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A man with deadly brain cancer that had spread to his spine saw his tumors shrink and, for a time, completely vanish after a novel treatment to help his immune system attack his disease – another first in this promising field.The type of immunotherapy that 50-year-old Richard Grady received already has helped some people with blood cancers such as leukemia. But the way he was given it is new, and may allow its use not just for brain tumors but also other cancers that can spread, such as breast and lung.

Grady was the first person to get the treatment dripped through a tube into a space in the brain where spinal fluid is made, sending it down the path the cancer traveled to his spine.He had “a remarkable response” that opens the door to wider testing, said Dr. Behnam Badie, neurosurgery chief at City of Hope, a cancer center in Duarte, California, where Grady was treated.The case is reported in this week’s New England Journal of Medicine.Each year in the United States, about 20,000 people are diagnosed with a type of brain tumor called glioblastoma. Grady, who lives in Seattle, had the usual surgery, radiation and chemotherapy, but the cancer came back.He enrolled in a clinical trial at City of Hope and had some of his own blood cells, called T cells, removed and genetically modified in the lab to turn them into specialized soldiers to seek and destroy cancer.

The treatment, called CAR-T cell therapy, has been used for blood cancers, but its value for solid tumors is unknown. City of Hope has been testing injecting the cells directly into the brain.First, Grady had more surgery to remove three of his largest tumors. Then he got six weekly infusions of the cells through a tube into his brain, where the biggest one had been. No cancer recurred there, but the remaining tumors continued to grow, new ones appeared, and cancer spread to his spine.

Doctors decided on a bold step: placing a second tube in his brain, into a cavity where spinal fluid is made, and putting the cells there.”The idea was to have the flow of the spinal fluid carry the T cells to different locations,” along the route the cancer had taken, Badie said.After three treatments, all tumors had shrunk dramatically. After the 10th treatment, “we saw all the tumors disappear,” and Grady was able to cut back on other medicines and return to work, Badie said.

New tumors, though, have now emerged in different spots in his brain and spine, and he is getting radiation treatment. But his response to immunotherapy lasted more than seven months, and “for him to live more than a year and half” after starting it is amazing for a situation where survival often is measured in weeks, Badie said.Side effects of the treatment were manageable, including headaches, fatigue and muscle aches, and some may have been due to other medicines Grady needed, doctors reported.

It’s early research, but it’s an advance for the field “that they showed this is safe, at least in this patient,” said Dr. Donald O’Rourke, a neurosurgeon heading a similar study at the University of Pennsylvania.O’Rourke treated 10 brain tumor patients with CAR-T cells but used a single IV dose. A paper detailing results is in the works, but “it’s pretty striking what we’ve found,” he said.At City of Hope, nine patients have been treated so far, but only three with infusions into the spinal fluid brain cavity. Two of the nine have not responded to treatment, Badie said.

His study is supported by the nonprofit Gateway for Cancer Research, the Food and Drug Administration, the California Institute for Regenerative Medicine and the National Institutes of Health. Some authors get royalties from pending patents or money from Mustang Bio, Inc., which has licensed some of the technology.



Understanding The Human Mind


Energy is this movement from possibility to actuality through a series of probabilities.

Dr. Dan Siegel is a clinical professor of psychiatry at the UCLA School of Medicine, the founding co-director of the Mindful Awareness Research Center at UCLA, and Executive Director of the Mindsight Institute. The author of multiple bestselling books on mindfulness, development, and neurobiology, Dr. Siegel joined Heleo’s Mandy Godwin on Facebook Live to discuss the mysteries of the human mind.

Mandy: Your new book, Mind, includes a quote by Albert Einstein, about how our idea of being separate from the rest of the world is an “optical delusion.” How is that?

Dan: Einstein used the word “delusion,” a psychotic belief that’s not consistent with reality. When you look at what the mind is, it might be something more than just brain activity. The interconnections we have make the self that comes from the mind not just a solo product, not just within your head. I think that’s what Einstein was referring to, that there’s something about the human condition that gets us to this false belief that we’re separate.

Mandy: Absolutely. In fact, something that you’ve brought up is that many of our disciplines aren’t even sure what we’re talking about when we refer to “mind.”

