The nerves in the brain communicate with each other by one nerve releasing serotonin and the next nerve absorbing the serotonin. Any extra serotonin that is left over is taken up by the nerve that released it which lowers the amount of serotonin available. The SSRIs stop the original nerve from “reuptaking” the serotonin so that there is more serotonin available for the second nerve to absorb. In depression and other related disorders by increasing the serotonin between the nerve endings results in messages being able to be sent more effectively.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
Psilocybin is a chemical found in magic mushrooms that causes the user to experience a sensory overload of saturated colors and patterns. Recent research has found that this effect happens because the brain becomes “hyperconnected” and allows for increased communication between different regions. It is hoped that this ability can be manipulated in order to manufacture drugs to treat neurological conditions. The paper was published in an open access format in the Journal of the Royal Society Interface with Giovanni Petri of Italy’s ISI Foundation serving as lead author.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
The chemical works by binding the same receptors in the brain as the neurotransmitter serotonin. This allows the drug to alter mood. While many people have a happy, meaningful experience, some can have a “bad trip” and experience extreme paranoia Prior studies have found that that getting high on psilocybin doesn’t just create a colorful, psychedelic experience for a couple of hours; it can cause neurological changes that last over a year. These changes resulted in a personality that was more open to the creative arts and became happier, even 14 months after receiving the psilocybin.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
Though previous research surmised that psilocybin decreased brain activity, the current study used functional magnetic resonance imaging (fMRI) to see what was really going on. The study used 15 participants with prior positive experiences with hallucinogens to avoid a bad trip inside the enclosed machine. Some of the participants received psilocybin, while the other half received a saline placebo.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
Simplified illustration of the connections tracked while receiving the placebo (a) and the psilocybin (b). Image credit: Petri et al., 2014.
Surprisingly, the researchers saw that upon receiving psilocybin, the brain actually re-organized connections and linked previously unconnected regions of the brain. These connections were not random, but appeared very organized and stable. Once the drug wore off, the connections returned to normal.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
“We can speculate on the implications of such an organization. One possible by-product of this greater communication across the whole brain is the phenomenon of synesthesia which is often reported in conjunction with the psychedelic state,” the authors wrote.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
Synesthesia is a subconscious pairing of two things, like colors and numbers. Someone experiencing this phenomenon might always view the number 2 as green or read 6 and think of the color purple. Because of these strange associations, individuals taking psilocybin likely have poor color perception, despite being inundated with the hallucinogenic colors.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
The mechanism of how psilocybin is creating these changes is not yet known and will require further study. The researchers believe that in understanding the drug’s mechanism for temporarily re-wiring the brain and altering mood, it could potentially be manipulated into making a functional treatment for depression or other disorders. However, there is much more to be learned before it can be used in that manner.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
An unusual item among our many different food sources, the mushroom is a fungus, not a plant. This means that it grows from a spore, usually in the dirt or on decaying plant material, such as a log. While some varieties contain vitamins and nutrients, mushrooms are mainly used to give an earthy flavor and meaty texture to everything from pizza to risotto.
https://science.howstuffworks.com/magic-mushroom.htm
Some mushrooms, however, are famous for more than their taste. Known as magic mushrooms, shrooms, mushies, psychedelic mushrooms, psychotropic mushrooms or psilocybin, these mushrooms cause differences in mood, perception and behavior that are commonly known as "tripping."
https://science.howstuffworks.com/magic-mushroom.htm
These types of mushrooms belong to the genus Psilocybe. Mushrooms of other genera can also cause hallucinations, but many purists insist that Psilocybe mushrooms are the "true" magic mushrooms. Psilocybe mushrooms cause hallucinations because they contain the psychotropic tryptamines psilocybin and psilocin (some species also contain other, weaker psychotropic compounds like baeocystin or norbaeocystin). A single mushroom contains anywhere from 0.2 to 0.4 percent psilocybin.
https://science.howstuffworks.com/magic-mushroom.htm
Magic mushrooms are one of the most widely used recreational psychotropic drugs because they can be found in the wild or grown fairly easily and inexpensively. According to the 2003 National Survey on Drug Use and Health, about 8 percent of adults over the age of 26 in the United States have used magic mushrooms [source: Substance Abuse & Mental Health Services Administration].
