlier, the spread of antibiotic resistance genes is common among many pathogens, and with little or no pending discovery or development of new classes of antibiotics, the need to find other agents for combating infections is vital.37,107,108 Recently, the World Health Organization announced an archive of 12 microorganisms that have developed antibacterial resistance and are now considered a severe threat to health care. Eight of these pathogens are Gram-negative and are spectacularly hard to cure, while the other four Gram-positive microorganisms are the most significant threat.109 The antimicrobial activity of Cannabis derives from essential oils (Eos) and purified cannabinoids, the latter receiving increased attention in recent years as possible therapeutic agents.16,19,56,110 This section will first consider the antimicrobial effects of impure extracts and Eos, then discuss studies on purified cannabinoids.

The disc diffusion assay and the two-fold serial broth dilution assay, which generate a MIC value in a 96-well microtiter plate, are the most commonly used methods to measure antimicrobial effects.111 The methodology for the MIC assay is standard and specified by the Clinical Laboratory and Standards Institute (CLSI).112 However, a problem highlighted by Sadgrove and Jones113 is that MIC values are normally quoted in µg/ml, which does not take into account molarity. The authors also noted that antimicrobial outcomes might be naively extrapolated beyond any reasonable systemic concentration level to show an effect. Even with method standardization, caution must be exercised when comparing inter-laboratory results to ensure that results cross-comparisons are valid. In one study, even though there was the bactericidal effect of both cannabinoids like THC and CBD against staphylococci and streptococci tested in broth media, the impact was much higher in horse blood agar or with 4% horse serum.109

Even though essential oils (Eos) can be extracted from low-THC Cannabis varieties cultivated without legal restrictions, relatively few studies have considered these Eos or extracts in terms of their antimicrobial activities. The use of Cannabis in this way strengthens the idea of growing hemp as a multi-use crop.54 A fundamental challenge in medical Cannabis and hemp research requires production methods or post-harvesting processes that maintain the uniform quality of the product. Also, drying, extraction, isolation, and purification techniques must be optimized to obtain pure chemical composition and pharma grade for different products.6,114–116

One problem with assessing multiple studies is that Cannabis extracts vary enormously in composition and contain multiple different compounds, making result comparisons extremely difficult. Some key variables that make inter-laboratory comparisons difficult include the absence of standardized antimicrobial testing methodologies; microbiological media components in disk diffusion tests reacting with or modifying extracts; plant extracts containing unstable compounds making accurate quantitative analysis impossible; synergistic or antagonistic effects between multiple compounds; different cultivars or parts of plants used in different studies; and extraction protocols of varying efficiency leading to different outcomes. In one study, C. sativa and Psidium guajava extracts contained various active compounds like alkaloids, saponins, flavonoids, steroids, cardiac glycosides, terpenes, resins, tannins, and phenols. However, steroids, resins, and cardiac glycosides were absent in another medicinal plant, Thuja orientalis. Furthermore, hemp essential oils demonstrated high antimicrobial activity against Gram-positive bacteria.20,54

Some studies have focused on extracts of seeds of Cannabis plants.117 Hemp seed extracts show good antimicrobial activity due to their composition of polyphenols, essentially caffeoyltyramine and cannabisin.118 In another study,117C. sativa L. seed extracts inhibited biofilm formation by S. aureus ATCC 35556. In contrast, adding hemp seed extract to media stimulated the growth of Bifidobacterium and Lactobacillus probiotic strains.117 The increased growth of Bifidobacterium Longum (B. longum) in the presence of hemp extract was due to protection from oxidative stress.119

Most studies on the effects of extracts use classical disc diffusion methods. However, recently, the study reported by Frassinetti et al.117 was to determine the lowest concentrations with activity via MIC and a biofilm production and inhibition assay. A further study by Iseppi et al.120 aimed to standardize the antibacterial method and provided better designs for experiments. Firstly, the separation of essential oils (EO) compounds was done by gas chromatography mass spectrometry (GC-MS). The EOs were tested via an agar well-diffusion assay, and MIC testing was done against multiple Gram-positive bacteria. The EOs and purified compounds were highly effective against Enterococcus, an opportunistic pathogen. These authors also found that two EOs and two purified compounds had lower MICs than amoxicillin or ampicillin against Bacillus cereus (B. cereus).

Another active compound extracted from the seed was flavonoids; these were shown to be active against Candida albicans, S. aureus, and P. aeruginosa.57 EOs of fiber-type hemp have also been applied to prevent food spoilage, incorporating antimicrobial extracts into food packaging. Further studies are needed on pure compounds.28

An exciting use of Cannabis extracts has been forming silver or zinc nanoparticles (Ag NPs and Zn NPs) with antimicrobial activity. Chouhan and Guleria,18 Chauhan et al.121 used C. sativa extracts to form stable nanoparticle emulsions with Ag-doped, Zn, and ZnO nanoparticles; AgNPs revealed an excellent antioxidant capacity and significant antibiotic activity against several human infection diseases by disc diffusion test, including E. coli, Klebsiella pneumoniae (K. pneumoniae), MRSA, P. aeruginosa, S. typhi, and S.aureus, and as an antifungal against Fusarium spp. Rosellinia necatrix C. sativa aqueous leaf extract (CSE) derived AgNPs also had antifungal and α-amylase inhibitory activity. There was minor activity against Bacillus subtilis, S. aureus, and K. pneumoniae tested by a well-diffusion assay with increasing concentrations of AgNPs. Other researchers122 suggested a synergistic or symbiotic effect between terpenes, flavonoids, and cannabinoids in industry hemp strains to improve the effect of silver nanoparticles (AgNPs). Other studies showed the effective use of hemp extracts to produce nanoparticles effective against biofilms.123 The main challenge with using nanoparticles based on C. sativa extracts is to develop suitable technologies for obtaining nanoparticles with specific properties used in pharmaceutical products. For recent reviews see.124,125

