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mr peabody

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Psilocybe semilanceata found to powerfully inhibit MRSA

Nevase MC, Bhujbal DS, Tapkir PV, Jathar SB, Dhumal SR

MRSA is a type of bacterial infection that is resistant to widely used antibiotics. The full name of MRSA is meticillin-resistant staphylococcus aureus. Staph aureus is a common type of bacteria. It is often carried on the skin and inside the nostrils and throat, and can cause mild infections of the skin such as boils and impetigo. If staph bacteria gets into a break in the skin, they can cause life-threatening infections, such as blood poisoning or endocarditis.

MRSA is a skin infection that cannot be fixed with a medicine that kills bacteria called antibiotics. Because the bacteria cannot be killed with medicine, the infection will keep spreading, eventually reaching other areas of the body. And with nothing to stop the infection from spreading, MRSA can eventually kill the patient. That is why it is important that people know about MRSA, what it is, and what to look for.

Normally, Staph aureus is present on our skin, and if you get a cut, your body goes to work to defend itself against this bacteria. If you get a normal staph infection, antibiotics can kill the bacteria and you will be better in a few days. But with MRSA, the antibiotics do not work to kill the bacteria and that makes this kind of infection very dangerous.

S. aureus most commonly colonizes the anterior nares (the nostrils). The rest of the respiratory tract, open wounds, intravenous catheters, and the urinary tract are also potential sites for infection. Healthy individuals may carry MRSA asymptomatically for periods ranging from a few weeks to many years. Patients with compromised immune systems are at a significantly greater risk of symptomatic secondary infection. In most patients, MRSA can be detected by swabbing the nostrils and isolating the bacteria found inside.

MRSA may progress substantially within 24–48 hours of initial symptoms. After 72 hours, MRSA can take hold in human tissues and eventually become resistant to treatment. The initial presentation of MRSA is small red bumps that resemble pimples, spider bites, or boils that may be accompanied by fever and, occasionally, rashes. Within a few days, the bumps become larger and more painful; they eventually open into deep, puss-filled boils. About 75% of community-associated (CA-) MRSA infections are localized to skin and soft tissue and usually can be treated effectively.

Some CA-MRSA strains display enhanced virulence, spreading more rapidly, and causing illness much more severe than traditional HA- MRSA infections, and they can affect vital organs and lead to widespread infection (sepsis),toxic shock syndrome, and necrotizing ("flesh-eating") pneumonia. This is thought to be due to toxins carried by CA-MRSA strains, such as PVL and PSM. It is not known why some healthy people develop CA-MRSA skin infections that are treatable while others infected with the same strain develop severe infections or die.

People are very commonly colonized with CA-MRSA and are completely asymptomatic. The most common manifestations of CA-MRSA are simple skin infections, such as impetigo, boils, abscesses, folliculitis and cellulitis. Rarer, but more serious, manifestations can occur, such as necrotizing fasciitis and pyomyositis, necrotizing pneumonia, infective endocarditis, and severe bone and joint infections. CA-MRSA often results in abscess formation that requires incision and drainage.

The psychedelic mushroom Psilocybe semilanceata has been shown to strongly inhibit the growth of Staph aureus. Studies have also shown CBD and CBG to powerfully inhibit MRSA.

www.wjpps.com/download/article/1522837412.pdf
 
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mr peabody

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Antimicrobial activity of P. harmala against MRSA

Mehdi Goudarzi, Hadi Azimi
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Staph aureus, as a major cause of infection in either hospital or within the community, is responsible for a diverse spectrum of human infections and diseases such as pneumonia and bacteremia. This pathogen has an outstanding capability to acquire resistance, especially against methicillin, making it able to persist in the hospitals and the community. Soon after the introduction of penicillin in the 1960s, methicillin resistant Staph Aureus (MRSA) emerged and it has been endemic in hospitals around the world since 1980s. MRSA strains are shown to be able to rapidly develop multi-drug resistance (MDR) although a variety of therapeutic measures, including antibiotic therapy, have been introduced. The emergence and spread of MRSA harboring multi-resistance genes have increased academic burden. Proof caused serious therapeutic problems, and worsened controlling infection in hospitals.

P. harmala is a medicinal plant used in the Iranian traditional medicine, due to the antimicrobial compounds found in its seeds and roots. The main objective of the study was to investigate the antibacterial activities of P. harmala seeds on MRSA strains. During an 11-month descriptive cross-sectional study, 90 MRSA strains isolated from hospitalized patients in ICU wards were investigated. Micro-broth dilution method was employed to evaluate the antimicrobial effects of the extract on MRSA strains. The results revealed that the P. harmala extract is very effective against MRSA strains isolated from ICU patients and may be useful in treating some of the infections.

Considering the antibacterial activity of the seed extract of P. harmala against MRSA clinical isolates, it can be concluded that this extract could be exploited as an affordable and available source of therapeutic agents as well as an alternative approach to resistance management. Hence, it can be suggested for the treatment of MRSA infections although it is recommended that more studies be carried out to elucidate the precise bioactive natural compounds that lead to cytotoxicity against HEK 293 cell line.

https://cdn.neoscriber.org/cdn/serve...ress-15592.pdf

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Harmaline against Multi-Drug Resistant E. coli

Harmaline is a fluorescent psychoactive indole alkaloid from the group of harmala alkaloids and beta-carbolines. The harmala alkaloids are psychoactive in humans.

Multidrug resistance (MDR) is a major challenge in the treatment of infectious diseases. The MDR in urinary tract infection causing bacteria, such as Escherichia coli, has made treatment of UTI very difficult. The aims of the current study were to synthesize a library of harmaline derivatives, and to evaluate their activity against various strains of multi-drug resistance (MDR) E. coli. Harmaline derivatives were synthesized by the reaction of harmaline with various acid halides and anhydrides. These compounds were subjected to susceptibility determination by in vitro MTT assay. The changes in morphology of the bacterial cells after the treatment with harmaline and its derivatives were studied through scanning electron, atomic force and fluorescence microscopy. The current study demonstrated that harmaline, and its derivatives were identified as anti-MDR agents against MDR strains of E. coli. Harmaline and its derivatives were identified as anti-MDR agents against various highly resistant MDR clinical isolates of E. coli. These compounds may serve as the leads for further studies towards the development of treatment against the infections caused by MDR E. coli.

https://www.ncbi.nlm.nih.gov/pubmed/28124613

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Cannabis kills MRSA, disrupts Prion Diseases

Cannabis is a potent antibiotic that can kill Methicillin-Resistant Staphylococcus Aureus (MRSA) and disrupt the progression of prion diseases such as Mad Cow and Creutzfeld-Jakob disease - a medical information resource for doctors sponsored by The Massachusetts Medical Society, publisher of the New England Journal of Medicine.

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

Cannabis 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.”

“These findings are encouraging, as prions are very difficult to kill. According to the National Institute of Neurological Disorders and Stroke, presently there is no FDA-approved treatment that can cure or even control Prion disease.”


MRSA kills about 18,000 Americans each year and sickens about 94,000.

https://www.eastbayexpress.com/Legal...prion-diseases
 
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mr peabody

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Is cannabis oil a super antibiotic?

by Ocean Malandra | reset.me | 26 Jun 2015

“Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era,” Dr. Keiji Fukuda, the Assistant Director General for the WHO's Health Security department, said last year after the WHO released its first ever report on antibiotic resistance. “Common infections and minor injuries which have been treatable for decades can once again kill,” he continued, explaining how antibiotic resistant bacteria are now one of the top health concerns of the world.

The horrible irony is that the evolution of bacteria into “superbugs” is driven in large part by the antibiotics that were designed to treat them in the first place. Methicillin-resistant Staphylococcus aureus (MRSA) for example, which causes over 10,000 deaths each year according to the Center for Disease Control (CDC), is a direct byproduct of over-using antibiotics, which bred a stronger and more dangerous version of the common Staph aureus bacteria.

MRSA, which infects open wounds and increases the chance of death in patients by over 60 percent according to the CDC, is now wreaking havoc in hospitals and other facilities where it can spread easily between people in close contact.

Although MRSA is often associated with those with lowered immune systems, recently there have been outbreaks among healthy populations, including at a New York State high school and even among members of the Buccaneers professional NFL football team – guard Carl Nicks was injured so badly by the infection he had to undergo surgery and ended up losing his place on the team.

The situation has become so severe that in late 2014, President Obama issued an executive order devoted to combating antibiotic resistant bacteria, which he called “a serious threat to public health and the economy.”

Obama even allotted $1.2 billion to the annual budget for the establishment of a special task force devoted to the issue, one that would develop an action plan for stopping the fast spread of antibiotic resistant bacteria like MRSA.

Game changing study

In 2008, however, a first of its kind study conducted by a team of British and Italian researchers had already found that one of the world’s most commonly cultivated plants could stop MRSA in its tracks: marijuana.

Specifically, the team tested five of marijuana’s most common cannabinoids against six different MRSA strains of “clinical relevance”, including epidemic EMRSA strains, which are the ones responsible for hospital outbreaks. They found that every single one of the cannabinoids tested showed “potent activity” against a wide variety of the bacteria.

Cannabinoids are substances unique to the cannabis plant that have wide-ranging medicinal properties: they fight cancer, reverse inflammation and act as powerful antioxidants. Now we know that they are also some of the most powerful antibiotics on earth.

“Everything points towards these compounds having been evolved by the plants as antimicrobial defenses that specifically target bacterial cells,” said Simon Gibbons, one of the authors of the study and head of the Department of Pharmaceutical and Biological Chemistry at the University College London School of Pharmacy.

Amazingly, the cannabinoids even showed “exceptional activity” against a strain of the MRSA that had developed extra proteins for increased resistance to antibiotics, showing that cannabis remained effective despite the bacteria’s adaptations.

“The actual mechanism by which they kill the bugs is still a mystery…” said Gibbons. “I really cannot hazard a guess how they do it, but their high potency as antibiotics suggests there must be a very specific mechanism.”

The researchers recommend cannabis as the source of new and effective antibiotic products that can be used in institutional settings right now.

“The most practical application of cannabinoids would be as topical agents to treat ulcers and wounds in a hospital environment, decreasing the burden of antibiotics,” said Giovanni Appendino, a professor at Italy’s Piemonte Orientale University and co-author of the study.

Since two of the most potently antibacterial cannabinoids were not psychoactive at all and appear in abundance in the common and fast-growing hemp plant, producing the antibiotics of the future could be quick and simple.

“What this means is, we could use fiber hemp plants that have no use as recreational drugs to cheaply and easily produce potent antibiotics,” Appendino concluded.

Hidden history of a miracle plant

But introducing cannabis into the formal healthcare system is nothing new; the plant has been used as medicine by different cultures for millennia. A 1960 paper by Professors Dr. J. Kabelik and Dr. F. Santavy of Palacky University in the Czech Republic entitled Marijuana as a Medicament is perhaps the most comprehensive look at marijuana’s traditional use around the globe ever written. Surprisingly, the authors claim that for most cultures and for most time periods, cannabis was used as an antibiotic and treatment for chronic illnesses first and foremost, while its narcotic use is limited to certain areas and historical periods.

“All the information obtained from European folk medicine with regard to treatment with cannabis shows clearly that there do not appear to be any narcotic substances in it, or if there are then only in a negligible amount,” the authors claim. “Instead of that, emphasis has been laid on the antiseptic effect, hence on the antibiotic and to a small extent even on the analgetic (analgesic) effect.”

The same pattern was found in ancient Egypt, where “papyruses point fundamentally to antiseptic use” and in modern African tribes, where the “analgetic, sedative and antibiotic properties of cannabis in internal and external application are well known.”

In South American folk medicine, marijuana was used for everything from gonorrhea to tuberculosis, according to the paper, and in Southern Rhodesia “it is a remedy for anthrax, sepsis, dysentery, malaria and for tropical quinine-malarial haemoglobinuria.”

