NEWS

[Bosche]

Es ist schon mal ein Fortschritt das sich ein bekannter Politiker dafür einsetzt. Betonköpfe sind schwer zu ändern. Das hat man an den selbstgefälligen Äußerungen des deutschen Innenminister De Maiziere zur Rückführung afghanischer Asylbewerber gesehen.

[syzygy]

Wasser besteht aus zwei Flüssigkeiten

Röntgenanalysen enthüllen zwei Strukturvarianten im flüssigen Wasser

Verborgenes Doppelleben: Physiker haben entdeckt, dass flüssiges Wasser in zwei unterschiedlichen Varianten existiert. Die vermeintliche einheitliche Flüssigkeit besteht in Wirklichkeit aus zwei verschiedenen, miteinander interagierenden Flüssigkeiten. Bisher wurden diese beiden Wasservarianten zwar nur bei sehr tiefen Minustemperaturen nachgewiesen, die Forscher halten es aber für wahrscheinlich, dass sie auch bei Raumtemperatur existieren.

(...)

http://www.scinexx.de/wissen-aktuell-21 ... 06-27.html

[אל תשאלו]

UN und WHO – für ein Ende der strafrechtlichen Verfolgung

Vereinte Nationen und Weltgesundheitsorganisation sprechen sich gemeinsam für ein Ende der strafrechtlichen Verfolgung von Konsumenten und damit für eine Entkriminalisierung von Drogen aus.


Ende letzter Woche ereignete sich etwas, das bereits lange herbeigesehnt wurde. In einem gemeinsamen Statement riefen WHO und die UN die Nationen zu einem Wechsel im Umgang mit Drogen und deren strafrechtlichen Konsequenzen auf. Diese Weisung ist ein Meilenstein für Cannabisaktivisten. Eine aus dem Jahre 1961 erlassene Drogenpolitik habe nun nach neuen Erkenntnissen und den Erfahrungen der letzten Jahrzehnte mehr Schaden angerichtet als Nutzen gebracht.

Die Nationen sind nun rechtlich dazu verpflichtet ihre Drogenpolitik neu auszurichten und die entsprechenden Maßnahmen zu ergreifen. Damit könne eine Entkriminalisierung der Drogen in Gang gebracht werden und der Heilmittelkonsument endlich zu seinem Recht kommen.

Seit Januar diesen Jahres hat die UN einen neuen Vorstand, den ehemaligen Premierminister von Portugal, António Guterres. Während der Amtszeit von Guterres wurden in Portugal die Gesetze von Bestrafung hin zur Behandlung geändert. Man kann nur hoffen, dass nun endlich das notwendige Umdenken stattfindet.

Quelle: http://www.who.int/mediacentre/news/sta ... h-care/en/ via http://www.hanf-magazin.com/news/un-und ... erfolgung/

[Zebra]

Japanisches Pharmahuasca:

This Guy Makes Bootleg Ayahuasca from Traditional Japanese Herbs

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Despite its progressiveness and advancements in other areas of culture and life, Japan has fairly archaic drug laws. These draconian preventative measures are the country's response to the waves of amphetamine addiction it's grappled with since the end of WWII. First time offenders, regardless of the particular illegal drug they're caught with, face steep fines, years in prison, and an almost guaranteed shunning from friends, families, and employers upon their release.

With risks this severe, coupled with a steady stream of government disinformation, it's no wonder that a minuscule percentage of the Japanese population has experimented with illicit substances. While the more square elements of society might chalk these low usage figures up to a win, one Japanese man fears the laws and taboos surrounding drugs in Japan may actually be robbing his fellow citizens of certain benefits.

By concocting a replication of the notorious South American psychedelic drink, ayahuasca, using only traditional Japanese herbs and antidepressants, Aoi Glass claims to have found a legal loophole for providing an ayahuasca-like experience to the masses.

Glass has been moonlighting as pseudo-shaman in a quiet, suburban Tokyo neighborhood for more than three years. I visited his home last month to ask about the psychedelic services he provides.

Glass, a graduate of Hirosaki University's Agriculture Biotechnology department, told me he initially began his research into ayahuasca as part of an effort to treat his friends' depression, after several acquaintances lost their jobs.