https://science.howstuffworks.com/magic-mushroom.htm
Unlike manufactured psychotropic drugs such as LSD, magic mushrooms have a long history dating back thousands of years as part of religious or spiritual ceremonies. However, magic mushrooms also have a lot in common with LSD. Let's start with looking at how eating them can affect people.
https://science.howstuffworks.com/magic-mushroom.htm
Psilocybin is the inactive precursor of psilocin, the chemical primarily responsible for the hallucinogenic effects of Psilocybe “magic mushrooms”. Though human cultures have used this entheogen for many centuries, we are only just beginning to understand the physiological mechanism by which it produces its psychedelic effects. This slow scientific progress is a result of harsh international drug policy, but I digress…
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
The psychedelic trip is often described as profoundly mind-expanding, and the brain is popularly presumed to run in overdrive while processing so many complex and non-linear thoughts. Until recently, our understanding of psilocin’s pharmacology has supported this theory of increased brain activity. Like most psychedelics, psilocin works by binding to serotonin receptors (with particular action at the 5-HT2A subtype). These serotonin receptors are most commonly found on excitatory neurons—neurons that, when activated, increase the firing rate of adjacent neurons—so it makes sense that psychedelics would cause increases in brain activity, at least in some regions of the brain. This has been a well-accepted theory for decades and little attention has been paid to other possibilities. However, recent research headed by Robin L. Carhart-Harris from Imperial College London has called this hypothesis into question.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Carhart-Harris and his team explored the short-term effects of psilocybin by using functional MRI (fMRI) techniques to compare normal and psychedelic brain activity. The group utilized two kinds of fMRI imaging (ASL and BOLD) to evaluate which parts of the brain showed increased or decreased activity after a “moderate” dose of psilocybin (2mg administered intravenously, roughly equivalent to 15mg orally).
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Check out the blue highlights on the images above. These indicate regions of the brain with significant decreases in arterial blood flow and blood-oxygen levels following psilocybin administration. No increases were found in any region. The group points out that these decreases were “localized to high-level association regions [such as the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC)] and important connector hubs, such as the thalamus, PCC and anterior cingulate cortex (ACC)”. Psilocin actually suppresses neurological traffic through these hubs, perhaps forcing the brain to adapt by changing the pathway through which signals are routed. For a visual, just imagine how New York City traffic patterns would change if Grand Central Station reduced its operations temporarily due to minor construction work. Additionally, the magnitude of the psychedelic effects experienced by the subjects was correlated with the decrease in blood flow in the two critical hubs, mPFC and PCC. That is, the lower the blood flow to these vital regions, the harder you trip.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
So, what does this mean exactly?
The regions of the brain showing reduced activated most consistently after psilocybin administration, the mPFC and PCC, are also the regions of the brain most disproportionately overactive during normal brain function. According to Carhart-Harris, “metabolism in the PCC is ~20% higher than most other brain regions, yet psilocybin decreased its blood flow by up to 20% in some subjects.” The PCC, a well-protected region supplied by a high number of blood vessels, is known to play a role in consciousness and “ego.” Additionally, the PCC is the centerpoint of the default mode network (DMN), which is known to be active during self-referencing and introspection. This default mode network hosts a high number of connections between different parts of the cortex (the outermost layer of the brain), indicating its critical role in the efficient transmission of signals throughout the entire brain.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
The effects on the anterior cingulate cortex, a region implicated in empathy and emotion, are intriguing as well. Decreased blood flow in this part of the brain confounds previous research, which revealed increases in metabolic activity in the ACC following psilocybin administration (Vollenweider FX et al. 1997, Neuropsychopharmacology).
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
In addition to the effects on the anterior and posterior cingulate cortices, decreased activity was observed in the mPFC, a region that plays a significant role in personality expression, decision-making, and social behavior. Elevated activity in both the ACC and mPFC is associated with depression, and has been shown to recede to healthy levels when patients are successfully treated with antidepressants such as Prozac.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Psilocin’s remarkable antidepressant effects are probably related to its suppressive effect on these regions. Findings from Roland Griffiths’ group at Johns Hopkins University and others indicate that psilocin is a highly effective and long-lasting antidepressant with a mechanism of action distinct from all commercially available medicines. Even the most treatment-resistant subjects, such as those with terminal illnesses, see remarkable improvements from a single dose of psilocin. But we can explore the antidepressant effects of psychedelics another time.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
So how do these findings correspond to the vivid mind-opening and spiritually awakening effects of psychedelics? Two theories in particular stand out: Aldous Huxley’s “reducing valve” and Karl Friston’s “free energy principle.”