Even as late as the 19th century, cannabis was used by Western doctors to combat serious illnesses at home and abroad. An 1843 article in London’s Provincial Medical Journal, for example, chronicles an Irish doctor’s success in treating both tetanus and cholera in India by using cannabis in the form of crude hemp resin. Both these diseases are caused by bacteria and were major killers at the time.

A potent and commonly used medicine, cannabis was added to the official U.S. Pharmacopoeia in 1851, where it remained until it was removed in 1942. Coincidentally, the widespread manufacture and use of early commercial antibiotics — like penicillin, which was first isolated in 1929 but not mass produced until 1945 — happened at the same time as cannabis was taken out of medicinal use.

The next half a century saw the touting of antibiotics as miracle drugs while marijuana came to be almost completely associated with getting “high” — its potent medicinal properties obscured behind a cloud of fear and propaganda.

It is only in the last couple of decades that the failure of antibiotics and clinical medicine to address a fast growing number of serious illnesses has driven people to rediscover the miraculous healing powers of this ancient plant.

Shelley’s story

“Within a few months, Cannabis oil had done what years of antibiotics had failed to do, it had given me my life back,” writes Shelley White in the preface to her recently published book, Cannabis for Lyme Disease and Related Conditions: Scientific Basis and Anecdotal Evidence for Medicinal Use.

“I most certainly believe it works as an antibacterial,” Shelley told Reset.Me. “I just am not comfortable calling it a cure due to the fact that the disease is so complex and each case is different.” Instead, Shelley says she is “symptom free” after nine years of battling the disease.

Confusion and mystery surround Lyme disease, which is now the most common vector borne illness in the United States according to the CDC, with 300,000 new cases reported each year. Caused by the spirochete bacteria Borrelia burgdorferi and transmitted through the bite of tick, Lyme is treated by several weeks of antibiotics.

But the International Lyme and Associated Diseases Society (ILADS) claims that at least 40 percent of Lyme patients end up with long term health problems, known as “chronic Lyme.” Not only has there never been a study that shows that antibiotics successfully treat chronic Lyme, but no accurate tests exist to indicate whether the bacteria has been eradicated or not after treatment, the ILADS website states. For chronic Lyme suffers, life becomes a nightmare without an end in sight.

“I was completely debilitated, I could not walk or talk and I was in a wheelchair being spoon-fed,” Shelley says in a YouTube video she posted in September of 2013 that chronicles her healing journey with cannabis oil. “I did antibiotics for over a year” she states, “They did not work for me they worked against me.”

“I took a shot in the dark and started using cannabis oil and it worked,”
she explains.

The video went viral, as for many people who suffer from chronic Lyme, news of a successful treatment is like catching wind of a miracle. It was this response that inspired Shelley to write the book.

A story of personal healing that is also strongly grounded in scientific research; the book begins with an overview of the antibacterial properties of cannabis. Then, chapter-by-chapter, it looks at evidence supporting the plant’s ability to alleviate every symptom of the disease — from nerve pain and seizures to memory loss and depression.

Finally, Shelly shares her recipe for homemade cannabis infused coconut and olive oils, which can be made on the stovetop in under a half an hour by anyone with basic cooking skills. The trick is in not heating it over the boiling point to extract as much of the healing properties as possible.

Medicine for the masses

It turns out that Shelley’s simple oil extract is possibly the most potent form of marijuana medicine on earth. Olive oil is actually the “optimal choice for preparation of Cannabis oils for self-medication,” states Biologist Dr. Arno Hazekamp of Leiden University in Holland in a 2013 study entitled Cannabis Oil: chemical evaluation of an upcoming cannabis-based medicine.

The study tested cannabis infused oil olive against several other extraction methods, including the popular solvent based “Rick Simpson” extraction method, which uses either naphtha or petroleum ether, and an ethanol extraction process.

While the naphtha method did result in a product with the highest THC levels, the olive oil extraction not only yielded the highest overall cannabinoid levels, but higher levels of terpenes than the other processes.

Terpenes are the essential oil compounds responsible for the distinctly pungent aroma of cannabis. Common strong smelling kitchen herbs like oregano are known for their powerful antibiotic properties, which is due to their terpene content. Volatile and delicate, terpenes can be quickly destroyed when heated too high.

“It can be concluded that it is not feasible to perform decarboxylation of cannabinoids, without significant loss of terpene components.” Dr. Hazekamp advises. The decarboxylation process, which heats marijuana to a point where the THC becomes psychoactive, happens automatically when cannabis is smoked, meaning tokers are not getting the full benefit of the herb’s medicinal power.

Likewise, expensive products that rely on processing marijuana, especially those that isolate certain cannabinoids, are also limiting its potential healing power. The terpene beta-Pinene for example, which has been found to be anti-fungal and to synergistically fight MRSA, was completely absent in the naphtha based “Rick Simpson” style cannabis oil tested, which tries to extract as much THC as possible. It remained at high levels in the olive oil extraction however.

“Retaining the full spectrum of terpenes present in fresh cannabis material should therefore be a major focus during optimal Cannabis oil production,” Dr. Hazekamp concludes. The wide array of cannabinoids and terpenes present in the plant in its natural state are what makes marijuana such a versatile remedy for a variety of conditions and an extremely potent antibiotic.

And although the White House just lifted many of the restrictions on medical marijuana research that had been in place since the 1990s, it is unlikely that science will ever come up with a more powerful marijuana based product than the simple homemade oil that can be used both topically and internally.

This means that even with a “post-antibiotic” era looming on the horizon and a growing tide of new mystery illnesses sweeping the land, the super medicine of the future remains right where it has been for most of the past — in nature, freely available for our use.

http://reset.me/story/marijuana-the-super-antibiotic-of-the-future/
 
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mr peabody

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Iboga congeners against parasitic Leishmaniasis
*

Jan Carlo Delorenzi, Leonardo Freire-de-Lima, Cerli Gattass, Deise de Andrade Costa, Liwen He, Martin Kuehne, Elvira Daraiva

Leishmaniasis is a parasitic disease found in parts of the tropics, subtropics, and southern Europe. Leishmaniasis is caused by infection with Leishmania parasites, which are spread by the bite of phlebotomine sand flies. There are several different forms of leishmaniasis in people. The most common forms are cutaneous leishmaniasis, which causes skin sores, and visceral leishmaniasis, which affects several internal organs (usually spleen, liver, and bone marrow).

In previous studies, we demonstrated the leishmanicide effect of coronaridine (COR), a natural indole alkaloid isolated from stem bark of Peschiera australis. In this study we show the leishmanicidal effect of Iboga congeners coronaridine and its 18-methoxylated analog, 18-methoxycoronaridine. Both alkaloids revealed a potent leishmanicide effect against Leishmania amazonensis, a causative agent of cutaneous and diffuse cutaneous leishmaniasis in the New World. Despite their potent leishmanicide effect, both alkaloids were neither toxic to murine macrophages nor did they modulate their oxidative or cytokine production responses.

Leishmaniasis, a disease that affects 12 million people worldwide, presents broad clinical manifestations, ranging from a single localized ulcer to fatal hepatosplenomegaly, depending on the parasite species and the immunological status of the host. Recently, a dramatic increase in leishmaniasis cases was observed, specifically associated with human immunodeficiency virus infection. The drugs currently available for leishmaniasis treatment, pentavalent antimonials, amphotericin B, and pentamidine, present many severe side effects, are expensive, and are frequently ineffective. Furthermore, large-scale clinical antinomy resistance has been reported. All these problems, together with the lack of a safe and effective vaccine, emphasize the importance of the development of new drugs against leishmaniasis.

Recently, we described the antiparasite effect of coronaridine (COR), isolated from the stem of the Peschiera australis shrub, against Leishmania amazonensis promastigotes and intracellular amastigotes. COR is an iboga-type indole alkaloid found in many species of the plant kingdom. Like others iboga alkaloids, COR was investigated for a wide variety of pharmacological effects, such as antitumor, anti-inflammatory, and bactericidal activities, as well as a stimulatory action on the central nervous system. COR has been studied for its potential antiaddictive properties, showing an effective decrease in morphine, cocaine, ethanol, and nicotine self-administration in laboratory animals analogous to that observed with ibogaine. Because of side effects such as tremor, cerebellar neurotoxicity, and bradycardia associated with ibogaine and COR, an 18-methoxylated COR analog was developed with the goal of reducing adverse effects. In pre-clinical studies, 18-methoxycoronaridine (18-MCOR) exerted few to none of the side effects associated with ibogaine or COR.

Discussion

In this work we describe the anti-leishmanial activities of the synthetic indole alkaloids COR and its analog, 18-MCOR, against amastigotes of L. amazonensis. Our previous observations of the leishmanicidal activity of COR purified from P. australis stem extract were confirmed with the congener synthetic drug, as well as with its 18-methoxylated analog.

COR was first isolated by Gorman et al. in 1960 and first synthesized by Kutney et al. in 1970. The synthesis of this compound yielded sufficient amounts of COR to permit the study of its pharmacological effects. In the same manner, structure modifications produced congeners with improved pharmacological activities and reduced side effects. COR and its related compound ibogaine seem to interact with opioid receptors, especially κ-opioids, and block N-methyl-d-aspartic acid and nicotinic ion channels. Ibogaine, notably lacking the carbomethoxy substituent of COR, provokes adverse effects, such as hallucinations and tremors, that limit its use in clinics. However, COR presents dramatically reduced, but not abolished, side effects in comparison with ibogaine. Therefore, modifications in COR chemical structure were made in order to improve its efficacy and to reduce even more its side effects, which was achieved with a methoxylation in carbon-18. The resulting analog, 18-MCOR, retained the pharmacological activity of COR without inducing toxic effects.

In our experiments, 18-MCOR was more effective than COR in killing amastigotes in infected murine macrophages. Like the natural COR, synthetic COR and 18-MCOR neither damaged macrophages nor inhibited fundamental physiological functions of these cells, as determined by trypan blue dye exclusion and phagocytosis tests. The effect of alkaloid exposure was also assessed by XTT assay, in which mitochondrial dehydrogenases metabolize the XTT reagent to a water-soluble formazan dye, indicating preserved mitochondrial activity and cell viability.

Leishmania organisms are obligate intracellular parasites that develop inside macrophages, and nitric oxide production by these cells is considered the most important mechanism in immunologically mediated amastigote killing. In order to verify the ability of COR and 18-MCOR to activate the NO synthase pathway, we measured nitric oxide production in COR- or 18-MCOR-treated macrophages, activated or not with IFN-y-LPS. Like natural COR, synthetic COR did not up regulate NO production, either in activated or in nonactivated macrophages. Although NO production was not altered by 18-MCOR in nonactivated macrophages, in activated macrophages it reduces 60% of this activity. Interestingly, it was reported that ibogaine, a COR- and 18-MCOR-related alkaloid, reduced nitric oxide synthase activity in the brains of parenterally treated mice. Taken together these results suggest that the observed parasite killing may not be mediated by increased activity of the NO synthase pathway.

The control of Leishmaniasis requires the induction of an immune response capable of activating macrophages to a microbicidal state. The most-potent cytokine for the induction of leishmanicidal activity in macrophages is IFN-γ, which is associated with a Th1-cell response. The role that IL-12 plays in the development of Th1 cells, potentiating cell-mediated immune responses against leishmanial infection, is well characterized. TNF-x is also required early on to control intracellular growth of Leishmania. On the contrary, macrophage treatment with IL-6, a cytokine recognized by its pro-inflammatory properties, induces a suppression of IFN-y and TNF-x activation for the killing of Leishmania. Likewise, IL-10 decreases IL-12 and TNF-x production by macrophages, preventing parasite killing. In our analysis we found that none of the tested cytokines (IL-6, IL-12, and TNF-x) were either stimulated or inhibited by both compounds in macrophages preactivated or not with IFN-y-LPS, suggesting that the amastigote killing by the alkaloids cannot be explained by alterations in the production of these cytokines. It has also been reported that IL-6 production by thioglycolate-elicited peritoneal macrophages was not affected by ibogaine exposure.

