How do mushrooms become magic?

Research examines why some fungi evolve psychedelic properties

Grant and Award Announcement

UNIVERSITY OF PLYMOUTH

 

VIDEO: A TIMELAPSE VIDEO OF PSYCHEDELIC AND NON-PSYCHEDELIC FUNGI GROWING IN THE LAB view more 

CREDIT: UNIVERSITY OF PLYMOUTH

Psychedelic compounds found in ‘magic mushrooms’ are increasingly being recognised for their potential to treat health conditions such as depression, anxiety, compulsive disorders and addiction.

However, very little is known about how such compounds have evolved and what role they play in the natural world.

To address that, scientists from the University of Plymouth are conducting a first-of-its-kind study using advanced genetic methods and behavioural experiments to address previously untested hypotheses into the origin of psychedelic compounds in fungi.

This includes exploring whether such traits have evolved as a form of defence against fungus-feeding invertebrates, or whether the fungi produce compounds that manipulate insect behaviour for their own advantage.

The project will particularly focus on psilocybin, commonly found in so-called ‘magic mushrooms’. In chemical terms, it is very similar to serotonin, which is involved in the sending of information between nerve cells in animals.

The researchers are sampling psychedelic and non-psychedelic fungi, and using next-generation DNA sequencing to test whether or not there is a diverse animal community feeding on psychedelic fungi.

They are also using laboratory tests to investigate fungal-insect interactions, and whether the fungi undergo genetic changes during attack and development. They will also investigate the effect of psilocybin on the growth of soil bacteria.

The research will also involve using cutting-edge gene editing technology to try and create mutant fungi that cannot synthesize psilocybin. It is hoped this will help researchers better understand the role of a wide range of fungal compounds in future.

The study is being led by a team of experienced researchers in molecular ecology, animal-plant interactions and fungal biology in the University’s School of Biological and Marine Sciences. Driving the study are Post-Doctoral Research Fellow Dr Kirsty Matthews Nicholass and Research Assistant Ms Ilona Flis.

Dr Jon Ellis, Lecturer in Conservation Genetics, is supervising the study. He said: “In recent years, there has been a resurgence of interest in psychedelic compounds from a human health perspective. However, almost nothing is known about the evolution of these compounds in nature and why fungi should contain neurotransmitter-like compounds is unresolved.

“The hypotheses that have been suggested for their evolution have never been formally tested, and that is what makes our project so ambitious and novel. It could also in future lead to exciting future discoveries, as the development of novel compounds that could be used as fungicides, pesticides, pharmaceuticals and antibiotics is likely to arise from ‘blue-sky’ research investigating fungal defence.”

Dr Kirsty Matthews Nicholass said: “Within Psilocybe alone, there are close to 150 hallucinogenic species distributed across all continents except Antarctica. Yet, the fungal species in which these ‘magic’ compounds occur are not always closely related. This raises interesting questions regarding the ecological pressures that may be acting to maintain the biosynthesis pathway for psilocybin.”

The research is being funded by the Leverhulme Trust and builds on the University’s long-running expertise in novel elements of conservation genetics.

Researchers involved in this project have previously explored the genetic diversity among UK pollinators, the feeding preferences of slugs and snails, and developed an early warning system for plant disease.

 

Scientists are looking to address untested hypotheses into the

 origin of psychedelic compounds in fungi

The researchers have sampled psychedelic and non-psychedelic fungi

from the wild to explore a range of currently untested hypotheses

CREDIT

University of Plymouth

Dr Jon Ellis talks about the history of research into psychedelic compounds in nature

“Fungi generally receive less attention overall than animals and plants, partly because they are less apparent, people interact with them less and they can be hard to study. Historically, there have also been legal barriers which meant certain research has not previously been possible. Saying that, there were some very interesting studies in the 1940s and 50s into the use of LSD as a psychotherapeutic treatment for alcoholism and obsessive-compulsive disorder. Around that time, people also became interested in fungi from an anthropological perspective.

"One couple, the Wassons, went to Mexico and witnessed the ritual use of fungi for the first time in religious ceremonies. Articles they published brought public attention to psychoactive mushrooms. Around this time, there were also other charismatic individuals, such as Timothy Leary, who advocated the use of LSD more widely by the general public. In the 1960s, psychedelic compounds really came to widespread public attention and that ultimately led to governments introducing new laws to restrict their use.

"For some time, that also restricted the fundamental research that could be carried out. More recently, people have returned to that initial research and found that compounds such as psilocybin can have psychotherapeutic benefits. However, that has not addressed their evolution in nature, which is what makes the research we are doing so exciting.

"I hope our project can change the public perception of magic mushrooms. But beyond that, asking questions about the biological world is a fundamental part of our human nature and this project fits into a long narrative of research asking questions about biodiversity and its evolution.”

Magic mushrooms could replace antidepressants within five years, says new psychedelic research centre

Exclusive: ‘People on antidepressants long-term say they feel blunted, with psychedelic therapy it’s the opposite, they talk about an emotional release, a reconnection’

Alex Matthews-King Health Correspondent

Hallucination-inducing drugs like magic mushrooms could be about to break big pharma’s stranglehold on the hugely lucrative market for antidepressants, according to the head of the world’s first centre for psychedelic research.

Antidepressant prescriptions have doubled in England in a decade with around seven million adults taking the drugs, and the global market is predicted to be worth $15.9bn (£12.5bn) by 2023.

At Imperial College London, Dr Robin Carhart-Harris is leading one of the first trials to test how therapy using psilocybin mushrooms, which are currently banned in the UK, compares to leading antidepressants.

