Single LSD dose provides lasting anxiety relief: Research

The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy status to an LSD formula to treat generalized anxiety disorder after an initial study has shown that a single dose of the drug could provide lasting relief.

The LSD therapy developed by Mind Medicine Inc. (MindMed) must still go through the standard FDA approval process and will soon enter Phase 3 clinical trials.

The study that prompted FDA advancement found the drug was “generally well-tolerated with most adverse events rated as mild to moderate, transient and occurring on dosing day, and being consistent with expected acute effects of the study drug,” according to a release on the findings.

The most common adverse effects on the initial “dosing day” — or when patients were first given the drug — included hallucinations, euphoric mood, abnormal thinking, headache, dizziness and nausea, among others.

The company plans to meet for an update with the FDA in the coming months and begin an expanded clinical program in the second half of the year.

MindMed, a pharmaceutical company focused on developing psychedelic drugs into medicines, has spent years researching possible medicinal uses for LSD, an illicit drug that has never been approved for medicinal use. The specific LSD formula from the study is dubbed MM120.

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A journalist’s twenty-year fascination with the Manson murders leads to “gobsmacking” (The Ringer) new revelations about the FBI’s involvement in this “kaleidoscopic” (The New York Times) reassessment of an infamous case in American history.

Over two grim nights in Los Angeles, the young followers of Charles Manson murdered seven people, including the actress Sharon Tate, then eight months pregnant. With no mercy and seemingly no motive, the Manson Family followed their leader’s every order — their crimes lit a flame of paranoia across the nation, spelling the end of the sixties. Manson became one of history’s most infamous criminals, his name forever attached to an era when charlatans mixed with prodigies, free love was as possible as brainwashing, and utopia — or dystopia — was just an acid trip away.

Twenty years ago, when journalist Tom O’Neill was reporting a magazine piece about the murders, he worried there was nothing new to say. Then he unearthed shocking evidence of a cover-up behind the “official” story, including police carelessness, legal misconduct, and potential surveillance by intelligence agents. When a tense interview with Vincent Bugliosi — prosecutor of the Manson Family and author of Helter Skelter — turned a friendly source into a nemesis, O’Neill knew he was onto something. But every discovery brought more questions:

  • Who were Manson’s real friends in Hollywood, and how far would they go to hide their ties?
  • Why didn’t law enforcement, including Manson’s own parole officer, act on their many chances to stop him?
  • And how did Manson — an illiterate ex-con — turn a group of peaceful hippies into remorseless killers?

O’Neill’s quest for the truth led him from reclusive celebrities to seasoned spies, from San Francisco’s summer of love to the shadowy sites of the CIA’s mind-control experiments, on a trail rife with shady cover-ups and suspicious coincidences. The product of two decades of reporting, hundreds of new interviews, and dozens of never-before-seen documents from the LAPD, the FBI, and the CIA, Chaos mounts an argument that could be, according to Los Angeles Deputy District Attorney Steven Kay, strong enough to overturn the verdicts on the Manson murders. This is a book that overturns our understanding of a pivotal time in American history.”

Margaret Mead’s LSD Memo

With her paper-cluttered desk spotlit underneath a pendant lamp, Margaret Mead’s office in the western turret in the American Museum of Natural History resembled a Broadway theater set. All around her in the shadows hung masks and carved figures, as if the museum dioramas from the floors below had begun to creep into her workspace.

Back in her spiritual home after spending the last six months of 1953 in Manus, she felt refreshed, confident. She was already thinking through her book about her experience; New Lives for Old would be the title, and it would describe the Noise, an apocalyptic religious movement which spread through the island of Manus, which lies northeast of New Guinea, in the aftermath of World War II. In 1947, a prophet had emerged on Manus who predicted a coming age of abundance, even immortality. But first, the old ways had to be cast out. Reports poured in of visionary experiences, trance states, even seizures. Hats of colonial officials were ritually burned, and a coming age of abundance was proclaimed. Mead found the Noise fascinating because she saw it as a prelude to other new cultural forms which she believed would appear elsewhere as a response to the rapid changes of the 20th century—including in the United States. She saw the movement in relatively benign terms. True, it really was an apocalyptic cult, she wrote, complete with mystical “prophetic dreams” and the promise of “a utopia to be immediately established on earth.” But who said utopian dreams were entirely bad?

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THE WEIRD AND WONDERFUL WORLD OF LSD

LSD is a drug which has had a bizarre inception and nuanced history. What began as a pharmacological experiment rapidly evolved into a substance which was used for a wide range of uses. From groundbreaking psychiatric work all the way to abuse in mind control military projects, let’s dive into some of the most significant examples of psychedelics’ use in society since its creation.

