Posted: June 29, 2017 | Author: Pundit Planet | Filed under: Health and Social Issues, Science & Technology | Tags: ABI Research, Chronic pain, Medicine, Neuroscience, Research |
Study in mice reveals how brain circuitry goes haywire after peripheral nerve damage.
Beth Mole reports: Chronic, aching pain after an injury or operation may be all in your head. Researchers now think they’ve figured out exactly how brain wiring goes haywire to cause persistent pain—and how to fix it.
In mice with peripheral nerve damage and chronic pain from a leg surgery, a broken circuit in a pain-processing region of mammalian brains caused hyperactive pain signals that persisted for more than a month. Specifically, the peripheral nerve damage seemed to deactivate a type of interconnected brain cells, called somatostatin (SOM) interneurons, which normally dampen pain signals. Without the restraints, neurons that fire off pain signals—cortical pyramidal neurons—went wild, researchers report in Nature Neuroscience.
But the circuitry could be repaired, the researchers found. Just by manually activating those pain-stifling SOM interneurons, the researchers could shut down the rodents’ chronic pain and keep the system working properly—preventing centralized, chronic pain from ever developing.
“Our findings suggest that manipulating interneuron activity after peripheral nerve injury could be an important avenue for the prevention of pyramidal neuron over-excitation and the transition from acute postoperative pain to chronic centralized pain,” the authors, led by neuroscientist Guang Yang at New York University School of Medicine, conclude. Yang and his colleagues envision future drugs or therapies, such as transcranial magnetic stimulation, to tweak the activity of the interneurons to prevent malfunctioning pain signaling.
The study is just in mice, so it needs repeating and verifying before the line of research can move forward. That said, the work is backed by and in-line with a series of human and animal studies on chronic pain. Read the rest of this entry »
Posted: February 7, 2015 | Author: Pundit Planet | Filed under: Health and Social Issues, Science & Technology | Tags: Acute lymphoblastic leukemia, Albert Hofmann, Andy Warhol, Behavioral health, Diagnostic and Statistical Manual of Mental Disorders, hallucinogens, Henry Kissinger, LSD, Medicine, Psilocybin mushrooms, Richard Nixon, War on Drugs, Washington DC |
The Trip Treatment
Michael Pollan writes: On an April Monday in 2010, Patrick Mettes, a fifty-four-year-old television news director being treated for a cancer of the bile ducts, read an article on the front page of the Times that would change his death. His diagnosis had come three years earlier, shortly after his wife, Lisa, noticed that the whites of his eyes had turned yellow. By 2010, the cancer had spread to Patrick’s lungs and he was buckling under the weight of a debilitating chemotherapy regimen and the growing fear that he might not survive. The article, headlined “Hallucinogens Have Doctors Tuning in Again,” mentioned clinical trials at several universities, including N.Y.U., in which psilocybin—the active ingredient in so-called magic mushrooms—was being administered to cancer patients in an effort to relieve their anxiety and “existential distress.” One of the researchers was quoted as saying that, under the influence of the hallucinogen, “individuals transcend their primary identification with their bodies and experience ego-free states . . . and return with a new perspective and profound acceptance.” Patrick had never taken a psychedelic drug, but he immediately wanted to volunteer. Lisa was against the idea. “I didn’t want there to be an easy way out,” she recently told me. “I wanted him to fight.”
“I felt a little like an archeologist unearthing a completely buried body of knowledge. Some of the best minds in psychiatry had seriously studied these compounds in therapeutic models, with government funding.”
— Anthony Bossis
Patrick made the call anyway and, after filling out some forms and answering a long list of questions, was accepted into the trial. Since hallucinogens can sometimes bring to the surface latent psychological problems, researchers try to weed out volunteers at high risk by asking questions about drug use and whether there is a family history of schizophrenia or bipolar disorder. After the screening, Mettes was assigned to a therapist named Anthony Bossis, a bearded, bearish psychologist in his mid-fifties, with a specialty in palliative care. Bossis is a co-principal investigator for the N.Y.U. trial.
