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ANTI-BACTERIAL PROPERTIES & cannabis studies

Overview

Antibacterial is an agent that interferes with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have evolved over the years to mean two different things.

Science & Research

2008 - Study - Antibacterial Cannabinoids from Cannabis sativa

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2011 - Study ~ Screening for Antiviral Activities of Isolated Compounds from Essential Oils

2012 - Study ~ Effect of extraction conditions on total polyphenol contents, antioxidant and
antimicrobial activities of Cannabis sativa L

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antimicrobial effectors against E. coli, S. aureus, HSV-1, and RSV.

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Antibacterial Cannabinoids from Cannabis sativa

 
Giovanni Appendino, Simon Gibbons, Anna Giana, Alberto Pagani, Gianpaolo Grassi, Michael Stavri, Eileen Smith and M. Mukhlesur Rahman
 
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Universit del Piemonte Orientale, Via Bovio 6, 28100 Novara, Italy, Consorzio per lo Studio dei Metaboliti Secondari (CSMS), Viale S. Ignazio 13, 09123 Cagliari, Italy, Centre for Pharmacognosy and Phytotherapy,
 
The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, U.K., and CRA-CIN Centro di Ricerca per le Colture Industriali, Sede distaccata di Rovigo, Via Amendola 82, 45100 Rovigo, Italy
J. Nat. Prod., 2008, 71 (8), pp 1427–1430
DOI: 10.1021/np8002673
 
Publication Date (Web): August 6, 2008
 
* To whom correspondence should be addressed. Tel: +39 0321 373744(G.A.); +44 207 753 5913(S.G.). Fax: +39 0321 375621 (G.A.); +44 207 753 5909 (S.G.). E-mail: [email protected] (G.A.); [email protected] (S.G.)., †

Universit del Piemonte Orientale.

Consorzio per lo Studio dei Metaboliti Secondari.

University of London.

Centro Ricerca Colture Industriali.

Abstract

Abstract Image

Marijuana (Cannabis sativa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated.

All five major cannabinoids (cannabidiol, cannabichromene, cannabigerol, Δ9-tetrahydrocannabinol, and cannabinol showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance.

Activity was remarkably tolerant to the nature of the prenyl moiety, to its relative position compared to the n-pentyl moiety (abnormal cannabinoids), and to carboxylation of the resorcinyl moiety (pre-cannabinoids).

Conversely, methylation and acetylation of the phenolic hydroxyls, esterification of the carboxylic group of pre-cannabinoids, and introduction of a second prenyl moiety were all detrimental for antibacterial activity.

Taken together, these observations suggest that the prenyl moiety of cannabinoids serves mainly as a modulator of lipid affinity for the olivetol core, a per se poorly active antibacterial pharmacophore, while their high potency definitely suggests a specific, but yet elusive, mechanism of activity.

Several studies have associated the abuse of marijuana (Cannabis sativa L. Cannabinaceae) with an increase in opportunistic infections, and inhalation of marijuana has indeed been shown to interfere with the production of nitric oxide from pulmonary macrophages, impairing the respiratory defense mechanisms against pathogens and causing immunosuppression.
 
The association of C. sativa with a decreased protection against bacterial infections is paradoxical, since this plant has long been known to contain powerful antibacterial agents. Thus, preparations from C. sativa were investigated extensively in the 1950s as highly active topical antiseptic agents for the oral cavity and the skin and as antitubercular agents.
 
Unfortunately, most of these investigations were done at a time when the phytochemistry of Cannabis was still in its infancy, and the remarkable antibacterial profile of the plant could not be related to any single, structurally defined and specific constituent. Evidence that pre-cannabidiol  is a powerful plant antibiotic was, nevertheless, obtained, and more recent investigations have demonstrated, to various degrees, antibacterial activity for the nonpsychotropic cannabinoids cannabichromene  cannabigerol CBG,  and cannabidiol as well as for the psychotropic agent Δ9-tetrahydrocannabinol (THC,).
 
These observations, and the inactivity of several noncannabinoid constituents of C. sativa as antibacterial agents, suggest that cannabinoids and their precursors are the most likely antibacterial agents present in C. sativa preparations.(8) However, differences in bacterial strains and end-points make it difficult to compare the data reported in these scattered studies, and the overall value of C. sativa as an antibacterial agent is therefore not easy to assess.
 
