Category Archives: Psychedelics

JOB CAN BE PRETTY OVERWHELMING AT TIMES. SOME UNWIND WITH MEDITATION, OTHERS GLASS OF WINE. BUT AS WVTM 13 LISA CRANE EXPLAINS, THESE DAYS SOME ARE CHOOSING AN ALTERNATIVE. YEAH. MICRODOSING. HERES THE STORY. LIFE JUST FEELS BETTER AND I FEEL LIKE I CAN JUST DO IT ALL AND IT DOESNT FEEL LIKE OVERWHELMING OR LIKE A DARK CLOUD, YOU KNOW, HOVERING DURING THE DAY. THIS MOM HAS BEEN MICRODOSING FOR TWO YEARS. SHE LIVES IN NEW ORLEANS AND AGREED TO TALK TO US WITHOUT REVEALING HER IDENTITY. BECAUSE PSILOCYBIN IS STILL LARGELY ILLEGAL ACROSS THE COUNTRY. SO SHES GOING BY THE NAME G AND SAYS TAKING MAGIC MUSHROOMS HAS DRAMATICALLY IMPROVED HER LIFE. HAPPY? JUST IN A VERY NORMAL, MORE BASE WAY. CONTINUOUS, YOU KNOW, FOUR YEARS AGO, SHE BECAME A NEW MOM AND FELT OVERWHELMED, STRESSED, DEPRESSED. FOR ME, I WAS JUST CRYING ALL DAY, EVERY DAY FOR LIKE, I DONT KNOW, A MONTH. SO SHE TURNED TO A THERAPIST WHO RECOMMENDED TAKING A MICRODOSE OF PSILOCYBIN. ONE CAPSULE CONTAINS 0.1 TO 0.2 GRAMS, A DOSE SO SMALL, SHE SAYS, YOU DONT FEEL A HIGH, BUT YOU DO FEEL HAPPY. SO WHEN I AM ON IT, I JUST FEEL MORE RELAXED WHILE MOMS SAY MICRODOSING HELPS MANAGE THEIR MOOD, DOCTORS SAY THE TREND IS STILL IN ITS EARLY STAGES AND THERES JUST NOT ENOUGH RESEARCH. ONE OF THOSE DOCTORS IS GS HUSBAND, WHO EXPRESSED CONCERN LARGE SCALE STUDIES SUPPORTING OR ASSESSING THE SAFETY OF OR EFFECTIVENESS OF THIS TYPE OF ELEMENTS OR PSYCHEDELIC SUBSTANCES HAVE YET TO BE CONDUCTED. AND THATS WHERE THE MAIN ISSUE LIES. THE OTHER ISSUE IS THE LACK OF REGULATION. SO HES AGAINST THE PRACTICE BUT IS SUPPORTIVE OF HIS WIFE. ABSOLUTELY. I MEAN, I MEAN, IF SHES HAPPY BUT BUT AT THE SAME TIME, IM CONCERNED BECAUSE BECAUSE OF THE LACK OF KNOWLEDGE ON THIS TYPE OF THINGS. DOCTOR JOSH WOOLLEY AT THE UNIVERSITY OF CALIFORNIA, SAN DIEGO IS AN EXPERT IN PSYCHEDELICS. SO I WOULD SAY THAT THE DATA IS REALLY OUT. ITS LIKE PEOPLE SWEAR BY IT. THERE ARE LOTS OF THINGS THAT PEOPLE SWEAR BY THAT ACTUALLY ARE HELPFUL, BUT WE DONT DO. WE HAVENT DONE CLINICAL TRIALS ON THEM YET IN ONE OF THE FEW STUDIES EVER CONDUCTED, IT SHOWED THAT MICRODOSING HAD MORE OF A PLACEBO EFFECT. THERE ARE SOME RISKS, THOUGH, AND I THINK THATS THE THING TO KEEP IN MIND THAT YOURE KIND OF EXPERIMENTING ON YOURSELF A LITTLE BIT, BUT FOR G, NONE OF THAT MATTERS BECAUSE SHE SAYS SHES FOUND SOMETHING THAT WORKS FOR HER. LIKE MAGIC, HELPING HER BE A MOM AND A POSITIVE MENTAL STATE, EVEN IF ITS, YOU KNOW, A PLACEBO EFFECT, WHICH I READ THAT COULD BE, UM, ITS BETTER THAN FEELING OVERWHELMED OR FEELING JUST IT JUST REALLY GIVES YOU THE MOOD STABILIZER WITHOUT ALL THE TOXIC CHEMICALS THAT, UM, MEDICINES CARRIES. I MEAN, BE OPEN MINDED, BE OPEN

Microdosing magic mushrooms is gaining traction for overwhelmed moms

Updated: 10:43 PM CDT Jul 29, 2024

Any mom will tell you the job can be pretty overwhelming at times. Come unwind with meditation, others with a glass of wine, but these days, some are choosing an alternative, a microdose of the psychedelic drug known as magic mushrooms.Life just feels better, and I feel like I can just do it all, and it doesn't feel, like, overwhelming or like a dark cloud hovering during the day," said a mom from Louisiana whos been microdosing for two years said. "And when I am on it, I just feel more relaxed, you know. She agreed to talk to us without revealing her identity because psilocybin is still largely illegal across the country. So she's going by the name "G" and says taking magic mushrooms has dramatically improved her life. She said, High, happy just in a normal way, more based way continuous, you know.>> FOLLOW US ON SOCIAL: Facebook | Twitter | Instagram | YouTube Four years ago, she became a new mom and felt overwhelmed, stressed, and depressed. She said, For me, I was just crying all day every day for like a month. So she turned to a therapist who recommended taking a microdose of psilocybin. One capsule contains 0.1 to 0.2 grams, a dose so small, she says you dont feel a "high," but you do feel "happy." She said, Not only are you happier and just kind of more relaxed, you're more productive.While moms say microdosing helps them manage their mood, doctors say the trend is still in its early stages, and theres not enough research. One of those doctors is G's husband, who expressed concern.He said, Large-scale studies supporting or assessing the safety or effectiveness of this type of elements or psychedelic substances have yet to be conducted. And that's where the main issue lies. The other issue is the lack of regulation. So, he's against the practice but is supportive of his wife, saying, Absolutely, ma'am, she's happy. But at the same time, I'm concerned because of the lack of knowledge on this type of thing.Dr. Josh Woolley at The University of California San Diego is an expert in psychedelics. He said, So I'd say the data is really out its like people swear by it, theres a lot of things people swear by that are actually helpful but we haven't done clinical trials yet.>> WVTM 13 ON-THE-GO: Download our app for freeOne of the few studies that were conducted showed that microdosing had more of a placebo effect. Woolley said, There are some risks, though, and keep in mind that you're experimenting on yourself a little bit.But for G," none of that matters because shes found something that works for her, like magic, helping her be a mom, whos in a positive mental state.She said, Even if its placebo effect which I read that could be it better than feeling overwhelmed or feeling just really gives you a mood stabilizer without all the toxic chemicals that medicines carry. I mean open minded, be open minded.

Any mom will tell you the job can be pretty overwhelming at times. Come unwind with meditation, others with a glass of wine, but these days, some are choosing an alternative, a microdose of the psychedelic drug known as magic mushrooms.

Life just feels better, and I feel like I can just do it all, and it doesn't feel, like, overwhelming or like a dark cloud hovering during the day," said a mom from Louisiana whos been microdosing for two years said. "And when I am on it, I just feel more relaxed, you know.

She agreed to talk to us without revealing her identity because psilocybin is still largely illegal across the country. So she's going by the name "G" and says taking magic mushrooms has dramatically improved her life. She said, High, happy just in a normal way, more based way continuous, you know.