The results shown in this work, besides supporting the antileishmanial activity of COR, present a congener, 18-MCOR, which effectively kills intracellular amastigotes at when used at concentrations nontoxic to human and murine macrophages. Moreover, the use of ibogaine, a related COR and 18-MCOR compound, as antiaddictive therapy in humans is indicative that COR and 18-MCOR may be safely used for treating Leishmaniasis. Other advantages of these compounds are their simple chemical structure and their already-described synthesis, which may facilitate not only their production but also the synthesis of derivatives with increased efficacy for treatment of Leishmaniasis.

A newly described form of Leishmaniasis transmission, directly from person to person through the sharing of needles, is becoming frequent among injecting drug users with human immunodeficiency virus coinfections. Thus, COR and 18-MCOR could have a double benefit in these patients based on their anti-addictive and anti-leishmanial properties.

*From the article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC127312/

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The Iboga Alkaloids

Lavaud C, Massiot G

Iboga alkaloids are a particular class of indolomonoterpenes most often characterized by an isoquinuclidine nucleus. Their first occurrence was detected in the roots of Tabernanthe iboga, a sacred plant to the people of Gabon, which made it cult object. Ibogaine is the main representative of this class of alkaloids and its psychoactive properties are well documented. It has been proposed as a drug cessation treatment and has a wide range of activities in targeting opioids, cocaine, and alcohol. The purpose of this chapter is to provide a background on this molecule and related compounds and to update knowledge on the most recent advances made. Difficulties linked to the status of ibogaine as a drug in several countries have hampered its development, but 18-methoxycoronaridine is currently under evaluation for the treatment of leishmaniasis. The chapter is divided into six parts: an introduction aiming at defining what is called an iboga alkaloid, and this is followed by current knowledge on their biosynthesis, which unfortunately remains a "black box" as far as the key construction step is concerned. Many of these alkaloids are still being discovered and the third and fourth parts of the chapter discuss the analytical tools in use for this purpose and give lists of new monomeric and dimeric alkaloids belonging to this class. When necessary, the structures are discussed especially with regard to absolute configuration determinations, which remain a point of weakness in their assignments. Part V gives an account of progress made in the synthesis, partial and total, which the authors believe is key to providing solid solutions to the industrial development of the most promising molecules. The last part of the chapter is devoted to the biological properties of iboga alkaloids, with particular emphasis on ibogaine and 18-methoxycoronaridine.

https://www.ncbi.nlm.nih.gov/pubmed/28194562

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18-methoxycoronaridine and Leishmaniasis

The leishmanicidal activities of coronaridine and its synthetic analog 18-methoxycoronaridine have been studied in vitro. Both demonstrated dose-dependent effects against the parasite but were nontoxic toward murine macrophages. Calculated 90% inhibitory concentrations were 22 and 16 μg/mL for coronaridine and 18-methoxycoronaridine, respectively. Tabernanthine has cardiac conduction effects characteristic of a calcium channel antagonist; it also has other pharmacologic actions that are caused by the inhibition of cellular calcium metabolism and are related to the turnover of intracellular calcium released by noradrenaline.

https://www.drugs.com/npp/iboga.html
 
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mr peabody

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Bufotenine able to block rabies virus infection

Rabies is a fatal disease that occurs in more than 150 countries, and kills more than 55,000 people every year. It is caused by an enveloped single stranded RNA virus that affects the central nervous system, through an infection initiated by the muscular nicotinic acetylcholine receptor, according to many authors. Alkaloids, such as acetylcholine, are widespread molecules in nature. They are present in numerous biological fluids, including the skin secretion of many amphibians, in which they act (together with proteins, peptides and steroids) as protection agents against predators and/or microorganisms. In the present work we describe the effects of bufotenine, which can inhibit the penetration of rabies virus in mammalian cells through an apparent competitive mechanism by the nicotinic acetylcholine receptor.

Bufotenine is an alkaloid derived from serotonin, structurally similar to LSD and psilocin. This molecule is able to inhibit the rabies virus infection in in vitro and in vivo models, increasing the survival rate of infected animals. Being a very promising molecule for an incurable disease and because of the fact that there is no consensus regarding its neurological effects, this study aimed to evaluate chronic treatment of bufotenine on behavior, pathophysiology, and pharmacokinetics of mice. Animals were daily treated for 21 consecutive days with 0.63, 1.05, and 2.1 mg/animal/day bufotenine and evaluated by open field test and physiological parameters during all the experiment. After this period, organs were collected for histopathological and biodistribution analysis. Animals treated with bufotenine had mild behavioral alterations compared to the control group, being dose-response relationship. On the other hand, animals showed normal physiological functions and no histological alterations in the organs. With high doses, an inflammatory reaction was observed in the site of injection, but with no cellular damage. The alkaloid could be found in the heart and kidney with all doses and in the lungs and brain with higher doses. These results show that the effective dose, 0.63 mg/day, is safe to be administered in mice, since it did not cause significant effects on the animals’ physiology and on the CNS. Higher doses were well tolerated, causing only mild behavioral effects. Thus, bufotenine might be a drug prototype for rabies treatment, an incurable disease.

From the articles here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203886/
https://www.hindawi.com/journals/bmri/2018/1032638/
 
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Understanding Dermaseptin, Kambo’s antiviral peptide that may treat Herpes

Psychedelic Times Staff | 9 Jan 2017

Kambo, the venom of the giant leaf frog 'Phyllomedusa bicolor,' is excreted through its skin. Long used by indigenous tribes for traditional rituals, kambo is administered by applying it onto freshly inflicted burn wounds. Kambo is said to generate an altered state of reality, clear inner sight and a resurgence of long forgotten memories.

Having suffered personally from oral herpes, finding alternative treatments for this challenging ailment is particularly important to me. For the past ten years, I have experienced the physical pain of outbreaks, the social stigma surrounding the virus, and the concern of passing it on to those I love, especially my children. Luckily, I have a relatively minor strain of the virus and my outbreaks have become more infrequent and manageable. But for those with more aggressive strains, it is paramount to find a cure, efficient suppression system, or vaccine for herpes. Unfortunately, more strains of the virus are becoming resistant to the traditional treatment with Acyclovir and little headway has been made with alternative treatment options. But there is one very promising treatment that comes from an unlikely place: the venom of frogs in the Amazon rain forest.

Kambo, the medicine made from this venom, contains the peptide Dermaseptin, which has been isolated as a potentially effective antiviral that works against both Herpes Simplex 1 and 2. At the moment, the mechanics of this peptide are still vague, but there are several ways that kambo—or the isolated peptide—may be able to mitigate the effects of herpes and prevent future outbreaks.

Kambo as a preventative vaccine

Indigenous tribes traditionally use kambo regularly as a preventative measure throughout pregnancy, childhood, and adult life. This contrasts with how it is currently used in Western society, which usually involves a single treatment or a short series of treatments rather than continual ceremonies. But the continual, preventative approach of indigenous tribes may hold some secrets as to why kambo can reduce the spread of the herpes infection.

Studies have shown that dermaseptin is most effective against free-herpes viruses as opposed to once the virus has already bonded to nerves. Although it may be able to reduce the amount of herpes once it has attached to a host cell, it works best by preventing the bonding altogether in people who have not already contracted the disease and allowing the virus to be washed out of your system. However, it is unclear how long dermaseptin remains active in the human body after it is administered, which may be why kambo requires multiple, continuous treatments to remain effective.

And while dermaseptin has been isolated as the most important peptide in kambo when it comes to treating herpes, researchers are still working to understand how much kambo’s other bioavailable peptides could increase the efficiency of dermaseptin by potentially infiltrating target nerves or attacking more mature herpes viruses. As scientists continue exploring how dermaseptin works in conjunction with kambo’s other peptides, they may be able to isolate a combination of peptides that provides a permanent, effective vaccine against herpes.

Reducing herpes outbreaks and the spread of herpes

Although dermaseptin was shown to be most effective in the early stages of infection, it was still somewhat effective after the virus had attached to nerves. While dermaseptin may not be able to completely eradicate an already established infection, it could potentially prevent the virus from actively reproducing and spreading. This means that, along with preventative treatments, kambo may provide some relief to those currently suffering from herpes, possibly by reducing the number or severity of outbreaks or curbing an outbreak if you catch it early enough.

If you’re hoping to use kambo to treat a herpes infection, always do so under the guidance of a trained professional. When looking for such a practitioner, it is a good idea to find someone with specific experience treating herpes. They will be more knowledgeable about dose amounts, frequency of application, and location of application—all of which can influence the treatment’s effectiveness. You may also look for a practitioner who utilizes meridian-specific placement, which uses the natural energy flow of the body—based on nerves, muscles, and blood flow—to encourage the kambo to reach specific problem areas. Practitioners with meridian training will likely know the best placement points for kambo to reach the nerves that host herpes in your body.

Eliminating herpes after exposure

One of the greatest potentials for kambo as a treatment option against herpes is protecting those who have recently been exposed to the virus. Because it is unclear how long dermaseptin remains active in your body, taking kambo immediately after exposure to herpes may be more effective than using it continuously as a vaccine. However, for this to work, a kambo treatment would need to be pursued before the virus was able to attach to your nerves—within hours or days of exposure. If you think you have been exposed to herpes recently but have not yet experienced an outbreak, you should talk to a kambo practitioner about the possibility of an emergency kambo session. This approach would be best if you had already undergone an initial treatment with kambo and prepared for the experience. After all, kambo can be a somewhat challenging experience physically and can require significant mental preparation before your first ceremony. After you have participated in a ceremony with a trusted practitioner, you will know what to expect and be able to arrange an emergency anti-herpes treatment more quickly.

Living with herpes is annoying at best and, at its worst, it is painful and isolating. A cure for herpes could help keep the virus under control and prevent future generations from suffering the recurring, endless herpes outbreaks that many in our current generation deal with. Researchers are only beginning to understand how the bio-available peptides in kambo work together to prevent and cure various diseases. While research may eventually lead to a more effective vaccine or treatment that can specifically target herpes, it is a good idea to be aware that traditional kambo treatments may still be able to offer more immediate relief in a variety of forms. To learn more about kambo treatments for herpes, you should talk with a trained kambo professional. And for those located in the San Francisco Bay Area, the staff at Psychedelic Times can help put you in contact with a skilled kambo practitioner.

https://psychedelictimes.com/tradit...mbos-antiviral-peptide-that-may-treat-herpes/
 
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Leishmaniasis/HIV co-infection

As reported above, the Iboga alkaloid congener 18-MC inhibits HIV-1 and may be uniquely useful for treating patients co-infected with Leishmaniasis and HIV.

A major threat to the control of visceral leishmaniasis (VL) is its interaction with HIV infection. VL has emerged as an important opportunistic infection associated with HIV. In areas endemic for VL, many people have asymptomatic infection. A concomitant HIV infection increases the risk of developing active visceral leishmaniasis by 100 to 2320 times. In southern Europe, up to 70% of cases of visceral leishmaniasis in adults are associated with HIV infection.

VL/HIV co-infection has important clinical, diagnostic and epidemiological implications. The two diseases are mutually reinforcing: HIV-infected people are particularly vulnerable to VL, while VL accelerates HIV replication and progression to AIDS. The risk of treatment failure for VL is high, regardless of the drug used, and all co-infected patients will relapse – and eventually die – unless they are given anti-retroviral therapy. Indirect methods of diagnosis such as serological tests for VL frequently fail; direct methods such as aspirations (bone marrow, lymph node or splenic) are reliable but are invasive, require skilled microscopy, and have less value in treated and relapsing patients. Further, co-infected patients can serve as human reservoirs, harboring numerous parasites in their blood and becoming a source of infection for the insect vector.