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Huxley suggests that our “normal” consciousness represents only a small fraction of the mind’s total inputs at any particular time. He speculates that psychedelics work to open this “valve,” allowing the infiltration of thoughts that are impossible to reach in a normal state. In his landmark book about a mescaline experience, The Doors of Perception, Huxley quotes the philosopher C.D. Broad, who in turn elaborates on a theory by Henri Bergson:
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Each person is at each moment capable of remembering all that has ever happened to him and of perceiving everything that is happening everywhere in the universe. The function of the brain and nervous system is to protect us from being overwhelmed and confused by this mass of largely useless and irrelevant knowledge, by shutting out most of what we should otherwise perceive or remember at any moment, and leaving only that very small and special selection which is likely to be practically useful.”
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
“According to such a theory,” Huxley continues,
brain-funnel
each one of us is potentially Mind at Large. But in so far as we are animals, our business is at all costs to survive. To make biological survival possible, Mind at Large has to be funneled through the reducing valve of the brain and nervous system. What comes out at the other end is a measly trickle of the kind of consciousness which will help us to stay alive on the surface of this particular planet.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
From his personal experience with mescaline, Huxley extrapolates that such chemicals can open the mind up to greater reality.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
[The] effects of mescalin are the sort of effects you could expect to follow the administration of a drug having the power to impair the efficiency of the cerebral reducing valve. …As Mind at Large seeps past the no longer watertight valve, all kinds of biologically useless things start to happen. In some cases there may be extra-sensory perceptions. Other persons discover a world of visionary beauty. To others again is revealed the glory, the infinite value and meaningfulness of naked existence, of the given, unconceptualized event. In the final stage of egolessness there is an “obscure knowledge” that All is in all—that All is actually each. This is as near, I take it, as a finite mind can ever come to “perceiving everything that is happening everywhere in the universe.”
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Huxley sounds like a modern mystic, but perhaps he is not so far off the mark. If certain regions of the brain are responsible for funneling reality down to a digestible stream, then perhaps psychedelics, by suppressing this activity, actually open us up to greater reality—the “Mind at Large.” That’s assuming that mescaline, like psilocin, produces decreases in blood flow and blood oxygenation within the brain.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Neuroscientist Karl Friston
Karl Friston’s “free energy principle” is similar in some ways to this reducing valve theory, but takes a more technical approach. This model suggests that in order to process sensory input, the brain must work actively to minimize this incoming information using shortcuts such as learned prediction processes (such as driving to a place and having no memory of the trip). Put simply, the brain saves itself work by maintaining a probabilistic model of its environment at all times. Carhart-Harris’s study corroborates this theory, suggesting that “a lot of brain activity is actually dedicated to keeping the world very stable and ordinary and familiar and unsurprising.” In the context of psychedelics this is especially relevant, as reducing this active prediction process likely allows for a freer and broader perception of information—the “far out, man” type of consciousness often experienced while tripping.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
This cutting edge research has provided us with a detailed perspective of how psychedelics elicit their mood- and mind-altering effects on the brain. By decreasing blood flow and neural activity in the regions most closely associated with self-awareness, ego, and personality expression, psilocin is able to facilitate, as Carhart-Harris so eloquently put it, “an unconstrained style of cognition.”
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
If you’re curious to know more about Robin Carhart-Harris and research, check out his website, psychedelicscience.org.uk. He also answered many questions in an excellent “IAmA” session on Reddit (summary of his answers here). And check out this video where Robin explains his psilocybin research.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Sources:
Carhart-Harris, RL et al. PNAS (2012); Vol. 109, No. 6. pp. 2138-2143.
Aldous Huxley (1953), The Doors of Perception.