Hofmann’s Accidental Ingestion

Dubbed as the father of the psychedelic movement due to his work on the synthesis of LSD, Albert Hofmann was the first to produce and ingest LSD. Albert Hofmann first synthesised Lysergic Acid Diethylamide (LSD) in November 1938 when studying the medicinal properties of the ergot fungus and the Mediterranean squill. Ergot is a fungus which grows on rye and can infect the grain causing muscle spasms, delusions, hallucinations, gangrenous symptoms and ultimately death to those who consume it. This process has been linked to plagues and famines which have killed hundreds of thousands of people in the past. 

Hofmann’s boss, Arthur Stoll, managed to isolate the toxic compounds in ergot: ergotamine and ergobasine. By utilising Aotamine, the medicinal compound in ergot, Stoll was able to produce medicines for his Swiss pharmaceutical company Sandoz. 

Hofmann originally intended for LSD to be used as a respiratory and circulatory stimulant. However, when he accidentally absorbed the drug in his lab in 1943, he discovered that it had a far more powerful impact on his state of consciousness. Hofmann originally was unsure of how he had experienced the effects, and believed that LSD couldn’t have been the cause for his symptoms as he had been meticulous in avoiding contamination due to his knowledge of the lethality of ergot. However, he attempted to reproduce his effects by consuming what he believed to be a miniscule dose of LSD to test whether it was the cause.

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Psilocybin, LSD And Other Psychedelics Improve Sexual Satisfaction For Months After Use, New Study Finds

Psychedelic substances, including psilocybin mushrooms, LSD and others, may improve sexual function—even months after a psychedelic experience, according to a new study.

The findings, published on Wednesday in Nature Scientific Reports, are based largely on a survey of 261 participants both before and after taking psychedelics. Researchers from Imperial College London’s Centre for Psychedelic Research then combined those responses with results of a separate clinical trial that compared psilocybin and a commonly prescribed selective serotonin reuptake inhibitor (SSRIs) for treating depression.

Authors say it’s the first scientific study to formally explore the effects of psychedelics on sexual functioning. While anecdotal reports and and qualitative evidence suggest the substances may be beneficial, the study says, “this has never been formally tested.”

“It’s important to stress our work does not focus on what happens to sexual functioning while people are on psychedelics, and we are not talking about perceived ‘sexual performance,’” said Tommaso Barba, a PhD student at the Centre for Psychedelic Research and the lead author of the study, “but it does indicate there may be a lasting positive impact on sexual functioning after their psychedelic experience, which could potentially have impacts on psychological wellbeing.”

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When America First Dropped Acid

One evening in September of 1957, viewers across America could turn on their television sets and tune in to a CBS broadcast during which a young woman dropped acid. She sat next to a man in a suit: Sidney Cohen, the researcher who had given her the LSD. The woman wore lipstick and nail polish, and her eyes were shining. “I wish I could talk in Technicolor,” she said. And, at another point, “I can see the molecules. I . . . I’m part of it. Can’t you see it?” “I’m trying,” Cohen replied.

Were some families maybe—oh, I don’t know—eating meat loaf on TV trays as they watched this nice lady undergo her mind-bending, molecule-revealing journey through inner space? Did they switch to “Father Knows Best” or “The Perry Como Show” afterward? One of the feats that the historian Benjamin Breen pulls off in his lively and engrossing new book, “Tripping on Utopia: Margaret Mead, the Cold War, and the Troubled Birth of Psychedelic Science” (Grand Central), is to make a cultural moment like the anonymous woman’s televised trip seem less incongruous, if no less fascinating.

In Breen’s telling, the buttoned-down nineteen-fifties, not the freewheeling nineteen-sixties, brought together the ingredients, some of them toxic, for the first large-scale cultural experiment with consciousness-expanding substances. The psychedelic flowering of the sixties has, it turns out, a prequel—a rich and partly forgotten chapter before the hippie movement, before the shamanistic preening and posturing of Timothy Leary, and before the war on drugs shut all that down. This earlier history encompasses not only the now notorious C.I.A. research into mind-altering drugs but also a lighter, brighter, more public dimension of better living through chemistry, buoyed by postwar scientific optimism and public reverence for expertise. “Timothy Leary and the Baby Boomers did not usher in the first psychedelic era,” Breen writes. “They ended it.”