 
There are currently considerable challenges with the treatment of infections caused by strains of clinically relevant bacteria that show multidrug-resistance (MDR), such as methicillin-resistant Staphylococcus aureus (MRSA) and the recently emerged and extremely drug-resistant Mycobacterium tuberculosis XDR-TB.
 
New antibacterials are therefore urgently needed, but only one new class of antibacterial has been introduced in the last 30 years.
 
Despite the excellent antibacterial activity of many plant secondary metabolites and the ability of some of them to modify the resistance associated with MDR strains and efflux pumps, plants are still a substantially untapped source of antimicrobial agents.
 
These considerations, as well as the observation that cross-resistance to microbial and plant antibacterial agents is rare, make C. sativa a potential source of compounds to address antibiotic resistance, one of the most urgent issues in antimicrobial therapy.
 
To obtain structure−activity data and define a possible microbiocidal cannabinoid pharmacophore, we investigated the antibacterial profile of the five major cannabinoids, of their alkylation and acylation products, and of a selection of their carboxylic precursors (pre-cannabinoids) and synthetic positional isomers (abnormal cannabinoids).
 

Results and Discussion


The antibacterial cannabinoid chemotype is poorly defined, as is the molecular mechanism of its activity.
 
Since many simple phenols show antimicrobial properties, it does not seem unreasonable to assume that the resorcinol moiety of cannabinoids serves as the antibacterial pharmacophore, with the alkyl, terpenoid, and carboxylic appendices modulating its activity.
 
To gain insight into the microbiocidal cannabinoid pharmacophore, we have investigated how the nature of the terpenoid moiety, its relative position compared to the n-pentyl group, and the effect of carboxylation of the resorcinyl moiety are translated biologically, assaying the major cannabinoids and a selection of their precursors and regioisomeric analogues against drug-resistant bacteria of clinical relevance.
 
Within these, we have selected a panel of clinically relevant Staphylococcus aureus strains that includes the (in)famous EMRSA-15, one of the main epidemic methicillin-resistant strains, and SA-1199B, a multidrug-resistant strain that overexpresses the NorA efflux mechanism, the best characterized antibiotic efflux pump in this species. SA-1199B also possesses a gyrase mutation that, in addition to NorA, confers a high level of resistance to certain fluoroquinolones.
 
A macrolide-resistant strain (RN4220),(15) a tetracycline-resistant line overexpressing the TetK efflux pump (XU212), and a standard laboratory strain (ATCC25923) completed the bacterial panel.
 
Δ9-Tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), cannabichromene (CBC), and cannabinol (CBN) are the five most common cannabinoids.
 
They could be obtained in high purity (>98%) by isolation from strains of C. sativa producing a single major cannabinoid (THC, CBD, CBG), by total synthesis (CBC), or by semisynthesis (CBN). Their antimicrobial properties are listed in Table 1.
 
All compounds showed potent antibacterial activity, with MIC values in the 0.5−2 μg/mL range. Activity was exceptional against some of these strains, in particular the multidrug-resistant (MDR) SA-1199B, which has a high level of resistance to certain fluoroquinolones. Also noteworthy is the potent activity demonstrated against EMRSA-15 and EMRSA-16, the major epidemic methicillin-resistant S. aureus strains occurring in U.K. hospitals.
 
These activities compare highly favorably with the standard antibiotics for these strains. The potent activity against strains possessing the NorA and TetK efflux transporters suggests that cannabinoids are not substrates for the most common resistance mechanisms to current antibacterial agents, making them attractive antibacterial leads.
 
Table 1. MIC (μg/mL) Values of Cannabinoids and Their Analogues toward Various Drug-Resistant Strains of Staphylococcus aureus
 
compoundSA-1199BRN-4220XU212ATCC25923EMRSA-15EMRSA-16
1a222222
1b1110.511
2221222
3a424424
3b111121
3f64c64ccc
4a848484
4b211120.5
511111c
6111111
7210.512c
8323216161632
106464641286464
norfloxacin321410.5128
erythromycin0.2564>1280.25>128>128
tetracycline0.250.251280.250.1250.125
oxacillin0.250.251280.12532>128
a

Compounds 1cg, 3ce, 3g, and 9 exhibited MIC values of >128 μg/mL for all organisms in which they were evaluated.

b

Compound 11 exhibited MIC values of >256 μg/mL for all organisms in which they were evaluated.

c

Not tested.