After four meetings with Bossis, Mettes was scheduled for two dosings—one of them an “active” placebo (in this case, a high dose of niacin, which can produce a tingling sensation), and the other a pill containing the psilocybin. Both sessions, Mettes was told, would take place in a room decorated to look more like a living room than like a medical office, with a comfortable couch, landscape paintings on the wall, and, on the shelves, books of art and mythology, along with various aboriginal and spiritual tchotchkes, including a Buddha and a glazed ceramic mushroom. During each session, which would last the better part of a day, Mettes would lie on the couch wearing an eye mask and listening through headphones to a carefully curated playlist—Brian Eno, Philip Glass, Pat Metheny, Ravi Shankar. Bossis and a second therapist would be there throughout, saying little but being available to help should he run into any trouble.
“I thought the first ten or twenty people were plants—that they must be faking it. They were saying things like ‘I understand love is the most powerful force on the planet,’ or ‘I had an encounter with my cancer, this black cloud of smoke.’ People who had been palpably scared of death—they lost their fear. The fact that a drug given once can have such an effect for so long is an unprecedented finding. We have never had anything like it in the psychiatric field.”
I met Bossis last year in the N.Y.U. treatment room, along with his colleague Stephen Ross, an associate professor of psychiatry at N.Y.U.’s medical school, who directs the ongoing psilocybin trials. Ross, who is in his forties, was dressed in a suit and could pass for a banker. He is also the director of the substance-abuse division at Bellevue, and he told me that he had known little about psychedelics—drugs that produce radical changes in consciousness, including hallucinations—until a colleague happened to mention that, in the nineteen-sixties, LSD had been used successfully to treat alcoholics. Ross did some research and was astounded at what he found.
“I felt a little like an archeologist unearthing a completely buried body of knowledge,” he said. Beginning in the nineteen-fifties, psychedelics had been used to treat a wide variety of conditions, including alcoholism and end-of-life anxiety. The American Psychiatric Association held meetings centered on LSD. “Some of the best minds in psychiatry had seriously studied these compounds in therapeutic models, with government funding,” Ross said.
Between 1953 and 1973, the federal government spent four million dollars to fund a hundred and sixteen studies of LSD, involving more than seventeen hundred subjects. (These figures don’t include classified research.) Through the mid-nineteen-sixties, psilocybin and LSD were legal and remarkably easy to obtain. Sandoz, the Swiss chemical company where, in 1938, Albert Hofmann first synthesized LSD, gave away large quantities of Delysid—LSD—to any researcher who requested it, in the hope that someone would discover a marketable application. Psychedelics were tested on alcoholics, people struggling with obsessive-compulsive disorder, depressives, autistic children, schizophrenics, terminal cancer patients, and convicts, as well as on perfectly healthy artists and scientists (to study creativity) and divinity students (to study spirituality). The results reported were frequently positive. But many of the studies were, by modern standards, poorly designed and seldom well controlled, if at all. When there were controls, it was difficult to blind the researchers—that is, hide from them which volunteers had taken the actual drug. (This remains a problem.)
- Also see – Psychedelics: Poised for a Comeback (punditfromanotherplanet.com)
By the mid-nineteen-sixties, LSD had escaped from the laboratory and swept through the counterculture. In 1970, Richard Nixon signed the Controlled Substances Act and put most psychedelics on Schedule 1, prohibiting their use for any purpose. Research soon came to a halt, and what had been learned was all but erased from the field of psychiatry. “By the time I got to medical school, no one even talked about it,” Ross said.
“People don’t realize how few tools we have in psychiatry to address existential distress. Xanax isn’t the answer. So how can we not explore this, if it can recalibrate how we die?”
The clinical trials at N.Y.U.—a second one, using psilocybin to treat alcohol addiction, is now getting under way—are part of a renaissance of psychedelic research taking place at several universities in the United States, including Johns Hopkins, the Harbor-U.C.L.A. Medical Center, and the University of New Mexico, as well as at Imperial College, in London, and the University of Zurich. As the drug war subsides, scientists are eager to reconsider the therapeutic potential of these drugs, beginning with psilocybin. (Last month The Lancet, the United Kingdom’s most prominent medical journal, published a guest editorial in support of such research.) The effects of psilocybin resemble those of LSD, but, as one researcher explained, “it carries none of the political and cultural baggage of those three letters.” LSD is also stronger and longer-lasting in its effects, and is considered more likely to produce adverse reactions. Researchers are using or planning to use psilocybin not only to treat anxiety, addiction (to smoking and alcohol), and depression but also to study the neurobiology of mystical experience, which the drug, at high doses, can reliably occasion. Forty years after the Nixon Administration effectively shut down most psychedelic research, the government is gingerly allowing a small number of scientists to resume working with these powerful and still somewhat mysterious molecules.