Karl Friston et al. Journal of Physiology – Paris (2006); Vol 100, pp. 70-87.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
0 
===Depression===
Depression is a serious global problem. It’s the leading cause of disability worldwide, is linked to over half of all suicides, and affects some 350 million people. Worse still, the prevalence of depression is increasing; the World Health Organisation estimates that depression will become the leading overall contributor to the global burden of disease by 2030. (
http://psychedelicscience.org.uk/)
Psilocybin
Psilocybin changes brain activity in a manner that is consistent with a large range of effective treatments for depression. More specifically, we found that circuits that are over-active and reinforced in depression become loosened and normalised under psilocybin. Psilocybin works to mimic some serotonin actions. That psilocybin does this, may explain why it may be useful in depression. (http://psychedelicscience.org.uk/)
In 2012, Imperial College London were awarded a research grant from the UK government’s Medical Research Council (MRC) to set-up a clinical trial to investigate the antidepressant potential of psilocybin. The study is sponsored by Imperial College London and has ethical approval. The UK Home Office have licensed the importation and storage of the psilocybin that we will use.
Can Magic Mushrooms treat depression?- Robin Carhart-Harris at New Scientist Live 2017
Could psychedelic drugs make the world a better place? Come and find out more at New Scientist Live 2017 https://live.newscientist.com/talks?&searchTerm=robin&searchgroup=00000001-talks
Psychedelics: Lifting the veil | Robin Carhart-Harris | TEDxWarwick
Robin has been conducting pioneering brain imaging studies of psychedelic drugs. Most recently, he has completed the first phase of a clinical trial looking at the potential of psilocybin to treat depression, and his talk looks at how these drugs can be used in treatment. After completing his PhD at the University of Bristol in 2009, Robin moved to Imperial College London, where he has worked for the last few years on the brain effects of LSD, psilocybin (magic mushrooms) and MDMA, conducting some pioneering brain imaging studies of these drugs. Most recently he has completed the first phase of a clinical trial looking at the potential of psilocybin to treat major depression. This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at http://ted.com/tedx
EXCLUSIVE: Could magic mushrooms treat depression? BBC Newsnight
Could the "magic" element of magic mushrooms – psilocybin – treat people with severe depression? Researchers at Imperial College have just published the results of a trial looking at exactly this. Newsnight had exclusive access to this controversial drugs trial. James Clayton reports. The film was produced and directed by David Fuller. Newsnight is the BBC's flagship news and current affairs TV programme – with analysis, debate, exclusives, and robust interviews. YouTube: https://www.youtube.com/user/BBCNewsnight Twitter: https://twitter.com/BBCNewsnight Facebook: https://www.facebook.com/bbcnewsnight Snapchat: https://www.snapchat.com/add/bbcnewsnight
Can Magic Mushrooms Unlock Depression? | Rosalind Watts | TEDxOxford
A clinical psychologist from Imperial College describes how Magic Mushrooms (Psilocybin), when used in a therapeutic setting, have been found to be a very effective treatment for depression. In this talk she draws on her experiences as working as a therapist on the groundbreaking Psilocybin for Depression study, and introduces us to some of the patients and their stories of transformation. Dr Rosalind Watts completed her clinical psychology training at University College London. After six years of practicing psychotherapy in the NHS, she joined a clinical trial at Imperial College, investigating psilocybin (magic mushrooms) as a treatment for depression. Her research explores patients' positive views of this intriguing therapy. This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at http://ted.com/tedx
Mendel Kaelen: Psychological & Neurophysiological Effects of Music in Combination with Psychedelics
Learn more and donate: http://www.maps.org/ Mendel Kaelen, PhDc The Psychological and Neurophysiological Effects of Music in Combination with Psychedelics 2017 Psychedelic Science Conference http://psychedelicscience.org/ A six-day global gathering of the international scientific community in Oakland, California to explore new research into the benefits and risks of MDMA, LSD, psilocybin, ayahuasca, ketamine, ibogaine, medical marijuana, and more.
Robin Carhart Harris 20th July 2016
Robin Carhart-Harris – Psychedelics in Science and Medicine
Other Videos of interest
Filmed at Breaking Convention: 3rd International Conference on Psychedelic Consciousness, 10-12th July, 2015
Johns Hopkins Psilocybin Project: Psychedelics Research History & the Mystical Experience
Roland R. Griffiths, Ph.D., is Professor in the Departments of Psychiatry and Neurosciences at the Johns Hopkins University School of Medicine. His principal research focus in both clinical and preclinical laboratories has been on the behavioral and subjective effects of mood-altering drugs. His research has been largely supported by grants from the National Institute on Health and he is author of over 300 journal articles and book chapters.