Given their nonpsychotropic profiles, CBD (1b) and CBG (3b) seemed especially promising, and were selected for further structure−activity studies. Thus, acetylation and methylation of their phenolic hydroxyls (compounds 1ce and 3ce, respectively) were both detrimental for activity (MIC >100 μg/mL), in accordance with the essential role of the phenolic hydroxyls in the antibacterial properties. However, in light of the potent activity of the monophenols CBC, THC (4b), and CBN, it was surprising that monomethylation of the diphenols CBD (1b) and CBG (3b) was so poorly tolerated in terms of antibacterial activity.
 
Cannabinoids are the products of thermal degradation of their corresponding carboxylic acids (pre-cannabinoids).
 
Investigation of the antibacterial profile of the carboxylated versions of CBD, CBG, and THC (compounds 1a, 3a, and 4a, respectively) showed a substantial maintenance of activity. On the other hand, methylation of the carboxylic group (compounds 1f and 3f, respectively) caused a marked decrease of potency, as did esterification with phenethyl alcohol (compounds 1g and 3g, respectively).
 
This operation is associated with a potentiation of the antibacterial properties of phenolic acids, as exemplified by phenethyl caffeate (CAPE), the major antibacterial from propolis, compared to caffeic acid.(20) Remarkably, the synthetic abnormal cannabinoids abn-CBD and abn-CBG (7)(22) showed antibacterial activity comparable to, although slightly less potent than, their corresponding natural products, while olivetol  showed modest activity against all six strains, with MICs of 64−128 μg/mL, and resorcinol did not exhibit any activity even at 256 μg/mL.
 
Thus, the pentyl chain and the monoterpene moiety greatly enhance the activity of resorcinol.
 
 
 
Taken together, these observations show that the cannabinoid antibacterial chemotype is remarkably tolerant to structural modification of the terpenoid moiety and its positional relationship with the n-pentyl chain, suggesting that these residues serve mainly as modulators of lipid affinity, and therefore cellular bioavailability. This view was substantiated by the marked decrease of activity observed when the antibacterial activity of CBG (3b) was compared to that of its polar analogue carmagerol.
 
The results against the resistant strains confirm this suggestion, and it is likely that the increased hydrophilicity caused by the addition of two hydroxyls greatly reduces the cellular bioavailability by substantially reducing membrane permeability. Conversely, the addition of a further prenyl moiety, as in the bis-prenylated cannabinoid 9, while increasing membrane solubility, may result in poorer aqueous solubility and therefore a lower intracellular concentration, similarly leading to a substantial loss of activity.
 
A single unfunctionalized terpenyl moiety seems therefore ideal in terms of lipophilicity balance for the antibacterial activity of olivetol derivatives. The great potency of cannabinoids suggests a specific interaction with a bacterial target, whose identity is, however, still elusive.
Given the availability of C. sativa strains producing high concentrations of nonpsychotropic cannabinoids, this plant represents an interesting source of antibacterial agents to address the problem of multidrug resistance in MRSA and other pathogenic bacteria. This issue has enormous clinical implications, since MRSA is spreading throughout the world and, in the United States, currently accounts for more deaths each year than AIDS.
 
Although the use of cannabinoids as systemic antibacterial agents awaits rigorous clinical trials and an assessment of the extent of their inactivation by serum,(25) their topical application to reduce skin colonization by MRSA seems promising, since MRSA resistant to mupirocin, the standard antibiotic for this indication, are being detected at a threatening rate.
 
Furthermore, since the cannabinoid anti-infective chemotype seems remarkably tolerant to modifications in the prenyl moiety, semipurified mixtures of cannabinoids could also be used as cheap and biodegradable antibacterial agents for cosmetics and toiletries, providing an alternative to the substantially much less potent synthetic preservatives, many of which are currently questioned for their suboptimal safety and environmental profile.

Experimental Section


General Experimental Procedures
 
IR spectra were obtained on a Shimadzu DR 8001 spectrophotometer. 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were obtained at room temperature with a JEOL Eclipse spectrometer.
 
The spectra were recorded in CDCl3, and the solvent signals (7.26 and 77.0 ppm, respectively) were used as reference.
 
The chemical shifts (δ) are given in ppm, and the coupling constants (J) in Hz. Silica gel 60 (70−230 mesh) and Lichroprep RP-18 (25−40 mesh) were used for gravity column chromatography.
 