"I started by smoking all the random grass seeds I found on the street for three years and writing down the effects. Also with random mushrooms and leaves," he explained. "Then I studied ayahuasca for one year. I studied all the elements that it contains and tried to recreate them from the seeds and herbs I had smoked and studied while also ejecting the elements that induce vomiting."

From there, Glass says he began growing ingredients, testing his concoctions on himself twice a week for six months straight, tweaking the recipe along the way. After settling on a formula, Glass claims he had medical tests done on his blood, urine, and semen to ensure his recipe, served as a brewed tea, wouldn't inadvertently be poisoning people.

When it comes to the mixture's ingredients, Glass offers full transparency, both to me and the world. He's posted the recipe, along with those for other illegal drug facsimiles on Cookpad, a Japanese recipe sharing site. The main ingredients for Glass's mixture are "acacia root, a leaf from a different breed of acacia, and mountain lespedeza (which adds the tryptophan)," which he brews into a tea. He then crushes up Aurorix antidepressant pills, which he asks the customer to source and bring on their own due to their controlled status, to keep everything legal.

Glass shies away from comparing himself to a shaman and his tea to actual ayahuasca, preferring instead to call himself a "counselor" offering "treatment."

Since Glass has never tried authentic ayahuasca himself, I spoke with one of his customers who claims to have also tried legitimate ayahuasca in Bueno Aires. "What I experienced was exactly the same," the customer told me, wishing to stay anonymous due to the taboos surrounding drug use in Japan. "The ayahuasca [in Buenos Aires] enabled me to access some specific, deep part of my consciousness. It looked like a kaleidoscopic labyrinth. When I did ayahuasca for the second time, in Tokyo [using Glass's brew], I saw the same vision and felt like 'wow, I came back here again.' I could clearly feel it was the same room in my mind."

Another anonymous patient of Glass's, who sought the purported therapeutic benefits of the brew, told me that the experience helped her battle depression brought about by problems she'd been having with her parents. "You can't legally say it's a medical cure unless the government approves," she qualified. "But, in my personal opinion, this cured me of these feelings."

As this all sounded great but possibly too good to be true, I asked author and ayahuasca expert Robert Tindall to assess Glass's novel take on the traditional medicine. Tindall was relieved to hear of Glass's apprehension about outright calling his brew an imitation ayahuasca, stating that "as an ethnologist coming from the more indigenous perspective, there is no such thing as a substitute for ayahuasca. In the indigenous way, you come to know the plant by imbibing it and getting to know its spirit and teaching capacities and you develop a relationship with it. We [non-indigenous people] simply can't do that."

Glass's approach of molecularly breaking down "sacred plants that have been used for thousands of years in traditional societies," isn't necessarily a bad thing, though, said Tindall. "It sounds like what he's innovated could be very helpful, and he's actually done what many shamans do, which is combine plants based on instinct, intuition, and empirical study." Tindall added that Glass's treatment might be arriving "just in time," as "Westerners' hunger for ayahuasca is stripping the rainforest bare. Even the reputable shamans are looking forward and endeavoring to develop other ways to do their healing work with other plants."

Curious about what is actually happening to users imbibing Glass's drink, I reached out to Dr. Gerald Thomas, a Collaborating Scientist at The Centre for Addictions Research of British Columbia, who has extensively researched ayahuasca and its abilities to treat maladies like addiction.

"There is no great mystery here," Thomas said after I asked him to weigh in on the ingredient list. "Both [lespedeza and acacia] are potent sources of DMT and the pharmaceutical is a safe and well regarded MAO inhibitor. Most things we ingest contain trace amounts of DMT, which is among the most powerful psychedelics known. Humans digestive systems create an enzyme (MAO) that instantly breaks DMT down so we don't get high from what we eat. The drug listed above, like the bark from the Ayahuasca Vine, deactivates MAO so the DMT becomes bioavailable when ingested."

While he acknowledged the potential problems this (and any) psychedelic experience could have, Thomas concluded that, "with the right preparation and if used in the right circumstances with clear intent, psychedelics can be potent healing aids."