While he won’t prejudge the results of the study, he says participants describe a cathartic emotional “release” with psilocybin therapy – the polar opposite of antidepressants, which patients complain leave their emotions, whether positive or negative, “blunted”.
It is the first of many studies planned under the banner of the new Centre for Psychedelic Research at London’s Imperial College.

Read more

The medicinal wonders of psychedelics are finally being recognised

A large empty floor of the university’s Hammersmith campus will house a bank of treatment rooms that make it the UK’s first psychedelic therapy research clinic, and a “prototype and inspiration” for licensed psychedelic medicine clinics of the future.

Trials of psilocybin in treating eating disorders, and a study of the effects of powerful hallucinogenic DMT on the brain, are already planned following Imperial’s commitment to the centre.



The future home of the Psychedelic Research Centre treatment rooms which could become the model for future clinics (The Independent)

But it is the work on depression where research is most advanced, and most promising.

On the current trial, around 60 participants with moderate to severe depression will receive psilocybin treatment accompanied by a therapy session with a clinical psychologist.

The participants will also be randomly allocated to receive either a placebo or the drug escitalopram, with neither researchers or patients knowing who is in each group.


Magic mushrooms could be bought in the UK until 2005 (Getty)

Escitalopram is a type of selective serotonin reuptake inhibitors (SSRIs), the drugs which account for the largest chunk of the antidepressant market.

“If you ask people who are taking SSRIs chronically, they often say ‘I feel blunted’,” Dr Carhart-Harris told The Independent, meaning both negative and positive emotions are suppressed.

“With psilocybin therapy they say the opposite, they talk about an emotional release, a reconnection, and this key emotional centre being more responsive.”




Patients will have MRI scans to test changes in their brains after
psilocybin therapy (Centre for Psychedelic Research)

The team use MRI scans to study psychedelics’ effects on the brain and the drug appears to reduce activity in the coordinating regions, releasing their grip and allowing the more primitive emotional centres to the fore.

Other early indications are that the list of side-effects is “twice as long” for escitalopram as it is for psilocybin therapy, and it is much faster acting than antidepressants – which can take months to work.



Treatment rooms are a soothing environment where participants are 
supported through their psychedelic experience (Centre for Psychedelic Research)

However, the treatment may not be suitable for everyone.

During the therapy sessions, patients are encouraged to follow the stream of the psychedelic experience which can be extremely vivid and may require them to confront past traumas or experiences.

“We don’t call it a ‘bad trip’,” Dr Carhart-Harris says. “We call it a ‘challenging psychological experience’ and we’re honest with people that it can be hellish.

“It can be nightmarish, but we’re prepared for this and this treatment model requires you literally face your demons.”

Psychedelic therapy is unlikely to be suitable for people with psychosis and regulators will need evidence of its effectiveness and safety from clinical trials.

But there is little evidence that they pose a risk of overdose or addiction and that could speed their route to approval.

Fresh magic mushrooms could be picked or bought in shops legally in the UK until 2005, when a change in law closed the loop hole and made them Class A drugs alongside crack cocaine.

“I would imagine if you had some bookmakers doing the odds, there would be strong odds on that [psychedelic therapy] will be licensed sometime in the next five to 10 years – maybe sooner,” Dr Carhart-Harris says.

That could put it on a collision course with powerful interests of the pharmaceutical industry, particularly if trials show psilocybin therapy to be superior to SSRIs




Psilocybin therapy may allow depressed people’s brains to rewire in 
a positive way, rather than suppressing good and bad emotion (Centre for Psychedelic Research)

“The implications of that are actually frightening to me, thinking of the power and influence of big pharma,” Carhart-Harris says. “What are they going to do with that if there’s this big public demand for the ‘mushroom therapy’, and not the Prozac?”

While there is a growing trend for “microdosing” psilocybin or LSD, the evidence to date suggests it is the combination of therapy and psychedelic experience that offers the best option of a lasting alternative to chronic antidepressants.




Psychedelics research has had to rely on philanthropic funding for years, 
but latest wave of trials show the field is set on not repeating the mistakes 
of the past (The Independent)

“If you strip the drug away from therapy you start seeing the adverse events that were being reported in the 1960s, when psychedelics left the clinic and became popularised,” Dr Carhart-Harris adds.

“None of us want those mistakes to be made again.”

Dr James Rucker is another of those researching the potential benefits of psychedelics, over at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London.

The King’s team are launching two trials, one looking at whether psilocybin therapy can help people whose depression is resistant to treatment with conventional antidepressants.

He says it was “possible” the drug could be licensed in five years. “But only if everything goes to plan, and you know what they say about best-laid plans.”

In Dr Rucker’s mind the process is similar to the approval of ketamine, where the first trials in depression took place in the 1990s and the first ketamine-based medicines are only now being licensed.

Psilocybin has much lower potential for abuse and overdose, but watchdogs will still need stage three trials which haven’t even begun.

“Like all treatments, they will suit some people but not others,” he told The Independent. “The trick, as ever, is trying to work that out before administration. But that trick has proven to be remarkably difficult to pull off, particularly in psychiatry.

Psychedelics research has had to rely on philanthropic funding for years, but latest wave of trials show the field is set on not repeating the mistakes of the past (The Independent)

“If you strip the drug away from therapy you start seeing the adverse events that were being reported in the 1960s, when psychedelics left the clinic and became popularised,” Dr Carhart-Harris adds.

“None of us want those mistakes to be made again.”

Dr James Rucker is another of those researching the potential benefits of psychedelics, over at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London.

The King’s team are launching two trials, one looking at whether psilocybin therapy can help people whose depression is resistant to treatment with conventional antidepressants.