Reactions were monitored by TLC on Merck 60 F254 (0.25 mm) plates and were visualized by UV inspection and/or staining with 5% H2SO4 in ethanol and heating.
 
Organic phases were dried with Na2SO4 before evaporation. All known cannabinoids were identified according to their physical and spectroscopic data.(28) Semisynthetic cannabinoids 1cf, and 3cf were prepared and identified according to their corresponding literature references.
 
Synthetic abnormal and polyprenyl cannabinoids were synthesized and characterized according to the literature.
 
Plant Material
The three strains of Cannabis sativa used for the isolation of THC, CBD, and CBG came from greenhouse cultivation at CRA-CIN, Rovigo (Italy), where voucher specimens are kept for each of them, and were collected in September 2006. The isolation and manipulation of all cannabinoids were done in accordance with their legal status (License SP/101 of the Ministero della Salute, Rome, Italy).
 
Isolation of Cannabinoids (1b, 3b, 4b)
 
The powdered plant material (100 g) was distributed in a thin layer on cardboard and heated at 120 °C for 2 h in a ventilated oven to affect decarboxylation, then extracted with acetone (ratio solvent to plant material 3:1, ×3). The residue (6.5 g for the CBD chemotype, 4.1 g for the CBG chemotype, 7.4 g for the THC chemotype) was purified by gravity column chromatography on silica gel (ratio stationary phase to extract 6:1) using a petroleum ether−ether gradient. Fractions eluted with petroleum ether−ether (9:1) afforded 1b (628 mg, 0.63%, from the CBD chemotype) and 3b (561 mg, 0.56%, from the CBG chemotype), precipitated from hot hexane to obtain white powders. Crude THC (3.2 g, 3.2%, from the THC chemotype) was obtained as a greenish oil, part of which (400 mg) was further purified by RP-18 flash chromatography with methanol−water (1:1) as eluant, affording 4b as a colorless oil (315 mg).
 
Isolation of Pre-cannabinoids (1a, 3a, 4a)
 
The powdered plant material (100 g) was extracted with acetone (ratio solvent to plant material 5:1, ×3). After removal of the solvent, the residue (7.7 g for the CBD chemotype, 4.9 g for the CBG chemotype, 7.9 g for the THC chemotype) was fractionated by vacuum chromatography on RP-18 silica gel (ratio stationary phase to extract 5:1) using methanol−water (75:25) as eluant.
 
Fractions of 100 mL were taken, and those containing pre-cannabinoids were pooled, concentrated to ca. half-volume at 30 °C, saturated with NaCl, and extracted with EtOAc. After removal of the solvent, the residue was further purified by gravity column chromatography on silica gel (ratio stationary phase to crude compound 5:1) using a petroleum ether−EtOAc gradient (from 8:2 to 5:5) to afford 1.59 g (1.6%) of 1a from the CBD chemotype, 0.93 g (0.93%) of 3a from the CBG chemotype, and 2.1 g (2.1%) of 4a from the THC chemotype. All pre-cannabinoids were obtained as white foams that resisted crystallization.
 
Synthesis of CBC and CBN
CBG was synthesized from olivetol,(6) and CBN was prepared from THC by aromatization with sulfur.
Mitsunobu Esterification of Pre-cannabinoids (synthesis of 3g as an example)
 
To a cooled (ice bath) solution of 3a (360 mg, 1.1 mmol) in dry CH2Cl2 (4 mL) were added sequentially phenethyl alcohol (92 μL, 0.76 mmol, 0.75 molar equiv), triphenylphosphine (TPP) (220 mg, 0.84 mmol, 0.80 molar equiv), and diisopropyldiazodicarboxylate (DIAD) (228 μL, 1.1 mmol, 1 molar equiv).
 
At the end of the addition, the cooling bath was removed, and the reaction was stirred at room temperature.
 
After 16 h, the reaction was worked up by evaporation, and the residue was dissolved in toluene and cooled at 4 °C overnight to remove most of the TPPO-dihydroDIAD adduct. The filtrate was evaporated and purified by gravity column chromatography on silica gel (10 g, petroleum ether as eluant) to afford 126 mg (32%) of 3g. Under the same reaction conditions, the yield of 1g from 1a was 26%.
 