Synergistic effects between Cannabis sativa and plants such as Allium sativum (Garlic) have been shown.126 Further research is required to study the impact of terpenes, in particular, as antimicrobial agents.127 There may also be a synergistic effect when these compounds are applied with antibiotics simultaneously, as demonstrated for other plant extracts by Blesson et al.128 In comparative testing, the presence of other compounds must be considered.

Several reviews have summarized the antimicrobial properties of the major cannabinoids against essential pathogenic microorganisms or viruses, including Gram-negative pathogens, MRSA, and SARS-CoV-2.3,19,22,129,130 From this extensive compilation of data, there is a need for standardization of methodology and approaches so that valid comparisons and conclusions between laboratories can be made. This includes how in vitro results can be extrapolated to determine in vivo efficacy, determined (usually) by using animal models.37 However, further in vivo or animal model investigation is required to determine how the body reacts and responds to cannabinoids, including side effects.

Another challenge for using cannabinoids in terms of antimicrobial activity is to control their stability and bioavailability once introduced into the body. Cannabinoids have significant pharmacological activities but may show poor water solubility and become labile during processing and storage.131 A commonly used method for the delivery of cannabinoids and improvements in bioavailability is using nanocarriers (NCs) to protect core materials from degradation during passage through the gastrointestinal (GI) tract.132 Transmucosal oral routes of delivery offer distinct advantages.5 Determining dosage forms for any medicinal product must consider product instability, such as at room temperature. In this regard, CBD is highly unstable and sensitive to oxidation.133

Future directions

For the potential of Cannabis plant extracts and phytochemicals to be applied as natural antimicrobials, further work is required to standardize and harmonize research. As is genuine for all-natural extracts, variability in natural bioactive contents between plants, parts of plants, and extracts needs to be addressed with assessment and clear transparent reporting of properties. Additional research to identify active compounds (in isolation and synergistic applications) will potentially circumvent these issues by refining test substances. However, challenges persist regarding stability, delivery, safety, non-uniform testing procedures, and negative perceptions of these products. A multi-disciplinary approach is required to facilitate the progress from promising potential antimicrobials to pharmacological success, with roles for biological sciences, pharmacology, chemistry, and social and other sciences.

Conclusions

The evolution of antibiotic-resistant bacteria and the emergence of new viruses such as COVID-19 have stimulated the search for non-traditional antimicrobial or antiviral treatments. In the case of bacteria, this includes alternatives to using antibiotics. While the use of Cannabis as a medicinal agent has been known for thousands of years, there is now great interest in discovering and analyzing potent antimicrobial agents derived from this plant, including its cannabinoids, terpenes, phenolics, and alkaloids. While this is welcome, inter-laboratory comparisons of results showing antimicrobial or antiviral activities are complex, as many variables affect results (such as plant-to-plant variations, differences in extraction protocols, synergistic/antagonistic effects of other compounds, and differences in antimicrobial assay protocols). There are also challenges for commercial applications, such as finding the best method for extraction and isolation of the active compound, not to mention understanding the stability and bioavailability of the cannabinoids and their pharmacokinetics once introduced into the body. Also, more study is necessary to determine the synergic effect of natural therapeutic plants in combination with Cannabis, to design functional nanoparticle delivery devices, and to test the safety and efficacy of an experimental new antibiotic in clinical trials.

Abbreviations

Δ8-THC: 

Delta-8-Tetrahydrocannabinol

ABTS: 

2,2′-Azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt

ACE-2: 

Angiotensin-converting enzyme-2

AgNPS: 

Silver nanoparticles

B. cereus: 

Bacillus cereus

B. longum: 

Bifidobacterium longum

B. subtilis: 

Bacillus subtilis

CBC: 

Cannabichromene

CBCA: 

Cannabichromene acid

CBD: 

Cannabidiol

CBDA: 

Cannabidiol acid

CBDV: 

Cannabidivarin

CBDVA: 

Cannabidivarin acid

CBG: 

Cannabigerol

CBGA: 

Cannabigerolic acid

CBL: 

Cannabicyclol

CBN: 

Cannabinol

CBNA: 

Cannabinol acid

CLSI: 

Clinical Laboratory and standards Institute

COVID-19: 

Human coronavirus

SARS-CoV2: 

severe acute respiratory syndrome coronavirus 2

DPPH: 

2,2-diphenyl-1-picrylhydrazyl

E. coli: 

Escherichia coli

E. faecalis: 

Enterococcus faecalis

EOs: 

Essential Oils

GC-MS: 

Gas Chromatography Mass Spectrometry

GI: 

Gastrointestinal

GOT: 

Geranyl pyrophosphate, Olivetolate geranyltransferase

GPP: 

Geranyl pyrophosphate

HBV: 

Hepatitis B virus

HCV: 

Hepatitis C virus

K. pneumoniae: 

Klebsiella pneumoniae

KSHV: 