You can now view our YouTube channel
Videos
===Mendel Kaelen: Psychological & Neurophysiological Effects of Music in Combination with Psychedelics===
Dennis McKenna is an ethnopharmacologist, author, and brother to well-known psychedelics proponent Terence McKenna.
Konference ISPD50.com
The nerves in the brain communicate with each other by one nerve releasing serotonin and the next nerve absorbing the serotonin. Any extra serotonin that is left over is taken up by the nerve that released it which lowers the amount of serotonin available. The SSRIs stop the original nerve from “reuptaking” the serotonin so that there is more serotonin available for the second nerve to absorb. In depression and other related disorders by increasing the serotonin between the nerve endings results in messages being able to be sent more effectively.
http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
Psilocybin is a chemical found in magic mushrooms that causes the user to experience a sensory overload of saturated colors and patterns. Recent research has found that this effect happens because the brain becomes “hyperconnected” and allows for increased communication between different regions. It is hoped that this ability can be manipulated in order to manufacture drugs to treat neurological conditions. The paper was published in an open access format in the Journal of the Royal Society Interface with Giovanni Petri of Italy’s ISI Foundation serving as lead author. http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
The chemical works by binding the same receptors in the brain as the neurotransmitter serotonin. This allows the drug to alter mood. While many people have a happy, meaningful experience, some can have a “bad trip” and experience extreme paranoia Prior studies have found that that getting high on psilocybin doesn’t just create a colorful, psychedelic experience for a couple of hours; it can cause neurological changes that last over a year. These changes resulted in a personality that was more open to the creative arts and became happier, even 14 months after receiving the psilocybin. http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
Though previous research surmised that psilocybin decreased brain activity, the current study used functional magnetic resonance imaging (fMRI) to see what was really going on. The study used 15 participants with prior positive experiences with hallucinogens to avoid a bad trip inside the enclosed machine. Some of the participants received psilocybin, while the other half received a saline placebo.http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
Simplified illustration of the connections tracked while receiving the placebo (a) and the psilocybin (b). Image credit: Petri et al., 2014.
Surprisingly, the researchers saw that upon receiving psilocybin, the brain actually re-organized connections and linked previously unconnected regions of the brain. These connections were not random, but appeared very organized and stable. Once the drug wore off, the connections returned to normal. http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
“We can speculate on the implications of such an organization. One possible by-product of this greater communication across the whole brain is the phenomenon of synesthesia which is often reported in conjunction with the psychedelic state,” the authors wrote. http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
Synesthesia is a subconscious pairing of two things, like colors and numbers. Someone experiencing this phenomenon might always view the number 2 as green or read 6 and think of the color purple. Because of these strange associations, individuals taking psilocybin likely have poor color perception, despite being inundated with the hallucinogenic colors.http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
The mechanism of how psilocybin is creating these changes is not yet known and will require further study. The researchers believe that in understanding the drug’s mechanism for temporarily re-wiring the brain and altering mood, it could potentially be manipulated into making a functional treatment for depression or other disorders. However, there is much more to be learned before it can be used in that manner.http://www.iflscience.com/brain/magic-mushroom-chemical-hyper-connects-brain/
An unusual item among our many different food sources, the mushroom is a fungus, not a plant. This means that it grows from a spore, usually in the dirt or on decaying plant material, such as a log. While some varieties contain vitamins and nutrients, mushrooms are mainly used to give an earthy flavor and meaty texture to everything from pizza to risotto.https://science.howstuffworks.com/magic-mushroom.htm
Some mushrooms, however, are famous for more than their taste. Known as magic mushrooms, shrooms, mushies, psychedelic mushrooms, psychotropic mushrooms or psilocybin, these mushrooms cause differences in mood, perception and behavior that are commonly known as "tripping."https://science.howstuffworks.com/magic-mushroom.htm
These types of mushrooms belong to the genus Psilocybe. Mushrooms of other genera can also cause hallucinations, but many purists insist that Psilocybe mushrooms are the "true" magic mushrooms. Psilocybe mushrooms cause hallucinations because they contain the psychotropic tryptamines psilocybin and psilocin (some species also contain other, weaker psychotropic compounds like baeocystin or norbaeocystin). A single mushroom contains anywhere from 0.2 to 0.4 percent psilocybin.https://science.howstuffworks.com/magic-mushroom.htm