Pre-cannabigerol Phenethyl Ester (3g):
 
colorless foam; IR νKBrmax 3746, 3513, 3313, 1715, 1589, 1421, 1274, 1164, 980, 804, 690 cm−1; 1H NMR (300 MHz, CDCl3) δ 12.08 (1H, s), 7.25 (5H, m), 6.02 (1H, s), 5.98 (1H, s), 5,25 (1H, br t, J = 7.0 Hz), 5.01 (1H, br t, J = 6.5 Hz), 4.56 (2H, t, J = 6.6 Hz), 3.40 (2H, d, J = 7.3 Hz), 3.1 (2H, t, J = 6.6 Hz), 2.7 (2H, t, J = 6.6 Hz), 2.05 (4H, m), 1.79 (3H, s), 1.65 (3H, s), 1.57 (3H, s), 1.24 (6H, m), 0.88 (3H, t, J = 7.1 Hz); 13C NMR (75 MHz, CDCl3) δ 172.1 (s), 162.7 (s), 159.5 (s), 148.8 (s), 139.1 (s), 137.4 (d), 132.1 (s), 128.8 (d), 126.8 (d), 125.9 (d), 121.5 (d), 111.5 (s), 110.8 (s), 65.8 (t), 39.8 (t), 36.6 (t), 35.0 (t), 32.0 (t), 31.5 (t), 26.5 (t), 25.8 (q), 22.2 (t), 17.8 (q), 16.3 (q), 14.2 (q); CIMS m/z [M + H] 465 [C30H40O4 + H].
 
Pre-cannabidiol Phenethyl Ester (1g):
colorless oil; IR (KBr) νmax 3587, 3517, 3423, 3027, 1642, 1499, 1425, 1274, 1172, 1143, 980, 894 cm−1; 1HNMR (300 MHz, CDCl3) δ 12.13 (1H, s), 6.23 (5H, m), 6.48 (1H, s), 6.19 (1H, s), 5,55 (1H, s), 4.52 (3H, m), 4.4 (1H, s), 4.08 (1H, br s), 3.08 (2H, t, J = 7.0 Hz), 2.7 (2H, m), 2.11 (1H, m), 1.78 (3H, s), 1.71 (3H, s), 1.5 (4H, m), 1.28 (6H, m), 0.88 (3H, t, J = 6.9 Hz); 13C NMR (75 MHz, CDCl3) δ 172.2 (s), 171.5 (s), 163.5 (s), 160.0 (s), 148.8 (s), 147.0 (s), 145.9 (s), 140.2 (s), 137.4 (s), 128.7 (d), 126.7 (d), 124.0 (d), 114.4 (t), 112.3 (d), 105.8 (s), 65.6 (t), 46.6 (d), 39.1 (t), 37.0 (d), 31.9 (d), 31.5 (t), 27.8 (t), 25.3 (q), 22.6 (t), 21.9 (t), 18.5 (q), 14.1 (q); CIMS m/z [M + H] 463 [C30H38O4 + H].
 
Bacterial Strains and Chemicals
A standard S. aureus strain (ATCC 25923) and a clinical isolate (XU212), which possesses the TetK efflux pump and is also a MRSA strain, were obtained from E. Udo.
 
Strain RN4220, which has the MsrA macrolide efflux pump, was provided by J. Cove.(30) EMRSA-15(13) and EMRSA-16(19) were obtained from Paul Stapleton. Strain SA-1199B, which overexpresses the NorA MDR efflux pump, was the gift of Professor Glenn Kaatz. Tetracycline, norfloxacin, erythromycin, and oxacillin were obtained from Sigma Chemical Co. Oxacillin was used in place of methicillin as recommended by the NCCLS. Mueller-Hinton broth (MHB; Oxoid) was adjusted to contain 20 mg/L Ca2+ and 10 mg/L Mg2+.
 
Antibacterial Assays
Overnight cultures of each strain were made up in 0.9% saline to an inoculum density of 5 × 105 cfu by comparison with a MacFarland standard. Tetracycline and oxacillin were dissolved directly in MHB, whereas norfloxacin and erythromycin were dissolved in DMSO and then diluted in MHB to give a starting concentration of 512 μg/mL. Using Nunc 96-well microtiter plates, 125 μL of MHB was dispensed into wells 1−11. Then, 125 μL of the test compound or the appropriate antibiotic was dispensed into well 1 and serially diluted across the plate, leaving well 11 empty for the growth control.
 