Kaposi’s sarcoma-associated herpesvirus

L. donovani: 

Leishmania donovani

M. smegmatis: 

Mycobacterium smegmatis

MBC: 

minimum bactericidal concentration

MIC: 

minimum inhibitory concentration

MRSA: 

Methicillin-resistant Staphylococcus aureus

NCs: 

Nanocarriers

OLA: 

olivetol acid

P. aeruginosa: 

Pseudomonas aeruginosa

P. falciparum: 

Plasmodium falciparum

P. guajava: 

Psidium guajava

S. aureus: 

Staphylococcus aureus

S. milleri: 

Streptococcus milleri

S. mutans: 

Streptococcus mutans

S. pyogenes: 

Streptococcus pyogenes

SFE-CO2: 

Supercritical fluid extraction with carbon dioxide

THC: 

Tetrahydrocannabinol

THCA: 

Tetrahydrocannabinolic acid

THCAA: 

Delta9-tetrahydrocannabinolic acid-A

THCAS: 

Tetrahydrocannabinolic acid synthase

THCV: 

Tetrahydrocannabivarin

THCVA: 

Tetrahydrocannabivarin acid

TMPRSS2: 

Transmembrane serine protease 2

ZnNPS: 

Zinc Nanoparticles

Δ9-THC: 

Delta-9-trans-Tetrahydrocannabinol

Declarations

Acknowledgement

None.

Funding

HMSAU and AF were funded by MGC Pharmaceuticals Limited, Australia.

Conflict of interest

Funding received from a commercial company (MGC Pharmaceuticals Limited) is a potential conflict.

Authors’ contributions

Conceptualization and design (HMSAU); writing original draft preparation, Abstract, New classes of potent antimicrobial agents, A novel mode of action, Conclusion (HMSAU); Introduction and future research directions (ELB); A novel mode of action (MK); Abstract, Introduction, Challenges on applications of Cannabinoids as an antimicrobial agent (CP); Figure design (HMSAU); writing a review, and editing (AF, CP, ELB, HMSAU). All authors have read and agreed to the published version of the manuscript.

