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Substances found in cannabis could be used to fight potentially lethal superbugs, such as antibiotic-resistant bacteria, without the mood-altering effects, according to researchers in Italy and the UK. Cannabis sativa (L. Cannabinaceae) extracts may also provide an alternative to synthetic antibacterial substances used in personal hygiene products, including hand wash and cosmetics. Giovanni Appendino, Anna Giana, and Alberto Pagani of the University of East Piemonte in Novara, and the Consorzio per lo Studio dei Metaboliti Secondari (CSMS), Cagliari, Gianpaolo Grassi, of the Centro di Ricerca per le Colture Industriali, in Rovigo, Italy and Simon Gibbons, Michael Stavri, Eileen Smith, and Mukhlesur Rahman of the University of London, UK, point out in the Journal of Natural Products how the plant has long been known to contain antibacterial cannabinoids. This is a rather paradoxical property as several research teams have demonstrated an association between cannabis use and an increase in opportunistic infections. Indeed, the researchers explain, inhalation of cannabis is thought to interfere with the production of nitric oxide by white blood cells in the lungs and so impairs the respiratory defence mechanisms against pathogens. "The antibacterial cannabinoid chemotype is poorly defined, as is the molecular mechanism of its activity," the researchers explain. They point out that numerous simple phenolic compounds also show antimicrobial activity and so it was assumed that the so-called resorcinol part of the cannabinoid skeleton somehow affects bacteria in a lethal way; the attendant alkyl, terpenoid, and carboxylic groups controlling the specific activity. They also point out that preparations from cannabis were investigated keenly in the 1950s. In particular, it was soon recognised that such preparations might act as topical antiseptics in the mouth and on the skin to prevent tuberculosis. However, at that time, the detailed chemistry of cannabis was immature and scientists could not then correlate the plant's remarkable antibacterial profile with any specific compound or compounds found in the leaves. Appendino, Gibbons, and colleagues have now used various techniques, including NMR spectroscopy to analyse and study all five major cannabinoids (cannabidiol, cannabichromene, cannabigerol, tetrahydrocannabinol, and cannabinol. They found that all the compounds showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains. Their investigations of the structure-activity relationship between efficacy against these clinically relevant strains of bacteria revealed that the so-called "prenyl" group of the cannabinoids somehow acts to modulate how well these compounds interact with fatty, lipid, molecules. This could provide new insights into how to design even more effective analogues as viable pharmaceutical products against superbugs. "There are currently considerable challenges with the treatment of infections caused by strains of clinically relevant bacteria that show multidrug-resistance (MDR), such MRSA and the recently emerged and extremely drug-resistant Mycobacterium tuberculosis XDR-TB," the researchers explain. Novel antibiotics to which bacteria are not resistant and cannot easily evolve resistance are urgently needed given the current clinical plight. However, only one new class of antibiotics has been marketed in the last three decades. "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 remain a substantially untapped source of antimicrobial agents," the researchers add. There is a problem with administering cannabinoids to hospital patients, of course. With just two exceptions, these compounds not only have potent antibacterial properties, but also have potent mood-altering effects. It is the two psychotropically inactive cannabinoids on which research into developing antibacterial drugs from them must focus. These could be developed into marijuana-based drugs without causing a "high." Despite the demonstrated high potency of the compounds against MRSA, the researchers concede that while there is a specific mode of action, for now, it remains elusive. What is important, the researchers explain, is that these substances appear to kill bacteria through entirely different mechanisms to conventional antibiotics. This could imply that they will preclude the emergence of bacterial resistance, at least in the short term. Related links: The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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 THC and its congeners have antibacterial activity against MRSA
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