Dan: This is the reason I wrote the book, because the word “mind” does not have a definition in my original field, which is psychiatry. It doesn’t have a definition in the field of medicine. It doesn’t even have a definition in the field of psychology.

Mandy: What was the working definition of “mind” that you came up with?

Dan: The “mind” is some aspect of energy and information flow. Flow means change; information is a pattern of energy with symbolic value. Energy is this movement from possibility to actuality through a series of probabilities.

Mind, in the subjective experience of it, consciousness and information processing, can be some emergent property of energy and information flow.

Mandy: And where is our mind exactly?

Dan: Yes, people often say, “Well, my mind is. But where is it?” A lot of people turn to what Hippocrates said 2,500 years ago, which has been affirmed by scientists—it’s the common view: “mind is what brain does.” That puts the mind only in your head.

Of course the brain affects mental life, your feelings, your thoughts, your consciousness, memory, meaning, beliefs, attitudes, for sure, but is it limited to your skull? This is the issue.

Mandy: You mean, it’s not exclusively neural, it’s also social and interactive. So if it’s not just in your head, just in your skull, then where can you find the mind?

“The mind isn’t just influenced by other people—which is classic to social neuroscience— the mind emerges in the between-ness.”

Dan: You would find it throughout your whole body. Right now, your heart is influencing energy and information flow within your skin-encased body. It’s happening in your intestines. We know the bacteria that you ate this morning that you have in your intestines are going to affect the way you feel and think. Your intestines and your heart are a fundamental part of energy and information flow within your experience.

Right now, between me and you, we have energy and information flowing. Someone watching us could say, “Oh yeah, Mandy and Dan are talking. When Dan coughs, he keeps on putting his hand up [on the microphone],” because I have the mind of you and the mind of other people who are going to hear my coughing, so I cover this up so my coughing isn’t so loud. We have this interconnected mind.

If I were a person who were just thinking my mind came from my brain, I could say, “Well, our social signals influence each other.” What we’re saying here in this question, “Where is the mind?”, is the mind isn’t just influenced by other people—which is classic to social neuroscience—the mind emerges in the between-ness. There’s something happening right here, in the pattern of the way you’re responding to me. Studies show if we mirror each other, we’re going to secrete more oxytocin. We’re going to have a more compatible way of talking to each other than if I started doing stuff that showed I wasn’t resonating with you.

That’s a between-ness. We don’t become each other. We stay differentiated, but we become linked. That’s the “where,” as much between as within.

Mandy: Most of the time, what we hear about in studies is the mind as brain activity, neuroscience. We don’t hear much of that linkage outside. It seems novel in many ways.

Dan: I knew there would be people who would say, “Well, we know mind is just the brain activity, so why don’t you talk more about the brain?” I’ve written books like that, and there are lots of books written like that. Let’s look at the big picture of what the mind is. If you want a thing just on brain anatomy, go look at a book on brain anatomy. Let’s talk about the wholeness of the mind.

Mandy: You pose the question “when is the mind?” How does the concept of time apply to the mind?

Dan: You need to look into the science of time. Researching and writing this book helped illuminate something I had been feeling, but couldn’t really articulate, since I was about 11 years old. Sometimes in my mental life, I would have a feeling of, “Okay, time is passing, time is flowing, there’s not enough time, oh my God, things come and go.” At other times, I’d feel this timeless quality. Did you ever have that experience?

Mandy: Absolutely, especially when you’re really in the middle of something very engaging. There have been times where it seems as though a whole day can pass and you don’t even know, you’re immersed.

“It turns out that there isn’t something called time flowing, there’s just change happening. Time is really our awareness of change.”

Dan: Exactly, and other times you go, “Oh my God, I wish this would last forever.” Time is not something that flows like water in a river. Time as something that flows—we don’t have evidence for that. There is something called the arrow of time, which could be renamed the directionality of change. If you and I had an egg and cracked it open here, we couldn’t un-crack the egg. There’s a directionality of change. It’s now splayed all over the table. You can’t un-crack it.

It turns out that there isn’t something called time flowing, there’s just change happening. Time is really our awareness of change. There are macro-states that have this directionality of change, but there are micro-states that have no arrow of time, no directionality.