He says it was “possible” the drug could be licensed in five years. “But only if everything goes to plan, and you know what they say about best-laid plans.”

In Dr Rucker’s mind the process is similar to the approval of ketamine, where the first trials in depression took place in the 1990s and the first ketamine-based medicines are only now being licensed.

Psilocybin has much lower potential for abuse and overdose, but watchdogs will still need stage three trials which haven’t even begun.

“Like all treatments, they will suit some people but not others,” he told The Independent. “The trick, as ever, is trying to work that out before administration. But that trick has proven to be remarkably difficult to pull off, particularly in psychiatry.”

FOR ARTICLE WITH VIDEO'S AND PICTURES GO HERE

New study looks at 'magic' mushrooms as treatment for depression, without the psychedelic high

Megan DeLaire
CTVNews.ca Writer
 July 27, 2022 

A new study by the Centre for Addiction and Mental Health (CAMH) will attempt to harness the antidepressant power of psilocybin mushrooms, but without the psychedelic experience.

Psilocybin is the hallucinogenic chemical compound in "magic" mushrooms that generates a psychedelic high. However, clinical trials have shown psilocybin mushrooms also have antidepressant effects on people whose depression is resistant to other treatments, when combined with intensive psychotherapy.

Over a period of three years, researchers at CAMH will try to learn whether the psychedelic experience itself is necessary to treat depression in a federally-funded study that lead researcher Dr. Ishrat Husain says is the first of its kind.

"What we're trying to address with this study, which I think is a glaring question in the field, is whether the psychedelic high is required for the therapeutic benefits,” Husain told CTVNews.ca. “It's assumed that it is, but nobody's actually designed a clinical trial to answer that question."

Husain and his team will compare the outcomes of 60 adults with treatment-resistant depression. Over the course of the study, a third of the participants will receive a full dose of psilocybin plus a serotonin blocker to inhibit the drug’s psychedelic effect. Another group will be given psilocybin plus a placebo. The final group will receive a placebo, plus the serotonin blocker. All participants will also receive 12 hours of psychotherapy.

This is the second clinical psilocybin trial at CAMH, which was the Canadian site for the world’s largest clinical trial of psilocybin in mental health to date, in 2021.

If the new study shows psilocybin mushrooms have equal antidepressant effects with or without the psychedelic experience, Husain said it could be a “game changer” for people with treatment-resistant depression who aren’t candidates for a psychedelic high.

“There are certain physical and psychological contraindications to receiving potent psychoactive drugs like psilocybin,” he said. “If we're able to show that the psychedelic experience isn't entirely necessary, it could lead to a sort of new therapeutic development for the treatment of depression."

'HOPE OF INNOVATION'

Some day, Carole Dagher might need to put her trust in a new treatment. In fact, Dagher believes it’s inevitable. After years of trying to treat her depression, she’s in a good place. But she knows it won’t last.

"I will have another dip, there's no question about it,” Dagher told CTVNews.ca. “This is just going to be my life, it's something I'm going to have to manage."

Dagher is a patient of Husain’s who suffers from treatment-resistant major depressive disorder and anxiety disorder. She first developed postpartum depression following the birth of her oldest daughter 12 years ago. Her symptoms were compounded by trauma from childhood experiences growing up in Beirut during the Lebanese Civil War In the years since her initial diagnosis, she has struggled with suicidal ideation, tried five classes of antidepressant medication, seen psychologists and tried both electroconvulsive therapy and repetitive transcranial magnetic stimulation therapy.

After those methods failed, she turned to ketamine therapy, which was approved by Health Canada to treat major depressive disorder in 2020. Ketamine is an anaesthetic that induces strong psychedelic experiences in therapeutic doses. Dagher called those experiences “horrific,” and said they were so unbearable she nearly quit the therapy before finishing her eight sessions. She stuck with it, however, and awoke one morning after her final session feeling restored.

"I opened my eyes in the morning and the sky was blue, and the birds were chirping, and I smiled for the first time in 12 years and it was a genuine smile,” she said.

She’s still doing well, with help from an antidepressant and regular therapy sessions. But she’s waiting for the day her symptoms stop responding to ketamine. When that day comes, she'll need to look for another treatment — preferably one without a high. That's why she sees so much promise in Husain’s study.

"Without the hope of innovation, I cannot survive another day. I have to believe deep down in my heart that people like Dr. Husain and hospitals like CAMH will not stop innovating. Ketamine worked now, but it might not work later,” she said. “And I'd much rather not have the psychedelic trip, and take the [psilocybin] and have it do its thing."

On the subject of access to psilocybin therapy, while Johns Hopkins University scientist David Yaden agrees being able to offer the therapy without a psychedelic experience would make it accessible to more people, he worries about patients who may want or need the full experience.

Yaden is an assistant professor at the Johns Hopkins Center for Psychedelic and Consciousness Research who has published multiple scientific articles about the use of psilocybin as a potential treatment.

“What I worry about is an unintentional side-effect of characterizing the acute subjective effects of psychedelics — the trip, so to speak — as an unwanted side effect,” he told CTVNews.ca.

"As long as participants are screened and administered psilocybin in a supportive setting, we see that these experiences can be challenging, but they're overall very positive and deeply meaningful. That's just what the data say."

Yaden also believes, based on past studies, that a dose of psilocybin without the psychedelic side-effects likely only delivers short-term neurobiological benefits. In a report released in December 2020, he and fellow Johns Hopkins researcher Roland Griffiths argued there are long term, complex changes that can only take place in the brain during a psychedelic experience.

Regardless, he said the CAMH study is asking important questions in an area of research his team would like to explore more.