Not everyone is sold on Glass's concoction, however. Associate professor of pharmacology at Rush University, James T. O'Donnell, told me that, assuming I hadn't fallen victim to an elaborate hoax, the ingredients Glass is using are not without their dangers. Noting that "there's a suicide risk" for abusing the antidepressant Aurorix, which "is not approved in the USA."

"Hallucinogens are dangerous, and most are illegal," O'Donnell cautioned. "Trying to beat the system by using other substances to achieve a pseudo high is not without risks, health and legal."

However he chooses to market it and whatever the risks may be, it's clear Glass has lofty but benevolent ambitions for his therapeutic brew. Hoping his breakthrough will beget others, he plans to soon offer the treatment to major Japanese universities and tech incubators, in an attempt to foment some Silicon Valley–like outside-the-box thinking.

"All the innovations are coming from the US, like the iPhone and Google," laments Glass. "We have less in Japan, and I think it's because we've had less experience with hallucinatory drugs, which allow for more creativity to be unlocked. I want the smart people to have this experience so they will have more innovations and help the entire country."

https://www.vice.com/en_us/article/8xxq ... nese-herbs

[Zebra]

Hot Digital Shaman: New App Wavepaths Guides Users Through Therapeutic Trips

Brian Eno teamed up with neuroscientist Mendel Kaelen to create an app for therapeutic music – and it ended up expanding both their minds

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The last time I dropped acid alone was 14 years ago, and I swore I'd never do it by myself ever again.
But a few weeks ago, I spent ten hours alone with a blindfold over my eyes, headphones capped over my ears and LSD molecules plugged into my brain, listening to music in solitude. I'd done LSD plenty of times, but never blind and motionless. I wasn't worried I'd freak out – I thought I would go crazy with boredom. Instead I found myself crying cathartic tears for so hard for so long, I had to use two blindfolds because the first became soaked through.

I was testing a new form of technology that combines generative music – a style of music that is made not by a strict set of instructions like with sheet music, but by a set of rules that allow for ever-changing creations – with AI software being developed by musician Brian Eno and neuroscientist Dr. Mendel Kaelen from London's Imperial College.

"The surprises you get with an experience of generative music are gentle – not in the music, but in what happens to you, the listener," Eno tells Rolling Stone. He and Kaelen want everyone to be able to have the kind of experience I just did, with or without drugs.

While shutting myself in a room alone with just an iPhone for company was not my idea of a good time, it was necessary to understand the experience of using the app, called Wavepaths, which Kaelen unveiled at the Horizons psychedelic science conference in New York earlier this fall. Eno, Kaelen and a small team of psychotherapists and AI specialists already have seed funding from the European Institute of Innovation & Technology (EIT). The idea has been brewing for a year – now Eno and Kaelen are going public with the concept, looking to gather collaborators and funding.

Kaelen's formal pitch: "Using immersive art, psychotherapeutic techniques, and intelligent technologies, Wavepaths provides new ways to become more intimate with ourselves and others, to listen to what our emotions are telling us, to explore what can be discovered in the depths of our own minds, and to drive meaningful changes in our personal lives."

Perhaps the idea of giving people transformative experiences with a smartphone sounds odd, but the intention is to create experiences that are anything but trite. "The last thing we want is for people to think is that the app will provide funny or weird experiences," says Kaelen.

One form of the app will be for the public, and another with additional features will be available to professional psychotherapists who use music in their work. Plus special versions customized to certain drugs – such as MDMA or psilocybin – will be available for clinical work using psychedelics.

The idea of using music as medicine is hardly new; professional therapists already use music in scientifically tested formats to treat conditions like anxiety, depression and autism. Nor is the concept of psychedelic therapy new: psychiatrists widely deployed LSD in legit settings in the 1950s to patients ranging from institutionalized mental patients to Hollywood stars. Cary Grant – coping with the trauma of being abandoned by his mother at 11 - called the experience "an immeasurably beneficial cleansing".

Over the past decade, countless clinical trials have demonstrated the capacity for combining these contraband chemicals with therapy sessions to treat a huge range of ailments, from MDMA for PTSD and psilocybin for addiction to LSD for depression and ayahuasca for eating disorders.