To date, as many as 35 countries throughout the world have reported cases of VL/HIV co-infection, although most of the published literature concerns the countries of southern Europe. Under-reporting in most endemic areas is due to a lack of facilities to diagnose one or both of the diseases and to poor reporting systems. The fact that VL is not included in the CDC list of opportunistic infections further undermines reporting. In a particularly ominous trend, the spread of HIV infection is bringing the severe visceral form of leishmaniasis to new geographical areas and changing the epidemiology of the disease in dangerous ways.

Leishmaniasis-HIV co-infected people have a significantly higher chance of developing the full-blown clinical disease

Where leishmaniasis occurs in urban areas, conditions often favour explosive epidemics, thus transforming the disease from a sporadic to an epidemic threat. In persons infected with HIV, leishmaniasis accelerates the onset of AIDS by cumulative immunosuppression and by stimulating replication of the virus. The epidemiological significance of asymptomatic carriers of the parasite has also been amplified by the advent of HIV, as co-infection rapidly activates infection to disease in asymptomatic parasite carriers. Sharing of needles by intravenous drug users contributes to the spread of leishmaniasis in Europe, as well as that of HIV.

In 1991, WHO established a global surveillance network of 28 institutions, named Leishnet, to document the extent of the problem of co-infection and monitor trends. Initially, the sites involved in the network were predominantly European, reflecting the epidemiological situation at the time. A standardized case report form was developed to collect information on demographic, clinical and diagnostic features of the disease. In recent years, the network has expanded to all endemic areas and now includes institutions from Africa, South America and Asia. The network aims not only to monitor epidemiological trends but also to develop guidelines for disease management.

The number of reported co-infection cases increased rapidly during the 1990s with the spread of the HIV pandemic, increased awareness among reporting institutions, and the growing geographical overlap between the two diseases. By 2001, a total of 1911 co-infection cases had been reported, with more than 50% (1099) coming from Spain. Analysis using geographical information systems (GIS) showed that most cases were in coastal urban areas with high population densities. The spatial pattern suggested a progressive ruralization of co-infection cases, as HIV infection spread into rural areas and VL became increasingly periurban. The number of reported cases in southern Europe peaked between January 1996 and June 1998, then decreased steadily until 2001, remaining stable at a low level thereafter. The decrease is attributed to the routine use of ART since 1997.

In Ethiopia, 535 cases (>90 percent) were reported by the Medecins sans Frontieres VL treatment centre in Kafta Humera district, in the northwestern region of Tigray. They correspond to all co-infection cases treated between 2003 and 2008. In this highly endemic area for VL, the rate of HIV co-infection among VL patients is 15–30%. The position of the area near the Eritrean and Sudanese borders, and its high agricultural activity, attract a high influx of seasonal male migrant workers each year and make it an important transit point for cross-border trade and traffic. The increase in the male population also attracts a high annual influx of commercial sex workers, which probably contributes to the increasing rates of HIV transmission. As in Europe, most of the co-infection cases reported in Africa were in men (94.8 percent).

http://www.who.int/leishmaniasis/burden/hiv_coinfection/burden_hiv_coinfection/en/
 
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Ibogaine and Lyme Disease

I suppose I ought to state my bias from the very beginning was an "instinctual" feeling that ibogaine held these properties to actually kill certain bacteria or viruses before I had ever looked at any sort of data or personal accounts.. But of course the "proof" of this supposed property is only anecdotal evidence at this point as far I know. However, perhaps 16 days ago, I really could not ignore the evidence presented straight in my face. Despite the fact that I hold the bias that ibogaine can kill certain organisms, I still play to the devil's advocate.. but this was too obvious to ignore or "reason around" or suggest a placebo or...

Many people know I have Lyme disease (i.e., the bacteria "borellia burgdorferi" and related tick-born infections, which are all referred to collectively as "lyme disease"). Some people might also know or remember that I experience very.. strange.. reactions after floods or frankly any dose of ibogaine (even just 2mg/kg). Ironically, the reactions I have are all sudden severe lyme disease symptoms! For three years now exactly, I have had a theory on why this happens.. I asked anyone and everyone I could about if these things had happened to them, and I all got were confused looks; other providers had seen no such thing before. Hmm.. However, roughly 16 hours into any standard flood (I say "flood" meaning between 16-22mg/kg or so in this context) I begin to experience something along the lines of "my skin is burning" or if someone took a razor and was scraping it all over my body. At that point of course all you can do is just lie there or drag yourself outside for a cigarette, and not really mention anything else.

Around I believe 24 hours (pain progressing slowly but surely from ~16hrs), the intense painful burning is within my whole body, not just along the skin, and I begin to practically convulse from the neuropathy (nerves going haywire- the intense burning is nerve pain). It's something that looks sort of like a waking grand mal seizure for hours on end, full body flailing sort of spasms or convulsions.. frankly, it looks from the outside like a junkie kicking cold on their 2nd day. Tear the bed, covers, everything, into a complete tornado and knock anything within reach a good several feet away from the bed from the force of the involuntary muscle movements (all these things also happened on my first treatment, by the way; I almost knocked over a candle!). So what's natural provider instinct at that point? "Oh, breakthrough wds, they haven't had enough.." (Even though they've already taken plenty.. Strange eh?). And then provider instinct when this occurs when no detox is involved?- "Uh.. uh.. ummm.. What the hell..??" (Have experienced both of these occurrences.. it's not fun.)

Strange atheoid movements always happen as well, meaning bizarre curling movements of the wrists, ankles, and sometimes limbs; as well as bouncing of the head back and forth uncontrollably along with distinct neck pain, all three of which are known to be fairly lyme-specific symptoms. The strange reactions also feel distinctly "different" from withdrawal, very different, however that's impossible to explain.. Plus- crying repeatedly that your whole body is "on fire" (i.e. severe nerve pain) is not an opiate withdrawal symptom.. The spasms and involuntary movements lessen as time passes, maybe 5-7 days, nerve pain remains for perhaps a tad over a week, and the other cognitive symptoms I didn't mention here also lessen over two weeks or so (After a flood, for a couple weeks I will forget very common words such as trash can or refrigerator- a cognitive symptom also lyme-specific in nature.)

My theory on this for the past three years exactly is that ibogaine, in my case, sets off what is called a "Jarsch-Herxheimer Reaction" or die-off reaction, "Herxheimer reaction" or "herx" for short. This phenomena is fairly well known about in the Lyme community; the "herx die-off reaction" simply means that when the bacteria die, they release toxins into the blood. These toxins cause these horrible symptoms of the disease until the body can effectively remove the toxins. Anyone trying to clear lyme is well familiar with the pain of going through these reactions because they are practically unavoidable if all the bacteria are to be killed. Now if a whole bunch of bacteria are killed all at once, every Lyme literate doctor knows that would mean a person would, experience one hell of a "herx" or bacterial die-off reaction..Like what happens to me every time I flood.. A whole bunch of bacteria killed all at once. But I kept an open mind on it; didn't really hold any solid belief either way despite my instinctual bias.

This changed however when I was put on IV doxycycline (the premier drug for Lyme, though it is usually given orally).. It was a little over two weeks ago. I set up everything as instructed and administered the medication, and then attempted to go about my business eating dinner.. But suddenly, I realized could not control the fork! I knew quite well from experience.. Ibogaine flood experience.. Exactly what was going on (a "herx", a sudden large die-off reaction) and tried to move anything fragile away from me (knowing it would be knocked over or broken if it was within reach at all), but was a bit unsuccessful because the intense firey pain and practically seizure-like spasms took over within minutes after that.

If I didn't have all the flood experience I'd had in the past, I think I might have called 911 or tried to stagger out to a neighbor for help. All the "atheiod" i.e. curling movements when not involuntarily throwing my limbs in any direction were present, also the classic obvious neck pain and head bouncing from side to side.. Also classic strong stuttering (something that does not happen to me really with floods).. and an inability to "navigate" well I might call it, unable to walk upright while trying to exercise the muscles, with a bizarre gait, as well as having to practically put my arms out to navigate around properly. (From all my fun flood experience, I knew the only way to help stop the intense spasming was to walk if I was capable of it, and take a bunch of magnesium supplements or epsom salt baths [same thing, transdermal magnesium] however you cannot sit in a bath if you constantly hit the sides of the tub and hurt yourself with flailing limbs.)

I was almost completely incapacitated (barely even able to control my body well enough to take magnesium, or open the bottle, etc) while this went on at its most severe intensity for about 6-7 hours straight, then for the remaining 24 hours my limbs still burned like embers simmering at the bottom of a dying fire, as well as curling movements, and intermittent but not horrific sudden spasming. I was literally afraid to take the doxycycline again! (But I did keep taking it every day using some tricks I learned in the hospital to lessen the symptoms by slowing the drip rate drastically so I could at least somewhat tolerate them.) The whole time during that hell, very similar to what I used to call "post ibo hell", the few coherent thoughts in my head were "It's just like a flood," and "I'll be damned.. I was right."

Obviously I was not in withdrawal.. and for such symptoms to hit about an hour after administering the medication, taking about 10 minutes to reach full intensity? I think the proof is in the pudding on this one.. ibogaine does kill some kinds of bacteria, and caused the same extremely painful, almost identical die-off reaction as doxycycline did (recall that doxycycline is generally the number one lyme antibiotic}. Curious, hmmm..

Since spring I have not taken any medicine myself, and my jaw dropped when I saw my viral load (hep c 1a) today- 6.6 million (per 1cc of blood). That's over double when it had been in the spring. And it had stayed stable around 2-3 million something for several years.. But I realized I had two problems to deal with, the first being the two IV medications I take- one a strong penicillin type (Invanz, brand only) and generic doxycycline, each once per day. That's already a load on the liver. But I realized even more quickly that all the boosters and medicine I was able to take before this most likely kept the level of viruses in check (however this is speculation.. but I can't really figure another decent explanation). And the last flood was in the early spring..I realized I ought to take some medicine (which means stopping all antibiotics for a few days) so that I could get an antiviral in my system and perhaps make me act a bit nicer to people in the midst of this shit..

Anyways, the point.. Ibogaine IS some sort of antibiotic regardless of our lack of research.. at least it is on me, and I don't think my body chemistry could be all that special.. I am spasming mildly now from the antibiotic- just like post-flood spasming a couple days out of treatment.. As far as an antiviral, I have no idea. But it is an antibiotic. So, anyways, as I thought to myself from my mom's favorite saying, "The proof is in the damn pudding!"

http://www.mindvox.com/pipermail/ibogaine/2011-October/052289.html
 
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mr peabody

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Ibogaine against Candida Albicans*

IBOGA WELLNESS CENTRE

Iboga has been shown to kill Candida and chronic viral and bacterial infections. Candida can be the main cause of depression, chronic fatigue, and overall sluggishness. Many times Candida or other parasites are the underlying cause of these conditions.

Candida infections, aka Candidiasis, yeast infections or thrush are extremely common. Candida can live on mucosal membranes, the lining of our digestive tracts, mouth, vaginal walls, nasal passages and within our sinuses. There is also another form which is called Acute Disseminated Candidiasis, or Invasive Candidiasis which progresses to our organs. It is most common in individuals that are immuno-compromised. Some Candida in an individual’s body is normal, but when there is Candida overgrowth it can cause many problems.

Many people are unaware of the Iboga's anti-fungal properties. There are two studies in particular that stand out regarding Ibogaine for the treatment of Candida infections. The first being an in vitro study that has shown Ibogaine to suppress symptoms of cutaneous Candida albicans. The same study demonstrated the ability of ibogaine to accelerate the elimination of these yeast cells.

In the second study, Ibogaine was administered to mice that had disseminated Candidiasis (when candida has spread to other parts of the body) and gastrointestinal Candida infections. Not only did the ibogaine interfere with the early stages of the infection, but it significantly decreased mortality of the mice as well as decreasing the volume of Candida albicans from the kidney, liver and spleen.