“I support research like this study looking at the causal role of the acute subjective effects of psychedelics, because I think it's a very important question to examine,” he said.

"This research is important for both clinical and scientific reasons. It's great and I'm really glad it's happening. We've been trying to do this research as well. I'm very much for it."

___

If you or someone you know is struggling with suicidal thoughts or mental health matters, please call the National Suicide Prevention Lifeline at 800-273-8255 (or 988 beginning July 16, 2022) or Canada's Talk Suicide 1-833-456-4566. The following resources are also available to support people in crisis:

Hope for Wellness Helpline (English, French, Cree, Ojibway and Inuktitut): 1-855-242-3310

Embrace Life Council hotline: 1-800-265-3333

Trans Lifeline: 1-877-330-6366

Kids Help Phone: 1-800-668-6868

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The placebo effect and psychedelic drugs: tripping on nothing?

by McGill University

Credit: CC0 Public Domain

There has been a lot of recent interest in the use of psychedelic drugs to treat depression. A new study from McGill suggests that, in the right context, some people may experience psychedelic-like effects from placebos alone. The researchers reported some of the strongest placebo effects (these are effects from "fake" medication) on consciousness in the literature relating to psychedelic drugs. Indeed, 61% of the participants in the experiment reported some effect after consuming the placebo.

"The study reinforces the power of context in psychedelic settings. With the recent re-emergence of psychedelic therapy for disorders such as depression and anxiety, clinicians may be able to leverage these contextual factors to obtain similar therapeutic experiences from lower doses, which would further improve the safety of the drugs," said Jay Olson, a Ph.D. candidate in McGill's Department of Psychiatry and the lead author on the research paper that was recently published in Psychopharmacology.

Setting the mood

Participants, who were expecting to take part in a study of the effects of drugs on creativity, spent four hours together in a room that had been set up to resemble a psychedelic party, with paintings, coloured lights and a DJ. To make the context seem credible and hide the deception, the study also involved ten research assistants in white lab coats, psychiatrists, and a security guard.

The 33 participants had been told they were being given a drug which resembled the active ingredient in psychedelic mushrooms and that they would experience changes in consciousness over the 4-hour period. In reality, everyone consumed a placebo. Among the participants were several actors who had been trained to slowly act out the effects of the ostensible drug. The researchers thought that this would help convince the participants that everyone had consumed a psychedelic drug and might lead them to experience placebo effects.

Strong effects for a placebo

When asked near the end of the study, the majority (61%) of the participants reported some effect of the drug, ranging from mild changes to effects resembling taking a moderate or high dose of an actual drug, though there was considerable individual variation. For example, several participants stated that they saw the paintings on the walls "move" or "reshape" themselves. Others described themselves as feeling "heavy... as if gravity [had] a stronger hold", and one had a "come down" before another "wave" hit her. Several participants reported being certain that they had taken a psychedelic drug.

"These results may help explain 'contact highs' in which people experience the effects of a drug simply by being around others who have consumed it," says Samuel Veissière, a cognitive anthropologist who teaches in McGill's Department of Psychiatry and supervised the study. "More generally, our study helps shed light on the 'placebo boosting' component inherent in all medical and therapeutic intervention, and the social influences that modulate these enhancing effects. Placebo effects may have been under-estimated in psychedelic studies. The current trend towards 'micro-dosing' (consuming tiny amounts of psychedelic drugs to improve creativity), for example, may have a strong placebo component due to widespread cultural expectations that frame the response."


Explore furtherNew research confirms lingering mood benefit of psychedelics

More information: Jay A. Olson et al, Tripping on nothing: placebo psychedelics and contextual factors, Psychopharmacology (2020). DOI: 10.1007/s00213-020-05464-5
Provided by McGill University

TUNE IN, TURN ON, DROP OUT

IS A MATTER OF MIND

YOU CAN BE ANYBODY THIS 

TIME AROUND 

DR. TIMOTHY LEARY PSYCHEDELIC REBEL SHAMAN 

The Psychedelics Industry Could Offer a Whole New Approach to Work


Shelby Hartman and Madison Margolin
Sat, October 2, 2021,

psychedelic-column-industry - Credit: Illustration by Carolina Rodríguez Fuenmayor for Rolling Stone
This column is a collaboration with DoubleBlind, a print magazine and media company at the forefront of the psychedelic movement.

As the world of psychedelics matures to include both a grassroots movement and a burgeoning legal industry — echoing the process that cannabis went through a few years ago — many are wondering what kinds of new jobs will become available in the psychedelic space. Will psychedelics come to resemble most other mainstream, corporate North American industries — or can we expect something that more reflects the spirit and ethos of the medicines that have been used for generations?

For the question of what of jobs will be available, the short answer is, all different kinds. “As psychedelics go from the fringe to the mainstream, the same types of jobs for every other industry that went from fringe to mainstream apply to this one,” says Lewis Goldberg, a managing partner at KCSA, a communications consultancy that works with a handful of companies in the psychedelic space. “I would tell anyone who wants to get into the space to do it, but you better move fast. I’ll steal a line from Aldous Huxley: ‘The doors of perception are wide open, but the doors of opportunity are still closing.’”


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In the last couple of years, there’s been an exponential growth in the number of drug development companies seeking to take psychedelic compounds through the FDA approval process. MDMA, sometimes referred to as “ecstasy,” and psilocybin, one of the primary psychoactive components in psychedelic mushrooms, are both projected to be legal for prescription in the next five years. Meanwhile, more than a dozen drug development companies have now brought in hundreds of millions of dollars to research compounds from 5-MeO-DMT for depression to novel psychedelics they’re hoping will remove the possibility for a “bad trip.”