>> FOLLOW US ON SOCIAL: Facebook | Twitter | Instagram | YouTube

Four years ago, she became a new mom and felt overwhelmed, stressed, and depressed. She said, For me, I was just crying all day every day for like a month. So she turned to a therapist who recommended taking a microdose of psilocybin. One capsule contains 0.1 to 0.2 grams, a dose so small, she says you dont feel a "high," but you do feel "happy." She said, Not only are you happier and just kind of more relaxed, you're more productive.

While moms say microdosing helps them manage their mood, doctors say the trend is still in its early stages, and theres not enough research. One of those doctors is G's husband, who expressed concern.

He said, Large-scale studies supporting or assessing the safety or effectiveness of this type of elements or psychedelic substances have yet to be conducted. And that's where the main issue lies.

The other issue is the lack of regulation. So, he's against the practice but is supportive of his wife, saying, Absolutely, ma'am, she's happy. But at the same time, I'm concerned because of the lack of knowledge on this type of thing.

Dr. Josh Woolley at The University of California San Diego is an expert in psychedelics. He said, So I'd say the data is really out its like people swear by it, theres a lot of things people swear by that are actually helpful but we haven't done clinical trials yet.

>> WVTM 13 ON-THE-GO: Download our app for free

One of the few studies that were conducted showed that microdosing had more of a placebo effect. Woolley said, There are some risks, though, and keep in mind that you're experimenting on yourself a little bit.

But for G," none of that matters because shes found something that works for her, like magic, helping her be a mom, whos in a positive mental state.

She said, Even if its placebo effect which I read that could be it better than feeling overwhelmed or feeling just really gives you a mood stabilizer without all the toxic chemicals that medicines carry. I mean open minded, be open minded.

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Microdosing magic mushrooms is gaining traction for overwhelmed moms - WVTM13 Birmingham

Artwork by Hyphen Though narcotic drugs are forbidden in Islam, a growing number of Muslims are experimenting with psilocybin mushrooms to help treat depression, and even get closer to God

Sughra Ahmed had never even heard of psychedelics when a friend told her that religious leaders were being recruited for a study in which they would all be given two powerful doses of psilocybin, commonly known as magic mushrooms. At the time, in 2017, Ahmed was an associate dean of religious and spiritual life at Stanford University, San Francisco, and despite some initial scepticism, her curiosity was piqued.

Following deep reflection and conversations with trusted friends, she signed up. Key to her decision was her appraisal that intentional psychedelic use is in keeping with Islamic principles of growth and expansion, to become the best version of oneself to better serve God.

Ahmed was not expecting to arrive in a spiritual nirvana, but thats what happened over the course of two phenomenally energetic experiences in a living room-like setting at Marylands Johns Hopkins University (JHU) in 2018, with her visions coloured by soft hues of light.

I now feel a stronger connection to God, in everything that I do, says Ahmed, originally from Peterborough and after returning from the US now an honorary fellow at the University of Birminghams theology department. Its way more pronounced now, in a way that I didnt anticipate. Im much more conscious of God. Central to the awakening was a dawning realisation of the importance of expressing love in her everyday life and the importance of heart-to-heart communications. It was a reminder for me to return to that truth, Ahmed says. Six years later her life has never been the same and still today she has a greater focus on thriving, rather than simply plodding along, she says.

She was the only Muslim out of two dozen faith leaders to take part in the study, led by JHU psychologist William Richards and supported by the RiverStyx Foundation. Participants took two doses of psilocybin about one month apart, which were larger than what most recreational users take. The idea behind the research, which has yet to be published, is that mystical experiences are at the centre, even the origin, of most religions. The academics conducting the study, who kept data on participants in the months after their trips, wanted to investigate whether religious leaders lives were altered by their encounter with psychedelics.

Ahmed was the last person to enrol after attempts to interest other Muslims failed. Many organised religions are uneasy with or outright oppose the use of illegal substances. Narcotic drugs and alcohol are clearly forbidden in Islam and their consumption can lead to a veiling of the mind that renders people not their whole selves, says Ahmed. Psychedelics, however, may lead to an unveiling of the mind that brings emotional and spiritual benefits, as Ahmed learned through her research when she was deciding whether to participate in the study.

Being a religious leader, and a woman, I didnt want to pull the drawbridge up behind me, she says. I wanted to feel deep down that this was enhancing Islam in my life, in a way nothing else could. I wanted our people Muslims, women of colour to be at the table. Because these sorts of trials dont usually have people like me.

Ahmed has spoken publicly about her journey, and psychedelics and Islam, at events like the 2023 Psychedelic Science conference in Denver. Fellow Muslims subsequently approached her to share insights from their own psychedelic journeys, to ask how they can bring this truth that they experienced into the open and discuss how their expression of Islam has been altered, or deepened, thanks to tripping. Theres even a WhatsApp group with more than 20 members.

Its about emotional and psychological growth, Ahmed says of psychedelic-assisted therapy. Its about trauma, its about healing. That all speaks to my religious expression of what medicines ought to be.

Trials investigating the potential of psilocybin mushrooms to treat depression, and of MDMA to treat PTSD, have reported significant benefits, suggesting the psychedelics could be more efficacious than current drugs prescribed by medical professionals. But experts have said more large-scale randomised trials with more diverse treatment groups and longer term follow-up are required to fully understand the therapeutic potential of psychedelics.

Research does, however, also suggest that Muslims may be more likely to suffer from depression in some western countries, while potentially experiencing the condition over longer periods of time when compared to the general population.

Raad Seraj, who is from Bangladesh and now lives in Canada, says his first mushroom journey showed him that he could step outside of his mind.

A difficult upbringing, which included being subject to xenophobic abuse in Saudi Arabia where he lived as a child for a period, left him with anger and rage that he believes were symptoms of depression, though he never sought a formal diagnosis. In my culture, theres no time to be depressed, says Seraj, a manager at a technology company.

With psilocybin mushrooms, which he began taking with a group of friends in 2016, he was able to unlock latent, toxic emotions that were stored within. My life, and relationships, became much richer, because I wasnt just bottling everything up. I had a greater sense of self-awareness.

Since launching a podcast about psychedelics two years ago, Seraj has been open with his family about his use of not just mushrooms, but also LSD and 5-MeO-DMT. They couldnt understand it, he says, adding that there is a history of substance abuse in his family. They didnt quite understand what psychedelics are. All they knew was that theyre drugs, bad drugs.

They soon began to find greater acceptance. Serajs mother and father were in New York last year when Seraj was giving a talk for Psychedelics Today, an educational platform. They heard me speak not just about my own personal experience, he says. Thats when they understood Im not talking about drugs, but medicine. Its still difficult for them, but I think they understand my motivations, which helps them respect me.

Others have had similar journeys. Ibrahim, who is from Pakistan and now lives in the US, was diagnosed with acute stress disorder, anxiety and depression during the Covid-19 pandemic. He discovered mushrooms while undertaking research for a cancer therapy company, before watching the Fantastic Fungi documentary on Netflix. Honestly it was a game changer for my mental health, he says. Everything got clearer and I began feeling more content with how life was unfolding. I finally started dealing with all the stuff Id been avoiding.

Then, like Seraj, he started spreading the message. I couldnt wait for my struggling friends and family to try it, he recalls. Ibrahim, who asked to use his first name only, served the medicine to more than 20 close friends and relatives, and oversaw their trips. Most of them were suffering from depression, anxiety and stress, he says. Its amazing how it helped them face parts of themselves they had been dodging.

The first person was his conservative father, in Pakistan, in November 2022. I took my dad on a journey, he says. He met me with resistance because in the past he has caught me doing things that were haram, like drinking and using pot. But Ibrahim impressed upon his father that the beauty of the mushroom is that a pre-prepared intention can help define the experience. I said: Just watch these two documentaries with me and decide for yourself. He saw them and said: OK, why dont you try it on me.

Despite the initial scepticism, his father, and everyone else who took the mushrooms, completely changed their opinions about psychedelics after their journeys, according to Ibrahim. He came out of it amazed, says Ibrahim. He had a very clear vision and it gave him a whole new perspective. My mum and my uncle did it, too. People started calling me a doctor. He has now opened a mushroom microdosing company.

