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Tuesday 29 January 2019

Inside the Psychedelic Mind: The New Frontier for Consciousness Studies, Innovative Therapies, Micro-dosing & Creativity

This article first appeared in New Dawn Special Issue Volume 12, Number 6, 2018. © Brett Lothian




Inside the Psychedelic Mind: The New Frontier for Consciousness Studies, Innovative Therapies, Micro-dosing & Creativity.



“LSD is a psychedelic drug that occasionally causes psychotic behaviour in people who have NOT taken it.” ~ Timothy Leary, Ph.D.

Psychedelic plants and drugs have been a controversial subject ever since the late 1960’s and the hippy flower power movement, despite having a history of human use going back thousands upon thousands of years all over the world. In recent times, attitudes have begun to change in the way in which we see psychedelics and their potential applications for humanity, with new scientific research moving ahead in leaps and bounds after the long halt in official research caused by the American led ‘war on drugs.’ Today, we understand far more about how psychedelics actually work in the brain and how they affect our consciousness, often in very profound ways and are as such we are now on the verge of once again having psychedelic plants and drugs legalized and used in modern medicine. Interestingly, the ways in which psychedelics are being used and the reasons for doing so are also changing and evolving, opening up whole new vistas in the psychedelic field, modern medicine and even the very way in which we think about and solve the many and varied problems that are affecting our world today.


Firstly, if we want to truly understand the psychedelic experience and how it affects our minds and consciousness, we have to understand exactly what is happening in the brain when we take these substances. Research has shown that the classic psychedelic compounds primarily act upon the brain's neural cortex, where they activate specific receptors called 5-HT2A receptors that are usually activated by serotonin. "In order to function, (the cortex is) integrating different signals, for example glutamate signals and serotonin signals," said neuroscientist Stuart Sealfon of Mount Sinai School of Medicine in New York, "and what hallucinogens must be doing is they are disrupting this process so that sensory perception is altered by them." However, not all compounds that activate these receptors lead to psychedelic experiences. In the past, scientists perceived neurotransmitter receptors such as the 5-HT2A receptor as being like "locks and keys," in which certain compounds would fit into a specific receptor as a key fits into a lock. The receptor would then turn on and signal to the other molecules in the cell. But this has been found to not be the case for psychedelics. Research by Sealfon and his colleagues published in the journal Neuron revealed that the 5-HT2A receptor has in fact more than one "on" position. "When a non-hallucinogen activates the receptor, it causes one pattern of signaling of the cells in the brain that is not hallucinogenic," Sealfon told LiveScience. "When a hallucinogen turns on this receptor, the receptor we infer must go into a different position and that leads to a different pattern in responses in the cell and is what makes the hallucinogen have its unique effect."


In 1954, the author and philosopher Aldous Huxley in his seminal work The Doors of Perception proposed that the brain in its ordinary state, acts as a kind of ‘reducing valve,’ restricting conscious awareness. “The function of the brain and nervous system is in the main eliminative”, he observed, “leaving only that very small and special selection which is likely to be practically useful”. He theorized whilst under the influence of the psychedelic compound Mescaline (that is found in San Pedro and Peyote cacti) that the compound allowed him to see that what we normally call “reality” is in fact the product of a massive filtering out of reality, a systematic closing of the doors, leaving only the programs of measurement and utility, reality as it would necessarily appear “to an animal obsessed with survival.” Tom Wolfe in his classic book, The Electric Kool-Aid Acid Test, explained it as follows, “Aldous Huxley compared the brain to a ‘reducing valve.’ In ordinary perception, the senses send an overwhelming flood of information to the brain, which the brain then filters down to a trickle it can manage for the purpose of survival in a highly competitive world. Man has become so rational, so utilitarian, that the trickle becomes most pale and thin. It is efficient, for mere survival, but it screens out the most wondrous part of man's potential experience without his even knowing it. We're shut off from our own world.”
 