The final volume was dispensed into well 12, which being free of MHB or inoculum served as the sterile control. Finally, the bacterial inoculum (125 μL) was added to wells 1−11, and the plate was incubated at 37 °C for 18 h. A DMSO control (3.125%) was also included. All MICs were determined in duplicate. The MIC was determined as the lowest concentration at which no growth was observed. A methanolic solution (5 mg/mL) of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliium bromide (MTT; Lancaster) was used to detect bacterial growth by a color change from yellow to blue.

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Killing bacteria with cannabis

Pharmacists and chemists have found another use for the multipurpose cannabis as a source of antibacterial chemicals for multidrug resistant bacteria. Ironically, inhaling cannabis is known to damage the lung's ability to fend off invading pathogens, but the ingredients in cannabis, particularly the cannabinoids, have antiseptic properties. Although scattered research has been conducted since the 1950s, no comprehensive study existed that relates the structure of cannabinoids with antibacterial activity. Giovanni Appendino, Simon Gibbons, and coworkers attempted to remedy that problem by examining the activity of five common cannabinoids and their synthetic derivatives.


Five of the most common cannabinoids. 

All five cannabinoids (THC, CBD, CBG, CBC, and CBN) were potent against bacteria. Notably, they performed well against bacteria that were known to be multidrug resistant, like the strains of MRSA that plagued U.K. hospitals. CBD and CBG have the most potential for consumer use because they are nonpsychotropic.

Besides identifying antibacterial capability, the researchers wanted to figure out why these cannabinoids are so good at killing bacteria. They obviously are very effective at specifically targeting some vital process in the bacteria. Unfortunately, even after extensive work at modifying the cannabinoids and comparing their activities, that targeting mechanism remains a mystery. The scientists were able to figure out that the position of the n-pentyl chain (orange) relative to the terpenoid moiety (blue) serves to control lipid affinity.

These cannabinoids are promising enough to warrant rigorous clinical trials. They are applicable as topical antiseptics, biodegradable antibacterial compounds for cosmetics, and systematic antibacterial agents.

  1.  

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Chemicals in Marijuana May Fight MRSA

Study Shows Cannabinoids May Be Useful Against Drug-Resistant Staph Infections
By Caroline Wilbert
WebMD Health News
Reviewed by Louise Chang, MD
Pot Fights MRSA

Sept. 4, 2008 -- Chemicals in marijuana may be useful in fighting MRSA, a kind of staph bacterium that is resistant to certain antibiotics.

Researchers in Italy and the U.K. tested five major marijuana chemicals called cannabinoids on different strains of MRSA (methicillin-resistant Staphylococcus aureus). All five showed germ-killing activity against the MRSA strains in lab tests. Some synthetic cannabinoids also showed germ-killing capability. The scientists note the cannabinoids kill bacteria in a different way than traditional antibiotics, meaning they might be able to bypass bacterial resistance.

At least two of the cannabinoids don't have mood-altering effects, so there could be a way to use these substances without creating the high of marijuana.

MRSA, like other staph infections, can be spread through casual physical contact or through contaminated objects. It is commonly spread from the hands of someone who has it. This could be in a health care setting, though there have also been high-profile cases of community-acquired MRSA.

 

It is becoming more common for healthy people to get MRSA, which is often spread between people who have close contact with one another, such as members of a sports team. Symptoms often include skin infections, such as boils. MRSA can become serious, particularly for people who are weak or ill.

 

In the study, published in the Journal of Natural Products, researchers call for further study of the antibacterial uses of marijuana. There are "currently considerable challenges with the treatment of infections caused by strains of clinically relevant bacteria that show multi-drug resistance," the researchers write. New antibacterials are urgently needed, but only one new class of antibacterial has been introduced in the last 30 years. "Plants are still a substantially untapped source of antimicrobial agents," the researchers conclude.

 

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Cannabis Compounds Reduce Multi-Drug Resistant Infections

Cannabis Science, Inc. (OTCBB: GFON). Dr. Robert Melamede, PhD., Director and Chief Science Officer, reported to the Board on the current state of research into the use of natural plant cannabinoids to reduce the spread of drug-resistant bacteria, including methicillin-resistant Staphyloccus aureus (MRSA), and the prospects for development of topical whole-cannabis treatments.