Psychedelics have been very eye-opening to me about how I can best live my life as a Muslim, says Marwan Elgamal, director of a UK-based creative agency that promotes cannabis legalisation. He says that some believe that the mystical roots of Islam may hint towards the possibility of a lost history of psychedelic use. The Quran refers to the use of an undefined fungi. In the Sahihain, a collection of hadiths, the Prophet is reported to have said the Kamaah (mushroom truffles) are a kind of manna and that its juice is a medicine for the eyes. Elgamal suggests a medicine for the eyes could also be perspective shifting. I feel like these tools are here, from God, to help figure things out.

One British female Muslim, who preferred not to be named, said that her grandfather had told tales of eating naturally grown psychedelic mushrooms in Pakistan, but that any sort of drug-taking still generally remained taboo in her family.

I cant tell my family I microdose, she says. None of my Muslim friends do psychedelics. Its not something we talk about. Drugs all get lumped into one category, she adds: But I feel everyone should try psychedelics. I see the world differently now, Im more connected to people. At the time of writing, she was at a psychedelic retreat.

Ahmed, however, has not taken psychedelics since the study and she has no immediate plans to either. Yet, she says: I feel like the medicine continues to speak to me. I am still deeply connected with those experiences in a way that makes me feel it was quite recent. Im open minded but I dont want to do it for the sake of it. Its sacred.

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I see the world differently now: how psychedelics are helping people find spiritual growth - Hyphen

A new art installation near the White House is part of a push by two groups to encourage the Food and Drug Administration to greenlight psychedelic assisted therapy for treating veterans suffering from PTSD.

In Lafayette Park, just steps away from the White House, 17 pairs of boots sit side by side. They symbolize a grim statistic from the U.S. Department of Veterans Affairs: On average, 17 military veterans die by suicide each day.

The art installation is part of a push by two groups Healing Breakthrough and Heroic Hearts Project to encourage the Food and Drug Administration to greenlight psychedelic assisted therapy for treating veterans suffering from PTSD when the agency makes a final decision on Aug. 11.

Unfortunately, in this country, theres still a lot of stigma around psychedelics and similar drugs, said Army Ranger veteran Jesse Gould who heads the Heroic Hearts Project.

The therapy being considered by the FDA is known as MDMA-AT. MDMA is the active ingredient in ecstasy, which makes it a Schedule I narcotic, a barrier Gould said makes it difficult to study. The company behind the treatment, Lykos Therapeutics, said its study showed that 71% of trial participants had their PTSD diagnosis eliminated after the treatment.

However, the treatment was greeted by skepticism during a meeting of FDA advisers in June, with members voting 10-1 against the overall benefits of MDMA. Some of the members that voted against it expressed concerns about possible misuse that could come with approving the treatment.

Gould believes the committee fumbled the ball in its decision and hopes the FDA will vote differently when it decides on whether to approve the therapy next month.

Gould who has used psychedelics to treat his own PTSD said the drug would be used in a controlled setting with a therapist.

The reason it works in this context, with the safe setting, is because the chemical itself, the MDMA, allows people to be more vulnerable, more tapped into the emotions, and allows them to have more trust to the therapist, Gould said.

Gould said there is a critical need for more treatments for PTSD and he believes these types of drugs can help because they helped him, he said.

I dont think Id be here if it wasnt for the treatments I went through, Gould said.

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Why are there 17 pairs of Army boots lined up outside the White House? The answer has to do with PTSD and psychedelic drugs - WTOP

The company Prophet Premium Blends recalled its Diamond Shruumz edible mushroom products when several people became ill after consuming them. Psychedelics are growing in popularity, creating a market for accessible methods of consumption. Some experts have touted the potential benefits of magic mushrooms, especially for mental health treatments. However, these products lack regulation and so their contents are sometimes inexplicit and potentially unsafe.

There are a variety of species of psychedelic mushrooms. Psilocybin mushrooms, also called magic mushrooms, contain the chemical psilocybin which "can cause people to experience distorted sights and sounds and lose their sense of time and space," as well as cause people to "feel intense emotions ranging from bliss to terror and may have physical side effects such as increased heart rate or nausea," said the National Institute on Drug Abuse.

The other major variety of psychedelic mushroom is the Amanita muscaria, which "contains a number of chemicals, the most notable being muscimol, a hallucinogenic compound that can alter mood, perception and behavior," said NBC News. While psilocybin has been considered for its potential benefits, the compounds in the Amanita muscaria can be toxic. However, what constitutes a safe dosage of either compound is still unknown.

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Magic mushrooms have made their rounds recreationally in the form of edibles. Mushroom edibles are designed for microdosing, a usage that "refers to consuming small amounts of psychoactive or hallucinogenic substances, enough to reap the benefits while minimizing more debilitating effects," said NBC News. The problem is that these products are largely unregulated and several people have become sick and required hospitalization after consuming them.

"There is a lot of interest in the therapeutic potential for psilocybin and for good reason. But at the same time, a growing industry may be trying to capitalize on this interest by marketing other mushrooms," Eric Leas, an assistant professor at the UC San Diego Herbert Wertheim School of Public Health and Human Longevity Science said in a press release. "For example, some manufacturers are calling Amanita muscaria products 'magic mushroom gummies' and not disclosing what mushroom the gummies contain, or not making it clear Amanita muscaria is a different mushroom than psilocybin and has essentially no clinical evidence supporting its use as a therapy."

Mushroom edibles are considered a dietary supplement, which lacks proper federal oversight. Diamond Shruumz edible mushroom products have caused seizures, loss of consciousness, agitation, nausea and vomiting. The effects are a sharp contrast to what the product advertises as its ingredients. "Several toxicology experts said the mushrooms listed as ingredients, such as lions mane or ashwagandha, dont produce the potent effects that the company touts, like relaxation or euphoria," said NBC News. After the Food and Drug Administration tested the products, they found the bars had "higher than normal amounts" of muscimol along with 4-AcO-DMT, also called psilacetin, a "semisynthetic psychoactive drug that's similar to psilocybin, but not the real thing," said Slate. The health effects of psilacetin have not been widely studied. "There's not great quality control around some of these products to know exactly what's in them," Chris Hoyte, the medical director of the Rocky Mountain Poison Center, said to The New York Times.

Some experts and users swear by the therapeutic abilities of magic mushrooms. "People who are dealing with anxiety, depression, addictions or other types of mental health conditions that can be quite difficult to treat are trying to basically DIY and give themselves these different types of natural remedies," Albert Garcia-Romeu, a psychologist at Johns Hopkins University School of Medicine, told Slate. Interest in psychedelic mushrooms including Amanita muscaria has grown exponentially recently.

The lack of regulation on the product is the biggest risk. "Somebody could slap a label on a package saying it contains four grams of mushrooms, and really, it contains a synthetic," Caleb King, one of the founders of Tryptomics, a Colorado lab that began testing mushroom chocolate bars bought at San Francisco vape shops, said to The Washington Post. "So it comes down to the consumer having to do their research before they're going to be consuming anything." Banning magic mushroom products would also not help the situation. "It's kind of like whack-a-mole, where if you prohibit psilacetin then something else might crop up," Mason Marks, a senior fellow at the Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics at Harvard Law School, said to NBC News. "Prohibition is not the solution, but educating people about this can be quite helpful."

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Mushroom edibles are tripping up users - The Week

Regulatory approvals and registrations

Written informed consent was obtained from all participants in accordance with the Declaration of Helsinki and procedures established by the Washington University in Saint Louis Institutional Review Board. All participants were compensated for their time. All aspects of this study were approved by the Washington University School of Medicine (WUSOM) Internal Review Board, the Washington University Human Research Protection Office (WU HRPO), the Federal Drug Administration (IND no. 202002165) and the Missouri Drug Enforcement Agency (DEA) under a federal DEA schedule 1 research licence and registered with ClinicalTrials.gov identifier NCT04501653. Psilocybin was supplied by Usona Institute through Almac Clinical Services.

