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

Antibacterial activity of delta9-tetrahydrocannabinol and cannabidiol.

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Image result for Antonie Van Leeuwenhoek. journal

“The minimum inhibiting concentrations (MIC) of delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for staphylococci and streptococci in broth are in the range of 1-5 mug/ml.

In the same range, both compounds are also bactericidal.

In media containing 4% serum or 5% blood the antibacterial activity is strongly reduced (MIC 50 mug/ml). Gram-negative bacteria are resistant to THC and CBD.”

http://www.ncbi.nlm.nih.gov/pubmed/1085130

Cannabinoid Receptor 2 Protects against Acute Experimental Sepsis in Mice.

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“The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock. Despite significant advances in the understanding of the molecular and cellular mechanisms of septic shock, it is still one of the most frequent and serious problems confronting clinicians in the treatments. And the effects of cannabinoid receptor 2 (CB2R) on the sepsis still remain undefined.

 The present study was aimed to explore the role and mechanism of CB2R in acute sepsis model of mice. Here, we found that mice were more vulnerable for lipopolysaccharide- (LPS-) induced death and inflammation after CB2R deletion (CB2R(-/-)). CB2R agonist, GW405833, could significantly extend the survival rate and decrease serum proinflammatory cytokines in LPS-treated mice. GW405833 dose-dependently inhibits proinflammatory cytokines release in splenocytes and peritoneal macrophages as well as splenocytes proliferation, and these effects were partly abolished in CB2R(-/-) splenocytes but completely abolished in CB2R(-/-) peritoneal macrophages. Further studies showed that GW405833 inhibits LPS-induced phosphorylation of ERK1/2 and STAT3 and blocks I κ B α degradation and NF- κ B p65 nuclear translocation in macrophages.

 All data together showed that CB2R provides a protection and is a potential therapeutic target for the sepsis.”

http://www.ncbi.nlm.nih.gov/pubmed/23781122

Expression, surface immobilization, and characterization of functional recombinant cannabinoid receptor CB2.

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Human peripheral cannabinoid receptor CB2, a G protein-coupled receptor (GPCR) involved in regulation of immune response has become an important target for pharmaceutical drug development.

 Structural and functional studies on CB2 may benefit from immobilization of the purified and functional receptor onto a suitable surface at a controlled density and, preferably in a uniform orientation. The goal of this project was to develop a generic strategy for preparation of functional recombinant CB2 and immobilization at solid interfaces. Expression of CB2 as a fusion with Rho-tag (peptide composed of the last nine amino acids of rhodopsin) in E. coli was evaluated in terms of protein levels, accessibility of the tag, and activity of the receptor. The structural integrity of CB2 was tested by ligand binding to the receptor solubilized in detergent micelles, captured on tag-specific monoclonal 1D4 antibody-coated resin. Highly pure and functional CB2 was obtained by sequential chromatography on a 1D4- and Ni-NTA- resin and its affinity to the 1D4 antibody characterized by surface plasmon resonance (SPR). Either the purified receptor or fusion CB2 from the crude cell extract was captured onto a 1D4 -coated CM4 chip (Biacore) in a quantitative fashion at uniform orientation as demonstrated by the SPR signal. Furthermore, the accessibility of the extracellular surface of immobilized CB2 and the affinity of interaction with a novel monoclonal antibody NAA-1 was studied by SPR.

 In summary, we present an integral strategy for purification, surface immobilization, ligand- and antibody binding studies of functional cannabinoid receptor CB2.”

http://www.ncbi.nlm.nih.gov/pubmed/23777860

Drug War Blocking Potential Treatments for Cancer, Alzheimer’s, Journal Claims – TIME

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“Potential treatments for Alzheimer’s disease, cancer and many other illnesses are being blocked by anti-drug laws, according to a new editorial review published in Nature Reviews Neuroscience.”

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Smoking Pot Eases Tremors in Parkinson’s

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“Smoking cannabis appeared to reduce tremor and pain and improve sleep among Parkinson’s disease patients, researchers from Israel reported here.

Overall, patients’ scores on the standard Unified Parkinson’s Disease Rating Scale (UPDRS) averaged 33 before they smoked cannabis in the laboratory and averaged 24 after 30 minutes (P<0.01), Ruth Djaldetti, MD, of Tel Aviv University Israel, reported at her poster presentation at the International Congress on Parkinson’s Disease and Movement Disorders.

“We not only saw improvement in tremor in these patients, but also in rigidity and in bradykinesia,” Djaldetti told MedPage Today. “I would recommend use of marijuana to my patients as a last resort if nothing else was working for them or if they had pain.””

http://www.medpagetoday.com/meetingcoverage/mds/39933

Large Study Finds No Link between Marijuana and Lung Cancer – Scientific American

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“…Scientists were therefore surprised to learn that a study of more than 2,000 people found no increase in the risk of developing lung cancer for marijuana smokers.

“We expected that we would find that a history of heavy marijuana use–more than 500 to 1,000 uses–would increase the risk of cancer from several years to decades after exposure to marijuana,” explains physician Donald Tashkin of the University of California, Los Angeles, and lead researcher on the project. But looking at residents of Los Angeles County, the scientists found that even those who smoked more than 20,000 joints in their life did not have an increased risk of lung cancer.

The study does not reveal how marijuana avoids causing cancer. Tashkin speculates that perhaps the THC chemical in marijuana smoke prompts aging cells to die before becoming cancerous. Tashkin and his colleagues presented the findings yesterday at a meeting of the American Thoracic Society in San Diego.”

More: http://www.scientificamerican.com/article.cfm?id=large-study-finds-no-link