According to studies published in the Journal of the American Medical Association and by the Center for Disease Control in 2007, MRSA is responsible for more than 18,500 hospital-stay related deaths each year, and increased direct healthcare costs of as much as $9.7 billion.

Dr. Melamede stated, "Research into use of whole cannabis extracts and multi-cannabinoid compounds has provided the scientific rationale for medical marijuana's efficacy in treating some of the most troubling diseases mankind now faces, including infectious diseases such as the flu and HIV, autoimmune diseases such as ALS (Lou Gehrig's Disease), multiple sclerosis, arthritis, and diabetes, neurological conditions such as Alzheimer's, stroke and brain injury, as well as numerous forms of cancer. One common element of these diseases is that patients often suffer extended hospital stays, risking development of various Staphyloccus infections including MRSA. A topical, whole-cannabis treatment for these infections is a functional complement to our cannabis extract-based lozenge."

Investigators at Italy's Universita del Piemonte Orientale and Britain's University of London, School of Pharmacy reported in the Journal of Natural Products that five cannabinoids - THC, CBD, CBG, CBC, and CBN - "showed potent antibacterial activity" and "exceptional" antibacterial activity against two epidemic MRSA occurring in UK hospitals. The authors concluded: "Although the use of cannabinoids as systemic antibacterial agents awaits rigorous clinical trials, … their topical application to reduce skin colonization by MRSA seems promising. … Cannabis sativa … represents an interesting source of antibacterial agents to address the problem of multidrug resistance in MRSA and other pathogenic bacteria."

About Cannabis Science, Inc.

Cannabis Science, Inc. is at the forefront of medical marijuana research and development. The Company works with world authorities on phytocannabinoid science targeting critical illnesses, and adheres to scientific methodologies to develop, produce, and commercialize phytocannabinoid-based pharmaceutical products. In sum, we are dedicated to the creation of cannabis-based medicines, both with and without psychoactive properties, to treat disease and the symptoms of disease, as well as for general health maintenance.

Forward-Looking Statements

This Press Release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Act of 1934. A statement containing works such as "anticipate," "seek," intend," "believe," "plan," "estimate," "expect," "project," "plan," or similar phrases may be deemed "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Some or all of the events or results anticipated by these forward-looking statements may not occur. Factors that could cause or contribute to such differences include the future U.S. and global economies, the impact of competition, and the Company's reliance on existing regulations regarding the use and development of cannabis-based drugs. Cannabis Science, Inc. does not undertake any duty nor does it intend to update the results of these forward-looking statements.

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Cannabis Science, Inc.

 

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Biologically Active Cannabinoids from High-Potency Cannabis sativa

Radwan MM, Elsohly MA, Slade D, Ahmed SA, Khan IA, Ross SA 
Biologically Active Cannabinoids from High-Potency Cannabis sativa. [JOURNAL ARTICLE]
J Nat Prod 2009 Apr 3.


Nine new cannabinoids (1-9) were isolated from a high-potency variety of Cannabis sativa. Their structures were identified as (+/-)-4-acetoxycannabichromene (1), (+/-)-3''-hydroxy-Delta((4'',5''))-cannabichromene (2), (-)-7-hydroxycannabichromane (3), (-)-7R-cannabicoumarononic acid A (4), 5-acetyl-4-hydroxycannabigerol (5), 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol (6), 8-hydroxycannabinol (7), 8-hydroxycannabinolic acid A (8), and 2-geranyl-5-hydroxy-3-n-pentyl-1,4-benzoquinone (9) through 1D and 2D NMR spectroscopy, GC-MS, and HRESIMS. The known sterol beta-sitosterol-3-O-beta-d-glucopyranosyl-6'-acetate was isolated for the first time from cannabis. Compounds 6 and 7 displayed significant antibacterial and antifungal activities, respectively, while 5 displayed strong antileishmanial activity.

More from this journal Journal of natural products

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Antibacterial preparation from hemp (Cannabis sativa) (1958)

Ferenczy, L.; Gracza, L.; Jakobey, I.

Naturwissenschaften (1958), 45, 188 CODEN: NATWAY; ISSN: 0028-1042. English.

Exts. of resinous organs of the plant gives an active antibacterial compound (I). I has little activity against gram-neg. bacteria, yeasts, or molds, but is active against Streptomyces griseus and gram-pos. bacteria, especially in slightly acidic media. I shows an intensive hashish reaction which appears proportionate to its antibacterial activity.