References

  1. Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M, et al. Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol 2018;227:300-315 View Article PubMed/NCBI
  2. Fischedick JT, Hazekamp A, Erkelens T, Choi YH, Verpoorte R. Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes. Phytochemistry 2010;71(17-18):2058-2073 View Article PubMed/NCBI
  3. Klahn P. Cannabinoids-Promising Antimicrobial Drugs orIntoxicants with Benefits?. Antibiotics (Basel) 2020;9(6):E297 View Article PubMed/NCBI
  4. Simiyu DC, Jang JH, Lee OR. Understanding Cannabis sativa L.: Current Status of Propagation, Use, Legalization, and Haploid-Inducer-Mediated Genetic Engineering. Plants (Basel) 2022;11(9):1236 View Article PubMed/NCBI
  5. Fathordoobady F, Singh A, Kitts DD, Pratap Singh A. Hemp (Cannabis Sativa L.) extract: anti-microbial properties, methods of extraction, and potential oral delivery. Food Rev Int 2019;35(7):664-684 View Article
  6. Al Ubeed HMS, Bhuyan DJ, Alsherbiny MA, Basu A, Vuong QV. A Comprehensive Review on the Techniques for Extraction of Bioactive Compounds from Medicinal Cannabis. Molecules 2022;27(3):604 View Article PubMed/NCBI
  7. Rosenthal E, Zeman G. Beyond buds: Next generation-marijuana extracts and cannabis infusions. CA: Quick American Archives; 2018, 149-167
  8. Dias DA, Urban S, Roessner U. A historical overview of natural products in drug discovery. Metabolites 2012;2(2):303-336 View Article PubMed/NCBI
  9. Baker D, Pryce G, Giovannoni G, Thompson AJ. The therapeutic potential of cannabis. Lancet Neurol 2003;2(5):291-298 View Article PubMed/NCBI
  10. Andre CM, Hausman JF, Guerriero G. Cannabis sativa: The Plant of the Thousand and One Molecules. Front Plant Sci 2016;7:19 View Article PubMed/NCBI
  11. Ferri M, Ranucci E, Romagnoli P, Giaccone V. Antimicrobial resistance: A global emerging threat to public health systems. Crit Rev Food Sci Nutr 2017;57(13):2857-2876 View Article PubMed/NCBI
  12. Vouga M, Greub G. Emerging bacterial pathogens: the past and beyond. Clin Microbiol Infect 2016;22(1):12-21 View Article PubMed/NCBI
  13. Danis-Wlodarczyk KM, Wozniak DJ, Abedon ST. Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application. Antibiotics (Basel) 2021;10(12):1497 View Article PubMed/NCBI
  14. Rios AC, Moutinho CG, Pinto FC, Del Fiol FS, Jozala A, Chaud MV, et al. Alternatives to overcoming bacterial resistances: State-of-the-art. Microbiol Res 2016;191:51-80 View Article PubMed/NCBI
  15. David MZ, Dryden M, Gottlieb T, Tattevin P, Gould IM. Recently approved antibacterials for methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive pathogens: the shock of the new. Int J Antimicrob Agents 2017;50(3):303-307 View Article PubMed/NCBI
  16. Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M, et al. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod 2008;71(8):1427-1430 View Article PubMed/NCBI
  17. Blaskovich MAT, Kavanagh AM, Elliott AG, Zhang B, Ramu S, Amado M, et al. The antimicrobial potential of cannabidiol. Commun Biol 2021;4(1):7 View Article PubMed/NCBI
  18. Chouhan S, Guleria S. Green synthesis of AgNPs using Cannabis sativa leaf extract: Characterization, antibacterial, anti-yeast and α-amylase inhibitory activity. Materials Science for Energy Technologies 2020;3:536-544 View Article
  19. Karas JA, Wong LJM, Paulin OKA, Mazeh AC, Hussein MH, Li J, et al. The Antimicrobial Activity of Cannabinoids. Antibiotics (Basel) 2020;9(7):E406 View Article PubMed/NCBI
  20. Chakraborty S, Afaq N, Singh N, Majumdar S. Antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus. J Integr Med 2018;16(5):350-357 View Article PubMed/NCBI
  21. Nashra A, Sujatha R, Sameer D, Bagoliwal A, Mishra V, Kumar A, et al. Comparative Evaluation of Antibacterial Efficacy of Cannabis sativa, Allium sativum, Allium cepa, Thuja orientalis and Psidium guajava against Drug Resistance Pathogens. International Journal of Health Sciences and Research 2018;8(8):89-97
  22. Mahmud MS, Hossain MS, Ahmed ATMF, Islam MZ, Sarker ME, Islam MR. Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review. Molecules 2021;26(23):7216 View Article PubMed/NCBI
  23. Salami SA, Martinelli F, Giovino A, Bachari A, Arad N, Mantri N. It Is Our Turn to Get Cannabis High: Put Cannabinoids in Food and Health Baskets. Molecules 2020;25(18):E4036 View Article PubMed/NCBI
  24. Elsohly MA, Slade D. Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 2005;78(5):539-548 View Article PubMed/NCBI
  25. Radwan MM, Ross SA, Slade D, Ahmed SA, Zulfiqar F, Elsohly MA. Isolation and characterization of new Cannabis constituents from a high potency variety. Planta Med 2008;74(3):267-272 View Article PubMed/NCBI
  26. Radwan MM, Elsohly MA, Slade D, Ahmed SA, Wilson L, El-Alfy AT, et al. Non-cannabinoid constituents from a high potency Cannabis sativa variety. Phytochemistry 2008;69(14):2627-2633 View Article PubMed/NCBI
  27. Eisohly HN, Turner CE, Clark AM, Eisohly MA. Synthesis and antimicrobial activities of certain cannabichromene and cannabigerol related compounds. J Pharm Sci 1982;71(12):1319-1323 View Article PubMed/NCBI
  28. Khan BA, Warner P, Wang H. Antibacterial properties of hemp and other natural fibre plants: a review. BioResources 2014;9(2):3642-3659 View Article