The answer to the “when” of mind is that macro-state energy and information flow patterns, like a thought, have a directionality—they come and they go. In this practice called “the wheel of awareness,” I think you can drop into a micro-state condition where consciousness arises and has no directionality of change. It is timeless. Some states of pure consciousness, which you can get at when you’re in the flow of things or when you do reflective practice, can enter this timeless state.

Mandy: You’ve talked about meditative practice, and how that might lead to more awareness.

Dan: Yes, you can open your awareness to all sorts of things. This is the issue of the immersion of the book. I wanted the book to be an experience, not just a download of information, to be relational as writing, to ask these questions rather than just give final answers, and to let the questioning connect the reader to their own inner experience, as well as to me, as we go on the journey together. Also to say, “Look, these questions can open up your own experience of your mind.”

The “why” of mind was, emotionally, the most challenging to write, because it’s a little audacious. It’s really a question: “Is there a why of mind?” For me, when I say the mind is a self-organizing emergent embodiment of the relational process, then the “why” of self-organization has an answer, and it’s integration.

Integration is where you take different parts and link them to create more well-being. Relationally, what it means is you create more kindness and compassion toward others, and even toward yourself. Another outcome is curiosity and creativity, and openness to life as it unfolds.

Mandy: That’s very hopeful. There’s a really interesting anecdote where you bring in this concept of feelings not having a scientific basis. That struck me—science doesn’t want to encounter feelings. One thing that your project has been taking on is that integration of the emotional life and the neural life.

Dan: I think the way to begin is to honor that science wants and needs to carefully observe things. Usually, it wants to measure things with numbers, to do statistical analyses, that’s fine. But what if the entity that we want to explore is something called subjective experience? Which would include emotions, but it also includes thoughts, perceptions, memories, beliefs, hopes, dreams, longings, attitudes, desires. That’s all the stuff of the mind. We put that under the phrase “subjective experience,” meaning you cannot really objectively measure it, or even observe it.

You and I see red, right? Even if we put 18 different options of red and we both pick the same one of the 18, I have no idea if the way you see red and the way I see red is the same. Poetry and art evoke subjective experiences. Even if I took a photograph, I have no idea if the feeling it evoked in me will be the feeling it evokes in you. You will have a subjective experience, and honoring that is important.

“You only get about 100 years in the body, but if you realize you are much more than your body, you’ve just achieved connection to people and living beings that were before you, and will be afterwards. You get this very different sense of vitality and meaning and purpose to life.”

From a scientific point of view, it’s important to recognize that you can’t observe subjective experience. The other thing is that, if we have teachings from our parents, from our schools, from society, that the self is a solo job that comes from your head, and that the mind is just brain activity, then what you say is, “Who you are is just your body.”

The sad outcome of that teaching is that you’re alone in this life. People feel so isolated because they see the “me” as separate. Then of course all you want to do is accumulate more stuff for “me,” get more for “me,” it’s about “me.” There’s not much in that that’s going to produce happiness or any positive outcome for the planet. What I talk about is an integrated identity, honoring that you have a “me” in the body, you get about 100 years to live in that body, awesome. Take care of the body well, exercise the body, feed the body, great. No one is saying the body isn’t important.

We’re also saying that differentiating the “me” within the body needs to be balanced with differentiating the “we” that is so under-recognized. That “we” identity needs to be talked about in homes and in classrooms and in the media. What’s been so exciting about it is people feel this opening up to a more authentic and real way of imagining where is your mind, who you are, why you’re here, what you can do with your life. You only get about 100 years in the body, but if you realize you are much more than your body, you’ve just achieved connection to people and living beings that were before you, and will be afterwards. You get this very different sense of vitality and meaning and purpose to life.

Unfortunately, in modern society, we’ve been living this very isolationist life. It’s a partial truth. To return to Einstein’s words, it’s an “optical delusion,” a psychotic belief. To be bold about it, it’s a lie that may be lethal. The more we believe that lie, the more we treat the planet like a trashcan, and there’s not much hope for the future.