Albert Hofmann
“Thirty minutes after my taking the mushrooms, the exterior world began to undergo a strange transformation. Everything assumed a Mexican character.”
— Albert Hofmann
As I chatted with Tony Bossis and Stephen Ross in the treatment room at N.Y.U., their excitement about the results was evident. According to Ross, cancer patients receiving just a single dose of psilocybin experienced immediate and dramatic reductions in anxiety and depression, improvements that were sustained for at least six months. The data are still being analyzed and have not yet been submitted to a journal for peer review, but the researchers expect to publish later this year.
“I thought the first ten or twenty people were plants—that they must be faking it,” Ross told me. “They were saying things like ‘I understand love is the most powerful force on the planet,’ or ‘I had an encounter with my cancer, this black cloud of smoke.’ People who had been palpably scared of death—they lost their fear. The fact that a drug given once can have such an effect for so long is an unprecedented finding. We have never had anything like it in the psychiatric field.”
Aldous Huxley. Huxley proposed a research project involving the “administration of LSD to terminal cancer cases, in the hope that it would make dying a more spiritual, less strictly physiological process.” Huxley had his wife inject him with the drug on his deathbed; he died at sixty-nine, of laryngeal cancer, on November 22, 1963.
I was surprised to hear such unguarded enthusiasm from a scientist, and a substance-abuse specialist, about a street drug that, since 1970, has been classified by the government as having no accepted medical use and a high potential for abuse. But the support for renewed research on psychedelics is widespread among medical experts. “I’m personally biased in favor of these type of studies,” Thomas R. Insel, the director of the National Institute of Mental Health (N.I.M.H.) and a neuroscientist, told me. “If it proves useful to people who are really suffering, we should look at it. Just because it is a psychedelic doesn’t disqualify it in our eyes.” Nora Volkow, the director of the National Institute on Drug Abuse (nida), emphasized that “it is important to remind people that experimenting with drugs of abuse outside a research setting can produce serious harms.”
Many researchers I spoke with described their findings with excitement, some using words like “mind-blowing.” Bossis said, “People don’t realize how few tools we have in psychiatry to address existential distress. Xanax isn’t the answer. So how can we not explore this, if it can recalibrate how we die?”
Herbert D. Kleber, a psychiatrist and the director of the substance-abuse division at the Columbia University–N.Y. State Psychiatric Institute, who is one of the nation’s leading experts on drug abuse, struck a cautionary note. “The whole area of research is fascinating,” he said. “But it’s important to remember that the sample sizes are small.” He also stressed the risk of adverse effects and the importance of “having guides in the room, since you can have a good experience or a frightful one.” But he added, referring to the N.Y.U. and Johns Hopkins research, “These studies are being carried out by very well trained and dedicated therapists who know what they’re doing. The question is, is it ready for prime time?”
The idea of giving a psychedelic drug to the dying was conceived by a novelist: Aldous Huxley. In 1953, Humphry Osmond, an English psychiatrist, introduced Huxley to mescaline, an experience he chronicled in “The Doors of Perception,” in 1954. (Osmond coined the word “psychedelic,” which means “mind-manifesting,” in a 1957 letter to Huxley.) Huxley proposed a research project involving the “administration of LSD to terminal cancer cases, in the hope that it would make dying a more spiritual, less strictly physiological process.” Huxley had his wife inject him with the drug on his deathbed; he died at sixty-nine, of laryngeal cancer, on November 22, 1963.
Psilocybin mushrooms first came to the attention of Western medicine (and popular culture) in a fifteen-page 1957 Life article by an amateur mycologist—and a vice-president of J. P. Morgan in New York—named R. Gordon Wasson. In 1955, after years spent chasing down reports of the clandestine use of magic mushrooms among indigenous Mexicans, Wasson was introduced to them by María Sabina, a curandera—a healer, or shaman—in southern Mexico. Wasson’s awed first-person account of his psychedelic journey during a nocturnal mushroom ceremony inspired several scientists, including Timothy Leary, a well-regarded psychologist doing personality research at Harvard, to take up the study of psilocybin. After trying magic mushrooms in Cuernavaca, in 1960, Leary conceived the Harvard Psilocybin Project, to study the therapeutic potential of hallucinogens. His involvement with LSD came a few years later. Read the rest of this entry »
Posted: January 12, 2015 | Author: Pundit Planet | Filed under: Health and Social Issues, U.S. News | Tags: Andrew Jackson, drugs, Federal government of the United States, Medicine, NIH, Pain, Time Magazine, United States, United States Department of Justice, United States federal courts |
A new federal report reveals holes in how we treat chronic pain
Alexandra Sifferlin
writes: Chronic pain affects an estimated 100 million Americans, and between 5 to 8 million use opioids for long-term pain management. Data shows the number of prescriptions written for opioids as well opioid overdose deaths have skyrocketed in recent years, highlighting a growing addiction problem in the U.S. In response, the National Institutes of Health (NIH) released a report on Monday citing major gaps in the way American clinicians are treating pain.