Indeed, it’s not just those developing the drugs who will be in on this industry — careers will span from lawyers who specialize in helping entrepreneurs navigate the legal landscape, to therapists who help patients integrate their experiences after a psychedelic trip, to receptionists who greet visitors at psychedelic clinics across the country.

“If you think that in the last three years, something like $3 billion of venture money has been pumped into the industry, that’s a tremendous amount, but not a lot of money — it’s building the foundation for a multi-trillion-dollar industry,” says Goldberg. “Five of the top 25 selling drugs in the world are designed to treat central nervous system disorders. This collective group of [psychedelic] companies is going to disrupt that. Some are going to be the equivalents of Google or Amazon and some are going to be Pets.com.” Although Goldberg is a self-proclaimed “regular mainstream capitalist,” he says that “the companies looking to be open-source are more likely to be successful and have a societal impact than those that are looking to solely work on their own.” In the field of psychedelics, being open source means allowing everyone in the field access to your data and research, in the spirit of progressing the movement as a whole — as opposed to prioritizing your company’s profitability.

Of course, open source alone is not enough to ensure that key players in the space are working toward a compassionate and equitable psychedelic industry. “This will require a lot of personal and internal decolonization work by the emerging ‘leaders’ of this space,” says Charlotte James, co-founder of The Ancestor Project, an educational platform designed for people of color that offers workshops and resources for members on the plant medicine journey. “We believe that by doing this work first, it then becomes natural to understand your role in the collective liberation movement that this medicine wants us to usher in. An equitable ‘industry’ won’t be an ‘industry’ as we currently understand it to be, and instead a mycelial-like network of co-creation across diverse communities and environments.”

So far, James doesn’t know a single BIPOC-led organization that has significant financial support in the psychedelic space, which, she says, leads to a widening gap between the grassroots movement and the corporate. “More folks are recognizing that in order to move away from capitalism, we have to break the work patterns that are ingrained in us, [since] those patterns that contribute to the glorified ‘hustle and grind’ culture are actually just extensions of systemic oppression,” says James. “Reclaiming our relationship to creativity and productivity will support us in being able to imagine a different and more equitable future in which our value is not defined by our bodies or our productivity.”

The psychedelic approach to work culture may lie in the way we regard our professional life versus our personal life. There’s a paradigm shift in being able to “bring your full self to work,” says Gareth Hermann, co-founder and CEO at Magic, a marketing agency in the psychedelic space. “At Magic, we don’t like the term ‘balance’ because it brings up the image of being on a seesaw, so we’re creating a culture that’s more celebratory of work-life ‘presence’ to create a space for the whole human to show up at work,” says Jennifer Ellis, chief people officer at Magic. The agency even goes so far as to offer programs that support repatterning, helping teammates recognize states of response and triggers so that they can develop better emotional literacy. Ultimately, Hermann explains, those shifts in beliefs and values create more possibility for us to make foundational impacts in the world at large.

What psychedelics offer is an invitation to look at professional and economic systems more, well, psychedelically. But it takes time leaning into the paradigm shift: Mike Margolies, founder of the educational conversation series Psychedelic Seminars, used to work a corporate job before an ayahuasca trip set him off on a journey that led to quitting, traveling, and creating a career in psychedelics. “The irony was that after all that, I had created myself a desk job, and I was like wait, what am I doing here?” he says. “I was thinking a lot about how you spend your time is how you spend your life.”

Among tactics like designated days dedicated for “work or task mode” versus “flow mode,” he now makes space to “allow for ‘productivity’ to happen in a different way.” “We have this idea of what a job is, what being productive is, but even though we’re all psychedelic, we’ve put ourselves in the same old boxes,” he says. “Because we have to have a work ethic, a mission, and so much urgency, we end up embodying the systems that we’re purportedly working to reinvent.” Indeed, a question not uncommon among psychedelic folk is whether a company can really heal the ill effects of capitalism in individuals and the collective, while also working within a capitalist system. Capitalism has us thinking that “work” has to be a certain way—a 40-hour a week grind. “It’s crazy that that’s become the standard,” Margolies says. “The goal isn’t to get everyone working” — in the standard capitalistic sense — “but how do we get everyone self-actualized? Achieving collective self-actualization is intrinsically the pathway to creating the most value for each other.”

 Psychedelic drug-induced hyperconnectivity in the brain helps clarify altered subjective experiences

A first of its kind imaging study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging provides insights into how the brain works on psychedelic drugs and their potential use to treat psychiatric disorders

HEY MAN AM I IN YOUR HEAD OR ARE YOU IN MINE?!

ELSEVIER

 

IMAGE: 

A NEW STUDY FINDS A PATTERN OF PSILOCYBIN-INDUCED DYNAMIC HYPERCONNECTIVITY IN THE BRAIN, WHICH IS LINKED TO OCEANIC BOUNDLESSNESS.

view more 

CREDIT: BIOLOGICAL PSYCHIATRY: COGNITIVE NEUROSCIENCE AND NEUROIMAGING

Philadelphia, May 23, 2024 – A new study shows that the use of psilocybin, a compound found in the widely known “magic mushrooms,” initiates a pattern of hyperconnectivity in the brain linked to the ego-modifying effects and feelings of oceanic boundlessness. The findings, appearing in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, help explain the so-called mystical experiences people report during the use of psychedelics and are pertinent to the psychotherapeutic applications of psychedelic drugs to treat psychiatric disorders such as depression.

The concept of oceanic boundlessness refers to a sense of unity, blissfulness, insightfulness, and spiritual experience often associated with psychedelic sessions.