Part of why I wrote the book was to open the conversation up with questions that can become a win-win-win situation. You get closer to the truth in yourself, that’s one win. You feel how you can develop well-being in your relationships with others, that’s the second win. The third win is that the planet is waiting for this transformation of our understanding of who we are and what to do with our lives collectively on Earth.


Pain Medication From Natures Garden

Heres another example of how nature is indeed humanities medicine cabinet check out this article below!

Your body would never get used to the perfect painkiller, says Susruta Majumdar, a chemist at Memorial Sloan Kettering Cancer Center. So unlike the case with common opioids such as morphine or Oxycontin, you would not need to take ever-increasing doses to relieve the same amount of pain. The ideal analgesic would not have the high risk of addiction, withdrawal or fatal respiratory slowdowns that have turned opioid abuse into a massive epidemic. The holy grail of painkillers would not induce the seductive euphoria of common opioids or their less-pleasant side effects like itching or constipation.

A painkiller with just one of these properties would be great, but Majumdar thinks he has stumbled onto a class of chemicals that might have them all. They are found in kratom, a plant that the U.S. Drug Enforcement Administration intends to effectively ban from the U.S. in an emergency move as early as September 30. Without legal access to it, research on some of the most promising leads for a better painkiller may grind to a crawl.

Kratom comes from the Mitragyna speciosa tree native to parts of Southeast Asia, where people chew the leaves for a light, caffeine-like jolt of energy or as a traditional medicine for ailments ranging from diarrhea to pain. Kratom has been illegal since 1943 in Thailand, where it is believed to be addictive. Case studies have suggested that suddenly stopping regular kratom use may lead to withdrawal symptoms—but they are widely considered milder than those associated with opioids.

Majumdar first learned about kratom via a Web search a couple of years ago. By then there were stories in the West about how kratom tea could be used to manage pain—and to mitigate brutal opioid withdrawal. That caught Majmundar’s attention, and he found research from the 1970s that described some of the basic biochemistry of kratom’s two primary psychoactive compounds, mitragynine and 7-hydroxymitragynine, as well as one more molecule called mitragynine pseudoindoxyl, which is produced when kratom ferments. “We got excited because the chemical structure is almost completely unrelated to that of commonly used opioids,” says Andras Varadi, a colleague of Majumdar who is a medicinal chemist at Columbia University and Sloan Kettering.

When Majumdar and his team started studying the compounds in the laboratory, they realized all three molecules were binding to the mu-opioid receptor—one of three known kinds of opioid receptors in the brain—in an unconventional way. Think of this receptor as the ignition to a “hybrid car,” Varadi explains, and the opioids that bind to it as keys. A typical opioid such as morphine turns on the “electric engine,” and that leads to a desired effect like pain relief. But it also starts up the “gas engine,” causing negative side effects. The mitragynine molecules from kratom seem to activate mostly the “good” systems, leaving behind the unwanted effects yet keeping pain relief.

Scientists have been trying to develop next-generation drugs with this property. There is one candidate, pharmaceutical company Trevena’s TRV130, in clinical trials now. That’s part of what makes kratom exciting to researchers, says Laura Bohn, a biochemist at the Scripps Research Institute who was not involved with this work. “The more chemical structures you have [with this property] the more you can say, ‘here’s the right features of these, and let’s impart that into our drug development.’”

Majumdar noticed that the fermented-kratom compound mitragynine pseudoindoxyl—unlike most other drugs in development—also blocks off another opioid receptor, the delta receptor. “That’s when we got excited,” Majumdar says. Past experiments have shown that delta receptor blockers could reduce morphine tolerance and withdrawal symptoms in mice. “There were signs that delta antagonism is good,” Majumdar says. And if mitragynine pseudoindoxyl could both block the delta receptor and produce favorable behavior on the mu receptor, Majumdar says it might be better than any other pain drug science is currently investigating.

In an attempt to find out about these blocking capabilities Varadi injected mice with mitragynine pseudoindoxyl twice a day for a month. Then he checked if they could feel pain, using techniques such as putting them on a hot plate. In such experiments morphine usually loses its painkilling effects after five days. But after 30 days on a consistent dose of mitragynine pseudoindoxyl, the mice still showed numbness to pain. “It was the most exciting experiment I’ve ever done,” Varadi says. In other experiments Varadi and Majumdar reported that the mice exhibited few withdrawal symptoms from mitragynine pseudoindoxyl—and they displayed no indication that they actually enjoyed taking the drug. “[This is] early promise it’s nonaddictive,” Majumdar says. His team reported its findings in The Journal of Medicinal Chemistry last month.