So the era we’re living in now is not the first in which LSD and other psychedelics were poised to enter the mainstream. In the twenty-twenties, psychedelics sit comfortably within politely au-courant circles of wellness culture, startup capitalism, and clinical research. Some Gen X-ers are as likely to try ayahuasca for a midlife crisis, or sub out their Lexapro for microdoses of LSD, as they might once have been to troop into the woods behind campus the day after finals with a few friends and a freezer bag full of shrivelled mushrooms. A number of recent studies have shown that psychedelics hold promise for treating depression, easing end-of-life anxiety, and helping people cope with grief. The best-selling 2018 book about this new science and its ramifications, “How to Change Your Mind,” by Michael Pollan, has been so influential in piquing hopes for hallucinogens that scientific papers have identified what they call the Pollan Effect. (It describes the high expectations that some subjects bring to psychedelic studies, which can potentially influence how they report their experiences.) In 2019, Denver became the first U.S. city to decriminalize the use of psilocybin, the psychoactive compound in hallucinogenic mushrooms, and in 2020 Oregon became the first state to legalize it for use in therapy. Voters in several other localities, from Santa Cruz to Detroit to Washington, D.C., have since approved similar initiatives. This year, the F.D.A. will consider approving MDMA, the drug many of us know in its street form as Ecstasy (and may still associate with raves), for the treatment of post-traumatic stress disorder. Even big pharmaceutical companies are looking to get in on the action.

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LSD And Psilocybin Could Be Powerful Treatments For Pain—Without Opioids’ Dwindling Effects Over Time, Study Says

LSD and psilocybin could offer promising therapeutic potential for the treatment of chronic pain “on a mechanistic and experiential level,” according to a newly published literature review that highlights scientific findings happening as part of the “psychedelic renaissance”—a recent thawing of stigma and opposition into psychedelics research after decades of prohibition.

What’s more, authors note, the pain-relieving effects of LSD and psilocybin seem to increase with repeated treatment, unlike opioids, which display “decreased therapeutic effect” over time.

The narrative review, published last month in the South African Medical Journal, charts both the history of the two substances as well as scientists’ emerging understanding of their methods of action. It notes that the drugs seem not just to reduce pain but also better manage the experience of pain.

“Recent neuroimaging studies combined with small sample interventions with classic psychedelic agents,” authors wrote, “may point towards a possible means of improving the treatment of chronic pain on a mechanistic and experiential level.”

Classic psychedelics, the literature review explains, are those that bind to the central nervous system’s 5-HT2A receptors. They include both LSD and psilocybin.

The way psilocybin binds to receptors in the central nervous system “has similar effects to LSD on cognition, emotional processing, self-awareness and the perception of pain,” says the literature review, “which underpins its potential therapeutic benefit in treating people suffering with pain. Numerous small trials of LSD and psilocybin for chronic pain have already shown a good safety profile, with minimal physical dependence, withdrawal syndrome, or compulsive drug seeking compared with other analgesic agents.”

While the two drugs are part of the same family of alkaloids, their history is, of course, much different. The review describes explains that LSD was first synthesized in 1938, meaning humans have used it for less than a century. Psilocybin’s use stretches back thousands of years. In the modern U.S., psilocybin use was popularized in the late 1950s, while LSD grew to prominence in the ’60s and ’70s.

While there have been no reports of direct mortality from either substance and no withdrawal following chronic use, the study says, “the use of psilocybin in clinical research ended at the same time as LSD research as the Controlled Substances Act was enforced.”

Associations with counterculture and anti-government sentiment meant LSD and psilocybin research was abandoned, authors wrote. “From 1977 until the early 2000s, no more LSD research was published, despite overwhelming evidence pointing towards therapeutic benefit.”

Prior research had indicated LSD might be useful in treating depression, pain, and physical suffering in cancer patients and others. Among seven patients with phantom limb pain, participants treated with LSD reduced their analgesic requirements, and two patients’ pain was resolved.

During what the review refers to as the modern “psychedelic renaissance” or “the new wave of psychedelic research,” studies have found that psilocybin or LSD may help reduce cluster headaches, end-of-life depression in cancer patients and chronic pain.

In a pain study, a small sample of patients who self-medicate with the psychedelics “revealed a decrease in the experience of pain during the psychedelic session and for up to 5 days after treatment, before their pain returned to baseline.”

“The most exciting revelation from these interviews relates to the lasting psychological and emotional effect the psychedelics had on those interviewed,” the review says. “They describe increased resilience, body-self-awareness and psychological flexibility and psychological flexibility, which led to feelings of acceptance, agency and hope.”

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Did a dose of LSD spawn some of cinema’s greatest films?