“The prevalence of chronic pain and the increasing use of opioids have created a ‘silent epidemic’ of distress, disability, and danger to a large percentage of Americans.”
In September, the NIH held a workshop to review chronic pain treatment with a panel of seven experts and more than 20 speakers. The NIH also reviewed relevant research on how pain should be treated in the United States. On Monday the NIH published its findings in the Annals of Internal Medicine, detailing a lack of research into better treatment methods and poor preparedness among physicians. “The prevalence of chronic pain and the increasing use of opioids have created a ‘silent epidemic’ of distress, disability, and danger to a large percentage of Americans,” the report authors write. “The overriding question is: Are we, as a nation, approaching management of chronic pain in the best possible manner that maximizes effectiveness and minimizes harm?”
“The overriding question is: Are we, as a nation, approaching management of chronic pain in the best possible manner that maximizes effectiveness and minimizes harm?”
The answer is no, the report reveals. The number of opioid prescriptions for pain has gone from 76 million in 1991 to 219 million in 2011, and according to recent Centers for Disease Control and Prevention (CDC) data, the latest figures show around 17,000 opioid-related overdose deaths in 2011. Between 2007 and 2010, the number of hospitalizations for opioid addiction increased four-fold. As TIME recently reported, the growing opioid problem means the nation also has a growing heroin problem, since both drugs offer similar highs, and heroin is cheaper and doesn’t need a prescription. Read the rest of this entry »
Posted: December 2, 2014 | Author: Pundit Planet | Filed under: Science & Technology | Tags: Brain, Medicine, Organs, self-directed morphogenesis, Sonic Hedgehog protein, Spinal cord, Stem cells |
As regenerative medicine and stem cell technologies continue to progress, so the list of tissues and organs that can be grown from scratch – and potentially replaced – continues to grow. In the past few years, researchers have used stem cells to grow windpipes, bladders, urethras and vaginas in the lab, and, in some cases, successfully transplanted them into patients.
Others are making progress in growing liver and heart tissue; one team in London is busy growing blood vessels, noses and ears; and some have even managed to grow tiny chunks of brain tissue, the most complex of all the tissues in the human body. Now, researchers in Germany report that they have grown complete spinal cords from embryonic stem cells.
Most efforts to grow tissues and organs rely on biodegradable scaffolds. When ‘seeded’ with a patient’s stem cells, these scaffolds provide a surface for the cells to latch on to and provide them with nutrients. The scaffold delivers the signals needed for the stem cells to differentiate along the correct path, and its structure coaxes them to form tissue of the right shape.
Nervous tissue is extremely complex, however. It starts off as a flat sheet of cells on the top surface of the embryo, called the neural plate, which, through a series of elaborate deformations, buckles and folds in on itself to form a hollow tube. One end of this neural tube will eventually form the brain, and the other the spinal cord. This complexity makes scaffolds unsuitable for growing nervous tissue, as they cannot be manufactured in the intricate shapes needed.
Andrea Meinhardt of the Dresden University of Technology and her colleagues therefore exploited a property of stem cells known as self-directed morphogenesis, first discovered by the late Yoshiki Sasai. About 10 years ago, Sasai and his colleagues developed a method for growing embryonic stem cells in three-dimensional suspension, and found that cells grown in this way can, when fed the right combination of signalling molecules, go through the motions of development and organize themselves to form complex tissues such as eyes, glands and bits of brain.
Meinhardt and her colleagues used a variation of Sasai’s technique, and embedded single-cell suspensions of mouse embryonic stem cells within a three-dimensional nutrient gel on Petri dishes. When left untreated, the cells begin to differentiate into immature neurons, giving rise to spherical structures containing immature cells resembling those found in the neural plate. Read the rest of this entry »
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