In one of the first brain imaging studies in psychedelic research, investigators found a specific association between the experiential, psychedelic state and whole-brain dynamic connectivity changes. While previous research has shown increases in static global brain connectivity under psychedelics, the current study shows that this state of hyperconnectivity is dynamic (changing over time) and its transition rate coincides with the feeling of oceanic boundlessness, a hallmark dimension of the psychedelic state.

Lead investigator Johannes G. Ramaekers, PhD, Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, says, "Psilocybin has been one of the most studied psychedelics, possibly due to its potential contribution in treating different disorders, such as obsessive-compulsive disorder, death-related anxiety, depression, treatment-resistant depression, major depressive disorder, terminal cancer-associated anxiety, demoralization, smoking, and alcohol and tobacco addiction. What was not fully understood is what brain activity is associated with these profound experiences."

Psilocybin generates profound alterations both at the brain and the experiential level. The brain's tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental perspectives. The findings of the new study illuminate the intricate interplay between brain dynamics and subjective experience under psilocybin, providing insights into the neurophysiology and neuro-experiential qualities of the psychedelic state.

Dr. Ramaekers adds, "Taken together, averaged and dynamic connectivity analyses suggest that psilocybin alters brain function such that the overall neurobiological pattern becomes functionally more connected, more fluid, and less modular."

Previously acquired functional magnetic resonance imaging (fMRI) data were analyzed for two groups of people; one group of 22 individuals received a single dose of psilocybin, the other 27 participants received a placebo. During the drug's peak effects, participants who received psilocybin reported substantial phenomenological changes compared to placebo. Also, brain connectivity analysis showed that a pattern characterized by global region-to-region connectivity was re-appearing across the acquisition time in the psilocybin group, potentially accounting for the variant mental associations that participants experience.

Moreover, this hyperconnected pattern was linked to oceanic boundlessness and unity, which indicates an important mapping between brain dynamics and subjective experience, pointing towards “egotropic effects” (vs hallucinergic) of the drug.

PhD candidate and co-author of the paper Larry Fort, University of Liège, emphasizes: “Psychedelic drugs like psilocybin are often referred to as hallucinogens both scientifically and colloquially. As such, we expected that the hallucinatory dimensions of experience would correlate the highest with psilocybin’s hyperconnected pattern. However, hallucinatory experience had a strong, but weaker correlation with this pattern than ego-modifying experiences. This led us to formulate the term ‘egotropic’ to draw attention to these ego-modifying effects as important, perhaps even more so than their hallucinogenic counterparts.”

Editor-in-Chief of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Cameron S. Carter, MD, University of California Irvine, comments, “This study uses readily available resting state fMRI images acquired after psilocybin ingestion to provide new insights into the neurophysiological mechanisms underlying the subjective and clinical effects of the drug. It sets the stage for future studies using other psychedelic agents to examine whether the dynamic connectivity effects reflect a general mechanism for the therapeutic effects of these compounds.

Lead investigator Athena Demertzi, PhD, Physiology of Cognition, GIGA-CRC In Vivo Imaging Center, University of Liège, adds, "We were pleasantly surprised to learn that the brain pattern of hyperconnected regions was further characterized by lower global signal amplitude, which works as a proxy to heightened cortical arousal. So far, this is the first time that such approximation of arousal levels using fMRI was attempted in psychedelic research. This might be an important correlation as we move towards a full characterization of brain states under psychedelics."

She concludes, "Given the resurgence in research regarding the psychotherapeutic applications of psychedelic drugs, our results are pertinent to understanding how subjective experience under psychedelics influences beneficial clinical outcomes. Is the effect driven by ego-dissolution? By hallucinations? As such, our work exemplifies how the strong inter-relatedness between egotropic effects of moderate dose psilocybin and its hyperconnected brain pattern can inform clinical focus on specific aspects of phenomenology, such as ego-dissolutions. With this information, healthcare professionals may learn how to best engineer psychedelic therapy sessions to produce the best clinical outcomes."

 

 

 

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JOURNAL

Biological Psychiatry Cognitive Neuroscience and Neuroimaging

DOI

10.1016/j.bpsc.2024.04.001 

METHOD OF RESEARCH

Imaging analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Dynamic Functional Hyperconnectivity after Psilocybin Intake Is Primarily Associated with Oceanic Boundlessness

ARTICLE PUBLICATION DATE

6-Apr-2024

COI STATEMENT

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article. Cameron S. Carter, MD, is Chair of the Department of Psychiatry & Human Behavior at the University of California, Irvine School of Medicine. His disclosures of financial and conflicts of interests are available at http://www.biologicalpsychiatrycnni.org/bpsc-editorial-disclosures.

BETTER LIVING THROUGH CHEMISTRY

Psychedelics plus psychotherapy can trigger rapid changes in the brain − new research at the level of neurons is untangling how

The Conversation
October 2, 2023 

Psychedelic art (Shutterstock)

The human brain can change – but usually only slowly and with great effort, such as when learning a new sport or foreign language, or recovering from a stroke. Learning new skills correlates with changes in the brain, as evidenced by neuroscience research with animals and functional brain scans in people. Presumably, if you master Calculus 1, something is now different in your brain. Furthermore, motor neurons in the brain expand and contract depending on how often they are exercised – a neuronal reflection of “use it or lose it.”

People may wish their brains could change faster – not just when learning new skills, but also when overcoming problems like anxiety, depression and addictions.

Clinicians and scientists know there are times the brain can make rapid, enduring changes. Most often, these occur in the context of traumatic experiences, leaving an indelible imprint on the brain.