And the idea of mixing music with LSD as a legit medical therapy isn't new either – in fact, before the hippies got their hands on the it, LSD was legally deployed by psychiatrists in the 1950s to work through trauma, depression and addiction. Shrinks would dose blindfolded patients with the drug, play classical music and ask gentle questions to prompt introspection. Hundreds of people experienced this form of therapy at legit institutions in Europe and North America before it leaked from the lab out into the counterculture.

The difference with Wavepaths is that the app will create unique musical scores tailored to every listener based on their tastes and psychological needs, such as the need to calm anxiety, or to soothe rage. Artificial intelligence software and generative music algorithms will create the music but the interface will be responsive, so users (or their therapists) will be able to alter the flavor of the music on the fly. Plus the app will gather data from users, and using machine learning, build repertoires of musical modes and spectrums. It will learn over time which musical settings users like the most – both what individual people like, but also what's popular with everybody. The musical library will constantly evolve.

Put it all together, and you get a 70-year-old idea – musical psychedelic therapy - brought back to life using modern technology. "It is very gratifying to see the world once again waking up to the power of psychedelic therapy. We hope it's only a matter time before it returns to mainstream medicine, and when it does, we want therapists to have the right tools for the job," says Amanda Feilding of the Beckley Foundation, who has worked in psychedelic research for 40 years and who funded Kaelen's PhD.

Music therapists in the Twentieth century adhered to the belief that certain kinds of music were inherently more therapeutic or nourishing than others - mostly classical and western music - and many developed strict playlists not to be deviated from. In therapy, whether music should be chosen by the listener or prescribed by the counsellor – human or mechanical – is a matter of debate.

"I sit in the middle of the debate – I don't think there's a problem with using music that you have already been exposed to, but if music is unsettling, you should have the capacity to change it," says Dr. Charles Grob of UCLA, who researches how MDMA can treat trauma and how psilocybin alleviates anxiety in terminal-stage cancer. "Mendel is very gifted in adapting music to psychedelic experiences, and he is working with a world-class musician, so I'm excited to see what they do."

Eno will curate the soundscapes, and composers Gregory Haines, Jon Hopkins, Laraaji, Robert Rich and Steve Roach are already on board. Eno says he also plans to include the "godfathers" of generative music – Philip Glass, Steve Reich, Terry Riley, Harold Budd, as well as younger acts like David Darling, Sigur Ros, Boards of Canada, and Aphex Twin.

The key is that all the music will be 100 percent generative – what Eno describes as "self-evolving compositions". Generative music can be created by a machine, a computer, a human orchestra, or at its simplest level a set of wind-chimes: it's created by a system that is set in place, and then let to play itself and evolve on its own. No two recreations made using that system will ever be the same.

Eno made the term "generative" famous with his 1978 album Music for Airports, which he originally designed as a sound installation using several continuous loops of tape of varying lengths played on a number of speakers, set to run in an airport terminal. Eno was not the only musician creating such compositions – Terry Riley's "In C" is one of the best-known. A simple set of instructions, it is designed to be played by humans – modern performances have featured classical musicians, students at the Royal Irish Academy of Music using synthesizers, and an orchestra from Mali at the Tate Modern in London, with Blur's Damon Albarn.

But when computers are used instead of humans or tape reels, songs can produce themselves for theoretically infinite lengths of time – important considering an acid trip can last eight hours or more. Crucially, the music provided by Wavepaths is designed to be "incommensurable" – unlikely to ever be repeated. This ensures there is no chance that a familiar song – one that reminds you of a dead parent, lost friend, or ex-lover – could crop up and hijack your experience.

"Generative music is deliberately 'discreet' – it doesn't try to grab your attention, but instead invites you into itself," says Eno. "That can be very welcome in a world where everything else is trying to grab you by the lapels and make you pay attention."

Though Music for Airports was a total flop when it came out – dismissed by critics as "muzak" – some people understood what he was trying to do with this new style, today termed "ambient".