More human studies are needed on iboga and Candida in order for the word to spread to the Western World. However, the Bwiti in Gabon, Africa have known about the healing properties of iboga for hundreds of years. Iboga can help you detox from Candida and jump start your healing. After a cleansing iboga treatment, it is important to make lifestyle choices to continue your renewed health.

*From the article here: https://ibogawellness.com/2013/12/16/iboga-for-treating-candida-overgrowth/
 
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In vitro activities of the iboga alkaloid congeners coronaridine and 18-MC against Leishmaniasis

Jan Carlo Delorenzi, Leonardo Freire-de-Lima, Cerli R. Gattass, Deise de Andrade Costa, Liwen He, Martin E. Kuehne, Elvira M. B. Saraiva

In previous studies, we demonstrated the leishmanicide effect of coronaridine, a natural indole alkaloid isolated from stem bark of Peschiera australis. In this study we show the leishmanicidal effect of the synthetic coronaridine and its analog, 18-methoxycoronaridine. Both alkaloids revealed a potent leishmanicide effect against Leishmania amazonensis, a causative agent of cutaneous and diffuse cutaneous leishmaniasis in the New World. Despite their potent leishmanicide effect, both alkaloids were neither toxic to murine macrophages nor did they modulate their oxidative or cytokine production responses.



Leishmaniasis, a disease that affects 12 million people worldwide
, presents broad clinical manifestations, ranging from a single localized ulcer to fatal hepatosplenomegaly, depending on the parasite species and the immunological status of the host. Recently, a dramatic increase in leishmaniasis cases was observed, specifically associated with human immunodeficiency virus infection.

The drugs currently available for leishmaniasis treatment—pentavalent antimonials, amphotericin B, and pentamidine—present many severe side effects, are expensive, and are frequently ineffective. Furthermore, large-scale clinical antinomy resistance has been reported. All these problems, together with the lack of a safe and effective vaccine, emphasize the importance of the development of new drugs against leishmaniasis.

Recently, we described the antiparasite effect of coronaridine (COR), isolated from the stem of the Peschiera australis shrub, against Leishmania amazonensis promastigotes and intracellular amastigotes. COR is an iboga-type indole alkaloid found in many species of the plant kingdom. Like others iboga alkaloids, COR was investigated for a wide variety of pharmacological effects, such as antitumor, anti-inflammatory, and bactericidal activities, as well as a stimulatory action on the central nervous system. COR has been studied for its potential antiaddictive properties, showing an effective decrease in morphine, cocaine, ethanol, and nicotine self-administration in laboratory animals analogous to that observed with ibogaine. Because of side effects such as tremor, cerebellar neurotoxicity, and bradycardia associated with ibogaine and COR, an 18-methoxylated COR analog was developed with the goal of reducing adverse effects. In preclinical studies, 18-methoxycoronaridine (18-MCOR) exerted few to none of the side effects associated with ibogaine or COR.

In the present study, we describe the leishmanicidal activities of the synthetic COR and its analog, 18-MCOR, which were similar to the antiparasite effect of the natural COR. The synthetic compounds, like the natural COR, did not induce nitric oxide production, nor did they stimulate the synthesis of interleukin 6 (IL-6), IL-12, and tumor necrosis factor alpha (TNF-x) by drug-treated macrophages.

In this work we describe the antileishmanial activities of the synthetic indole alkaloids COR and its analog, 18-MCOR, against amastigotes of L. amazonensis. Our previous observations of the leishmanicidal activity of COR purified from P. australis stem extract were confirmed with the congener synthetic drug, as well as with its 18-methoxylated analog.

COR was first isolated by Gorman et al. and first synthesized by Kutney et al. The synthesis of this compound yielded sufficient amounts of COR to permit the study of its pharmacological effects. In the same manner, structure modifications produced congeners with improved pharmacological activities and reduced side effects. COR and its related compound ibogaine seem to interact with opioid receptors, especially k-opioids, and block N-methyl-d-aspartic acid and nicotinic ion channels. Ibogaine, notably lacking the carbomethoxy substituent of COR, provokes adverse effects, such as hallucinations and tremors, that limit its use in clinics. However, COR presents dramatically reduced, but not abolished, side effects in comparison with ibogaine. Therefore, modifications in COR chemical structure were made in order to improve its efficacy and to reduce even more its side effects, which was achieved with a methoxylation in carbon-18. The resulting analog, 18-MCOR, retained the pharmacological activity of COR without inducing toxic effects.

In our experiments, 18-MCOR was more effective than COR in killing amastigotes in infected murine macrophages, showing an IC90 of 16 ug/ml, in comparison with an IC90 of COR of 22 ug/ml. Like the natural COR, synthetic COR and 18-MCOR neither damaged macrophages nor inhibited fundamental physiological functions of these cells, as determined by trypan blue dye exclusion and phagocytosis tests. The effect of alkaloid exposure was also assessed by XTT assay, in which mitochondrial dehydrogenases metabolize the XTT reagent to a water-soluble formazan dye, indicating preserved mitochondrial activity and cell viability.

Leishmania organisms are obligate intracellular parasites that develop inside macrophages, and nitric oxide production by these cells is considered the most important mechanism in immunologically mediated amastigote killing. In order to verify the ability of COR and 18-MCOR to activate the NO synthase pathway, we measured nitric oxide production in COR- or 18-MCOR-treated macrophages, activated or not with IFN-y-LPS. Like natural COR, synthetic COR did not up regulate NO production, either in activated or in nonactivated macrophages. Although NO production was not altered by 18-MCOR in nonactivated macrophages, in activated macrophages it reduces 60% of this activity. Interestingly, it was reported that ibogaine, a COR- and 18-MCOR-related alkaloid, reduced nitric oxide synthase activity in the brains of parenterally treated mice. Taken together these results suggest that the observed parasite killing may not be mediated by increased activity of the NO synthase pathway.

The control of leishmaniasis requires the induction of an immune response capable of activating macrophages to a microbicidal state. The most-potent cytokine for the induction of leishmanicidal activity in macrophages is IFN-y, which is associated with a Th1-cell response. The role that IL-12 plays in the development of Th1 cells, potentiating cell-mediated immune responses against leishmanial infection, is well characterized. TNF-x is also required early on to control intracellular growth of Leishmania. On the contrary, macrophage treatment with IL-6, a cytokine recognized by its proinflammatory properties, induces a suppression of IFN-y and TNF-a activation for the killing of Leishmania. Likewise, IL-10 decreases IL-12 and TNF-a production by macrophages, preventing parasite killing. In our analysis we found that none of the tested cytokines (IL-6, IL-12, and TNF-x) were either stimulated or inhibited by both compounds in macrophages preactivated or not with IFN-y-LPS, suggesting that the amastigote killing by the alkaloids cannot be explained by alterations in the production of these cytokines. It has also been reported that IL-6 production by thioglycolate-elicited peritoneal macrophages was not affected by ibogaine exposure.

The results shown in this work, besides supporting the antileishmanial activity of COR, present a congener, 18-MCOR, which effectively kills intracellular amastigotes at when used at concentrations nontoxic to human and murine macrophages. Moreover, the use of ibogaine, a related COR and 18-MCOR compound, as antiaddictive therapy in humans is indicative that COR and 18-MCOR may be safely used for treating leishmaniasis. Other advantages of these compounds are their simple chemical structure and their already-described synthesis, which may facilitate not only their production but also the synthesis of derivatives with increased efficacy for treatment of leishmaniasis.

A newly described form of leishmaniasis transmission, directly from person to person through the sharing of needles, is becoming frequent among injecting drug users with human immunodeficiency virus coinfections. Thus, COR and 18-MCOR could have a double benefit in these patients based on their antiaddictive and antileishmanial properties.

https://aac.asm.org/content/46/7/2111
 
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Anti-Leishmanial activity of Coronaridine, an Indole Alkaloid Peschiera australis)
*

Delorenzi, Attias, Gattass, Andrade, Rezende, da Cunha Pinto, Henriquez, Bou-Habib, Saraiva

Leishmaniasis is a parasitic disease found in parts of the tropics, subtropics, and southern Europe. Leishmaniasis is caused by infection with Leishmania parasites, which are spread by the bite of phlebotomine sand flies. There are several different forms of leishmaniasis in people. The most common forms are cutaneous leishmaniasis, which causes skin sores, and visceral leishmaniasis, which affects several internal organs (usually spleen, liver, and bone marrow).

In this study, we show the leishmanicidal effects of a chloroform fraction (CLF) and a purified indole alkaloid obtained from crude stem extract of Peschiera australis against Leishmania amazonensis, a causative agent of cutaneous leishmaniasis in the New World. In a bioassay-guided chemical fractionation, the leishmanicidal activity in CLF completely and irreversibly inhibited promastigote growth. This fraction was also active against amastigotes in infected murine macrophages. Chemical analysis of CLF identified the iboga indole alkaloid coronaridine as one of its major compounds. Coronaridine showed potent antileishmanial activity, inhibiting promastigote and amastigote growth. Promastigotes and amastigotes treated with CLF or coronaridine showed pronounced alterations in their mitochondria as assessed by transmission electron microscopy.

The species Peschiera australis, which flourishes in Brazil, Argentina, Uruguay, and Paraguay, has been poorly investigated with regard to its chemical composition and specific pharmacological activities. The study reported here was undertaken to examine the potential antileishmanial activity of P. australis. We found that an ethanolic extract from the stems of P. australis inhibited the growth of Leishmania amazonensis promastigotes in axenic cultures and of amastigotes in infected murine macrophages. A compound purified by a bioassay-guided chemical fractionation of this extract was identified as the indole alkaloid coronaridine, which exhibited potent antileishmanial activity.

Our results reveal a novel pharmacological activity of coronaridine, besides its anti-addictive property. Laboratory synthesis and the possibility to modify coronaridine's chemical structure constitute important advantages for development of new antileishmanial therapy.

From the article here: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.602.5067&rep=rep1&type=pdf
 
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Albert Hofmann

Anti-viral effects of Ibogaine

Dr. Vic Hernandez

Ibogaine in its administered forms has typically been applied to persons seeking a chemical dependence addiction treatment. The target population not only has had to contend with chemical dependence issues but issues concerning other infections, most notably HIV and/or HCV or co-infection. As antidotal and preliminary scientific information is noted concerning Ibogaine treatments, trends suggest potential applications to these pathogens. Medical science has not rigorously pursued investigation into the potential applications of Iboga alkaloids in in vitro work, animal and human studies.

I am a public health wonk. I have had the luxury of doing what interests me in what I call Public-Health. I get off on effecting and affecting the public's health. My work in HIV has concerned oxidative stress and HIV and its contribution to the understanding of pathogenesis and pathophysiology. I've been involved in developing guidelines for physicians treating HIV, trial design and methodology. I have worked on developing practitioner education forums to support understanding and treatment for isolated populations infected with HIV, notably active users. My unique relationship to communities affected by HIV, activism and passion for my work has brought me to unique understandings and relationships that I have brought to other public health work. I received a congressional citation for this work. Working with Lynn Mofenson at the NIH we moved to look at micro-nutrient intervention in HIV non-progressors to affect HIV progression and delay ARV intervention without compromising patient health by allowing HIV to run unabated. The fruits of this work have been born out in the African studies noted in US papers recently. Working with Lynn, Fauzi at Harvard and others, we established a treatment approach that was frowned upon when we started back in 1993 into accepted and respected reality.

