from the the-chicken-crossed-the-road-to-do-LSD dept.
A group of volunteers who took a trip in the name of science have helped researchers uncover how LSD messes with activity in the brain to induce an altered state of consciousness.
Brain scans of individuals high on the drug revealed that the chemical allows parts of the cortex to become flooded with signals that are normally filtered out to prevent information overload.
The drug allowed more information to flow from the thalamus, a kind of neural gatekeeper, to a region called the posterior cingulate cortex, and it stemmed the flow of information to another part known as the temporal cortex. [...] The scientists wanted to test a hypothesis first put forward more than a decade ago. It states LSD causes the thalamus to stop filtering information it relays to other parts of the brain. It is the breakdown of this filter that gives rise to the weird effects the drug induces, or so the thinking goes.
Effective connectivity changes in LSD-induced altered states of consciousness in humans (open, DOI: 10.1073/pnas.1815129116) (DX)
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From 'problem Child' to 'prodigy'? LSD Turns 75
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.
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. Through the mid-nineteen-sixties, psilocybin and LSD were legal and remarkably easy to obtain. Sandoz, the Swiss chemical company, gave away large quantities of Delysid—LSD—to any researcher who requested it, in the hope that someone would discover a marketable application.
Now, 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.
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.
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.
The results taste orange.
Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use (DOI: 10.1016/j.cobeha.2016.10.009) (DX)
Psychedelics not linked to mental health problems or suicidal behavior: A population study (open, DOI: 10.1177/0269881114568039) (DX)
In small studies around the country, a handful of researchers have been investigating how MDMA-assisted psychotherapy can help heal the psychological and emotional damage caused by sexual assault, war, violent crime, and other traumas. Now, federal regulators have approved the drug for use in large-scale clinical trials too—a move that could set the stage for making "ecstasy" legally available as a new medicine. The Phase III trials will involve at least 230 patients, and will be sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS), an organization that advocates for the medical use of various psychedelics, including MDMA (otherwise known as ecstasy or Molly or millennial aspirin). The organization funded early safety and efficacy trials of the drug in the past. And in one pilot study involving 19 PTSD patients, more than half experienced decreased symptoms for up to six years after receiving three doses of MDMA.
Scientists may have found why a LSD trip lasts so long:
By freezing an LSD molecule bound to a single brain cell receptor as a crystal in a lab, researchers were able to get a 3-D x-ray image of the drug and the protein locked together. "My lab has been trying to do this since the early 1990s," says Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill and senior author on the paper. "I remember Dan Wacker [a co-author, also at U.N.C.] showing the image. It was basically a moment of silence. I started to fight back tears of gratitude that we had finally gotten it." It is the first 3-D image of a psychedelic bound to a brain receptor, Roth says.
The image showed Roth and his co-authors something strange about the way LSD fit inside this receptor. Drugs typically come and go from receptor proteins like ships pulling in and out of a port. But when an LSD molecule lands on the receptor, the molecule snags onto a portion of the protein and folds it over itself as the molecule binds to the receptor. "There was this lid that came over the molecule. It looked like it trapped LSD in the receptor," Roth says. "That immediately suggested to us why LSD lasts so long."
LSD seems to stimulate the receptor for the entire time it is trapped underneath the protein "lid," Roth says. Proteins are in constant motion, so he thinks the lid eventually flops open, allowing the drug to fly out and the effects to wear off. But the team ran computer models that suggest it could take hours for that to happen. Until then, the trip goes on.
Submitted via IRC for chromas
Lysergic acid diethylamide was labelled a "problem child" by the man who discovered its hallucinogenic properties in 1943: as it turns 75, the drug known as LSD may now be changing its image.
The late Swiss chemist Albert Hofmann famously learned of LSD's psychedelic effects when he inadvertently took a small dose while doing lab work for pharmaceutical company Sandoz.
He wanted the drug to be medically researched, convinced it could be a valuable psychiatric tool and lead to a deeper understanding of human consciousness.
But through the 1960s, LSD became synonymous with counterculture and anti-authority protests.
By the early 1970s, it had been widely criminalised in the West, prompting Hofmann to publish his 1979 memoir, "LSD: My Problem Child".
Of the 16 million American adults who live with depression, as many as one-quarter gain little or no benefit from available treatments, whether drugs or talk therapy. They represent perhaps the greatest unmet need in psychiatry. On Tuesday, the Food and Drug Administration approved a prescription treatment intended to help them, a fast-acting drug derived from an old and widely used anesthetic, ketamine.
The move heralds a shift from the Prozac era of antidepressant drugs. The newly approved treatment, called esketamine, is a nasal spray developed by Janssen Pharmaceuticals Inc., a branch of Johnson & Johnson, that will be marketed under the name Spravato. It contains an active portion of the ketamine molecule, whose antidepressant properties are not well understood yet. "Thank goodness we now have something with a different mechanism of action than previous antidepressants," said Dr. Erick Turner, a former F.D.A. reviewer and an associate professor of psychiatry at Oregon Health & Science University. "But I'm skeptical of the hype, because in this world it's like Lucy holding the football for Charlie Brown: Each time we get our hopes up, the football gets pulled away."
[...] Esketamine, like ketamine, has the potential for abuse, and both drugs can induce psychotic episodes in people who are at high risk for them. The safety monitoring will require doctors to find space for treated patients, which could present a logistical challenge, some psychiatrists said.
The wholesale cost for a course of treatment will be between $2,360 and $3,540, said Janssen, and experts said it will give the company a foothold in the $12 billion global antidepressant market, where most drugs now are generic.
[...] One question that will need to be answered is how well esketamine performs in comparison to intravenous ketamine.
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