Magic mushrooms are one of the most widely used recreational psychotropic drugs because they can be found in the wild or grown fairly easily and inexpensively. According to the 2003 National Survey on Drug Use and Health, about 8 percent of adults over the age of 26 in the United States have used magic mushrooms [source: Substance Abuse & Mental Health Services Administration].https://science.howstuffworks.com/magic-mushroom.htm
Unlike manufactured psychotropic drugs such as LSD, magic mushrooms have a long history dating back thousands of years as part of religious or spiritual ceremonies. However, magic mushrooms also have a lot in common with LSD. Let's start with looking at how eating them can affect people.https://science.howstuffworks.com/magic-mushroom.htm
Psilocybin is the inactive precursor of psilocin, the chemical primarily responsible for the hallucinogenic effects of Psilocybe “magic mushrooms”. Though human cultures have used this entheogen for many centuries, we are only just beginning to understand the physiological mechanism by which it produces its psychedelic effects. This slow scientific progress is a result of harsh international drug policy, but I digress…http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
The psychedelic trip is often described as profoundly mind-expanding, and the brain is popularly presumed to run in overdrive while processing so many complex and non-linear thoughts. Until recently, our understanding of psilocin’s pharmacology has supported this theory of increased brain activity. Like most psychedelics, psilocin works by binding to serotonin receptors (with particular action at the 5-HT2A subtype). These serotonin receptors are most commonly found on excitatory neurons—neurons that, when activated, increase the firing rate of adjacent neurons—so it makes sense that psychedelics would cause increases in brain activity, at least in some regions of the brain. This has been a well-accepted theory for decades and little attention has been paid to other possibilities. However, recent research headed by Robin L. Carhart-Harris from Imperial College London has called this hypothesis into question.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Carhart-Harris and his team explored the short-term effects of psilocybin by using functional MRI (fMRI) techniques to compare normal and psychedelic brain activity. The group utilized two kinds of fMRI imaging (ASL and BOLD) to evaluate which parts of the brain showed increased or decreased activity after a “moderate” dose of psilocybin (2mg administered intravenously, roughly equivalent to 15mg orally).http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Check out the blue highlights on the images above. These indicate regions of the brain with significant decreases in arterial blood flow and blood-oxygen levels following psilocybin administration. No increases were found in any region. The group points out that these decreases were “localized to high-level association regions [such as the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC)] and important connector hubs, such as the thalamus, PCC and anterior cingulate cortex (ACC)”. Psilocin actually suppresses neurological traffic through these hubs, perhaps forcing the brain to adapt by changing the pathway through which signals are routed. For a visual, just imagine how New York City traffic patterns would change if Grand Central Station reduced its operations temporarily due to minor construction work. Additionally, the magnitude of the psychedelic effects experienced by the subjects was correlated with the decrease in blood flow in the two critical hubs, mPFC and PCC. That is, the lower the blood flow to these vital regions, the harder you trip.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
So, what does this mean exactly?
The regions of the brain showing reduced activated most consistently after psilocybin administration, the mPFC and PCC, are also the regions of the brain most disproportionately overactive during normal brain function. According to Carhart-Harris, “metabolism in the PCC is ~20% higher than most other brain regions, yet psilocybin decreased its blood flow by up to 20% in some subjects.” The PCC, a well-protected region supplied by a high number of blood vessels, is known to play a role in consciousness and “ego.” Additionally, the PCC is the centerpoint of the default mode network (DMN), which is known to be active during self-referencing and introspection. This default mode network hosts a high number of connections between different parts of the cortex (the outermost layer of the brain), indicating its critical role in the efficient transmission of signals throughout the entire brain.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
The effects on the anterior cingulate cortex, a region implicated in empathy and emotion, are intriguing as well. Decreased blood flow in this part of the brain confounds previous research, which revealed increases in metabolic activity in the ACC following psilocybin administration (Vollenweider FX et al. 1997, Neuropsychopharmacology).http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
In addition to the effects on the anterior and posterior cingulate cortices, decreased activity was observed in the mPFC, a region that plays a significant role in personality expression, decision-making, and social behavior. Elevated activity in both the ACC and mPFC is associated with depression, and has been shown to recede to healthy levels when patients are successfully treated with antidepressants such as Prozac.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Psilocin’s remarkable antidepressant effects are probably related to its suppressive effect on these regions. Findings from Roland Griffiths’ group at Johns Hopkins University and others indicate that psilocin is a highly effective and long-lasting antidepressant with a mechanism of action distinct from all commercially available medicines. Even the most treatment-resistant subjects, such as those with terminal illnesses, see remarkable improvements from a single dose of psilocin. But we can explore the antidepressant effects of psychedelics another time.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