Copyright © 2011 American Chemical Society
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Hemp (Cannabis sativa)-an antibiotic drug. II. Methods and results of bacteriological investigations and preliminary clinical experiences (1958)

Krejci, Z.

Pharmazie (1958), 13, 155-66 CODEN: PHARAT; ISSN: 0031-7144. Unavailable.

cf. C.A. 52, 4929d. In the course of a systematic investigation of Central European plants for antibacterial components, substances in hemp were found to have high activity.

Ascending paper chromatography was used to sep. the components of the extract, and strips of the chromatogram were laid on plate cultures of Staphylococcus aureus (in prelim. expts.) to demonstrate activity through inhibitory effects. Under conditions of low conch., chlorophyll so tested with the chromatogram was without antibiotic action (perhaps because of low concentration). The active principle was an amorphous resinous substance, soluble in EtOH, pert. ether, and C6H6, of acid nature, with phenolic and COOH groups, and could be acetylated. The Ac derivs., crystalline substances, showed slight reductions in antibacterial activity over the amorphous material, and were not studied as antibiotics.

Purified exts. of Cannabis representing antibiotic-active materials were prepared as follows (cf. Krejci and Santav.acte.y, C.A. 50, 12080d): the comminuted drug was extracted with petr. ether, light benzene, or C6H6; the extract was shaken with N NaOH to form a water-soluble salt; HCl added to precipitate the resin, and this extracted with Et2O, the latter evaporated to leave the antibacterial substance.

This could be crystallized by acetylation. This extract was antibacterial to Mycobacterium tuberculosis, even when diluted to 1:150,000. Gram-neg. organisms of the coli-typhus group, Pseudomonas aerogenes, and Proteus vulgaris were not affected. Blood, blood plasma, and Blood serum partially inactivated this substance, reducing the antibiotic effect. Thus, a diln. of 1:100,000, which inhibited S. aureus, was inactivated by adding 10% blood or blood plasma; there was lesser inactivation at 1:10,000 dilns.

Antibiotic activity was compared at different pH values (cf. Stoll, et al., Schweiz. Z. allgem. Pathol. Bakteriol. 14, 591(1952)) with penicillin and streptomycin. Na salts of the isolated amorphous substance in aqueous alkaline solution showed increasing activity with increase of pH from 5 to 7.5, whereas crystallized Ac derivs. (acids) showed increasing activity when the pH was decreased from 8 to 5.

The rapidity of antibacterial action varied with differing dilns., using S. aureus cultures for testing. Thus, 1: 100 dilns. produced immediate sterilization, 1:10,000 were sterile after 3 hrs., and 1:100,000 dilns. were sterile after 8 hrs. Clinical usage in stomatology, otorhinolaryngology, dermatology, and treatment of tuberculosis is reviewed. 44 references.


Copyright © 2011 American Chemical Society
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Characterization and antimicrobial activity of essential oils of industrial hemp varieties (Cannabis sativa L.).

Nissen L, Zatta A, Stefanini I, Grandi S, Sgorbati B, Biavati B, Monti A.

Microbiology Area, DiSTA (Department of Agroenvironmental Sciences and Technologies), Italy. [email protected]

Abstract

The present study focused on inhibitory activity of freshly extracted essential oils from three legal (THC<0.2% w/v) hemp varieties (Carmagnola, Fibranova and Futura) on microbial growth. The effect of different sowing times on oil composition and biological activity was also evaluated. Essential oils were distilled and then characterized through the gas chromatography and gas chromatography-mass spectrometry.

Thereafter, the oils were compared to standard reagents on a broad range inhibition of microbial growth via minimum inhibitory concentration (MIC) assay.

Microbial strains were divided into three groups: i) Gram (+) bacteria, which regard to food-borne pathogens or gastrointestinal bacteria, ii) Gram (-) bacteria and iii) yeasts, both being involved in plant interactions.

The results showed that essential oils of industrial hemp can significantly inhibit the microbial growth, to an extent depending on variety and sowing time. It can be concluded that essential oils of industrial hemp, especially those of Futura, may have interesting applications to control spoilage and food-borne pathogens and phytopathogens microorganisms.

Copyright 2009 Elsevier B.V. All rights reserved.
 
 

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