"David Bowie once told me that he listened to nothing other than the [1975] album Discreet Music during a three-month period when he was touring and struggling with drugs," says Eno. "The music is so calm and slow that it induces a similar calmness in listeners." (Incidentally, when Bowie was in his 1978 recovery phase in Berlin, Eno co-wrote the track "Heroes".)

Eno also discovered that hospitals were using Discreet Music in birthing rooms for the same reason Bowie loved it during his tumultuous time: the sense of calm. Now his work on generative music has found new life in the age of touch screens: apps such as Bloom and Reflection, created with musician and software designer Peter Chilvers, allow anyone to carry their own tool for creating self-evolving music in their pocket.

On a tablet or smartphone screen, Bloom behaves like the flat surface of a pond – at first there are no sounds, but touch the screen and a note is created, replaying itself every few seconds, the volume decreasing with every subsequent note. Ripples that emanate outwards from wherever you touch the screen trigger notes anywhere else you touch the screen – a bit like the audio effect of throwing pebbles repeatedly into a pond. It is designed to never play the same thing twice – and it is eerily soothing. Autistic children, Eno tells me, tend to be particularly fond of Bloom. This app was released in 2008 – other apps followed, most recently Reflection, which features even more interactive features, and is designed to make subtly different music throughout the time of day and year.

Wavelengths takes it a step further – it's designed explicitly as a therapeutic tool. In the same way that guided mediation apps like Headspace and Insight Timer aim to help people learn new ways to relate to their own thoughts, Kaelen and Eno hope to build listening exercises into Wavepaths to help people develop new ways to listen to music.

"When you allow yourself to be deeply touched and fully moved by music, then music can carry you beyond the boundaries of your daily sense of self – and you can see your life from a new perspective," says Kaelen. "What we have learned from both psychedelic therapy research, introspective music therapy formats and deep-listening practices, is the power of fully surrendering to an experience of art."

As for the psychedelic side of things, Eno says as "a non-experimenter", he'd never considered the possibility of using music in combination with drugs until he met Kaelen.

Kaelen – to put it mildly – knows a thing or two about psychedelics. He has spent the past five years as part of the research team that last year published the world's first brain-scanning study that revealed what happens in the brain under the influence of LSD. "The world waited 70 years for this," says lead author Professor David Nutt, director of the Neuropsychopharmacology Unit at Imperial. "It was the most difficult study I've ever gotten approved."

In the simplest terms possible, the study found that LSD causes "increased connectivity": regions of the brain that wouldn't normally communicate suddenly babble at one another.

Or, as Kaelen's colleague in psychedelic research, Dr. Robin Carhart-Harris, once explained to me: "Taking a psychedelic is like shaking up a snow-globe."

Why should the combination of music and psychedelics be so intense?

"The human brain is a highly hierarchically organised system," says Kaelen. "Psychedelics allow regions that process emotions and memories to do so more freely. And then there's music, which directly activates these regions. So in the temporarily absence of the usual control systems, this may explain why we observe such profound interactions between psychedelics and music. Vivid recollection of personal memories, strong emotions and new perspectives"

For now, the app is the first step – but that will take some years to develop. However next year as a "taster" for what it will feel like: sound installations created by Eno in London, featuring samples of what will appear on the app. For decades, Eno has created sound and light installations in spaces ranging from museums to hospitals – 150 designs so far.

"These spaces in London will be where immersive art and psychotherapy meet to give people access to personally meaningful experiences in a secular context and embedded in real-life human communities," says Kaelen. "We believe in the power of art to facilitate life-changing experiences, independent of your world-views."

Though the final app will take a while, in the meantime there's a playlist Kaelen (mendelkaelen.com/Psilocybin%20Playlist%20v1.3.pdf) crafted for a clinical study that used psilocybin for depression. It features many of the same musicians that have signed up already to work on Wavepaths, such as Max Richter, Robert Rich and Brian Eno.

A neuroscientist in London tells me she tried out using that playlist with LSD and a blindfold. Though she has studied the neuroscience of psychedelics for years, and done them recreationally many times, she never experienced anything like doing it blind. "People put way too much emphasis on the visual aspects of psychedelics – seeing pink elephants or whatever – and pay far too little attention to the emotional and cognitive effects," she says. "I really found that once you took away the visual input, then you could really experience what's going on."