  29. Turner CE, Elsohly MA. Biological activity of cannabichromene, its homologs and isomers. J Clin Pharmacol 1981;21(S1):283S-291S View Article PubMed/NCBI
  30. Ahmed SA, Ross SA, Slade D, Radwan MM, Zulfiqar F, Matsumoto RR, et al. Cannabinoid ester constituents from high-potency Cannabis sativa. J Nat Prod 2008;71(4):536-542 View Article PubMed/NCBI
  31. Molnár J, Csiszár K, Nishioka I, Shoyama Y. The effects of cannabispiro compounds and tetrahydrocannabidiolic acid on the plasmid transfer and maintenance in Escherichia coli. Acta Microbiol Hung 1986;33(3):221-231 PubMed/NCBI
  32. Fellermeier M, Zenk MH. Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett 1998;427(2):283-285 View Article PubMed/NCBI
  33. Sirikantaramas S, Morimoto S, Shoyama Y, Ishikawa Y, Wada Y, Shoyama Y, et al. The gene controlling marijuana psychoactivity: molecular cloning and heterologous expression of Delta1-tetrahydrocannabinolic acid synthase from Cannabis sativa L. J Biol Chem 2004;279(38):39767-39774 View Article PubMed/NCBI
  34. Taura F, Morimoto S, Shoyama Y, Mechoulam R. First direct evidence for the mechanism of. DELTA. 1-tetrahydrocannabinolic acid biosynthesis. J Am Chem Soc 1995;117(38):9766-9767 View Article
  35. Feng J, Gu Y, Quan Y, Gao W, Dang Y, Cao M, et al. Construction of energy-conserving sucrose utilization pathways for improving poly-γ-glutamic acid production in Bacillus amyloliquefaciens. Microb Cell Fact 2017;16(1):98 View Article PubMed/NCBI
  36. Feldman M, Sionov RV, Mechoulam R, Steinberg D. Anti-Biofilm Activity of Cannabidiol against Candida albicans. Microorganisms 2021;9(2):441 View Article PubMed/NCBI
  37. Farha MA, El-Halfawy OM, Gale RT, MacNair CR, Carfrae LA, Zhang X, et al. Uncovering the Hidden Antibiotic Potential of Cannabis. ACS Infect Dis 2020;6(3):338-346 View Article PubMed/NCBI
  38. Centers for Disease Control and Prevention (U.S.); National Center for Emerging Zoonotic and Infectious Diseases (U.S.). Division of Healthcare Quality Promotion. Antibiotic Resistance Coordination and Strategy Unit. Antibiotic resistance threats in the United States, 2019. https://stacks.cdc.gov/view/cdc/82532
  39. Kosgodage US, Matewele P, Awamaria B, Kraev I, Warde P, Mastroianni G, et al. Cannabidiol Is a Novel Modulator of Bacterial Membrane Vesicles. Front Cell Infect Microbiol 2019;9:324 View Article PubMed/NCBI
  40. Grassi L, Maisetta G, Esin S, Batoni G. Combination Strategies to Enhance the Efficacy of Antimicrobial Peptides against Bacterial Biofilms. Front Microbiol 2017;8:2409 View Article PubMed/NCBI
  41. Loza-Tavera H. Monoterpenes in essential oils. Biosynthesis and properties. Adv Exp Med Biol 1999;464:49-62 View Article PubMed/NCBI
  42. Bertoli A, Tozzi S, Pistelli L, Angelini LG. Fibre hemp inflorescences: From crop-residues to essential oil production. Industrial Crops Products 2010;32(3):329-337 View Article
  43. Dewick PM. The biosynthesis of C5-C25 terpenoid compounds. Nat Prod Rep 2002;19(2):181-222 View Article PubMed/NCBI
  44. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol 2011;163(7):1344-1364 View Article PubMed/NCBI
  45. Gagne SJ, Stout JM, Liu E, Boubakir Z, Clark SM, Page JE. Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Proc Natl Acad Sci U S A 2012;109(31):12811-12816 View Article PubMed/NCBI
  46. Thomas BF, Elsohly M. The analytical chemistry of cannabis: Quality assessment, assurance, and regulation of medicinal marijuana and cannabinoid preparations. Elsevier; 2015
  47. Muscarà C, Smeriglio A, Trombetta D, Mandalari G, La Camera E, Occhiuto C, et al. Antioxidant and antimicrobial activity of two standardized extracts from a new Chinese accession of non-psychotropic Cannabis sativa L. Phytother Res 2021;35(2):1099-1112 View Article PubMed/NCBI
  48. McPartland JM, Russo EB. Cannabis and cannabis extracts: greater than the sum of their parts?. Journal of Cannabis Therapeutics 2001;1(3-4):103-132 View Article
  49. Nagy DU, Cianfaglione K, Maggi F, Sut S, Dall’Acqua S. Chemical Characterization of Leaves, Male and Female Flowers from Spontaneous Cannabis (Cannabis sativa L.) Growing in Hungary. Chem Biodivers 2019;16(3):e1800562 View Article PubMed/NCBI
  50. Novak J, Franz C. Composition of the essential oils and extracts of two populations of Cannabis sativa L. ssp. spontanea from Austria. J Essent Oil Res 2003;15(3):158-160 View Article
  51. Ross SA, ElSohly MA. The volatile oil composition of fresh and air-dried buds of Cannabis sativa. J Nat Prod 1996;59(1):49-51 View Article PubMed/NCBI
  52. Turner CE, Elsohly MA, Boeren EG. Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod 1980;43(2):169-234 View Article PubMed/NCBI
  53. Chen F, Tholl D, Bohlmann J, Pichersky E. The family of terpene synthases in plants: a mid-size family of genes for specialized metabolism that is highly diversified throughout the kingdom. Plant J 2011;66(1):212-229 View Article PubMed/NCBI
  54. 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(5):413-419 View Article PubMed/NCBI
  55. Nostro A, Guerrini A, Marino A, Tacchini M, Di Giulio M, Grandini A, et al. In vitro activity of plant extracts against biofilm-producing food-related bacteria. Int J Food Microbiol 2016;238:33-39 View Article PubMed/NCBI