Varadi says his results indicate that mitragynine pseudoindoxyl may have the peculiar ability to both activate the mu receptor—possibly making it a powerful painkiller that also reduces addictive and potentially deadly side effects—as well as lower withdrawal and tolerance. “It’s a double whammy,” Varadi says.

Although the kratom compounds have yet to be clinically studied in humans, Andrew Kruegel, a pharmacologist at Columbia who was not involved in Varadi’s study, says the results hold promise for better designer painkillers. “Those compounds alone may already be superior to codeine and oxycodone. At a minimum, if you can get rid of respiratory [problems] then you can save thousands of lives,” Kruegel says. “But we can tweak their properties to make them even better than the natural starting point.” Or they would do so if the research were able to legally continue, he adds.

The DEA plans to place kratom and its psychoactive ingredients in the agency’s most restricted controlled substance category, Schedule I, on September 30 at the earliest. That would place it in the same group as heroin, ecstasy and marijuana. All Schedule I drugs are supposed to have a high potential for abuse and harm, and to have no medical use.

Scientists can obtain a license to study Schedule I drugs but they are hard to acquire and significantly slow down research, says Chris McCurdy, a kratom researcher at the University of Mississippi. “I don’t oppose it being regulated, I just oppose Schedule I,” he says. “That’s where the frustration comes in, realizing you have to shut everything down because we don’t have a Schedule I license.”

At the moment, neither do several other kratom researchers, including Majumdar. “We’ll have to destroy all our samples in the lab,” Kruegel says. The DEA’s emergency scheduling of kratom will expire after two years if the agency does not move to make the scheduling permanent. But for that to happen, Kruegel thinks scientists will likely need to show further proof that kratom is medically useful. “That we’ll have any progress in the next two years is very unlikely,” he says.

Russ Baer, a spokesperson for the DEA, says the reason for putting kratom and its psychoactive ingredients in the most restrictive drug category is to protect public safety and stop misuse. “Independent of the DEA, the Food and Drug Administration has issued a number of public health warnings and import alerts, most recently about July 2016, and concerns they have about kratom representing a health risk,” he says. “And it’s been on our radar for awhile as a drug of concern.”

A DEA announcement cited 15 kratom-related deaths between 2014 and 2016, and there have also been accounts of kratom being misused. “One of my [research] partners has treated people in the emergency room who would dissolve and then inject kratom extract,” says Ed Boyer, a professor of emergency medicine at University of Massachusetts Medical School and a kratom researcher. Most of these incidences of abuse probably involved other substances as well, he adds.

Some Kratom purchased in the U.S. has been found to be adulterated with other compounds, including common opioids like hydrocodone. “People think they’re getting kratom; they could be getting anything,” says Kavita Babu, a toxicologist at UMass Memorial Medical Center who was not involved with Majumdar’s study. “In terms of death, we really only get into that issue when it’s combined with other substances,” says Alicia Lydecker, also a toxicologist at UMass. She was not involved in the study.

Mitragynine seems to be a fairly weak drug on its own, Majumdar says. It is about 55 times less potent than morphine in terms of pain relief. “I did drink kratom tea,” he says, “and I felt nothing.” Another compound, 7-hydroxymitragynine, is about six times more potent than morphine—but Majumdar says it occurs in such small amounts in the plant that it is probably not responsible for most effects experienced by consumers of unaltered, natural kratom.

The DEA’s decision on kratom has even begun to draw critical attention from U.S. lawmakers. Rep. Mark Pocan (D–Wis.) has urged Congress to sign a letter asking the DEA to delay making it a controlled substance. But the impending ban has left an especially bitter taste with many researchers who feel there is already ample evidence the plant has clear medical potential. “It is frustrating,” Bohn says. “I totally empathize with trying to prevent misuse, but it has to be thoughtful and protective. For us, [kratom] is a valuable, valuable research tool.”

SOURCE …www.scientificamerican.com