And she was right: I've done LSD plenty of times, but it never felt like this. The physical sensations were unlike anything I'd ever experienced – especially from the music itself, which uncannily felt like it was speaking to me directly. As weird as it sounds, it felt like it was holding me in its arms and telling me everything was going to be ok.

Kaelen tells me this is actually a common experience with music therapy: "Music has the capacity to give people the sensation they are being heard." I understand now why Kaelen calls music, "the hidden therapist".

http://www.rollingstone.com/culture/new ... ps-w511245

[Zebra]

BBC Click’s Spencer Kelly spends an afternoon talking art, science, music and potatoes with music legend and godfather of ambient music Brian Eno. His new app, Reflection, is a “generative” piece of music that changes every time you listen. In this extended chat we look in-depth at the rules and maths behind Reflection, where notes are altered depending on certain probabilities. We also hear some of Eno’s other ground-breaking generative work, including a very human robot drummer, some super-evil funk and a robot guitarist that could give Nile Rogers a run for his money. We look at his sound and visual art, including 77 million paintings, get a sneak peek inside his notebooks, and find out how he invented the legendary Oblique Strategies cards.

[Bosche]

FDA warns of ‘deadly risks’ of the herb kratom, citing 36 deaths

The Food and Drug Administration issued a strong warning Tuesday to consumers to stay away from the herbal supplement kratom, saying regulators are aware of 36 deaths linked to products containing the substance.

Consumers are increasingly using the supplement, which comes from a plant in Southeast Asia, for pain, anxiety and depression, as well as symptoms of opioid withdrawal. The herb also is used recreationally because it produces symptoms such as euphoria. Proponents say it is a safe way to deal with chronic pain and other ailments, and some researchers are exploring its therapeutic potential, including helping people overcome addictions.

But in a statement, FDA Commissioner Scott Gottlieb said that there is no “reliable evidence” to support the use of kratom as a treatment for opioid-use disorder, and that there are no other FDA-approved uses for kratom.

Rather, he said, evidence shows that the herb has similar effects to narcotics like opioids, “and carries similar risks of abuse, addiction and, in some cases, death.” He said that calls to U.S. poison control centers involving kratom increased tenfold between 2010 and 2015, and that the herb is associated with side effects including seizures, liver damage and withdrawal symptoms.

Last year, the Drug Enforcement Administration proposed temporarily placing the drug into Schedule 1 of the Controlled Substances Act, which effectively would have banned its use. But the agency backtracked after a public outcry and pressure from some members of Congress. It asked the FDA to expedite a scientific and medical evaluation — including whether kratom has any medical use — and a recommendation for how to handle the compounds in kratom.

DEA spokesman Melvin Patterson said Tuesday that once the agency receives FDA's report, it will decide whether kratom should be regulated as a controlled substance and if so, into which schedule, or classification, it should be placed.

The herb is banned in several states, including Alabama, Arkansas, Indiana, Tennessee and Wisconsin. Gottlieb said the FDA is treating kratom as an unapproved drug and also has taken action against kratom-containing dietary supplements. If the plant is useful in treating various conditions, a manufacturer should go through the agency's regular drug-approval process to prove the product is safe and effective, he added. Meanwhile, the FDA is working to prevent shipments of kratom from entering he country.

Jack Henningfield, an addiction specialist who works at the drug policy consulting group Pinney Associates, which has done work for the American Kratom Association, said that surveys have shown that people using opioids to treat pain or satisfy an addiction were able to stop using them by drinking kratom tea. He argued that kratom's “overall abuse potential and risk of death isn't anything close to narcotics like opioids” and warned that restricting or banning the substance could drive some people back to opioids or onto the black market to get kratom.

In a study last year for the American Kratom Association, Henningfield, an adjunct professor of behavior policy at Johns Hopkins, found that effectively banning kratom “is not warranted from a public health perspective and is more likely to cause public health problems that do not exist.”