Noted work included the resurrection of Alfa Lipoic Acid as a micronutrient effecting Liver toxicity. It would later be applied to HCV cases. In recent years, needing and wanting a break from HIV, I've worked in the realm of cancer, looking at the role of genetics in identifying trends in non-progressors utilizing non-conventional therapies or no therapeutic interventions. This work has allowed me to look at orthomolecular medicine (effect of micro-nutrients on the biochemistry of the body, pathogen infection, self cells run amuck and wellness and quality of life). Working with colleagues and mentors as Lynn Margulis at U Mass Amherst and Walter Willet at Harvard, I began to understand as Lynn puts it: the symbiosis of medicine, and as Walter puts it, as the effect of the basic building blocks of body systems and their abilities to stay healthy. Why mention this blather? You need to know where I am going with this information, so we can understand where we headed, now and in the future.

HIV. Where we are, and what it means

HIV research and treatment approaches have been checkered and somewhat baffling in approach and far too complex to delve into at this meeting or in this short of time. From a conventional medicine perspective, there are three steps required for HIV to enter cells: Attachment, Binding to a co-receptor, and Fusion of HIV into CD-4 cell. The currently available classes of drugs work to prevent the process of HIV reproducing itself and infecting new cells after HIV enters the CD-4 cell: They are Nucleoside Analogues, Non-nucleoside Analogues and Protease Inhibitors. These drugs have been administered in combination, at varied intervals, and in varying doses to tease out efficacy for the particular viral strain(s) expressed by the patient. Toxicities to body systems and healthy cells require strict and watchful management.

There is a new class of drugs called Entry Inhibitors which block HIV from entering CD-4 cells. They work by blocking the HIVs ability to enter and infect a cell. Essentially there are two steps to entry of HIV into the CD-4 cell. HIV attaches to the CD-4 cell and then fuses with it. After fusing with the cell, HIV can dump its genetic material into the CD-4 cell, the material it needs to reproduce itself in the CD-4 cell. There are two steps to attachment: attaching to the CD-4 receptor and then to a co-receptor, either CCR5 or CXCR4.

Basically, how Entry Inhibitors work is first by:

- Attachment
- Co-receptor binding
- Fusion

Currently available HIV drugs other than Fuzeon, prevent HIV from reproducing once HIV in the cell.

HIV Super-infection and HIV Drug Resistance. Let's start with HIV super-infection. Studies over the past two years suggest this is a real problem. Super-infection is when a person who has HIV gets infected with a second viral strain of HIV. Super-infection, based on study, occurs 5 to 13 months after estimated date of initial infection. The super-infection strain can be associated with ARV susceptibility and adherence. In some cases, a person can be infected with a drug resistant strain and then become infected with a super-infection wild-type or visa-versa. Initial co-infection cannot be ruled be ruled out. Molecular investigation determines evidence of super-infection coupled with progression and ARV response. The rate of the super-infection based on study hovers somewhere around 6.5% annually. Harm reduction counseling is recommended by the researchers.

There are some in the medical science community that are trying to link the super-infection to a patient zero that originated from New York. Nonsense! This was tried at the beginning of the HIV/AIDS pandemic by saying that HIV started in North America with a Canadian airline steward. It is impossible to narrow down such a claim. By the way, in that case, it was refuted by the testing of IDU blood samples from the early seventies that had been banked at Beth Israel. HIV was found in those cohorts, long before the Canadian air-steward stuff. At a recent conference, Paul Volberding MD from UCSF noted that the super-infection business hinged on one reliable case and that the bally-who was uncalled for. This should not minimize sound and reliable public health interventions such as safer sex practices.

Unfortunately, we are learning about HIV pathophysiology and pathogenesis as we go along instead of developing the understanding first. This may deal a blow to 18-MC, if applied to HIV or not.

As for HIV drug resistance, it was not until ICAAC in October of 2004 did the rates found seem alarmingly worrisome. Soon after, the media has grabbed a hold on this information. Studies are finding an escalation of HIV drug resistance during primary infection period (shortly after infection). And the resistances vary among drug classes. Drug resistant HIV acquired at time of infection can establish itself as the dominant virus population and become archived in the latent cellular reservoir. This may result in sub-optimal response to ARV interventions and promote the accumulation of mutations and jeopardize already limited treatment options. In further study, HIV drug resistance has been found in 1 of 7 treated in the US of a cohort of 317 in 40 US cities. The prominent resistance was found in the non-nukes class of drugs. Ethnic differences were noted. Latinos and Asian patients had a lower prevalence of reduced susceptibility (6 percent, with Caucasians at 27 percent, and Blacks at 23 percent. There were no gender differentiations or comparisons done. These were among male cohorts.

HCV and co-infection

HCV therapeutic interventions are limited in pharmaceutical application (interferon and pegalated interferon [riboviron and interferon]) are limited. There are surfacing reports indicating significant efficacy with TCM. In the co-infected individual, treatment options reduce due to the environment of the liver.

When Howard approached me with this paper, I read it and got excited. I like new ideas and approaches especially if the science is tight and is respectful of change. No one has the ace card and false hope, especially for patients, is highly unethical. Ask David Ho MD at Rockefeller's Aaron Diamond Center regarding the premature delivery of HIV cure based on invitro data. After reading the paper Howard shared, the questions flooded through my head and as we talked, he suggested I say a few words. Reluctantly, I accepted. I have been trying to avoid public gigs (especially those that risk pissing contests). The paper (above) by Silva et al from Brazil entitled: Anti-HIV-1 Activity of Iboga Alkaloid Congener 18-MC is a significant piece of work. It was an in vitro (in lab) study using human cells. The Iboga alkaloid 18-MC was introduced to human Peripheral Blood Mononuclear cells (PBMCs) and monocyte-derived macrophages. The result was the significant inhibition of isolates of HIV-1 in a dose dependent manner.

The approach of this anti HIV-1 inhibitory activity study went something like this: An in vitro study of donor PBMCs cells from healthy donors was executed with monocyte-derived human macrophages isolated from the PBMCs. This was not a formal clinical trial with subjects. Materials and methods seemed valid and reliable. Then HIV-1 primary isolates (3) were used. AZT, a nucleoside analogue was used as a control probably because the mechanism of action of 18-MC is as reverse transcriptase inhibitor and AZT is a nucleoside analogue used to affect reverse transcriptase. PBMCs were exposed to viral suspensions of HIV-1 P-24 antigen. Viral replication was assessed by measuring P-24 antigen. Dose ranges from 12.5 to 50 micromolers significantly effected HIV proliferation. Time durations varied from 3, 10, 14 and 21 days. A variety of doses, durations were done to observe safety, and effect. Compared to the control (AZT) which was rigorous as expected, 18-MC faired very well. It should be noted that the infection assays were performed with primary cells (acutely infected PBMCs and macrophages) to avoid the genotypic and phenotypic changes that might occur during viral changes that might occur during viral passages in tumor cell lines. They also used primary isolates, which are phenotypically closer to the viral population present in HIV-1 infected patients. Additionally, they looked at the naturally occurring COR and its anti HIV-1 effect and found significant results, but the data was not reported. They did report the indole alkaloid congener 18-MC molecule of the natural COR, presenting little to none of the adverse effects associated with the original molecule in this antiviral study reported. These study design considerations contributed to a tight study with valid and reliable outcomes.

Basically, 18-MC inhibits HIV-1 replication in human PBMCs and in monocyte-derived macrophages. This antiviral effect of the alkaloids may be due to their action on different steps of viral replication, such as inhibition of syncytium formation and reducing the activity of HIV-1 enzyme reverse transcriptase. So how this applies to the HIV treatment intervention picture is up for grabs. Certainly, further study needs to be done on the mechanisms by which 18-MC decreases HIV replication in vitro, in addition to inhibition of HIV reverse transcriptase. It is worth doing for a number of potential reasons:

1. 18-MC has a lower toxicity profile compared to the drugs in the study control class (nucleoside analogues). And I would venture to say in the other three classes that prevent the process of HIV from reproducing itself and perhaps infecting new cells after HIV enters the CD-4 cell.

2. 18-MC provides a potentially safe ARV therapeutic intervention in less virulent strains of HIV and minimizing toxicities.

3. Co-therapeutic intervention can be matched with micro-nutrient regimens which have been shown in study to delay ARV therapeutic intervention for up to 5 years, notably in women and infected infants.

4. 18-MC, based on its mechanism of action against HIV in comparable drug classes, could be applied to HIV infected pregnant women to affect mother to fetus transmission rates. The studies among these populations used AZT, the control for the 18-MC. I believe 18-MC has a less toxic profile than AZT even thought AZT showed significant interruption of mother to fetus HIV transmission.

5. Given the pharmacodynamics of Iboga alkaloids in the brain, the potential for crossing the blood brain barrier is significant.

6. As mentioned earlier in Dr. Onaivis presentation, the potential of Ibogaine to regulate inflammation (genetically) is significant for persons living with HIV/AIDS where inflammatory states are hallmark.

7. I believe it would be cost effective in poorer nations struggling with HIV infection.

There are issues here, too.

1. Since this 18-MC affects HIV-1 at reverse transcriptase, such as other classes of drugs, perhaps there is a chance for drug resistance as found in other drugs in that class or a shorter duration to it?

2. Perhaps it can be used in initial therapy in super-infections or drug-resistant strains until it succumbs to those viral expressions.

3. In combination with other drug classes such as nukes, non-nukes and protease, there is a strong potential for side effects. But given their toxicity to body systems and healthy cell lines that the nukes, non-nukes and protease inhibitors have, pairing them up with this group may not be wise. This is dependent on dose levels and state of the patient.

4. Perhaps it can be paired up with the new Entry Inhibitors to provide a well-rounded combination to thwart HIV. This I see as the most promising combination.

5. In the case of co-infection, particularly for those with HIV/HCV infection and dicey livers, this may prove to be questionable. I believe the verdict is not in, and further research is needed.

6. Regarding potential psychedelic effects, it should be noted that Sustiva reports similar side effects (like hypnogocic hallucinations) and has been controlled through a variety of provider and patient interventions.

What medical science needs to do

Simple, more study, but the politics of what gets studied and how it gets funded are sad realities. But history has shown us that vigilant activism can effect epistemology, study approach even study design and recruitment. For example, a medical treatment support group comprised of non-active injection drugs users (IDUs) based in the Bronx found the Hypericin study at Bellevue Medical Center in NYC to be of interest. But they found the route of administration (subcutaneous) a bit unwelcoming since it brought up potential triggers to use again. They met with the principal investigator (PI) Fred Valentine MD and persuaded him to add an arm that was orally administered. He agreed and they (the patients) help recruit for the study.

Since the study was done in Brazil and not in the US, the chances for further investigation are probably more promising. Based on this limited work, an Investigational New Drug (IND) designation can be developed, funding lined up, bring it up with Community Review Boards (CRBs), cultivate interested researchers are among the many avenues medical science must go with this. Working with the Institutional Review Boards (IRBs), who wheel a lot of political power to support pursuit of an Iboga-alkaloid as an anti-viral. This is most effective if you have a PI lined up with a clear focus, good science under his/her belt coupled with sufficient funding source(s).

What can patients and advocates do?

I believe there are many things that can be done here, to name a few:

1. Brainstorm with constituencies of patients in effected populations. Dr. Ken Alper and others have mentioned the comradery of the group having been treated with Ibogaine. These people serve as a constituency who can affect the fast tracking of treatments.

2. Develop proactive treatment support groups that can be involved in trial design, methodology, trial recruitment, trial implementation, and adherence. For example, I have started HIV/AIDS treatment support groups called AMEN (Attitude, Medications, Exercise, Nutrition). These groups encourage patients to be their own primary healthcare advocate. They are involved in all aspects of patient treatment intervention(s), advocacy, and often times drug development.

3. Treatment support group can not only promote such objects as patients being their own primary healthcare advocate but also informal researchers. For example, setting up simple databases that encourage the observation of trends of persons taking Ibogaine and the effect on say HCV or HIV. Blood work-up can be a point measure to observe trends.

4. Cultivate active and fruitful relationships between the treatment support group members and their healthcare providers, especially when it comes to understanding the population of active and non-active users, their medical conditions and predispositions, and above all the dynamic of behavior notably addiction.