Huxley proposed that when we are under the influence of a psychedelic substance, this ‘reducing valve’ is opened up and that we are able to consciously perceive a much richer, more meaningful and wondrous existence. Modern research is showing us now that Huxley was in fact right all along. A 2016 study headed by lead researcher David Nutt, the UK government’s former drugs advisor and professor of neuropsychopharmacology at Imperial College London, showed the profound changes that LSD has upon the brain and consciousness, changes that dramatically altered the activity and connectivity across the human brain. Brain scans revealed in those studied that they experienced images through information drawn from many parts of their brains, not just the visual cortex that normally processes visual information. Using three different brain imaging techniques, named arterial spin labelling, resting state MRI and magnetoencephalography, the scientists measured blood flow, functional connections within and between brain networks, and brainwaves in the volunteers both on and off of the psychedelic compound. Under the influence of LSD, entire regions of the brain that are normally cut off from each other, instead worked together to produce the altered state of perception and consciousness. “The drug can be seen as reversing the more restricted thinking we develop from infancy to adulthood,” said Nutt, whose study was published in the journal Proceedings of the National Academy of Sciences.


Further images also showed that the brain regions that usually form a network in ordinary consciousness, became more separated as those studied experienced “feelings of oneness with the world and a loss of personal identity” that is often called ego dissolution or as it known in traditional shamanism, as ego death. “You don’t recognize yourself as a separate being from the universe. It feels, in a way, like transferring the consciousness from within your own body to the outside world; the focus is in the objects that surround you rather than outside.” Scans revealed a loss of connections between parts of the brain called the parahippocampus and another region known as the retrosplenial cortex. “This experience is sometimes framed in a religious or spiritual way, and seems to be associated with improvements in wellbeing after the drug’s effects have subsided,” Carhart-Harris said. Importantly, researchers noted in this study that the regions in the brain involved with introspection (thinking about one’s self) and the way one perceives the outside world, communicated with each other much more intensely under the influence of LSD. “When we measured the brains of subjects who were really blown away by LSD, who had a really strong feeling of ego dissolution, they were also the ones who had the strongest increase in communication between the network regions in charge of introspection and the network regions in charge of perceiving the external world.”



Another researcher involved in the study, Robin Carhart-Harris, said that whilst under the influence of LSD, the brain scans suggested that the volunteers were “seeing with their eyes shut, we saw many more areas of the brain than normal were contributing to visual processing under LSD, even though volunteers’ eyes were closed.” The more pronounced the effect in the brain, the more intense people rated their psychedelic visions. Under the influence of LSD, brain networks that deal with vision, attention, movement and hearing became far more connected, leading to what looked like a “more unified brain”, he said. David Nutt, went on to say that neuroscientists had waited 50 years for this moment. “This is to neuroscience what the Higgs boson was to particle physics,” he said. “We didn’t know how these profound effects were produced. It was too difficult to do. Scientists were either scared or couldn’t be bothered to overcome the enormous hurdles to get this done.” Amanda Feilding, director of the Beckley Foundation, said in response to this study that “we are finally unveiling the brain mechanisms underlying the potential of LSD, not only to heal, but also to deepen our understanding of consciousness itself.”


Furthering this important work, the researchers at Imperial College London as well as researchers from the University of Sussex, measured the activity of neurons in people’s brains under the influence of the psychedelics LSD, ketamine and psilocybin (the active ingredient in magic mushrooms). The brain scans revealed the first scientific evidence for what appears to be a heightened state of consciousness. The volunteers studied were found to have more random brain activity than normal while under the influence of these psychedelics. The shift in brain activity came with a plethora of peculiar sensations that the participants described as ranging from floating and finding inner peace, to distortions in time and a conviction that the self was disintegrating. “What we find is that under each of these psychedelic compounds, this specific measure of global conscious level goes up, so it moves in the other direction. The neural activity becomes more unpredictable,” said Anil Seth, a professor of neuroscience at the University of Sussex. “Until now, we’ve only ever seen decreases compared to the baseline of the normal waking state.” The scans found the most notable effects in parts of the brain that are known to be important for perceptions, rather than other roles such as language and movement. “I think people would have the intuitive idea that their experience on psychedelic compounds is a bit more random, a bit less constrained, that there’s a mixing of the senses, and all kinds of connections that are experienced between things that are previously unconnected,” Seth said.


