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.

 

Study shows psychedelic drug psilocybin gives comparable long-term antidepressant effects to standard antidepressants, but may offer additional benefits

Psilocybin as good as SSRI for depression, but doesn’t lower sex drive, gives better sense of well-being and psychosocial functioning

European College of Neuropsychopharmacology

A direct comparison between the experimental psychedelic drug psilocybin and a standard SSRI antidepressant shows similar improvement of depressive symptoms, but that psilocybin offers additional longer-term benefits.

The comparison, between psilocybin (the active ingredient in “magic mushrooms”) and the SSRI escitalopram gave similar long-term improvements in depressive symptoms over a 6-month period, however patients taking psilocybin also reported better psychosocial functioning including experiencing a greater sense of meaning in life and psychological connectedness.

The work is presented for the first time at the ECNP Congress in Milan. A related paper will appear in the peer-reviewed journal Lancet eClinicalMedicine1 to coincide with the conference presentation (see details below). Lead researcher Mr Tommaso Barba (PhD candidate from Imperial College, London) said:

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression.  In previous work we had found that both treatments led to comparable improvements in alleviating symptoms of depression at the 6-week mark, such as sadness and negative emotions.  However, this work shows that psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work and social functioning. These results appeared to be maintained over a 6-month follow-up period. In addition, in previous work* we had found that psilocybin also improves sexual drive, in contrast to SSRIs which tend to lower libido in many patients. So overall it seems psilocybin might give additional positive mental health benefits.”  

SSRI drugs (selective serotonin reuptake inhibitors), such as Prozac, Paxil and Zoloft, are one of the main types of drugs used to treat depression. However, around a third of patients don’t respond to SSRI treatment, so for them psilocybin may offer an alternative, although this was not studied in this trial.

Tommaso Barba continued:

“SSRIs work well, but not for everyone. They are also associated with some side effects. However this work implies that psilocybin generally seems to offer a real alternative, and perhaps additional benefits, to people who are worried about taking conventional antidepressants”.

The researchers, from Imperial College in London, undertook a 6-month study (phase 2, double-blind, randomised controlled trial) with 59 patients with moderate to severe depression. 30 were treated with a single dose of psilocybin, 29 patients were given a six-week course of escitalopram. Each group received similar psychological support of around 20 hours in total. Both groups showed significant improvement in depressive symptoms, even up to 6 months after treatment (the researchers stopped monitoring at 6 months). However those given psilocybin reported greater improvements in social functioning and psychological connectedness, with large effect sizes.

Co-first author Dr David Erritzoe, Clinical Director and Deputy Head of the Centre for Psychedelic Research, Imperial College, London, commented:

“This is important because improving connectedness and having greater meaning in life can significantly enhance a person's quality of life and long-term mental health. The study suggests that psilocybin therapy might be a more holistic treatment option for depression, addressing both the symptoms of depression and overall well-being. This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment”.

The researchers note that the patients were only treated for 6 weeks, and that many of the patients received additional treatments over the 6-month follow up.

Dr Erritzoe cautioned:

“Psilocybin is still an experimental drug; it has not yet been approved for general use. It is administered in highly controlled and protected environments: these precautions are not found in recreational psychedelic use, which is known for having unpredictable and potentially harmful effects, especially for vulnerable people struggling with mental health issues”. 

Commenting, Johan Lundberg (Adjunct Professor of Psychiatry at the

Department of Clinical Neuroscience, Karolinska Institute, Stockholm) said:

“This report is an important attempt to compare the clinical value of psilocybin compared to a state-of-the-art treatment of major depressive disorder. The results come with several caveats, including the lack of a non-inferiority analysis and failure to report other interventions given during the follow-up period. That said, as a hypothesis generating piece it may benefit the field substantially.  For now, we don’t know if psilocybin will be approved for the treatment of major depression, but if so, it won’t be for everyone. Some future patients might prefer psychedelic treatment over SSRI, but some patients may be intimidated by the dramatic alterations in perception and confrontations with challenging emotions that psychedelic drugs promote”.