Healthy young adults (n=7, 1845years) were enrolled between April 2021 and March 2023 in a randomized cross-over precision functional brain mapping study at Washington University in Saint Louis (seeSupplementary Methods for inclusion and exclusion criteria). The purpose of the study was to evaluate differences in individual-level connectomics before, during and afterpsilocybin exposure. Participants underwent imaging during drug sessions (with MRI starting 1h after drug ingestion) with 25 mgpsilocybin or 40 mgMTP, as well as non-drug imaging sessions. Drug condition categories were (1) baseline, (2) drug 1 (MTP or psilocybin), (3) between, (4) drug 2 and (5) after. Randomization allocation was conducted using REDCap and generated by team members who prepared study materials including drug or placebo but otherwise had no contact with participants. A minimum of three non-drug imaging sessions were completed during each non-drug window: baseline, between and after drug sessions. The number of non-drug MRI sessions was dependent on availability of the participant, scanner and scanner support staff. Dosing day imaging sessions were conducted 60180min following drug administration during peak blood concentration98. One participant (P2) was not able tolerate fMRI while on psilocybin,and had trouble staying awake on numerous fMRI visits after psilocybin and was thus excluded from analysis (except for data quality metrics in Extended Data Fig. 1).

MTP was selected as the active control condition to simulate the cardiovascular effects and physiological arousal (that is, controlling for dopaminergic effects) associated with psilocybin99. Usona Institute, a US non-profit medical research organization, provided good manufacturing practices for psilocybin.

Drug sessions were facilitated by two clinical research staff who completed an approved in-person or online facilitator training programme provided by Usona Institute, as part of the phase 2 study (ClinicalTrials.gov identifier NCT03866174). The role of the study facilitators was to build a therapeutic alliance with the participant throughout the study, prepare them for their drug dosing days and to observe and maintain participant safety during dosing day visits64. The pair consisted of an experienced clinician (lead clinical facilitator) and a trainee (cofacilitator).

The predefined primary outcome measure was precision functional mapping (numerous visits, very long scans to produce individual connectomes) examining the effects of psilocybin on cortical and cortico- subcortical brain networks that could explain its rapid and sustained behavioural effects. Predefined secondary outcome measures included (1) assessment of hemodynamic response to evaluate how 5-HT2A receptor agonism by psychedelics may alter neurovascular coupling, (2) assessment of acute psychological effects of psilocybin using the MEQ30 score (Supplementary Methods) and (3) assessment of personality change using the International Personality Item Pool-Five-Factor Model100. Changes in pulse rate and respiratory rate during psilocybin and placebo were later added as secondary outcome measures and personality change was abandoned because it was clear that we would not be powered to detect personality change.

Participants were invited to return 612months after completing the initial cross-over study for a replication protocol. This included 12 baseline fMRIs, a psilocybin session (identical to the initial session, except for lack of blinding) and 12 after sessions within 4days of the dose.

Healthy adults aged 1845years were recruited by campus-wide advertisement and colleague referral. Participants (n=7) were enrolled from March 2021 to May 2023. Participants were required to have had at least one previous lifetime psychedelic exposure (for example, psilocybin, mescaline, ayahuasca, LSD), but no psychedelics exposure within the past 6months. Individuals with psychiatric illness (depression, psychosisor addiction) based on the DSM-5 were excluded. Demographics and data summary details are provided in Supplementary Table 1. One of the authors (N.U.F.D.) was a study participant.

Participants were scanned roughly every other day over the course of the experiment (Extended Data Fig. 1). Imaging was performed at a consistent time of day to minimize diurnal effects in FC101. Neuroimaging was performed on a Siemens Prisma scanner (Siemens) in the neuroimaging laboratories at the Washington University Medical Center.

Structural scans (T1w and T2w) were acquired for each participant at 0.9mm isotropic resolution, with real-time motion correction. Structural scans from different sessions were averaged together for the purposes of Freesurfer segmentation and nonlinear atlas registrations.

To capture high-resolution images of blood oxygenation level-dependent (BOLD) signal, we used an echo-planar imaging sequence102 with 2mm isotropic voxels, multiband 6, multi-echo 5 (times to echo: 14.20, 38.93, 63.66, 88.39, 113.12ms)103, repetition or relaxation time: 1,761ms, flip angle of 68 and in-plane acceleration104 (IPAT or grappa) of 2. This sequence acquired 72 axial slices (144mm coverage). Each resting scan included 510 frames (lasting 15min, 49s) as well as three frames at the end used to provide estimate electronic noise.

Every session included two 15-min resting-state fMRI (rs-fMRI) scans, during which participants were instructed to hold still and look at a white fixation crosshair presented on a black background. Head motion was tracked in real time using Framewise Integrated Real-time MRI Monitoring software (FIRMM)105. An eye-tracking camera (EyeLink) was used to monitor participants for drowsiness.

Participants also completed a previously validated event-related fMRI task. This was a suprathreshold auditoryvisual matching task in which participants were presented with a naturalistic visual image (duration 500ms) and coincident spoken English phrase, and were asked to respond with a button press to indicate whether the image and phrase were congruent (for example, an image of a beach and the spoken word beach) or incongruent. Both accuracy and response time of button presses were recorded. Each trial was followed by a jittered inter-stimulus interval optimized for event-related designs. In a subset of imaging sessions, two task fMRI scans were completed following the two resting scans. Task fMRI scans used the same sequence used in resting fMRI, included 48 trials (24 congruent, 24 incongruent) and lasted a total of 410s. In analyses, high motion frames were censored106 andthe two task scans were concatenated to better match the length of the rs-fMRI scans. Note the stimulus order in the two trials did not vary across session. The order of rest and task scans was not counterbalanced across sessions to avoid concern that task scans may influence subsequent rest scans.

Resting fMRI data were preprocessed using an in-house processing pipeline. In brief, this included removal of thermal noise using NORDIC denoising107,108,109, correction for slice timing and field distortions, alignment, optimal combination of many echoes by weighted summation110, normalization, nonlinear registration, bandpass filtering and scrubbing at a movement threshold of 0.3mm to remove reduce the influence of confounds111. Tissue-based regressors were computed in volume (white matter, ventricles, extra-axial cerebrospinal fluid)112 and applied following projection to surface. Task-based regressors were only applied when indicated. Details on rs-fMRI preprocessing are provided inSupplementary Methods. Visualizations of motion, physiological traces and signal across the brain (grayplots) before and after processing113 are provided in Supplementary Video1.

Surface generation and processing of functional data followed similarprocedures to Glasser et al.114. To compare FC and resting-state networks across participants, we used a group-based surface parcellation and community assignments generated previously62.

For subcortical regions, we used a set of regions of interest115 generated to achieve full coverage and optimal region homogeneity. A subcortical limbic network was defined on the basis of neuroanatomy: amygdala, anteromedial thalamus, nucleus accumbens, anterior hippocampus and posterior hippocampus116,117. These regions were expanded to cover anatomical structures (for example, anterior hippocampus)31.

To generate region-wise connectivity matrices, time courses of all surface vertices or subcortical voxels within a region were averaged. FC was then computed between each region timeseries using a bivariate correlation andthen Fisher z-transformed for group comparison.

We identified canonical large-scale networks using the individual-specific network matching approach described previously43,44,62. In brief, cortical surface and subcortical volume assignments were derived using the graph-theory-based Infomap algorithm118. In this approach, we calculated the correlation matrix from all cortical vertices and subcortical voxels, concatenated across all a participants scans. Correlations between vertices within 30mm of each other were set to zero. The Infomap algorithm was applied to each participants correlation matrix thresholded at a range of edge densities spanning from 0.01 to 2%. At each threshold, the algorithm returned community identities for each vertex and voxel. Communities were labelled by matching them at each threshold to a set of independent group average networks described previously62. In each individual and in the average, a consensus network assignment was derived by collapsing assignments across thresholds, giving each node the assignment it had at the sparsest possible threshold at which it was successfully assigned to one of the known group networks. See Extended Data Fig. 4 and Supplementary Fig. 1 for individual and group mode assignments, respectively. The following networks were included: the association networks including the DMN, fronto-parietal, dorsal attention, parietal memory, ventral attention, action-mode, salience and context networks; and the primary networks including the visual, somato-motor, somato-motor face and auditory networks.