The American Kratom Association says on its website that kratom is not habit forming but that if taken in high amounts over long periods of time, consumers may experience a dependence similar to caffeine dependence.

https://www.washingtonpost.com/news/to- ... ba3a2b92ed

[Gaius]

In einer Studie hat sich "R-MDMA" als sehr vielversprechend erwiesen:

Highlights
• R-MDMA increases prosocial behavior and facilitates fear-extinction learning in mice.
• High doses of R-MDMA do not produce hyperthermia or signs of neurotoxicity in mice.
• Lower dopamine release may explain why R-MDMA lacks these adverse effects of SR-MDMA.
• R-MDMA may be a safer and more viable therapeutic than racemic MDMA.

http://www.sciencedirect.com/science/ar ... 0817304707

[Attic]

Sehr interessant, danke für den Link!

[Zebra]

From the jungle to the clinic

Deep in the jungle, two researchers go on a hunt. What sounds like an adventurous trip, is part of Markus Muttenthaler’s research at the Faculty of Chemistry. The ERC Starting Grant holder is looking for new therapeutic strategies to combat gastrointestinal diseases based on natural substances.

About ten to 15 percent of the Western population is affected by chronic diseases of the gastrointestinal tract. Inflammatory bowel disease or irritable bowel syndrome are the reason for many people’s misery. As for now, treatment options are limited. That's exactly what ERC Starting Grant recipient Markus Muttenthaler wants to change. At the Institute of Biological Chemistry of the University of Vienna, he is developing new therapeutic strategies based on natural substances.

"Many gastrointestinal disorders derive from a damaged, inflamed or leaky gut barrier, which over time results in chronic conditions. We are therefore interested in novel mechanisms to protect or rapidly repair the gut barrier," Muttenthaler explains and adds, "Rather than targeting the underlying causes, most current treatments only deal with the symptoms of the disease." In addition to treating chronic bowel diseases, the strategies developed by Muttenthaler and his team could also be used for gut protection during chemotherapy or as protective agents for patients who regularly take medication that damages the gut barrier in the long term.

From the jungle…

The greatest challenge is to find bioactive substances that can ultimately be useful for human therapy. Muttenthaler and his team focus on venom compounds since they interact with mammalian receptors with incredible potency and selectivity: "Since animal receptors are structurally similar to human receptors, many of these compounds are also active in humans, where they could be used therapeutically," Muttenthaler explains.

The first part of the preclinical development aims at acquiring these substances. Venoms of animals, such as spiders, scorpions or snakes, comprise hundreds to thousands of active compounds and every animal has its own special mix. However, they are not easy to come by, since most venomous animals don't have their habitat in cities – unless you live in Australia. Instead, the researchers need to travel to faraway places like the Great Barrier Reef or the Amazonian jungle. When it gets dark, Muttenthaler and his team go on a hunt. Deep in the jungle, they look for venomous spiders.

…to the clinic?

The beauty about chemistry is that you can make identical copies of natural substances, but at much larger scale. "Animals had often millions of years to optimise their venom against prey and predators," Muttenthaler explains. Back from their hunting trip, they collect the venom and test it against a panel of receptors that have been associated with diseases such as pain, cancer or inflammation. Once they have a hit, they synthesise the active molecule and characterise it further.

"If a synthesised compound holds up, we use Medicinal Chemistry to optimise the lead, so that it stays stable in the human body and actually reaches its target organ," Muttenthaler explains the process. His great hope is to develop therapeutic lead compounds that could ultimately be moved forward to the clinic.

Developing drugs based on natural substances is not unusual. On the contrary, many well-known drugs derive from natural substances: morphine derived from the flowering poppy plant, aspirin from the bark of the willow tree. A more recent example is the peptide drug Prialt, which is produced from the venom of the cone snail. The snail uses it to paralyse fish, but in humans Prialt can treat severe chronic pain.

Reducing chronic pain

But not only venoms play a significant role in Muttenthaler’s research: Oxytocin, the so-called "love hormone", is another piece of the puzzle of developing new therapeutic approaches. Oxytocin is mainly known for its function of mother-child bonding and love, but it is also present in the gut. "We have recently shown that people suffering from chronic abdominal pain also have increased levels of oxytocin receptors, and now we are interested in studying this observation further," says Muttenthaler.