Remember, some of the most profound discoveries and epistemology in medical science have come from non-medical and/or science trained patients and their advocates.

https://ibogainedossier.com/v_hernandez.html
 
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Crepe Jasmine shrub, the source of Voacamine

Voacamine effective in killing Leishmania parasites resistant to other drugs

by Anusha Krishnan | 26 May 2017

Leishmaniasis is a parasitic disease found in parts of the tropics, subtropics, and southern Europe. Leishmaniasis is caused by infection with Leishmania parasites, which are spread by the bite of phlebotomine sand flies. Leishmaniasis affects 12 million people worldwide, presents broad clinical manifestations, from a single localized ulcer to fatal hepatosplenomegaly, depending on the parasite species and the immunological status of the host. Recently, a dramatic increase in Leishmaniasis cases was observed, specifically associated with human immunodeficiency virus infection.

A recent study by scientists from India, Brazil and Belgium has found a new agent, Voacamine, to be effective against even drug-resistant Indian strains of Leishmania. The study, was published in the journal Biochemical Pharmacology.

Voacamine is an indole alkaloid extracted from the bark of the crepe jasmine shrub (Tabernaemontana coronaria), which is a common house and garden plant in India. The chemical was reported as being moderately effective in killing Plasmodium falciparum, the causal agent of cerebral malaria. Since Leishmania and Plasmodium are similar, both being protozoan parasites, Hemanta Majumder and Sibabrata Mukhopadhyay from the CSIR-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata, initiated a study to study the effects of Voacamine on Leishmania donovani.

They found that not only was Voacamine effective in killing Leishmania donovani parasites growing in a culture of human cells, but it was also able to clear Visceral Leishmaniasis infections from mice in three weeks. What is even more important, is that Voacamine could kill Leishmania strains that are resistant to several drugs currently used to treat the disease.

The paper further elucidates the mode of Voacamine action on Leishmania by pinpointing the drug’s target – an enzyme called Topoisomerase 1B which helps DNA maintain its topological structure, during different cellular processes such as replication or transcription. When topoisomerase 1B is bound to DNA, it forms a ‘cleavage complex’, to which Voacamine binds. Once bound, Voacamine ‘stabilises’ this complex. When the cell’s replication or transcription machinery collides with this ‘stabilised complex’, it causes breaks in the DNA that ultimately lead to the death of the parasite.

“We have long been interested in studying the Topoisomerase 1B from Leishmania as a possible drug target, since it is very different from its human counterpart. This difference makes it possible for us to look for drug molecules that could target the parasite specifically, without affecting human cells,” says Majumder. “Although Voacamine can kill some kinds of cancer cells, it shows almost no toxicity to normal human cells. Since it is required in much lower doses to clear Leishmania infections, it has potential as a drug candidate to treat Leishmaniasis,” he adds.



Leishmaniasis is a neglected tropical disease spread by the bite of blood-sucking sandflies, and is endemic in 65 countries, which puts about 1 billion people at risk of infection. Of the 200,000 to 400,000 cases reported annually, roughly 90% of new cases occur in India, Nepal, Bangladesh, Sudan and Brazil.

The most severe form of Leishmaniasis, called visceral Leishmaniasis or Kala-azar is rife in Bihar, which records 90% of Leishmania infections in India. No vaccine is available against Leishmaniasis as of now. The situation is rendered even uglier with the emergence of drug-resistant strains of Leishmania that leave conventional agents such as pentavalent antimonials, Miltefosine and Amphotericin B useless in combating the disease.

“This is the first report demonstrating the efficacy of a compound to reduce the burden of drug resistant parasites, unresponsive to SAG (Sodium Antimony Gluconate), amphotericin B and miltefosine, in experimental BALB/c mice model of Visceral Leishmaniasis,” says Neeloo Singh, a Professor from the Central Drug Research Institute, Lucknow, who works on Leishmaniasis. “Since drug resistance in Leishmaniasis is a grave problem, Voacamine is a welcome entrant as a prospective anti-Leishmanial,” she adds.

Somenath Roy Chowdhury, a member of Majumder’s team at CSIR-IICB is excited about using Voacamine against parasites other than L. donovanii. “Voacamine was also effective against intracellular forms of the Brazilian strain of Leishmania amazonensis, the pathogen for Cutaneous Leishmaniasis; and the epimastigotes of Trypanosoma cruzi, the pathogen for Chagas diseases”, he says.

Majumder, however, cautions that to bring Voacamine into the market as a drug, many more tests and trials are necessary. “Voacamine extraction from its plant source may also not be very viable for large-scale drug production, so a chemical method for Voacamine synthesis will be needed to bring down manufacturing costs. We have completed the first, very important step of drug discovery. But from here to actual practical use of Voacamine in treating Leishmaniasis, there is much more to be done,” he adds.

https://indiabioscience.org/news/2017/a-new-hope-to-combat-kala-azar

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Study uncovers the cause of aggressive Leishmania RNA virus strain

by Fabíola Ortiz, | SciDev.Net | Dec 16 2019

After six years of research, Brazilian scientists have discovered that the presence of the Leishmania RNA virus in disease-carrying parasites leads to more aggressive forms of leishmaniasis, a discovery they say opens the way to new treatments.

Considered a neglected disease, leishmaniasis is endemic in 98 countries and causes 70,000 deaths a year, according to the World Health Organization (WHO). The disease comes in three forms: visceral (the most severe form), cutaneous (the most common), and mucocutaneous.

Biologist Dario Zamboni, of the University of São Paulo's Ribeirão Preto Medical School, said: "Our study demonstrates that the presence of the virus increases by at least three times the possibility of mucocutaneous leishmaniasis, which destroys and disfigures a patient's face."

Leishmaniasis is caused by protozoan Leishmania parasites which are transmitted by the bite of infected female phlebotomine sandflies.

Zamboni, who led the team that made the discovery, told SciDev.Net that it was already known that parasites are sometimes infected with Leishmania RNA virus—or LRV—which is associated with a greater severity of the disease and the appearance of its mucocutaneous form. But, he explained: "We didn't know how it could lead to more aggravated forms of the disease."

Scientists discovered that the aggravation of the disease by LRV relies on the activation of various molecules, particularly the toll-like receptor 3 (TLR3) inside the macrophages—white blood cells that become infected with Leishmania.

They also found that this inhibits another key molecule in parasite control, NLRP3, allowing LRV to "bypass" our immune system. This in turn facilitates the survival and multiplication of parasites, triggering the mucocutaneous form of the disease.

The mucocutaneous form disfigures the face of affected patients by spreading through mucous membranes of the nose, mouth and throat, and may eventually lead to death from secondary infection. More than 90 percent of this form of the disease occurs in Brazil, Bolivia, Ethiopia and Peru.

According to the WHO, poverty increases the risk of contracting leishmaniasis. Poor quality, densely populated housing and inadequate sanitation systems may foster sandfly breeding sites and increase their access to humans.

The research, published in the journal Nature Communications, was conducted with in vitro cell culture and wild and genetically modified mice. It was then validated with clinical material from 49 patients from Brazil's state of Rondonia, where the cutaneous and mucocutaneous forms are endemic.

Zamboni says the findings show that several molecules of the human immune system may potentially enable the development of drugs.

"By discovering the molecules of the immune system with which the virus interacts and may 'silence' the microbicidal mechanisms of our cells, we also identified several molecules that could in the future be attacked by drugs," he explained.

"New drugs that are combined with those already in use may promote a patient's healing or prevent the disease developing into mucocutaneous leishmaniasis."

Lilian Cantanhêde, a post-doctoral researcher at the leishmaniasis research laboratory of the Oswaldo Cruz Institute (Fiocruz), Rio de Janeiro, believes it is important to understand how the Leishmania virus, also popularly known as "angry wound," acts on the human body in endemic areas.

During her doctoral research, she was in charge of the Fiocruz genetics laboratory in Rondonia, the same state where the clinical sample used by Zamboni's team came from. She has been involved in researching the molecular diagnosis and detection of the Leishmania virus since 2011.

"The group coordinated by Zamboni has been unraveling the mechanisms related to inflammasome [a set of proteins in the immune system that help fight infection] in the development of leishmaniasis and made important discoveries," said Cantanhêde.

But she added that clinical follow-up in endemic areas is a challenge due to low population density and poor adherence to treatment.

 
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Ibogaine and Hepatitis C


The hepatitis C virus (HCV), common among drug users, was first identified in 1989 by genetic engineering of the hereditary material. In Europe, most people are now vaccinated against the hepatitis A virus and the hepatitis B virus, but there is currently no available immunisation against HCV.

Symptoms of hepatitis C include an inflamed liver, pain in the liver and increased production of liver enzymes. There are different treatment options for HCV. The standard treatment option combines interferon with ribavirin. However, this treatment option has no guaranteed success. In addition, the long treatment period of 24-72 weeks is unpleasant due to the numerous side effects.

In 1990, the antiviral effect of Ibogaine was reported for the first time. Since then, there have been reports of cures and documented reductions in HCV concentration after Ibogaine treatment. In 2005, Howard Lotsof filed a patent application for the use of Ibogaine and other Iboga alkaloids to treat hepatitis C and related symptoms.

The results of Ibogaine-assisted HCV therapy are promising. Repeated administration of small doses of Ibogaine HCL lowers the viral load slightly but continuously. A single staggered treatment of a high dose of Ibogaine HCl, significantly reduces the viral load of the hepatitis C genotype 3, comparable with the interferon-ribavirin therapy. The reduction in viral load continues even after the end of the Ibogaine treatment.

Ibogaine HCL is significantly less toxic than the conventional therapy.
 However, within the pharmaceutical industry and doctors, there seems to be no particular interest in alternative methods of treatment. Meanwhile, Ibogaine therapy is far more cost effective than monthly treatment with interferon-ribavirin. Unfortunately, there are no other clinical studies, only anecdotal reports.

http://iboga.info/hepatitis-c-2/

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Ibogaine in the treatment of Hepatitis C

The hepatitis C virus (HCV), which is common among drug users, was first described as non-hepatitis A and non-hepatitis B virus in 1973, until it was finally identified in 1989 by genetic engineering of the hereditary material. In Central Europe, most people are now vaccinated against the hepatitis A virus and the hepatitis B virus, but there is currently no available immunisation against HCV.

Symptoms of hepatitis C include an inflammed liver, pain in the liver and increased production of liver enzymes. There are different treatment options for HCV. The standard treatment option combines interferon with ribavirin. However, this treatment option has no guaranteed success. In addition, the long treatment period of 24 to 72 weeks is unpleasant due to the numerous side effects.

In 1990, the antiviral effect of Ibogaine was reported for the first time. Since then, there have been reports of cures and documented reductions in HCV concentration after Ibogaine treatment. In 2005, Howard Lotsof filed a patent application for the use of Ibogaine and other Iboga alkaloids to treat hepatitis C and related symptoms.

The results of Ibogaine-assisted HCV therapy are promising. Repeated administration of small doses of Ibogaine HCL lowers the viral load slightly but continuously. A single staggered treatment of a high dose of Ibogaine HCl, significantly reduces the viral load of the hepatitis C genotype 3 and is favourably comparable with the interferon-ribavirin therapy. The reduction in viral load continues even after the end of the Ibogaine treatment.

In addition, Ibogaine HCL is significantly less toxic than the conventional therapy.
 However, within the pharmaceutical industry and many Western doctors, there seems to be no particular interest in alternative methods of treatment. Meanwhile, Ibogaine therapy is far more cost effective than monthly treatment with interferon-ribavirin. Unfortunately, there are no other clinical studies, only anecdotal reports.