To compute local (areal) desynchronization, we also defined brain areas at the individual level using a previously described areal parcellation approach39. In brief, for each participant, vertex-wise FC was averaged across all sessions to generate a dense connectome. Then, abrupt transitions in FC values across neighbouring vertices were used to identify boundaries between distinct functional areas.

To take advantage of the multilevel precision functional mapping study design, a LME model was used. Every scan was labelled on the following dimensions: participant identity (ID), MRI visit, task (task or rest), drug condition (prepsilocybin, psilocybin, MTP, postpsilocybin) and head motion (average framewise displacement). The rs-fMRI metrics (described below) were set as the dependent variable, drug (drug condition), task, framewise displacement (motion) and drugtask were defined as fixed effects, and participant ID and MRI session were random effects.

Let yij be the rs-fMRI metric (for example, FC change score at a given vertex) for the jth observation (15min fMRI scan) within the ith participant. The LME model can be written as:

$$begin{array}{l}{y}_{ij}={beta }_{0}+{beta }_{{rm{d}}{rm{r}}{rm{u}}{rm{g}}}cdot {{rm{d}}{rm{r}}{rm{u}}{rm{g}}}_{ij}+{beta }_{{rm{F}}{rm{D}}}cdot {{rm{F}}{rm{D}}}_{ij}+{beta }_{{rm{t}}{rm{a}}{rm{s}}{rm{k}}}cdot {{rm{t}}{rm{a}}{rm{s}}{rm{k}}}_{ij}\ ,,+{beta }_{{rm{task}} mbox{-} {rm{by}} mbox{-} {rm{drug}}}cdot {{rm{t}}{rm{a}}{rm{s}}{rm{k}}}_{ij}cdot {{rm{d}}{rm{r}}{rm{u}}{rm{g}}}_{ij}+{u}_{0i}+{v}_{0j}+{{varepsilon }}_{ij}end{array}$$

(1)

0 is the intercept term.

drug, FD, task and task-by-drug are the coefficients for the fixed effects predictors.

drugij, frame displacementij (FDij)and taskij are the values of the fixed effects predictors for the jth observation within the ith group.

u0i represents the random intercept for the ith participant, accounting for individual-specific variability.

v0j represents the random intercept for the jth observation within the ith participant, capturing scan-specific variability.

ij is the error term representing unobserved random variation.

In MATLAB (Wilkinsonian notation), this model is expressed for every vertex Y(vertex)=fitlme(groupd, FC_Change(vertex)~drug+framewise displacement+ task+task-by-drug+(1|SubID)+(1 |session)).

To compensate for the implementations of this LME model on many rs-fMRI-related dependent variables, differences were highlighted when P<0.001. All P values reported are not corrected for multiple comparisons.

FC change (distance) was calculated at the vertex level to generate FC change maps and a LME model (equation (1)) was used in combination with wild bootstrapping119,120 and threshold-free cluster enhancement (TFCE)95,121 to estimate P values for t-statistic maps resulting from the model (Figs. 1ad and4). Wild bootstrapping is an approach to permutation testing that was designed for models that are not independent and identically distributed, and are heteroscedastic.

First, a FC change map was generated for every scan by computing, for each vertex, the average distance between its FC seedmap and the FC seedmap for each of that participants baseline scans. As each participant had several baseline visits, FC change was computed for baseline scans by computing distance from all other baseline scans (excluding scans within the same visit). This provided a measure of day-to-day variability. Second, the distance value was used as the dependent variable yij in the LME model to generate a t-statistic. Third, a wild bootstrapping procedure was implemented as follows. Several bootstrap samples (B=1,000) were generated using the Rademacher procedure120, in which the residuals were randomly inverted. Specifically, a Rademacher vector was generated by randomly assigning 1 or 1 values with equal probability to the residual ofeach observation. By element-wise multiplication of the original residuals with the Rademacher vector, bootstrap samples were created to capture the variability in the data.

For the observed t-statistic-map and each bootstrap sample, the TFCE algorithm was applied to enhance the sensitivity to clusters of significant voxels or regions while controlling for multiple comparisons. The value of the enhanced cluster statistic derived from the bootstrap samples was used to create a null distribution under the null hypothesis. By comparing the original observed cluster statistic with the null distribution, P values were derived to quantify the statistical significance of the observed effect. The P values were obtained on the basis of the proportion of bootstrap samples that produced a maximum cluster statistic exceeding the observed cluster statistic.

The combined approach of wild bootstrapping with the Rademacher procedure and TFCE provided themethod to estimate P values for our multilevel (drug condition, participant, session, task) design. This methodology accounted for the complex correlation structure, effectively controlled for multiple comparisons and accommodated potential autocorrelation in the residuals through the Rademacher procedure. By incorporating these techniques, association with psilocybin and other conditions was reliably identified amid noise and spatial dependencies.

For analyses in Figs. 1e,g, 2 and 4a (bottom), Extended Data Fig. 3 and Supplementary Figs. 3, 4 and 6, distance calculations were computed on the FC matrix using z-transformed bivariate correlation of time courses from parcellated brain areas62. The effects of day-to-day, drug condition, task and framewise displacement and drugtask were directly examined by calculating the distance between functional network matrices generated from each scan. Root-mean-squared Euclidean distance was computed between the linearized upper triangles of the parcellated FC matrix between each pair of 15min fMRI scans, creating a second-order distance matrix (Extended Data Fig. 3). Subsequently, the average distance (reported as whole-brain FC change) was examined for FC matrices that were from the same individual within a single session, from the same individual across days (day-to-day), from the same participant between drug and baseline (for example, psilocybin), from the same individual but different tasks (task:rest), from the same individual between highest motion scans and baseline (hi:lo motion), from different individuals (between person). In the high head motion comparison (hi:lo motion in Supplementary Fig. 3), the two non-drug scans with the highest average framewise displacement were labelled and compared against all other baseline scans.

A LME model (equation (1)) and post hoc t-tests were used to assess statistical differences between drug conditions. A related approach using z-transformed bivariate correlation (similarity rather than distance) was also taken and results were unchanged (Supplementary Fig. 3c).

To test whether variability in participant-specific response to psilocybin was larger than would be expected by chance, we used a likelihood ratio test for variance of random slopes for a participant-specific response to psilocybin48. The difference in log likelihood ratios was compared to a null distribution of 1million draws from a mixture of chi-squared distributions with degrees of freedom 1 and 2. We note that the likelihood ratio test of variance components is a non-standard problem47 as the covariance matrix of the random effects is positive definite and the variances of random effects are non-negative. Finally,the test statistic for the likelihood ratio in this LME model was compared against a 50/50 mixture of two independent chi-squared distributions, each with one and two degrees of freedom, respectively.

Subjective experience was assessed for drug sessions using the MEQ3046(Supplementary Methods). The MEQ30 is designed to capture the core domains of the subjective effects of psychedelics (as compared to the altered states of consciousness rating scales that more broadly assess effects of psychoactive drugs122) and is related to the therapeutic benefits of psychedelics. We applied a LME model across all drug sessions, similar to the one described above, but with MEQ30 total score as the dependent variable. Whole-brain FC change and framewise displacement were modelled as fixed effects, and participant was modelled as a random effect. The same model was solved using FC change from every vertex to generate a vertex-wise map of the FC change versus MEQ30.