This is an independent comment, Professor Lundberg was not involved in this work.

Notes:

1. Publication details: Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial. In press at Lancet eClinicalMedicine. Authors: David Erritzoe, Tommaso Barba, Kyle T. Greenway, Roberta Murphy, Jonny Martell, Bruna Giribaldi, Christopher Timmermann, Ashleigh Murphy-Beiner, Michelle Baker Jones, David Nutt, Brandon Weiss, and Robin Carhart-Harris. Paper reference 10.1016/j.eclinm.2024.102799
2. See Psychedelic experiences linked with improved sexual function | Imperial News | Imperial College London

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Method of Research

Randomized controlled/clinical trial

Mount Sinai expands Psychedelic Research Center with new facility in upper Manhattan

The Mount Sinai Hospital / Mount Sinai School of Medicine

 

image: 

From left to right:

Dr. Amy Lehrner, Dr. Rachel Yehuda, Renee Parsons, Bob Parsons, Dr. Eric Nestler, Dr. Rene Kahn. 

view more 

Credit: Mount Sinai Health System

Mount Sinai Health System this week celebrated the opening of an expansion of its psychedelic psychotherapy research center into a new location and announced a foundational $5 million gift from The Bob & Renee Parsons Foundation. The center has been renamed The Parsons Research Center for Psychedelic Healing.

The new location is designed to support the Center's capacity to facilitate a growing number of rigorous clinical trials that focus on well-known compounds like MDMA, psilocybin, ketamine, and potentially others in the future. These chemical compounds have garnered significant attention in academic medicine for their potential to alleviate symptoms of post-traumatic stress disorder (PTSD), depression, anxiety, and other stress-related conditions.

The Foundation’s gift, which comes at a pivotal time for the field, will expand the Center's capacity for therapy, research, and therapist training, including a primary focus on veterans.

Located at 600 West 112th Street, on the southwest corner of Broadway, the new space will house six treatment rooms and a group therapy room, with features to enable therapy supervision, teaching, and research. Large floor-to-ceiling windows provide natural light and a view of the surrounding tree-lined streets.

“Since its initial launch in 2021, our psychedelic psychotherapy research center has made progress towards our understanding of the therapeutic potential for psychedelic-assisted psychotherapy,” said Rachel Yehuda, PhD, Director of The Parsons Research Center for Psychedelic Healing. “The recent decision by the Food and Drug Administration to withhold approval for MDMA-assisted therapy has cast some uncertainty as to how and when psychedelic therapy will be broadly available, but has also made clear that there is a critical need to advance rigorous psychedelic research. Our team remains steadfast in our commitment to this work and to ensure the incredible momentum that has been generated by academic researchers does not falter.”  

Dr. Yehuda went on to say, “This is an existential moment for the field of psychedelic research in mental health, and rather than backing away from investment, as some are doing, The Bob & Renee Parsons Foundation is shining a light on what has become a darker path forward. Thanks to their vision and commitment and the continued generosity of our donors, we will meet the needs of the moment.” 

“My own battle with PTSD lasted for decades after I returned from the Vietnam War.  It was psychedelic-assisted therapy that finally brought me home after all those years,” said Bob Parsons, United States Marine Corps Vietnam war veteran and co-founder of The Bob & Renee Parsons Foundation. “Despite the FDA’s recent decision on MDMA, we’re digging in and funding more research because I have all the evidence I need—I know it works.”

The expansion of the Center reflects Mount Sinai’s commitment to providing institutional resources, strong scientific vision, and the established track record necessary to push forward with groundbreaking clinical trials. The gift from The Bob & Renee Parsons Foundation reflects an understanding by the Foundation that the moment demands serious and careful research and a deep commitment to uncovering effective treatments for veterans, who disproportionately experience conditions like PTSD that have been resistant to conventional therapies.