“We see an increase in the diversity of signals from the brain,” said Seth. “The brain is more complex in its activity.” Previous studies have demonstrated that people in a state of wakefulness or ordinary consciousness, have more diverse patterns of brain activity than people who are asleep. The researchers have found that people who have taken psychedelics show an even greater amount of diversity, in fact the highest level of diversity ever measured. Robin Carhart-Harris, who also took part in this study, said the sudden increase in randomness and diversity in brain activity appears to show a deeper and richer state of consciousness. “People tend to associate phrases like ‘a higher state of consciousness’ with hippy speak and mystical nonsense. This is potentially the beginning of the demystification, showing its physiological and biological underpinnings,” he said. “Maybe this is a neural signature of the mind opening.” Beyond confirming what shaman all over the world have known for millennia and what the hippies learned back in the 60’s, the research could help scientists to finally understand exactly what types of neural activity correspond to the different levels of consciousness in humans.


It is also hoped that by understanding how different people respond to taking psychedelics, that doctors can more accurately predict which patients might benefit from taking psychedelics to treat mental disorders, such as depression, anxiety and post-traumatic stress. “The evidence is becoming clear that there is a clinical efficacy with these drugs,” said Seth. “I think there’s an awful lot of potential here, if you suddenly see things in a different way, it could give your outlook a jolt that existing antidepressants can’t because they work on the routine, wakeful state.” In fact, more and more research is confirming this to be exactly the case. In another study produced by David Nutt, Robin Carhart-Harris and others, the psychedelic compound psilocybin has been shown to be effective in alleviating symptoms in otherwise treatment resistant depression. There had been numerous studies suggesting psychedelics could play a role in treating depression by acting as a sort of "lubricant for the mind," allowing people to break destructive cycles of depressive symptoms, but the precise effect on brain activity was not yet known. The team at Imperial College London performed fMRI brain scans before treatment with psilocybin and then the day after, once the psychedelic effects had worn off. The study showed psilocybin affected two important areas of the human brain, the amygdala, which is largely involved in how we process emotions such as fear and anxiety, became less active. The greater the reduction, the greater the improvement in the reported symptoms. Also effected was the default-mode network, a collaboration of different brain regions which became more stable after taking psilocybin.


Dr Carhart-Harris, said that the depressed brain was being "clammed up" and that the psychedelic experience had "reset" it. He told the BBC News website: "Patients were very ready to use this analogy. Without any priming they would say, 'I've been reset, reborn, rebooted', and one patient said his brain had been defragged and cleaned up," with the effects lasting for weeks and even months. Prof Mitul Mehta, from the Institute of Psychiatry at King's College London, said: "What is impressive about these preliminary findings is that brain changes occurred in the networks we know are involved in depression, after just a single dose of psilocybin. This provides a clear rationale to now look at the longer-term mechanisms in controlled studies." Carhart-Harris believes that the use of psychedelics effectively "heats up" the mind from its rigidity, enabling people to overcome ingrained, self-destructive patterns of thinking. With support from a qualified therapist, those who have undergone the treatment can then "recalibrate in a healthier way, so you're revising your beliefs and assumptions and addictions", Carhart-Harris says. Furthermore and importantly, Dr Carhart-Harris acknowledges that psychedelics are never going to be for everyone. "Some people won't want to go to the depths of their soul or face demons or traumas they've experienced, or dark aspects of the human condition that are there in all of us," he said.


Another interesting psychedelic compound that is showing remarkable effectiveness in alleviating the symptoms of treatment resistant depression is Ketamine (commonly known as ‘Special K’), that has in recent times come to be thought of as one of the biggest breakthroughs in the psychiatric treatments for severe depression. In as little time as half an hour, it has been shown to banish severe depression symptoms and even suicidal thoughts in the patients tested, often after all other psychiatric options have been exhausted and the effects can last for weeks. A recent study published in the journal Nature, has been able to elucidate just how ketamine acts in the brain to achieve its impressive results. A team of doctors and neuroscientists from Zhejiang University in China have shown that ketamine switches off an erratic burst of electrical impulses firing in neurons in the brain region known as the lateral habenula. “The lateral habenula is like the ‘anti-reward center’ in the brain,” the study’s lead author Professor Hailan Hu told The Independent. When the lateral habenula is firing erratic bursts of electrical impulses, it acts against the areas where key mood-boosting neurotransmitters, dopamine and serotonin are produced by the brain. “The lateral habenula inhibits both of those reward centers,” she added. “So when it goes into the bursting mode, the suppression becomes much stronger, it’s like a machine gun compared to a single shot.” Whilst in the last decade or so, the lateral habenula has become thought of as a major driver for the negative moods involved in depression, the reasons for this have been difficult to exhibit.