But positive experiences, which alter one’s life for the better, can occur equally as fast. Think of a spiritual awakening, a near-death experience or a feeling of awe in nature.


A transformative experience can be like a fork in the road, changing the path you are on. Westend61 via Getty Images

Social scientists call events like these psychologically transformative experiences or pivotal mental states. For the rest of us, they’re forks in the road. Presumably, these positive experiences quickly change some “wiring” in the brain.

How do these rapid, positive transformations happen? It seems the brain has a way to facilitate accelerated change. And here’s where it gets really interesting: Psychedelic-assisted psychotherapy appears to tap into this natural neural mechanism.
Psychedelic-assisted psychotherapy

Those who’ve had a psychedelic experience usually describe it as a mental journey that’s impossible to put into words. However, it can be conceptualized as an altered state of consciousness with distortions of perception, modified sense of self and rapidly changing emotions. Presumably there is a relaxation of the higher brain control, which allows deeper brain thoughts and feelings to emerge into conscious awareness.


Psychedelic-assisted psychotherapy combines the psychology of talk therapy with the power of a psychedelic experience. Researchers have described cases in which subjects report profound, personally transformative experiences after one six-hour session with the psychedelic substance psilocybin, taken in conjunction with psychotherapy. For example, patients distressed about advancing cancer have quickly experienced relief and an unexpected acceptance of the approaching end. How does this happen?


Neuronal spines are the little bumps along the spreading branches of a neuron.

Patrick Pla via Wikimedia Commons, CC BY-SA


Research suggests that new skills, memories and attitudes are encoded in the brain by new connections between neurons – sort of like branches of trees growing toward each other. Neuroscientists even call the pattern of growth arborization.

Researchers using a technique called two-photon microscopy can observe this process in living cells by following the formation and regression of spines on the neurons. The spines are one half of the synapses that allow for communication between one neuron and another.

Scientists have thought that enduring spine formation could be established only with focused, repetitive mental energy. However, a lab at Yale recently documented rapid spine formation in the frontal cortex of mice after one dose of psilocybin. Researchers found that mice given the mushroom-derived drug had about a 10% increase in spine formation. These changes had occurred when examined one day after treatment and endured for over a month.




Tiny spines along a neuron’s branches are a crucial part of how one neuron receives a message from another. Edmund S. Higgins

A mechanism for psychedelic-induced change

Psychoactive molecules primarily change brain function through the receptors on the neural cells. The serotonin receptor 5HT, the one famously tweaked by antidepressants, comes in a variety of subtypes. Psychedelics such as DMT, the active chemical in the plant-based psychedelic ayahuasca, stimulate a receptor cell type, called 5-HT2A. This receptor also appears to mediate the hyperplastic states when a brain is changing quickly.

These 5-HT2A receptors that DMT activates are not only on the neuron cell surface but also inside the neuron. It’s only the 5-HT2A receptor inside the cell that facilitates rapid change in neuronal structure. Serotonin can’t get through the cell membrane, which is why people don’t hallucinate when taking antidepressants like Prozac or Zoloft. The psychedelics, on the other hand, slip through the cell’s exterior and tweak the 5-HT2A receptor, stimulating dendritic growth and increased spine formation.

Here’s where this story all comes together. In addition to being the active ingredient in ayahuasca, DMT is an endogenous molecule synthesized naturally in mammalian brains. As such, human neurons are capable of producing their own “psychedelic” molecule, although likely in tiny quantities. It’s possible the brain uses its own endogenous DMT as a tool for change – as when forming dendritic spines on neurons – to encode pivotal mental states. And it’s possible psychedelic-assisted psychotherapy uses this naturally occurring neural mechanism to facilitate healing.

A word of caution

In her essay collection “These Precious Days,” author Ann Patchett describes taking mushrooms with a friend who was struggling with pancreatic cancer. The friend had a mystical experience and came away feeling deeper connections to her family and friends. Patchett, on the other hand, said she spent eight hours “hacking up snakes in some pitch-black cauldron of lava at the center of the Earth.” It felt like death to her.

Psychedelics are powerful, and none of the classic psychedelic drugs, such as LSD, are approved yet for treatment. The U.S. Food and Drug Administration in 2019 did approve ketamine, in conjunction with an antidepressant, to treat depression in adults. Psychedelic-assisted psychotherapy with MDMA (often called ecstasy or molly) for PTSD and psilocybin for depression are in Phase 3 trials.


Edmund S. Higgins, Affiliate Associate Professor of Psychiatry & Family Medicine, Medical University of South Carolina

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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How the religiously unaffiliated are finding purpose and spirituality in psychedelic churches

Are psychedelics the answer to addiction and depression?

The Conversation

October 11, 2023

More and more surveys point to decreasing membership in religious institutions and a corresponding rise of “nones.” Many people might assume that this indicates the absence of belief or a lack of spirituality.

Particularly in the West, people tend to think about religion in terms of belief in a higher power, such as God. For many nones, however, spirituality does not need a god or the supernatural to address questions of purpose, meaning, belonging and well-being.

While abandoning mainstream religious affiliation, many turn to alternative expressions, including secular, atheist and psychedelic churches.

For about a decade, as a scholar who studies alternative expressions of spirituality, I have tracked these groups online, visited churches and interacted with attendees. At times, I have been able to attend services or simply visit locations. At other times, out of respect for participants, I have met members – but not during services and rituals.

These churches demonstrate not a rejection of religion, as surveys suggest, but continued interest in spiritual community, rituals and virtues.