“The space was designed to embrace the importance of setting in therapeutic outcomes. From the moment our patients enter the beautifully designed Center, they will feel that they are in a place of safety and healing, which is paramount to maximizing the impact of the therapy sessions,” said Amy Lehrner, PhD, Clinical Director of The Parsons Research Center for Psychedelic Healing. “The views of nature, natural light, and complementary design will communicate serenity and warmth, setting a new standard for applying this nascent science. While solutions for traumatized people have been few and far between until now, with the advances we have made through this new space and the highly trained practitioners within, we now see renewed hope and healing.”

The Center is currently developing protocols for several studies, including pivotal group therapy studies, which required the creation of a large group space. The Center's expanded capacity allows for multiple simultaneous dosing sessions and group integration sessions, essential for advancing this critical work.

Mount Sinai investigators affiliated with the Center will also be conducting research on ketamine-assisted psychotherapy and psilocybin for patients with major depression and for the treatment of intergenerational trauma, as well as MDMA-assisted therapy for patients with eating disorders. Almost all trials will examine the mechanism of action of psychedelics using the latest developments in neuroimaging, molecular neuroscience, and natural language processing. These initiatives underscore the Center's role as a leader in developing innovative and effective treatments for mental health conditions. The Center also plans to continue to expand its focus on training and education of mental health clinicians in the use of psychedelic-assisted therapies.  The Center has provided training and education free of charge to 250 clinicians thanks to a prior $5 million gift from The Bob & Renee Parsons Foundation in 2021.

“We are hopeful that the cutting-edge research and training being done at Mount Sinai will go on to transform the lives of veterans, and others, suffering from debilitating mental health conditions,” said Renee Parsons, co-founder of The Bob & Renee Parsons Foundation. “Bob and I know firsthand the detrimental impacts of PTSD—not only on the individual but their entire family. We remain committed to battling the stigma surrounding mental health and shining a light on promising treatments like psychedelic-assisted therapy.”

“New treatment options are desperately needed for the millions of people, both civilians and veterans, who suffer from mood and anxiety disorders like PTSD and major depression,” said Dennis S. Charney, the Anne and Joel Ehrenkranz Dean of Icahn Mount Sinai and President for Academic Affairs for the Mount Sinai Health System. “Mount Sinai researchers lead on the frontier of biomedicine, applying scientific rigor while also challenging clinical and scientific dogma to emerge as true innovators. Under Dr. Yehuda’s leadership and through the unwavering support of The Bob & Renee Parsons Foundation, this new space enables us to propel our efforts with the speed, safety, and quality that will have a meaningful impact on the field of psychedelic psychotherapy and the patients we serve.”

About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025. For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

About The Bob & Renee Parsons Foundation
The Bob & Renee Parsons Foundation offers support to nonprofit organizations successfully working to empower, educate, nurture and nourish people during what is often the darkest time of their lives. Founded in 2012 by philanthropists and business leaders Bob and Renee Parsons to provide hope and life-changing assistance to the country’s most vulnerable populations, The Bob & Renee Parsons Foundation offers critical funding at critical times to those in need. The Foundation’s giving is driven by the core belief that all people – regardless of race, religion, roots, economic status, sexual orientation or gender identity – deserve access to quality healthcare, education and a safe place to call home. Follow @WeDealInHope on social media or visit TBRPF.org, to learn more about partner organizations and the important work being done in the community.

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Entrance to The Parsons Research Center for Psychedelic Healing at Mount Sinai

Psychedelic-assisted psychotherapy treatment room within The Parsons Researh Center for Psychedelic Healing at Mount Sinai 

Waiting Area within The Parsons Research Center for Psychedelic Healing at Mount Sinai

Interior of The Parsons Research Center for Psychedlic Healing at Mount Sinai

Credit

Mount Sinai Health System