  56. Schofs L, Sparo MD, Sánchez Bruni SF. The antimicrobial effect behind Cannabis sativa. Pharmacol Res Perspect 2021;9(2):e00761 View Article PubMed/NCBI
  57. Onsare JG, Arora DS. Antibiofilm potential of flavonoids extracted from Moringa oleifera seed coat against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. J Appl Microbiol 2015;118(2):313-325 View Article PubMed/NCBI
  58. Das B, Mishra P. Antibacterial analysis of crude extracts from the leaves of Tagetes erecta and Cannabis sativa. International Journal of Environmental Sciences 2012;2(3):1605-1608 View Article
  59. Sambasivam S, Karpagam G, Chandran R, Khan SA. Toxicity of leaf extract of yellow oleander Thevetia nerifolia on Tilapia. J Environ Biol 2003;24(2):201-204 PubMed/NCBI
  60. Kayser O, Kiderlen AF, Croft SL. Natural products as potential antiparasitic drugs. Studies in Natural Products Chemistry 2002;26:779-848 View Article
  61. Varma J, Dubey N. Prospectives of botanical and microbial products as pesticides of tomorrow. Current Science 1999;76(2):172-179
  62. Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev 1999;12(4):564-582 View Article PubMed/NCBI
  63. Audu B, Ofojekwu P, Ujah A, Ajima M. Phytochemical, proximate composition, amino acid profile and characterization of marijuana (Cannabis sativa L.). The Journal of Phytopharmacology 2014;3(1):35-43 View Article
  64. Pollastro F, Minassi A, Fresu LG. Cannabis Phenolics and their Bioactivities. Curr Med Chem 2018;25(10):1160-1185 View Article PubMed/NCBI
  65. Zagožen M, Čerenak A, Kreft S. Cannabigerol and cannabichromene in Cannabis sativa L. Acta Pharmaceutica 2021;71(3):355-364 View Article
  66. Sampson PB. Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the “Big Two”. J Nat Prod 2021;84(1):142-160 View Article PubMed/NCBI
  67. Gildea L, Ayariga JA, Ajayi OS, Xu J, Villafane R, Samuel-Foo M. Cannabis sativa CBD Extract Shows Promising Antibacterial Activity against Salmonella typhimurium and S. newington. Molecules 2022;27(9):2669 View Article PubMed/NCBI
  68. Gray RA, Whalley BJ. The proposed mechanisms of action of CBD in epilepsy. Epileptic Disord 2020;22(S1):10-15 View Article PubMed/NCBI
  69. Cannabinoids as antimicrobial agents. New York: LAVVAN; 2022. Available from: https://www.lavvan.com/cannabinoids-as-antimicrobial-agents. Accessed May 9, 2022
  70. Aqawi M, Sionov RV, Gallily R, Friedman M, Steinberg D. Anti-Bacterial Properties of Cannabigerol Toward Streptococcus mutans. Front Microbiol 2021;12:656471 View Article PubMed/NCBI
  71. Bucekova M, Jardekova L, Juricova V, Bugarova V, Di Marco G, Gismondi A, et al. Antibacterial Activity of Different Blossom Honeys: New Findings. Molecules 2019;24(8):E1573 View Article PubMed/NCBI
  72. Martinenghi LD, Jønsson R, Lund T, Jenssen H. Isolation, Purification, and Antimicrobial Characterization of Cannabidiolic Acid and Cannabidiol from Cannabis sativa L. Biomolecules 2020;10(6):E900 View Article PubMed/NCBI
  73. Krejci Z, Horok M, Santavy F. Hanf (cannabis sativa)-antibiotishes heilmittel. 3. Mitteilung: Isolierung und Konstitution zweier aus Cannabis sativa gewonnener sauren. Die Pharmazie 1959;14:349-355
  74. Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 2009;30(10):515-527 View Article PubMed/NCBI
  75. Dalzell HC, Uliss DB, Handrick GR, Razdan RK. Hashish. 26. Factors influencing double-bond stability in cannabinoids. The Journal of Organic Chemistry 1981;46(5):949-953 View Article
  76. Clarke H, Roychoudhury P, Narouze SN. Cannabinoids and Pain. Cham: Springer; 2021, 87-92 View Article
  77. Tahsin KN, Watson D, Rizkalla A, Heinrichs D, Charpentier P. Antimicrobial Studies of Cannabidiol as Biomaterials against superbug MRSA. CMBES Proc 2021;44
  78. Palomares Cañero B. Non psychotropic cannabinoids for the treatment of inflammatory diseases [Dissertation]. Universidad de Córdoba, UCO Press; 2020. Available from: http://hdl.handle.net/10396/19632. Accessed May 9, 2022
  79. Mnekin L, Ripoll L. Topical Use of Cannabis sativa L. Biochemicals. Cosmetics 2021;8(3):85 View Article
  80. Khameneh B, Iranshahy M, Soheili V, Fazly Bazzaz BS. Review on plant antimicrobials: a mechanistic viewpoint. Antimicrob Resist Infect Control 2019;8:118 View Article PubMed/NCBI
  81. Sytar O, Brestic M, Hajihashemi S, Skalicky M, Kubeš J, Lamilla-Tamayo L, et al. COVID-19 Prophylaxis Efforts Based on Natural Antiviral Plant Extracts and Their Compounds. Molecules 2021;26(3):727 View Article PubMed/NCBI
  82. Pitakbut T, Nguyen GN, Kayser O. Activity of THC, CBD, and CBN on Human ACE2 and SARS-CoV1/2 Main Protease to Understand Antiviral Defense Mechanism. Planta Med 2022;88(12):1047-1059 View Article PubMed/NCBI
  83. Onay A, Ertaş A, Süzerer V, Yener İ, Yilmaz MA, Ayaz-Tilkat E, et al. Cannabinoids for SARS-CoV-2 and is there evidence of their therapeutic efficacy?. Turk J Biol 2021;45(4):570-587 View Article PubMed/NCBI
  84. Yadav V, Kaushik P. Phytochemicals against COVID-19 and a gap in clinical investigations: An outlook. Indian Journal of Biochemistry Biophysics 2021;58(5):403-407