So how do these findings correspond to the vivid mind-opening and spiritually awakening effects of psychedelics? Two theories in particular stand out: Aldous Huxley’s “reducing valve” and Karl Friston’s “free energy principle.”http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Huxley suggests that our “normal” consciousness represents only a small fraction of the mind’s total inputs at any particular time. He speculates that psychedelics work to open this “valve,” allowing the infiltration of thoughts that are impossible to reach in a normal state. In his landmark book about a mescaline experience, The Doors of Perception, Huxley quotes the philosopher C.D. Broad, who in turn elaborates on a theory by Henri Bergson:http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Each person is at each moment capable of remembering all that has ever happened to him and of perceiving everything that is happening everywhere in the universe. The function of the brain and nervous system is to protect us from being overwhelmed and confused by this mass of largely useless and irrelevant knowledge, by shutting out most of what we should otherwise perceive or remember at any moment, and leaving only that very small and special selection which is likely to be practically useful.”http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
“According to such a theory,” Huxley continues,
brain-funnel
each one of us is potentially Mind at Large. But in so far as we are animals, our business is at all costs to survive. To make biological survival possible, Mind at Large has to be funneled through the reducing valve of the brain and nervous system. What comes out at the other end is a measly trickle of the kind of consciousness which will help us to stay alive on the surface of this particular planet.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
From his personal experience with mescaline, Huxley extrapolates that such chemicals can open the mind up to greater reality.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
[The] effects of mescalin are the sort of effects you could expect to follow the administration of a drug having the power to impair the efficiency of the cerebral reducing valve. …As Mind at Large seeps past the no longer watertight valve, all kinds of biologically useless things start to happen. In some cases there may be extra-sensory perceptions. Other persons discover a world of visionary beauty. To others again is revealed the glory, the infinite value and meaningfulness of naked existence, of the given, unconceptualized event. In the final stage of egolessness there is an “obscure knowledge” that All is in all—that All is actually each. This is as near, I take it, as a finite mind can ever come to “perceiving everything that is happening everywhere in the universe.”http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Huxley sounds like a modern mystic, but perhaps he is not so far off the mark. If certain regions of the brain are responsible for funneling reality down to a digestible stream, then perhaps psychedelics, by suppressing this activity, actually open us up to greater reality—the “Mind at Large.” That’s assuming that mescaline, like psilocin, produces decreases in blood flow and blood oxygenation within the brain.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Neuroscientist Karl Friston
Karl Friston’s “free energy principle” is similar in some ways to this reducing valve theory, but takes a more technical approach. This model suggests that in order to process sensory input, the brain must work actively to minimize this incoming information using shortcuts such as learned prediction processes (such as driving to a place and having no memory of the trip). Put simply, the brain saves itself work by maintaining a probabilistic model of its environment at all times. Carhart-Harris’s study corroborates this theory, suggesting that “a lot of brain activity is actually dedicated to keeping the world very stable and ordinary and familiar and unsurprising.” In the context of psychedelics this is especially relevant, as reducing this active prediction process likely allows for a freer and broader perception of information—the “far out, man” type of consciousness often experienced while tripping.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
This cutting edge research has provided us with a detailed perspective of how psychedelics elicit their mood- and mind-altering effects on the brain. By decreasing blood flow and neural activity in the regions most closely associated with self-awareness, ego, and personality expression, psilocin is able to facilitate, as Carhart-Harris so eloquently put it, “an unconstrained style of cognition.”http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
If you’re curious to know more about Robin Carhart-Harris and research, check out his website, psychedelicscience.org.uk. He also answered many questions in an excellent “IAmA” session on Reddit (summary of his answers here). And check out this video where Robin explains his psilocybin research.http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
Sources:
Carhart-Harris, RL et al. PNAS (2012); Vol. 109, No. 6. pp. 2138-2143.
Aldous Huxley (1953), The Doors of Perception.
Karl Friston et al. Journal of Physiology – Paris (2006); Vol 100, pp. 70-87.
http://psychedelicfrontier.com/how-psilocybin-works-addition-by-subtraction/
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