Professor Hu’s team had been examining this region of the brain, using rats to study the differences in depressed and normal brains and had identified certain patterns of irregular electrical activity that they thought could be playing a role. “In previous experiments we had delivered ketamine generally into the body, so you wouldn’t know which brain region was being affected,” Professor Hu said. “But in this study we injected it directly into the lateral habenula and we were surprised to find that just affecting this very localized area was sufficient to have this very rapid antidepressant effect.” The findings in rats were akin to the extremely rapid relief of symptoms that can be seen in humans and suggests that ketamine’s remarkable effects could be largely derived from this one area, as no other parts of the brain were being treated. With further experimentation, the researchers were able to show that a group of receptors (NMDARs) are causing these signals and are effectively blocked by ketamine. Also published in the journal Nature, an analysis of the findings by Dr Paul Kenny, professor of neuroscience at the Icahn School of Medicine at Mount Sinai in New York, said that “ketamine is currently in clinical trials for the treatment of major depressive disorder with imminent risk of suicide, but the mechanisms by which ketamine acts have been a puzzle to scientists. These findings suggest that the therapeutic actions of ketamine might relate, at least in part, to its ability to block burst firing in the lateral habenula, this knowledge might facilitate the development of next-generation ketamine-related antidepressants that specifically target lateral habenula activity.”


A study released in June of this year has shed even more light on the impressive effects of ketamine in the brain and how it helps to treat mental illness. Importantly, the researchers tested a number of psychedelic compounds for comparison and the results were truly astounding. "These are some of the most powerful compounds known to affect brain function, it's very obvious to me that we should understand how they work," said senior author David E. Olson, assistant professor in the Department of Chemistry and the Department of Biochemistry & Molecular Medicine at the University of California, Davis. “One of the hallmarks of depression is that the neurites in the prefrontal cortex – a key brain region that regulates emotion, mood, and anxiety – those neurites tend to shrivel up,” said Olson. It had previously been believed that depression stems from imbalanced brain chemistry, but recent studies have shown that depression manifests as structural changes in brain circuitry or as an atrophy in parts of the brain. This does not mean that the neurons die off in those suffering mental illness, but that the neurites retract. Neurites are the sections of a neuron that bridge the gap between two neurons at the synapse to enable communication. These brain changes are also apparent in the cases of people suffering anxiety, addiction, and post-traumatic stress disorder. In the study, Olson and colleagues tested psychedelics from the amphetamine, tryptamine, tropane and ergoline drug classes. In both test tube and animal experiments, the psychedelics displayed functional and structural changes that were similar to those produced by ketamine in cortical neurons. Psychedelics increased both the density of dendritic spines and the density of synapses. Some psychedelics tested, including LSD, proved to be even more potent and effective than ketamine in promoting neurite growth.


What this basically means is that psychedelic compounds literally have the power to rewire damaged brains, confirming the intuitive findings of the people who say that psychedelics have “reset, rebooted or defragged” their minds. The researchers conducted their experiments in both vertebrates and invertebrates, showing that psychedelics produced similar effects across species. This demonstrates that the biological mechanisms involved with psychedelic effects have remained the same across millions of years of evolution and that psychedelics will most likely have the same brain growth or neural plasticity effects in humans. Olson and his team also set out to test exactly how these psychedelics produced neural plasticity. The researchers explored which biological pathways psychedelics activate to promote neural growth. Ketamine's neural plasticity effect was previously discovered to be largely dependent upon a protein named brain-derived neurotrophic factor (BDNF). When BDNF signaling was blocked, interestingly the psychedelics lost their capability to promote neurite growth. BDNF binds to a receptor, named TrkB that is part of a signaling pathway which includes mTOR that is known to play a major part in producing the proteins necessary for the creation of new synapses. When mTOR was also blocked, it also completely inhibited the psychedelics' ability to promote neurite growth. Intriguingly the one psychedelic tested that did not promote neural plasticity was ibogaine (the active ingredient in iboga) but that a metabolite of ibogaine, namely noribogaine did, which explains iboga’s effectiveness.