Federico Fellini, one of the greatest filmmakers of the 20th century, attributes much of his success to a single dose of LSD he took in the summer of 1964 ​“during a time of creative crisis”. According to a recent study looking into how this experience influenced his work, the dose was administered by Dr Emilio Servadio, one of the most prominent Italian psychoanalysts of the time. It induced a trip so intense that the filmmaker later needed sedative medication to put it to an end.

Fellini took part in the psychotherapy session directly after he had finished working on his masterpiece 8 ½, and before he started writing his next film Giulietta degli Spiriti. The talking therapy that occurred after the LSD dose was recorded with a magnetophone. The tapes have never been found by researchers, but in an interview with the BBC a year later, Fellini explained how the experience stimulated his creativity by altering his perception of colour and allowing him to perceive colours in an entirely different light.

“The doctor gave me an explanation and I agree with him,” he told a reporter in 1965. ​“He said that an artist lives always in the imagination so the barrier between sensorial reality and his imagination is very vague… I saw colours not like they normally are – we see colours in the objects, you know; we see objects that are coloured. I saw colours detached from the objects. I had for the first time the feeling of the presence of the colours in a detached way.” Fellini’s work after the acid trip was later praised for having ​“supernaturally brilliant colours”.

Fellini’s perception of time was also altered during his trip, which was was reflected in his work post-LSD trip – the authors of the study said his films started to incorporate plots involving ​“puzzling and disorienting flashbacks”. The filmmaker was also said to have had epiphanies during the trip involving space and perception of self, both of which were apparent in his subsequent work. ​“The world depicted in his post-LSD movies includes major changes in the perception of space, time and others,” the study concluded.

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FDA creates path for psychedelic drug trials

Federal regulators are laying out guidance for psychedelic drug trials for the first time, in a move that could encourage the mainstreaming of substances like magic mushrooms and LSD as behavioral health treatments.

Why it matters: Psychedelics are turning into a multi-billion industry and gaining widespread acceptance after decades of concerns about recreational use of the products — and the high risk for misuse. But research to date has largely been backed by private sponsors.

Driving the news: The Food and Drug Administration on Friday released first-ever draft guidance outlining considerations — including trial conduct, data collection and subject safety — for researchers looking into psychedelic treatments for a variety of conditions, including PTSD, depression and anxiety.

  • The agency filed the 14-page document two days after a bipartisan coalition in Congress led by Rep. Dan Crenshaw (R-Texas) introduced legislation directing the issuance of clinical trial guidelines.
  • It also came as 10,000 attendees and hundreds of exhibitors converged on Denver for what was billed as the “largest psychedelic conference in history,” with guests ranging from New York Jets quarterback Aaron Rodgers to National Institute of Mental Health director Joshua Gordon.

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Psychedelic drugs like LSD could enhance the effects of brain simulation

New research provides evidence that LSD alters the effects of brain stimulation and produces different and potentially larger changes in brain activity. The preliminary findings suggest that psychedelic drugs and brain stimulation may have a synergistic effect that could be used in innovative ways for treating various conditions. The proof-of-concept study has been published in the journal Psychedelic Medicine.

Psychedelic-assisted psychotherapy has shown promising potential as a therapeutic approach for various mental health conditions. This treatment combines the use of psychedelic substances, such as psilocybin or LSD, with psychotherapy sessions to enhance the therapeutic process.

The psychedelic substances used in this type of therapy are known to induce altered states of consciousness, leading to profound experiences that can have therapeutic benefits. These substances are thought to work by affecting brain receptors, particularly the serotonin 2A receptor, which influences perception, mood, and cognition.

These drugs have also been found to enhance neural plasticity, which refers to the brain’s ability to reorganize and form new connections. This may contribute to their long-term therapeutic effects. It is believed that combining psychedelic drugs with therapies like psychotherapy or brain stimulation could help direct these neuroplastic changes and lead to lasting behavioral changes.

“Current treatments like transcranial magnetic stimulation (TMS) have a large potential to help people with a variety of psychiatry disorders, however, these neuromodulatory treatments tend to have relatively short-lived effects,” explained study author Lucas Dwiel, a postdoctoral fellow at The Doucette Lab at the Geisel School of Medicine at Dartmouth. “So if we could prolong the effects of these treatments by first using drugs like LSD to make the brain more malleable or susceptible to change, we could help a large number of patients achieve their therapeutic goals.”

The researchers conducted experiments using rats to eliminate the biases inherent in human studies. The study focused on the effects of LSD and involved two main components: measuring brain activity changes after LSD administration and assessing the effects of brain stimulation combined with LSD.

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