 
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Recent studies have revealed that iboga alkaloids are active against the HIV-1 virus, Candida albicans and the tropical parasite Leishmania amazonesis.

https://pharmacologyonline.silae.it/files/newsletter/2009/vol3/91.Chiara.pdf

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People have found benefits from ibogaine therapy for the reduction in viral load counts for Hepatitis C, and the cessation of symptoms of Tourette’s syndrome.

https://www.ibogainealliance.org/ibogaine/therapy/

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Howard Lotsof’s last patent application was for using ibogaine to treat hepatitis C. He had data demonstrating a dramatic decline in viral load counts in those diagnosed with hepatitis C who had taken ibogaine.

https://www.psymposia.com/magazine/...kins-who-has-facilitated-over-700-treatments/

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Ibogaine possesses considerable antiviral potency. Various documented cases show how, following treatment with Ibogaine, the Hepatitis-C viral load was dramatically reduced and/or the virus could no longer be found.

http://iboga.info/iboga-ibogaine/

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I was raped in September last year. Before I got away from my attacker he told me that I would remember him. I didn't know what he meant until 2 weeks later when I had a an outbreak of genital herpes. Not long after I was treated with Ibogaine, and I am now completely clear of herpes. Ibogaine is the only possible reason! THANK YOU IBOGA!​

http://www.mindvox.com/pipermail/ibogaine/2005-June/017390.html
 
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Testing ibogaine as an inhibitor of the HIV-1 infection


Infection by the human immunodeficiency virus type 1 (HIV-1), the etiological agent of the acquired immunodeficiency syndrome (AIDS), is a global health problem affecting more than 42 million people worldwide. There were an estimated 34 million people living with HIV/AIDS in 2011. HIV-1 infects and replicates in CD4+ T lymphocytes and monocyte/macrophages, using the CD4 molecule and the chemokine receptors CCR5 or CXCR4 to enter the target cell. HIV-1 persistently replicates in the lymphoid tissues, leading to a progressive deterioration of the immune system, and to a severe clinical outcome of immunosuppression, the foremost characteristic of AIDS. An effective vaccine against HIV-1 infection has not been developed yet.

Two decades after the discovery of the first cases of AIDS, the clinical use of the abundant antiretroviral repertoire has resulted in an unequivocally favorable effect, decreasing the morbidity and mortality of HIV-1 infection. Thus, the search for other antiretroviral compounds is critical, and numerous new anti-HIV-1 agents that target different phases of viral replication cycle are under development or in clinical trials.

It was found that the Ibogaine congener 18-MC inhibits HIV-1 replication in human peripheral blood mononuclear cells and in monocyte-derived macrophages, and that this activity is at least partially mediated by reducing the activity of the HIV-1 enzyme reverse transcriptase. It is therefore hypothesized that the parent alkaloid Ibogaine (IBO) may be as effective or more effective than 18-MC in inhibiting replication of the HIV-1 virus in human blood cells.

http://genesisibogainecenter.com/tes...v-1-infection/
 
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Nanodecoys lure, trap Zika virus

by James Urquhart - 8 January 2019

Gelatin nanoparticles camouflaged by mosquito membrane mop up virus and stop it from crossing the placenta.

Chinese researchers have developed therapeutic nanoparticles that attract and trap the Zika virus in infected mice. The approach could potentially provide a much needed therapy for the virus in humans.

Transmitted by mosquitos, Zika hit the headlines in 2015 when the largest ever outbreak occurred in Brazil and swiftly spread across the Americas. This led scientists to connect the virus to neurological disorders, including Guillain–Barre syndrome, and birth defects including abnormally small heads and underdeveloped brains.

Before scientists had made the link to these serious conditions, it was long thought that the Zika virus was relatively benign. Only one in five infected people experience feverish symptoms and the illness is generally mild and brief. The upshot was there was no vaccine or treatment for it and efforts to develop one have been ongoing since the 2015 outbreak.

Now, Lang Rao and Wenbiao Wang at Wuhan University, and their colleagues have developed a therapeutic strategy that uses nanoparticle decoys disguised as host cells to lure and trap Zika pathogens. The team suggests that the approach could lead to ‘the development of safe and effective protection against Zika and other viruses.’

The nanodecoys comprise a gelatin nanoparticle core coated with a mosquito host cell membrane, which mimics the type of surface that the Zika virus naturally attaches to for it to invade a host cell and replicate. Zika virus pathogens that bind to the nanodecoys’ outer membrane, however, have no cell to enter and thus become trapped, preventing their replication or ability to infect genuine host cells. The gelatin core of the nanodecoy stabilises the cell membrane to help it survive longer in the bloodstream to mop up as many Zika virus pathogens as possible.

‘The study is interesting in advancing the concept of coating a cell membrane onto FDA-approved gelatin nanoparticles for potential antiviral development,’ comments Pei-Yong Shi who studies viruses at the University of Texas Medical Branch, US. ‘It is exciting that such nanodecoy particles could efficiently adsorb Zika virus and confer efficacy in mouse models.’

The team’s experiments with mice revealed that the nanodecoys neutralised inflammatory responses and degenerative changes caused by the Zika virus. What’s more, by trapping Zika pathogens on the nanodecoys, the researchers found that the Zika virus could not pass through the semi-permeable placental barrier between the pregnant mouse and its foetus, thereby suppressing Zika-induced foetal microcephaly.

Shi, however, notes that two issues need to be addressed for this technology to progress. ‘First, the safety of the mosquito cell membrane used in this platform remains to be further studied, although the researchers have already performed some initial analysis,’ he says. ‘Second, the potency of this technology remains to be further improved. Since the nanodecoy particles are considered as biologics, how does this technology perform when compared with antibody treatments?’

https://www.chemistryworld.com/news/nanodecoys-lure-and-trap-zika-virus/3009962.article
 
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New peptide first to destroy the Zika virus

by Gege Li | 25 Oct 2018

An engineered peptide has emerged as a viable drug candidate to treat Zika and other mosquito-borne viruses as it’s the first therapy of its kind that is able to enter the brain to fight infection.

Disrupting the lipid envelope of Zika virus particles has previously been shown to halt infection by reducing viral load and spread – but only in in vitro experiments. The breakthrough in vivo has come about thanks to a novel antiviral engineering strategy that uses D-amino acids.

Researchers from Singapore, Brazil and Belgium engineered an α-helical peptide from a D-enantiomer amino acid called AH-D that targets the highly curved membrane of small enveloped viruses such as Zika. The peptide can cross the blood–brain barrier to reach the brain, something that is notoriously difficult to do. This is a critical feature as the virus can cause neurodegeneration and brain damage.

‘We realised that in this specialised engineered form, in a few cases the peptides can actually cross the central nervous system in a very efficient way,’ says Nam-Joon Cho of Nanyang Technological University, Singapore, who led the work. ‘I believe it happened to be this peptide’s conformation that allowed it to do this and most importantly attack the virus in the brain.’

Cho’s team thinks the specific surface topology of AH-D allowed it to interact with the lipid membrane of virus particles, while the peptide’s amphipathicity allowed it to cross the blood–brain barrier. 'Why some amphipathic peptides can cross this barrier while others can’t is still unknown,' says Cho.

AH-D was highly effective at tackling the virus: not only could it rupture the virus’ lipid envelope much quicker than the L-isomer equivalent, it also worked against other neurotropic viruses in vitro such as Dengue and Chikungunya which have a similar structure to Zika. The peptide showed just as much promise in Zika virus-infected mice, reducing viral load and inflammation in the brain and protecting against death.

Avindra Nath, a physician at the National Institute of Neurological Disorders and Stroke in the US, is impressed. ‘Both their in vitro and mouse model data looks very encouraging,’ he says. He adds that 'it’s ‘surprising’ such a large 27 amino acid peptide can cross the blood–brain barrier but its size means ‘immune responses could be developed against it which would then negate its effects’.

As to why this technique hasn’t been used in the past, Cho puts it down to their unconventional yet powerful approach to characterising AH-D’s potency. ‘We used a unique type of assay where we can simultaneously monitor the interaction of the drug candidate with up to 1000 model virus particles with single-particle analysis,’ he explains. ‘I’m hoping that the antiviral attributes will mean the mechanism is more widely adopted as it demonstrates a new way to approach the problem.’

https://www.chemistryworld.com/news...virus-in-brain-for-first-time/3009666.article
 
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Newly identified virus similar to Ebola, Marburg

Mengla virus, detected in bats in China, infects cells through the same host receptor targeted by the deadly pathogens.

by Kerry Grens | Jan 9, 2019

Researchers have discovered of a new genus of filovirus carried by fruit bats in China. The genome of the so-called Mengla virus shares sequences with other filoviruses, including Ebola and Marburg, and all three use the same receptor on host cells to gain entry for infection, the scientists reported in Nature Microbiology on January 7.

So far, there is no indication that Mengla has infected humans. “What it means for human health? I don’t think anybody knows,” Jeremy Farrar, head of the Wellcome Trust, tells STAT. “Somebody’s just got to screen some populations around where it was found, human populations, to see how many people have got antibodies to it and how common human infection is.”

The research group previously collected three undescribed filoviruses from bats, and Mengla, found in Yunnan Province, is the first of them to get a detailed work up. Genomic sequencing of the virus allowed them to reconstruct its glycoprotein, which they found can be used to infect human cells in culture just as efficiently as Ebola’s and Marburg’s glycoproteins. All three viruses’ glycoproteins use the host’s Niemann–Pick C1 (NPC1) receptor to infiltrate the cell.

The scientists also observed that Mengla could infect cell lines from bats, humans, monkeys, hamsters, and dogs. The authors conclude in their report that, like Ebola and Marburg, Mengla “exhibits broad cell tropism and hence poses a high risk of interspecies transmission.”

“Studying the genetic diversity and geographic distribution of bat-borne filoviruses is very important for risk assessment and outbreak prevention as this type of infectious disease can affect the general public without warning with devastating consequences,”
coauthor Wang Lin-Fa, the director of the Emerging Infectious Diseases Signature Research Program at Duke-NUS Medical School in Singapore, says in a press release.

https://www.the-scientist.com/news-o...-marburg-65302
 
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Second patient in remission from HIV after stem cell transplant

by GMP news | 05.03.2019

An HIV positive man in London has become the second person ever to be declared in remission from the virus.

The case is a proof of the concept that scientists will one day be able to end AIDS, his doctors said, but does not mean a cure for HIV has been found. The patient has been free of HIV for 18 months without taking drugs used to prevent the growth of the virus. His doctors said highly sensitive tests showed no trace of the infection almost three years after a stem cell transplant.

“There is no virus there that we can measure. We can’t detect anything,” said Ravindra Gupta, a HIV biologist who co-led a team of doctors treating the man.

Professor Gupta described his patient as “functionally cured” and “in remission”, but cautioned: “It’s too early to say he’s cured.”

The man is being called “the London patient”, in part because his case is similar to the first known case of a functional cure of HIV.

An American man, Timothy Brown, who became known as the Berlin patient when he underwent similar treatment in Germany in 2007 which also cleared his HIV.



Timothy Ray Brown, known as "the Berlin patient"

Brown, who had been living in Berlin, has since moved to the United States and, according to HIV experts, is still HIV-free.

Some 37 million people worldwide are currently infected with HIV and the AIDS pandemic has killed around 35 million people worldwide since it began in the 1980s. Scientific research into the complex virus has in recent years led to the development of drug combinations that can keep it at bay in most patients.

Professor Gupta, now at Cambridge University, treated the patient in the UK capital when he was working at University College London. "The man had contracted HIV in 2003," Gupta said, "and in 2012 was also diagnosed with a type of blood cancer called Hodgkin’s Lymphoma."

In 2016, when he was very sick with cancer, doctors decided to seek a transplant match for him. “This was really his last chance of survival,” Professor Gupta said.

The donor – who was unrelated – had a genetic mutation known as CCR5 delta 32, which confers resistance to HIV.

The London patient asked his medical team not to reveal his name, age, nationality or other details.

https://gmpnews.net/2019/03/second-patient-in-remission-from-hiv-after-stem-cell-transplant/
 
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