  85. Zhao L, Yan Y, Dai Q, Wang Z, Yin J, Xu Y, et al. The CDK1 inhibitor, Ro-3306, is a potential antiviral candidate against influenza virus infection. Antiviral Res 2022;201:105296 View Article PubMed/NCBI
  86. Mabou Tagne A, Pacchetti B, Sodergren M, Cosentino M, Marino F. Cannabidiol for Viral Diseases: Hype or Hope?. Cannabis Cannabinoid Res 2020;5(2):121-131 View Article PubMed/NCBI
  87. Stieltjes N, Ounnoughene N, Sava E, Paugy P, Roussel-Robert V, Rosenberg AR, et al. Interest of transjugular liver biopsy in adult patients with haemophilia or other congenital bleeding disorders infected with hepatitis C virus. Br J Haematol 2004;125(6):769-776 View Article PubMed/NCBI
  88. Leopold SJ, Grady BP, Lindenburg CE, Prins M, Beuers U, Weegink CJ. Common bile duct dilatation in drug users with chronic hepatitis C is associated with current methadone use. J Addict Med 2014;8(1):53-58 View Article PubMed/NCBI
  89. Lowe HI, Toyang NJ, McLaughlin W. Potential of Cannabidiol for the Treatment of Viral Hepatitis. Pharmacognosy Res 2017;9(1):116-118 View Article PubMed/NCBI
  90. Bachmetov L, Gal-Tanamy M, Shapira A, Vorobeychik M, Giterman-Galam T, Sathiyamoorthy P, et al. Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity. J Viral Hepat 2012;19(2):e81-e88 View Article PubMed/NCBI
  91. Edmunds BL, Miller ER, Tsourtos G. The distribution and socioeconomic burden of Hepatitis C virus in South Australia: a cross-sectional study 2010-2016. BMC Public Health 2019;19(1):527 View Article PubMed/NCBI
  92. de Paula Farah K, Carmo RA, de Figueiredo Antunes CM, Serufo JC, Nobre Júnior VA, Fonseca de Castro LP, et al. Hepatitis C, HCV genotypes and hepatic siderosis in patients with chronic renal failure on haemodialysis in Brazil. Nephrol Dial Transplant 2007;22(7):2027-2031 View Article PubMed/NCBI
  93. Hegde VL, Nagarkatti PS, Nagarkatti M. Role of myeloid-derived suppressor cells in amelioration of experimental autoimmune hepatitis following activation of TRPV1 receptors by cannabidiol. PLoS One 2011;6(4):e18281 View Article PubMed/NCBI
  94. Lowe H, Steele B, Bryant J, Fouad E, Toyang N, Ngwa W. Antiviral Activity of Jamaican Medicinal Plants and Isolated Bioactive Compounds. Molecules 2021;26(3):607 View Article PubMed/NCBI
  95. Maor Y, Yu J, Kuzontkoski PM, Dezube BJ, Zhang X, Groopman JE. Cannabidiol inhibits growth and induces programmed cell death in kaposi sarcoma-associated herpesvirus-infected endothelium. Genes Cancer 2012;3(7-8):512-520 View Article PubMed/NCBI
  96. Camacho-Rivera M, Islam JY, Rodriguez DL, Vidot DC. Cannabis Use among Cancer Survivors amid the COVID-19 Pandemic: Results from the COVID-19 Cannabis Health Study. Cancers (Basel) 2021;13(14):3495 View Article PubMed/NCBI
  97. Beasley MB. Acute lung injury-from cannabis to COVID. Mod Pathol 2022;35(Suppl 1):1-7 View Article PubMed/NCBI
  98. van Laar MW, Oomen PE, van Miltenburg CJA, Vercoulen E, Freeman TP, Hall WD. Cannabis and COVID-19: Reasons for Concern. Front Psychiatry 2020;11:601653 View Article PubMed/NCBI
  99. Chong WW, Acar ZI, West ML, Wong F. A Scoping Review on the Medical and Recreational Use of Cannabis During the COVID-19 Pandemic. Cannabis Cannabinoid Res 2022;7(5):591-602 View Article PubMed/NCBI
  100. Chatow L, Nudel A, Nesher I, Hayo Hemo D, Rozenberg P, Voropaev H, et al. In Vitro Evaluation of the Activity of Terpenes and Cannabidiol against Human Coronavirus E229. Life (Basel) 2021;11(4):290 View Article PubMed/NCBI
  101. Loizzo MR, Saab AM, Tundis R, Menichini F, Bonesi M, Piccolo V, et al. In vitro inhibitory activities of plants used in Lebanon traditional medicine against angiotensin converting enzyme (ACE) and digestive enzymes related to diabetes. J Ethnopharmacol 2008;119(1):109-116 View Article PubMed/NCBI
  102. Nguyen LC, Yang D, Nicolaescu V, Best TJ, Ohtsuki T, Chen SN, et al. Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response. bioRxiv 2021 View Article PubMed/NCBI
  103. Perry E, Howes MJ. Medicinal plants and dementia therapy: herbal hopes for brain aging?. CNS Neurosci Ther 2011;17(6):683-698 View Article PubMed/NCBI
  104. Astuti I, Ysrafil. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes Metab Syndr 2020;14(4):407-412 View Article PubMed/NCBI
  105. Davidson AM, Wysocki J, Batlle D. Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor: Therapeutic Implications. Hypertension 2020;76(5):1339-1349 View Article PubMed/NCBI
  106. Sallenave JM, Guillot L. Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets?. Front Immunol 2020;11:1229 View Article PubMed/NCBI
  107. Anand U, Jacobo-Herrera N, Altemimi A, Lakhssassi N. A Comprehensive Review on Medicinal Plants as Antimicrobial Therapeutics: Potential Avenues of Biocompatible Drug Discovery. Metabolites 2019;9(11):E258 View Article PubMed/NCBI
  108. Cooper MA, Shlaes D. Fix the antibiotics pipeline. Nature 2011;472(7341):32 View Article PubMed/NCBI
  110. Datta S, Ramamurthy PC, Anand U, Singh S, Singh A, Dhanjal DS, et al. Wonder or evil?: Multifaceted health hazards and health benefits of Cannabis sativa and its phytochemicals. Saudi J Biol Sci 2021;28(12):7290-7313 View Article PubMed/NCBI