Unfortunately space in this article does not permit me to examine all of the interesting work that is being done in regards to psychedelics with depression, anxiety, PTSD and addiction as there has been literally a flood of recent studies that are all saying the same things, that they work and are far more effective and longer lasting (even at a single dose) than anything that is currently being prescribed in the treatments of these debilitating mental illnesses. A number of psychedelic compounds are presently being fast tracked through the clinical trial phases of human testing and will soon be available to doctors to help treat these diseases. I encourage our intrepid New Dawn readers to please do research the studies cited in the references for this article and the veritable compendium of scientific literature and anecdotal evidence that is freely available on the internet, as well my previous article for New Dawn on psychedelic research, Sacred Plant Healing: Shamanic Plant Medicine and the New Science, which appeared in the special issue volume 10, number 5 and is now freely available on my Tricho Serious Ethnobotany blog, for more in depth information. As our societies mental health issues, addictions and suicide rates continue to grow at an alarming rate, this extremely important information needs to be disseminated as widely as possible and brought to the attention of the wider public, and of course our policy and law makers.


Other debilitating mental scourges that are ever increasing in our modern society such as Dementia, Alzheimer’s and Down syndrome may also benefit from the use of psychedelic substances. In a study released by the D'Or Institute for Research and Education, it was discovered that harmine which is present in the popular psychedelic drink ayahuasca and which has been used by psychonauts to potentiate other psychedelics, inhibits what is known as DYRKIA which is located on chromosome 21 and is overly activated in patients suffering from Down syndrome and Alzheimer’s disease. Also it was ascertained that the beta-carboline harmine also led to an increase of 70% in the proliferation of human neural progenitor cells. "It has been shown in rodents that antidepressant medication acts by inducing neurogenesis. So we decided to test if harmine, an alkaloid with the highest concentration in the psychotropic plant decoction ayahuasca, would trigger neurogenesis in human neural cells," said Vanja Dakic, PhD student and one of the authors in the study. "Our results demonstrate that harmine is able to generate new human neural cells, similarly to the effects of classical antidepressant drugs, which frequently are followed by diverse side effects. Moreover, the observation that harmine inhibits DYRK1A in neural cells allows us to speculate about future studies to test its potential therapeutic role over cognitive deficits observed in Down syndrome and neurodegenerative diseases," suggests Stevens Rehen, researcher from IDOR and ICB-UFRJ. As we already know that psychedelics can promote new neuron growth and networks and that harmine promotes the growth of new brain cells, whilst also inhibiting the over active DYRKIA associated with Down syndrome and Alzheimer’s, ayahuasca could be just what the doctor ordered to help people with neurodegenerative diseases literally regrow and rewire their damaged brains.


A new trend that is emerging and growing in popularity with psychedelics, particularly among the genius Silicon Valley crowd, is micro-dosing which was first promoted by Dr. James Fadiman in his excellent book, The Psychedelic Explorers Guide that I reviewed for New Dawn issue 164. Micro-dosing is exactly as it sounds, taking small (non-psychedelic) amounts of these substances, to boost creativity, cognitive function and elevate mood. Whilst numerous studies have demonstrated a link between psychedelic use and increased creativity, artistic expression, problem solving and overall cognitive function, whether these substances could have the same effects in sub-perceptual or non-psychedelic dosages had never been tested, until now. Researchers from Leiden University in the Netherlands have released the first official study into micro-dosing in October of this year and their findings support the mounting anecdotal evidence that even in tiny amounts, psychedelics can have profound impacts upon the ways in which we think. “Our results suggest that consuming a micro-dose of truffles (magic mushrooms) allowed participants to create more out-of-the-box alternative solutions for a problem, thus providing preliminary support for the assumption that micro-dosing improves divergent thinking," lead author Luisa Prochazkova explained. "Moreover, we also observed an improvement in convergent thinking, that is, increased performance on a task that requires the convergence on one single correct or best solution." The authors of the study called this “changes in fluid intelligence” and noted that the participants created solutions that were more original and flexible than they had before micro-dosing. More studies are currently underway into the effects of micro-dosing with other psychedelic compounds, which will in all likelihood produce similar results.


