Category Archives: Staphyloccus infections

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

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“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

Therapeutic potential of cannabinoid medicines.

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Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Killing bacteria with cannabis

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“Pharmacists and chemists have found another use for the multipurpose cannabis as a source of antibacterial chemicals for multidrug resistant bacteria.”

 

“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…

CBD and CBG have the most potential for consumer use because they are nonpsychotropic…”

More: http://arstechnica.com/science/2008/08/killing-bacteria-with-cannabis/

“Antibacterial cannabinoids from Cannabis sativa: a structure-activity study.” http://www.ncbi.nlm.nih.gov/pubmed/18681481

Pot is good for you? Marijuana fights the superbugs

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Fact: Cannabis Kills MRSA, Disrupts Prion Diseases

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“Marijuana is a potent antibiotic that can kill methicillin-resistant Staphylococcus aureus and disrupt the progression of prion diseases such as Mad Cow disease and Creutzfeld-Jakob disease — just don’t expect the federal government to tell you any of this.”

A MRSA lesion

“Scientists from Italy and the United Kingdom reported in the August 2007 issue of the Journal of Natural Products that the main active ingredient in weed, THC, as well as four other pot molecules “showed potent antibacterial activity against six different strains of MRSA of clinical relevance.”

Pot also stops prions,  a type of protein that can cause neurodegenerative diseases that are invariably fatal. Once prions get into a brain they replicate rapidly and shred brain tissue “resulting in a ‘spongiform’ appearance on post-mortem histological examination of neural tissue.”

In 2007, American and French researchers reported that pot molecule cannabidiol “prevents prion accumulation and protects neurons against prion toxicity” in the Journal of Neuroscience.

Cannabidiol inhibited prion accumulation in mouse and sheep prion disease cell cultures and inhibited prion formation in the brain of infected mice given injections of CBD. “The authors conclude that CBD likely represents a new class of anti-prion drugs.””

More: http://www.eastbayexpress.com/LegalizationNation/archives/2013/07/29/fact-cannabis-kills-mrsa-disrupts-prion-diseases

“Antibacterial cannabinoids from Cannabis sativa: a structure-activity study.” http://www.ncbi.nlm.nih.gov/pubmed/18681481

“Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity” http://www.jneurosci.org/content/27/36/9537.full

Marijuana Kills MRSA and Inhibits Prions That Cause Neurodegenerative Disease; Still Recognized by Feds As a Dangerous Drug

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“Research indicates that marijuana could effectively fight off MRSA, as well as prions — the proteins that cause mad cow disease and Creutzfeld-Jakob disease.”

(Photo : Flickr, "it was 3 a.m.") Pot's constituent molecules kill bacteria and inhibit the formation of prions, a protein that can cause neurodegenerative diseases.

“New research reveals that several marijuana ingredients exhibit a potent antibiotic capacity in cases of methicillin-resistant Staphylococcus aureus (MRSA) infections as well as the ability to fight off proteins called prions that can lead to Mad Cow disease and Creutzfeld-Jakob disease (CDJ).”

More: http://www.medicaldaily.com/articles/17941/20130730/marijuana-mrsa-prions-mad-cow-disease.htm

Cannabis Compounds Reduce Multi-Drug Resistant Infections

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“Cannabis Science, Inc. 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.””

More: http://www.drugs.com/clinical_trials/cannabis-compounds-reduce-multi-resistant-infections-7080.html

Marijuana Ingredients Show Promise In Battling Superbugs

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“Substances in marijuana show promise for fighting deadly drug-resistant bacterial infections, including so-called “superbugs,” without causing the drug’s mood-altering effects, scientists in Italy and the United Kingdom are reporting.

Besides serving as infection-fighting drugs, the substances also could provide a more environmentally-friendly alternative to synthetic antibacterial substances now widely used in personal care items, including soaps and cosmetics, they say.

In the new study, Giovanni Appendino and colleagues point out that scientists have known for years that marijuana contains antibacterial substances. However, little research has been done on those ingredients, including studies on their ability to fight antibiotic resistant infections, the scientists say.

To close that gap, researchers tested five major marijuana ingredients termed cannabinoids on different strains of methicillin-resistant Staphylococcus aureus (MRSA), a “superbug” increasingly resistant to antibiotics.

All five substances showed potent germ-killing activity against these drug-resistant strains, as did some synthetic non-natural cannabinoids, they say. The scientists also showed that these substances appear to kill bacteria by different mechanisms than conventional antibiotics, making them more likely to avoid bacterial resistance, the scientists note. At least two of the substances have no known mood-altering effects, suggesting that they could be developed into marijuana-based drugs without causing a “high.””

http://www.sciencedaily.com/releases/2008/09/080908103045.htm

Biologically active cannabinoids from high-potency Cannabis sativa.

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Journal of Natural Products

“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.” http://www.ncbi.nlm.nih.gov/pubmed/19344127

“Biologically Active Cannabinoids from High-Potency Cannabis sativa”  http://pubs.acs.org/doi/abs/10.1021/np900067k

Antibacterial cannabinoids from Cannabis sativa: a structure-activity study.

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Journal of Natural Products

“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 (1b), cannabichromene (2), cannabigerol (3b), Delta (9)-tetrahydrocannabinol (4b), and cannabinol (5)) 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.” http://www.ncbi.nlm.nih.gov/pubmed/18681481

“Antibacterial Cannabinoids from Cannabis sativa: A Structure−Activity Study”  http://pubs.acs.org/doi/abs/10.1021/np8002673