  111. Eloff JN. A sensitive and quick microplate method to determine the minimal inhibitory concentration of plant extracts for bacteria. Planta Med 1998;64(8):711-713 View Article PubMed/NCBI
  112. CLSI Performance Standards for Antimicrobial Disk Susceptibility Tests. 12th Edition ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2017
  113. Sadgrove NJ, Jones GL. From Petri Dish to Patient: Bioavailability Estimation and Mechanism of Action for Antimicrobial and Immunomodulatory Natural Products. Front Microbiol 2019;10:2470 View Article PubMed/NCBI
  114. Al Ubeed HMS, Wills RBH, Chandrapala J. Post-Harvest Operations to Generate High-Quality Medicinal Cannabis Products: A Systemic Review. Molecules 2022;27(5):1719 View Article PubMed/NCBI
  115. Challa SKR, Misra N, Martynenko A. Drying of cannabis—state of the practices and future needs. Drying Technology 2021;39(14):2055-2064
  116. Chasiotis V, Tsakirakis A, Termentzi A, Machera K, Filios A. Drying and quality characteristics of Cannabis sativa L. Inflorescences under constant and time-varying convective drying temperature schemes. Thermal Science and Engineering Progress 2022;28:101076 View Article
  117. Frassinetti S, Gabriele M, Moccia E, Longo V, Di Gioia D. Antimicrobial and antibiofilm activity of Cannabis sativa L. seeds extract against Staphylococcus aureus and growth effects on probiotic Lactobacillus spp. LWT 2020;124:109149 View Article
  118. Patnaik T, Dey R, Gouda P. Antimicrobial Activity of Friedelan-3 [beta]-ol and trans-N-Caffeoyltyramine Isolated from the Root of Vitis trifolia. Asian Journal of Chemistry 2008;20(1):417-421
  119. Di Gioia D, Gaggia F, Baffoni L, Stenico VJB. Beneficial microbes in fermented functional foods. ; 2014, 291-308
  120. Iseppi R, Brighenti V, Licata M, Lambertini A, Sabia C, Messi P, et al. Chemical Characterization and Evaluation of the Antibacterial Activity of Essential Oils from Fibre-Type Cannabis sativa L. (Hemp). Molecules 2019;24(12):E2302 View Article PubMed/NCBI
  121. Chauhan A, Verma R, Kumari S, Sharma A, Shandilya P, Li X, et al. Photocatalytic dye degradation and antimicrobial activities of Pure and Ag-doped ZnO using Cannabis sativa leaf extract. Sci Rep 2020;10(1):7881 View Article PubMed/NCBI
  122. Csakvari AC, Moisa C, Radu DG, Olariu LM, Lupitu AI, Panda AO, et al. Green Synthesis, Characterization, and Antibacterial Properties of Silver Nanoparticles Obtained by Using Diverse Varieties of Cannabis sativa Leaf Extracts. Molecules 2021;26(13):4041 View Article PubMed/NCBI
  123. Singh P, Pandit S, Garnæs J, Tunjic S, Mokkapati VR, Sultan A, et al. Green synthesis of gold and silver nanoparticles from Cannabis sativa (industrial hemp) and their capacity for biofilm inhibition. Int J Nanomedicine 2018;13:3571-3591 View Article PubMed/NCBI
  124. Ying S, Guan Z, Ying S, Ofoegbu PC, Clubb P, Rico C, et al. Environmental Technology & Innovation. ; 2022, 102336 View Article
  125. Pal G, Rai P, Pandey A. Green synthesis, characterization and applications of nanoparticles. Elsevier; 2019, 1-26 View Article
  126. Chakarborty PS, Sapkota H, Prabhakar PK. Synergistic interaction of cannabis and garlic with commercial antibiotics. International Journal of Pharmacognosy Phytochemical Research 2015;7(1):193-196
  127. Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. Eur J Med Chem 2018;157:198-228 View Article PubMed/NCBI
  128. Blesson J, Saji C, Nivya R, Kumar R. Synergism of antibiotics and plant extracts in antibacterial activity against methicillin resistant Staphylococcus aureus. Journal of Bioavailability & Bioequivalence 2014;6(5)
  129. Janecki M, Graczyk M, Lewandowska AA, Pawlak Ł. Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection. Int J Mol Sci 2022;23(8):4170 View Article PubMed/NCBI
  130. Sionov RV, Steinberg D. Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles. Biomedicines 2022;10(3):631 View Article PubMed/NCBI
  131. Munjal M, ElSohly MA, Repka MA. Chemical stabilization of a Delta9-tetrahydrocannabinol prodrug in polymeric matrix systems produced by a hot-melt method: role of microenvironment pH. AAPS PharmSciTech 2006;7(3):71 View Article PubMed/NCBI
  132. Kumari A, Yadav SK, Pakade YB, Singh B, Yadav SC. Development of biodegradable nanoparticles for delivery of quercetin. Colloids Surf B Biointerfaces 2010;80(2):184-192 View Article PubMed/NCBI
  133. Fraguas-Sánchez AI, Fernández-Carballido A, Martin-Sabroso C, Torres-Suárez AI. Stability characteristics of cannabidiol for the design of pharmacological, biochemical and pharmaceutical studies. J Chromatogr B Analyt Technol Biomed Life Sci 2020;1150:122188 View Article PubMed/NCBI
Copyright © 2023 Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 License (CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • Journal of Exploratory Research in Pharmacology
  • pISSN 2993-5121
  • eISSN 2572-5505

Article Options

Metrics

Cite this Article

  • © 2024 Xia & He Publishing Inc.
  • Total visits : 1971707
  • Visits today : 2148
Back to Top

Potential Applications of Cannabis Plant Extracts and Phytochemicals as Natural Antimicrobials

Hebah M.S. AL Ubeed, Asgar Farahnaky, Emma L. Beckett, Momena Khandaker, Christopher J. Pillidge
  • Reset Zoom
  • Download TIFF