The conditions above were compared by calculating normalized FC change scores using the following procedure: we (1) determined FC change for each condition compared to baseline as described above, (2) subtracted within-session distance for all conditions (such that within-session FC change was 0), (3) divided all conditions by day-to-day distance (such that day-to-day FC change was equal to 1). Thus, normalized whole-brain FC change values (for example, psilocybin versus base was 3.52) could be thought of as proportional to day-to-day variability.

We used a classical MDS approach to cluster parcellated connectomes across fMRI scans, as previouslydescribed38. This data-driven approach was used to identify how different parameters (for example, task, drug, individual) affect similarity and/or distance between networks. MDS places data in multidimensional space on the basis of the dissimilarity (Euclidean distance) among data points, which in this case means a data point represents the linearized upper triangle of a FC matrix. Every matrix was entered into the classical MDS algorithm (implemented using MATLAB 2019, cmdscale.m). Many dimensions of the data were explored. The eigenvectors were multiplied by the original FC matrices to generate a matrix of eigenweights that corresponded to each dimension. These eigenweights were also applied to other rs-fMRI psychedelics datasets to generate dimensions scores (section Other datasets).

To assess network specificity of FC change values, we calculated average FC change of matched null networks consisting of randomly rotated networks with preserved size, shape and relative position to each other62,97. To create matched random networks, we rotated each hemisphere of the original networks a random amount around the x, y and z axes on the spherical expansion of the cortical surface62. This procedure randomly relocated each network while maintaining networks sizes, shapes and relative positions to each other. Random rotation followed by computation of network-average FC change score was repeated 1,000 times to generate null distributions of FC change scores. Vertices rotated into the medial wall were not included in the calculation. Actual psilocybin FC change was then compared to null rotation permutations to generate a P value for the 12 networks that were consistently present across every participants Infomap parcellation. For bar graph visualization (Fig. 1 and Supplementary Fig. 1b), networks with greater change (P<0.05 based on null rotation permutations) are shownin their respective colour and other networks are shown in grey.

We used an approach previously validated to assess spatial complexity (termed entropy) or neural signals61. Temporal principal component analysis was conducted on the full BOLD dense timeseries, which yielded m principal components (m roughly 80K surface vertices and subcortical voxels) and associated eigenvalues. The normalized eigenvalue of the ith principal component was calculated as

$${lambda }_{i}^{{prime} }=frac{{lambda }_{i}}{{sum }_{i=1}^{m}{lambda }_{i}^{{prime} }}$$

(2)

where m is the number of principal components, and i and i represent the eigenvalue and the normalized eigenvalue of the ith principal component, respectively. Last, the NGSC, defined as the normalized entropy of normalized eigenvalues, was computed using the equation:

$${rm{NGSC}}=-frac{{sum }_{i=1}^{m}{lambda }_{i}^{{prime} }log {lambda }_{i}^{i},}{log m}$$

(3)

The NGSC computed above attains values from the interval 0 to 1. The lowest value NGSC=0 would mean the brain-wide BOLD signal consisted of exactly one principal component or spatial mode, and there is maximum global FC between all vertices. The highest value NGSC=1 would mean the total data variance is uniformly distributed across all m principal components, and a maximum spatial complexity or a lowest FC is found.

NGSC was additionally calculated at the parcel level. To respect areal boundaries, this was done by first generating a set of individual-specific parcels in every participant (on all available resting fMRI sessions concatenated) using procedures described oreviously39,62.

NGSC maps were compared to PET-based 5-HT2A receptor binding maps published in ref. 33. Similarity was assessed by computing the bivariate correlation between NGSC values and 5-HT2A binding across 324 cortical parcels from the GordonLaumann parcellation.

To assess the persistent effects of psilocybin, we compared FC changes 121days postpsilocybin to predrug baseline. The FC change analysis (described above) indicated that connectivity at the whole-brain level did not change following psilocybin (Supplementary Fig. 1). A screen was conducted with P<0.05 threshold to identify brain networks or areas showing persistent effects. This analysis identified the anterior hippocampus as a candidate region of interest for persistent FC change (section Baseline/after psilocybin FC change analysis inSupplementary Methods).

We assessed change in anterior hippocampus FC change pre- versus postpsilocybin using the LME model described previously. In this model, all sessions before psilocybin (irrespective or cross-over order) were labelled as prepsilocybin and all sessions within 21days after psilocybin were labelled as postpsilocybin.

As a control, we tested anterior hippocampus FC change pre- versus post-MTP using both the LME model, and an equivalence test. To control for potential persistent psilocybin effects, only the block of scans immediately before and after MTP were used (for example, if a participant took MTP as drug 1, then all baseline scans were labelled as pre-MTP and all scans between drugs 1 and 2 were labelled post-MTP).

Equivalence testing (to conclude no change in anterior hippocampus after MTP) was accomplished by setting =0.5 standard deviation of FC change across pre-MTP sessions. We computed the 90% CI of change in FC change between pre- and post-MTP sessions. If the bounds of the 90% CI were within , then equivalence was determined123.

Raw fMRI and structural datapublished previously55,56 were run through our in-house registration and processing pipeline described above. These datasets were used for replication, external validation and generalization to another classic psychedelic (that is, LSD) for the measures described above (for example, NGSC and the MDS-derived psilocybin FC dimension, dimension 1).

Using the data from ref. 55: n=15 healthy adults (five women, mean age 34.1years, s.d. 8.2) completed two scanning sessions (psilocybin and saline) that included an eyes-closed resting-state BOLD scan for 6min before and following i.v. infusion of drug. fMRI data were acquired using a gradient-echo-planar imaging sequence, TR and TE of 3,000 and 35ms, field-of-view 192mm, 6464 acquisition matrix, parallel acceleration factor of 2 and 90 flip angle.

Using the data from ref. 56: healthy adults completed two scanning sessions (LSD and saline), which included an eyes-closed resting-state BOLD scan acquired for 22min following i.v. drug infusion lasting 12min. n=20 participants completed the protocol, but data were used for n=15 (four women; mean age 30.5, standard deviation 8.0) deemed suitable for BOLD analyses. fMRI data were acquired using a gradient-echo-planar imaging sequence, TR and TE of 2,000 and 35ms, field-of-view 220mm, 6464 acquisition matrix, parallel acceleration factor of 2, 90 flip angle and 3.4mm isotropic voxels.

The ABCD database resting-state functional MRI59 (annual release v.2.0, https://doi.org/10.15154/1503209) was used to replicate the effects of stimulant use on FC. Preprocessing included framewise censoring with a criterion of frame displacement less than or equal to 0.2mm in addition the standard predefined preprocessing procedures124. Participants with fewer than 600 frames (equivalent to 8min of data after censoring) were excluded from the analysis. Parcel-wise group-averaged FC matrices were constructed for each participant as described above for 385 regions on inter-test in the brain.

Use of a stimulant (for example, MTP, amphetamine salts, lisdexamfetamine) in the last 24h was assessed by parental report. Participants with missing data were excluded. Regression analysis was used to assess the relationship between FC (edges) and stimulant use in the last 24h. Framewise displacement (averaged over frames remaining after censoring) was used as a covariate to account for motion-related effects. The t-values that reflect the relationship between stimulant use and FC were visualized on a colour scale from 5 to +5 to provide a qualitative information about effect of stimulant use on FC.

Further information on research design is available in theNature Portfolio Reporting Summary linked to this article.

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Psilocybin desynchronizes the human brain - Nature.com

A study finds that psilocybin can desynchronize networks in the brain, potentially enhancing its plasticity. Sara Moser/Washington University School of Medicine in St. Louis hide caption

In the name of science, Dr. Nico Dosenbach had scanned his own brain dozens of times. But this was the first time he'd taken a mind-bending substance before sliding into the MRI tunnel.

"I was, like, drifting deeper into weirdness," he recalls. "I didn't know where I was at all. Time stopped, and I was everyone."