Psychedelic churches

One such church is The Divine Assembly, or TDA, in Salt Lake City, Utah. Founded in 2020 as “a magic mushroom church” by Steve Urquhart, a former member of The Church of Jesus Christ of Latter-day Saints, TDA conducts worship that connects people without dogma or intermediaries. TDA is not atheistic but maintains an inclusive notion of belief regarding God or a higher power.

Where members depart from traditional notions of religion and church, however, is within their practices and aims. Through psychedelic drugs, members believe they can directly experience the divine – as they define it – while gaining insight into their own and others’ well-being. Within the church, members participate in collective meaning-making rituals that fortify their everyday lives.

Distinctly, using psilocybin is not part of these activities, nor are instructions provided on conducting mushroom ceremonies. This is done on one’s own time, according to individual practices.

Through the church, members participate in practices to help cultivate the value of psychedelic exploration. These include a range of activities, from ice baths to meditation in a room with flashing lights. TDA also offers courses on growing psilocybin through its educational initiative “shroomiversity.”

To borrow from its stated mission, TDA works to connect “people to self, others and the Divine.” It also seeks to “protect responsible and religious use of psilocybin, and cultivate health and healing.” This mission does not deny the place of belief but highlights broader therapeutic concerns.

Through shared rituals, members cultivate community while enhancing their total well-being.


The Magic Mushroom Church.

Mushroom churches: an American tradition

Louisville, Kentucky’s Psanctuary Church brings “people together for healing and connection to divine revelation through communion with sacred mushrooms.” Nondenominational, Psanctuary defines itself as a “Constitutional Church.”

Indicating their legal status as a a nonprofit, tax-exempt, faith-based organization, Psanctuary situates itself as a uniquely American religion. For Psanctuary and other psychedelic churches, the use of psychedelics is simultaneously a sacred right and an expression of political freedom.

As with many psychedelic churches, Psanctuary is not atheistic. It understands divinity as “pure consciousness” that “permeates all being.” Positioned this way, religion moves away from monotheistic understandings of God.

Instead, it follows non-Western, indigenous and New Age understandings that view divinity as within everyone. It also reorients people from seeking salvation in a world to come by encouraging focus on the present.

Like TDA, religion for Psanctuary expresses the pursuit of “pure consciousness” as “the origin of health and well-being.” By experiencing this origin through psychedelics, members are “empowered to discover our own divinity.”

This dual emphasis on self-divinity and healing reflects common themes across psychedelic churches.

The Church of Ambrosia and Zide Door

Inspired by The Church of Ambrosia, a nondenominational, interfaith religion, Zide Door in Oakland, California, supports “the safe access and use of Entheogenic Plants.” Founded in 2019 by Dave Hodges, Zide Door affords space for members to “explore their spirituality.”

Commonly, mainstream religion requires believers to interact with the sacred through designated leaders or texts. At Zide Door and other psychedelic churches, the emphasis is on self-realization and interconnection through direct experience.

Psychedelics offer members firsthand access to religious understanding. Church, accordingly, becomes a place to support individual awakening.

Sacred Garden Community captures this shift. Also located in Oakland, SGC – as it announces on its website – is a “post-modern church” based on “faith of least dogma.” Through psychedelic sacraments, SGC claims to facilitate “direct experience of and relationship to Divine presence for individuals and community.”

Beyond the experience, SGC helps members integrate “the benefits” the “experience and relationship can bring” into everyday life. Like other psychedelic churches, SGC highlights how rejection of conventional religion is often accompanied by new avenues to pursue spirituality.

Ayahuasca churches and healing


A participant at an ayahuasca ceremony at a Hummingbird Church retreat in Hildale, Utah, in October 2022.  AP Photo/Jessie Wardarski

Ayahuasca churches rely on indigenous understandings of ayahuasca, a plant-based psychedelic brew. For Indigenous people of South America, ayahuasca is a sacred rite based on local knowledge. They argue that removing ayahuasca from that context takes away its power and impact.

Indigenous practitioners and scholars thus warn about both the appropriation and commodification of indigenous practices. While such concerns should not be ignored, ayahuasca churches tell us much about contemporary religion.

The turn to ayahuasca rituals highlights the growing connection between spiritual needs and healing. The emergence of ayahuasca churches in the U.S. suggests that such healing requires the support of community.

California-based Hummingbird Church, for example, draws from ayahuasca rituals to provide “participants with opportunities to recharge their body, mind and soul with positive energy and reconnect with themselves.” Its “Statement of Faith” emphasizes this commitment to holistic healing.

It also situates the divine in “earthly” terms. Members, they believe, “should seek within Nature that which is contributory to our health and well-being.”

Located in Orlando, Florida, members of Soul Quest Ayahuasca Church of Mother Earth believe likewise. As members contend, “What is of the Earth is our holy sacrament.” Like others, they position psychedelics “as tools” that benefit “physical health, spiritual growth, and personal evolution.”

Through ayahuasca, members of both churches see psychedelic rituals as aiding in individual rejuvenation. Once rejuvenated, members believe they help restore nature or assist in another’s healing.

Well-being as spirituality

Collectively, these churches demonstrate not a rejection of religion, as the term “none” might suggest, but an embrace of well-being as spirituality.

And while they are distinct in many ways, they also share some common goals: They seek to provide members and practitioners ways to heal emotionally, psychologically and spiritually.

A key lesson members connect to psychedelics is the intrinsic sacredness of each person: The divine is not elsewhere but within everyone.

To be a none might reflect one’s total rejection of supernatural belief. But as psychedelic churches illustrate, identifying that way can also indicate spiritual pursuits that refuse to fit nicely within traditional religious categories.

Morgan Shipley, Foglio Endowed Chair of Spirituality & Associate Chair of Religious Studies, Michigan State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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