Whilst the use of psychedelics has long been advocated for improving intelligence and creativity by such mental luminaries as Dr. Francis Crick who discovered the double helix nature of DNA, Apple computers founder Steve Jobs and Microsoft founder Bill Gates, whether psychedelics actually changed what we think was largely speculation. A new study released earlier this year has given us an intriguing insight into the potential changes in just what we think through the use of psychedelic plants and compounds. “Our findings tentatively raise the possibility that given in this way, psilocybin may produce sustained changes in outlook and political perspective, here in the direction of increased nature relatedness and decreased authoritarianism,” researchers Taylor Lyons and Robin Carhart-Harris wrote in the study. “Before I enjoyed nature, now I feel part of it. Before I was looking at it as a thing, like TV or a painting… [But now I see] there’s no separation or distinction, you are it,” one participant said in the follow-up exam. “This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation,” the study concluded. Could these feelings of increased nature relatedness and anti-authoritarianism explain the peace and love hippy counter culture revolution of the late 1960’s and why these plants and substances were subsequently banned by the ever increasingly authoritarian, nanny state governments of the world? I will leave that for the reader to decide.


Perhaps the most important of all the changes in what we think, our beliefs and our attitudes that psychedelics produce is in removing the fear of death and the experience of the mystical. In a recent study by the Johns Hopkins Medical School, 51 terminally ill patients were given magic mushrooms and a remarkable 80% of them said that it had helped them to feel more optimistic and less scared of death. Matthew W. Johnson who was involved in the study offered that the experience produced by the mushrooms "appear indistinct, oftentimes from religious experiences." Research conducted by Griffiths et al. showed that the mystical experiences participants had under the influence of psilocybin were “among the most personally meaningful and spiritually significant of their lives” and that they were very long lasting. Charles Grob, UCLA professor of psychiatry and pediatrics who also conducted a study that gave psilocybin to late-stage cancer patients has said that "the reports I got back from the subjects, from their partners, from their families were very positive, that the experience was of great value, and it helped them regain a sense of purpose, a sense of meaning to their life. The quality of their lives notably improved."

As the famed mystic and inspiration for Aldous Huxley’s greatest work, The Doors of Perception, William Blake once wrote, “If the doors of perception were cleansed, everything would appear to man as it is, infinite.” ~*




References:

How Do Hallucinogens Work?

How Do Psychedelics Work? A Look Inside the Hallucinating Brain

The Doors of Perception. By Aldous Huxley

The Electric Kool-Aid Acid Test. By Tom Wolfe

LSD's impact on the brain revealed in groundbreaking images

Psychedelic drugs induce 'heightened state of consciousness', brain scans show

Psychedelic drugs push the brain to a state never seen before

Magic mushrooms can 'reset' depressed brain

Could psychedelics transform mental health?

Psychedelic drug ayahuasca improves hard-to-treat depression

Psychedelic ayahuasca works against severe depression, study finds

Psychedelic Drugs: LSD Changes Brain, Could Be Used for Depression, Addiction Treatment

Ketamine nasal spray rapidly relieves depression and suicidal thoughts, finds trial

Remarkable secrets of ketamine's antidepressant effect unlocked by scientists

Psychedelics Promote Structural and Functional Neural Plasticity

Psychedelic drugs promote neural plasticity in rats and flies

LSD and magic mushrooms could heal damaged brain cells in people suffering from depression, study shows

Does ibogaine treatment for depression help?

Psychedelics and MDMA are helping cure PTSD, addiction, depression and anxiety

Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles

Sacred Plant Healing: Shamanic Plant Medicine and the New Science

A brief history of psychedelic psychiatry

Substance present in ayahuasca brew stimulates generation of human neural cells

The Psychedelic Explorers Guide. By James Fadiman, Ph.D.

Microdosing Magic Mushrooms Could Spark Creativity And Boost Cognitive Skills, Claims New Study

Study Says Psychedelic Mushrooms Make People More Resistant To Authority

Dying humans are taking mushrooms to study our fear of the unknown

'My fear of dying was gone': Former cancer patient says psychedelic drugs helped him cope with end of life anxiety

What Is So Important About The Mystical Experience?

The most convincing argument for legalizing LSD, shrooms, and other psychedelics




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