Dosenbach, an associate professor of neurology at Washington University School of Medicine in St. Louis, had been given a high dose of psilocybin, the active substance in magic mushrooms, by his colleagues.

It was all part of a study of seven people designed to show how psilocybin produces its mind-altering effects.

The results, which appear in the journal Nature, suggest that psychedelic drugs work by disrupting certain brain networks, especially one that helps people form a sense of space, time and self.

"For the first time, with a really high degree of detail, we're understanding which networks are changing, how intensely they're changing and what persists after the experience," says Dr. Petros Petridis of New York University's Langone Center for Psychedelic Medicine, who wrote an editorial accompanying the study.

The research also provided a close look at how these drugs temporarily enhance the brain's ability to adapt and change, an ability known as plasticity.

The disruptions in brain networks appear to be "where the plasticity effects of psychedelics are coming from," says Dr. Joshua Siegel, a researcher at Washington University and the study's lead author.

If that's true, he says, it could explain why psychedelics appear to help people with addiction or depression.

Dosenbach and other participants were randomly assigned to receive either a stimulant or 25 milligrams of psilocybin, a dose high enough to cause hallucinations.

"It was definitely an awesome experience for a neuroscientist," he says.

"It's really fascinating how your brain can fall apart because how something breaks tells you how something works."

Dosenbach's trip took him places only a neuroscientist is likely to go.

"I was inside the brain, and I was riding brain waves, and I was Marc Raichle," he says, referring to Dr. Marcus Raichle, a colleague and co-author of the study, who also happens to be a towering figure in the world of neuroscience.

As part of the study, participants' brains were scanned an average of 18 times over a three-week period. Four repeated the experiment six to 12 months later.

"You're bringing in single individuals many times," Siegel says, "and that allows you to get a very detailed and precise map of their brain networks."

The scans showed that psilocybin caused swift and dramatic changes to certain brain networks. Usually the neurons in a given network become active at the same time often in tandem with other networks too.

"What's going on during psilocybin is that populations of neurons that are normally in synchrony are out of synchrony," Siegel says.

The brain "falls apart." And it appears to respond by entering a state of enhanced plasticity that can last for weeks.

"Desynchronization probably is a critical clue as to where the plasticity effects of psychedelics are coming from," Siegel says.

The loss of synchrony was greatest in a brainwide group of neurons called the default mode network, which is active when the brain is daydreaming or otherwise not focused on the outside world.

This network was discovered by scientists including Raichle, the man who became Dosenbach's alter ego in the scanner.

The default mode network is critical to self-referential memory, which helps the brain keep track of information like, Who am I? And what was I doing? Siegel says.

The study hints at how psychedelic drugs could be incorporated into the treatment of people with addiction, depression or post-traumatic stress.

"There seems to be this time of increased change that could be taken advantage of by therapists," Petridis says.

A patient with addiction, for example, might be able to reframe their relationship with substances in the days and weeks following a dose of psilocybin, he says.

But the approach has risks, says Dr. Ginger Nicol, a psychiatrist at Washington University whose husband was in the study and took psilocybin twice.

"He had an almost religious experience the first time," she says. "The second time, he saw demons."

Even so, psychedelics may offer a way to help psychiatric patients recognize their own capacity to change, Nicol says.

"It takes years to figure that out in therapy," she says. "This gives us a different way of thinking about learning and recovery."

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A scientist took a psychedelic drug and watched his own brain 'fall apart' - NPR

Early next year, the state of Colorado will start issuing licenses for psychedelic therapy centers, places where people can pay to take a supervised dose of psychedelic mushrooms and other forms of psilocybin.

Close to 100 people have told the state theyre interested in opening psilocybin businesses, including mushroom cultivation facilities, testing labs and therapy centers. Those therapy centers will be the only formal, legal businesses that are able to sell psilocybin, and the drug will have to be taken under supervision.

It will be the fulfillment of a change that voters approved back in 2021.

But what will those healing centers look like? What forms will the psilocybin come in? Who will produce the drug, and who can work in the industry?

Those are questions the state is trying to answer now. On Thursday, regulators published the latest draft rules that will govern the psilocybin industry here.

Its a key step. With the new publication, facilitators and businesses really have what they need to make informed decisions, said Shawn Hauser, a partner at Vicente LLP, a law firm that has been closely involved in Colorados cannabis and psilocybin industries.

Therapy centers could take a variety of forms, from a typical therapists office to a retreat or even an outdoor setting. Although each facility would need to be based in a building, regulators said they know customers might want to go outside.

They want to be able to move around and be in nature, said Allison Robinette, policy director for the Department of Revenues natural medicine and cannabis teams.

The industry could be allowed to offer psilocybin in multiple forms, including dried mushrooms; capsules; tea bags; tinctures; and chocolates and confections.

The idea of psilocybin chocolates is stirring some debate, with childrens safety advocates worried that it will normalize the idea of sweet and candy-based doses, similar to what happened with cannabis gummies and soda.

Proponents say chocolates may be more palatable for some than whole mushrooms or capsules, and may help quell nausea. The state is considering more safeguards for psilocybin chocolates, such as limits on how they are handled and transferred, Robinette said. Psilocybin will only be available to people 21 and older for use in controlled settings.

The state is set to offer a micro-cultivation license that may be more practical to obtain for smaller growers. That might be helpful for healing centers that want to grow their own mushrooms.

Applicants for psilocybin businesses will have to demonstrate a commitment to minimum environmental and social impact criteria, which they can achieve through strategies like waste reduction and inclusive hiring.

The new rules will be up for public comment at a hearing on July 25.

So far, the strongest interest from entrepreneurs has been in opening healing centers, rather than the other potential related businesses, Robinette said.

The 120-page draft also touches on numerous other requirements, including for testing, packaging, labeling and tracking products.

Weve looked across what other state agencies do. Weve leaned on our experience regulating in the cannabis space, she said.

At the meeting next Thursday, we will walk through every section, well provide context, well ask any outstanding question we as the division will still have, Robinette said.

State officials have been working on these rules since earlier this year. Regulators are trying to learn from Colorados experience with legal cannabis, in which an initial lack of regulation allowed an explosion of different THC products.

They have also been talking to cultivators of gourmet culinary mushrooms, who have shared their expertise on how larger-scale mushroom facilities might be run. And theyve also looked to Oregon, the only state with a similar program.

Despite all the interest, the industry may get a slow start, compared to legal marijuana, said Tasia Poinsatte, director of the Healing Advocacy Fund of Colorado, a major force behind the new law.

The scale of this is astronomically smaller than cannabis. The information weve gotten from Oregon is that the entire state program has only consumed in the vicinity of 20 to 30 kilograms of dried mushrooms so far, she said.

Hauser similarly said its unclear just how profitable and attractive the new industry will be to businesses, especially with competition from the current gray market.

The economics and viability of the program will really remain to be seen, she said, though she praised state officials for their work on the rules.

One big question still hasnt been answered: How much will businesses have to pay to get licensed? That will be addressed in the next and final rulemaking process.

The new draft rules cover how the various businesses will operate. But the state has already drafted or approved several other sets of rules for the individual facilitators who will oversee each psilocybin trip.

Facilitators will have to take coursework of at least 150 hours and undergo 40 hours of supervised training and 50 hours of consultation. Other draft rules offer guidance on more specific topics, like when and how a facilitator can offer a supportive touch to a participant, or how to respond to health problems during a session.

The Department of Regulatory Agencies is already accepting applications from organizations that would like to offer training programs for the psilocybin industry. These rules only cover the regulated part of the new world of psychedelics. Meanwhile, a flourishing gray market has emerged. The new laws allowances for personal use and sharing have led to people openly growing and offering psilocybin mushrooms, and touting their services as guides. While it is still illegal to charge for mushrooms, ads selling them abound online.

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Tinctures, chocolates and more: The future of Colorados psychedelic industry is coming into focus - Colorado Public Radio

Users of hip Amazonian psychedelic ayahuasca favored by celebrities are having a bad trip at Alcoholics Anonymous meetings.

At least five recovering alcoholics who also indulge in ayahuasca and other psychedelics told The Post they are getting shunned by the group.

Jennifer Bruce described being berated when she continued to participate in mainstream 12-step meetings after taking ayahuasca to address past trauma.

When she picked up a chip denoting her length of sobriety at a meeting, attendees shouted she needed to turn my chip back in and start over because I had relapsed, Bruce said.

So it was very difficult to be there, she said.

At another meeting she shared her story, including her experience with ibogaine, a naturally occurring psychoactive compound.

I got attacked so bad that I was sobbing in tears at the end, Bruce said.

AA members who use psychedelics or even cannabis are often seen as breaching the organizations premise of total abstinence, though AA as an organization has no opinions on controversial issues and its co-founder, Bill Wilson, experimented with LSD.

Those who take psychedelics say they maintain their sobriety because the plant-based psychedelic is non-addictive and is being used medicinally or for spiritual enlightenment not to numb out.

Ayahuasca, the psychedelic brew, is popular with celebrities including pop star Miley Cyrus, actress Megan Fox and her boyfriend, pop-punk musician Machine Gun Kelly.

This is not about using a mind-altering substance for anything, said Michele Medal, who is in recovery for 20 years and has several psychedelic businesses. This is about healing at a cellular level. And once you heal at a cellular level, really heal, then that addiction is gone not that it cant come back.

Psychedelics, which advocates refer to as plant-based drugs, remain under heavy regulation federally and in most states. Oregon and Colorado have legalized some uses and legislation is pending in nine other states, including New Jersey, but legalization proposals in New York have gone nowhere so far.

Limited research suggests that use of psychedelic drugs does not typically lead to addiction, according to the National Institute on Drug Abuse. Ongoing studies supported by the federal agency are exploring whether they can be used to treat substance use disorders.

Erin V., who said a weeklong shaman-led ayahuasca ceremonial retreat in Peru can run anywhere between $600 and $3,000, was too afraid in 12-step meetings to reveal she indulged medicinally, and said she ditched AA because she feared being banished.

Members are being punished and expelled from their recovery groups and fellowships due to ignorance, judgment and misinformation in direct violation of our traditions, Vanessa Crites, a person in long-term recovery who uses psychedelic medicines and remains in a mainstream 12-step program,postedon LinkedIn.

Alcoholics Anonymous insisted it doesnt kick anyone out, a spokesperson said in an email, and it does not have a position or opinion on this matter.

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Recovered alcoholics tripping on ayahuasca say theyre being ostracized at AA meetings - New York Post

Are psychedelic drugs about to begin a long, strange trip toward use in a clinical setting? Or do the challenges of studying psychedelics, and the ethical risks of therapy, raise too many questions to introduce them into mainstream medicine?

Dominic Sisti, an associate professor of medical ethics and health policy in the Perelman School of Medicine, is part of a group of nearly 30 experts including bioethicists, psychiatrists, Indigenous scholars, researchers, and others to begin charting a path toward crafting guidelines for the ethical use of psychedelics. The groups work is published in JAMA Network Open, setting the stage for the next phase of psychedelics in psychiatry.

As debate continues ifand howpsychedelics should be used, a Food and Drug Administration advisory committee recently voted down a proposal brought by a drugmaker to use MDMA to treat post-traumatic stress disorder (PTSD), in combination with talk therapy. The committee recognized the promise of psychedelics but raised serious concerns about the science and the ethics of psychedelic treatments.

However, the FDA can still eventually approve its use. If so, there is a growing movement of cross disciplinary experts crafting guardrails for how psychedelic drugs should be used.

Though popular culture often depicts psychedelic drug use as a product of 1960s counterculture, mind-altering drugs have been used by humans in some form for millennia. In 2008, archeologists at a 1,000-year-old site in Bolivia discovered psychoactive botanical substances found in a hallucinogenic cocktail known as ayahuasca.

According to Sisti, recognizing history like this was a central theme of his groups work examining the potential for psychedelic use in modern medicine.

Just imagining that if psilocybin is commercializedshould shamans in Mexico and Central America, where some of these medicines originated, receive some sort of direct benefit from the research? Sisti says. Its an issue at the intersection of ethnobotany, colonialism, research ethics, reciprocity, and respect.

Read more at Penn Medicine News.

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Charting a new frontier with psychedelic drugs - Penn Today

A new study led by the Washington University School of Medicine in St. Louis has shown how psilocybin, the psychedelic compound in magic mushrooms, affects the brain.

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials, wrote the study authors.

In animal models, psilocybin induces neuroplasticity in cortex and hippocampus. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics.

The researchers discovered that psilocybin temporarily disrupts the default mode network, a crucial brain area involved in introspective thinking, such as daydreaming and remembering.

This desynchronization leads to the characteristic psychedelic experience and could explain psilocybins potential to treat mental illnesses like depression and PTSD.

Theres a massive effect initially, and when its gone, a pinpoint effect remains, said so-senior author Dr. Nico U. F. Dosenbach of WUSTL. Thats exactly what youd want to see for a potential medicine.

Dosenbach went on to explain that you wouldnt want peoples brain networks to be obliterated for days, but you also wouldnt want everything to snap back to the way it was immediately. You want an effect that lasts long enough to make a difference.

The experts utilized functional MRI scans to observe the brain activity of seven healthy adults before, during, and after consuming psilocybin or methylphenidate. The researchers aimed to correlate changes in brain networks with subjective experiences.

These days, we know a lot about the psychological effects and the molecular/cellular effects of psilocybin, said first author Dr. Joshua S. Siegel. But we dont know much about what happens at the level that connects the two the level of functional brain networks.

Psilocybin caused profound but temporary changes in the brains functional networks, particularly the default mode network.

After the acute effects of the drug wore off, small differences from pre-psilocybin scans persisted for weeks.

The idea is that youre taking this system thats fundamental to the brains ability to think about the self in relation to the world, and youre totally desynchronizing it temporarily, explained Dr. Siegel.

In the short term, this creates a psychedelic experience. The longer-term consequence is that it makes the brain more flexible and potentially more able to come into a healthier state.

During the experience, participants rated their feelings of transcendence, connectedness, and awe using the validated Mystical Experience Questionnaire.

The changes in functional networks corresponded with the intensity of each participants subjective experience.

We were able to get very precise data on the effects of the drug in each individual, said co-senior author Dr. Ginger E. Nicol.

This is a step toward precision clinical trials. In psychiatry, we often dont know who should get a particular medicine and how much or how often. By using this approach in clinical trials, we can identify the factors that determine who benefits and who doesnt, and make better use of the medicines we have.

However, the researchers caution against self-medicating with psilocybin, which is not FDA-approved and carries risks if taken without professional supervision.

The dramatic departure from typical synchronized patterns of co-activity may be key to understanding the acute effects of psilocybin and also its persistent neurotrophic effects, wrote the researchers.

Changes in resting activity are linked to shifts in glutamate-dependent signaling during psilocybin exposure.

This phenomenon, shared by ketamine and psychedelics, engages homeostatic plasticity mechanisms, a neurobiological response to large deviations in typical network activity patterns.

Psychedelics rapidly induce synaptogenesis in the hippocampus and cortex, effects that seem to be necessary for rapid antidepressant-like effects in animal models.

However, understanding the underpinnings of the behavioral effects of psychedelics requires human studies.

Advances in precision functional mapping and individual-level characterization enabled us to identify desynchronization of resting-state fMRI signals, connect these changes with subjective psychedelic effects and localize these changes to depression-relevant circuits (DMN, hippocampus).

These analyses rely on precise characterization of an individuals baseline brain organization (for example, individual definition of brain areas, networks and day-to-day variability) to understand how that organization is altered by an intervention.

The study is published in the journal Nature.

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Psychedelics give the brain flexibility to enter a healthier state - Earth.com