Researchers studying the loss of ego commonly experienced while tripping on psychedelics such as magic mushrooms have discovered that a key neurotransmitter may be linked to the phenomenon. A report on the research by scientists at Maastricht University in the Netherlands was published last month in the journal Neuropsychopharmacology.
Quite often, those who use psychedelic drugs such as psilocybin mushrooms and LSD experience a change in the perception of self and one’s connection to the larger world. Known as ego-dissolution, ego-disintegration, or ego-loss, the experience can result in a reduced state of self-awareness and a disruption of the boundaries of self and the world, leading to an increased feeling of unity with the environment. For some, the experience of ego-dissolution is a positive one, or a good trip, while others may have a negative, sometimes terrifying, bad trip.
Previous research has shown that ego and self-awareness may be related to levels of glutamate, the brain’s most abundant neurotransmitter. To test the theory, the team of researchers at Maastricht University designed a double-blind and placebo-controlled experiment to study the effect that psilocybin had on the glutamate levels of 60 healthy volunteers. Brain activity of the test subjects was monitored using magnetic resonance imaging (MRI).
The researchers discovered that psilocybin led to increased levels of glutamate in an area of the brain known as the prefrontal cortex, which is thought to be responsible for planning complex behavior, personality expression, decision-making, and moderating social behavior. They also recorded lower levels of glutamate in the hippocampus, an area of the brain that has been linked to the formation of memories and one’s sense of self-esteem.
The researchers also noted that the higher levels of glutamate in the prefrontal cortex caused by taking psilocybin were associated with a good trip, while the lower levels of glutamate in the hippocampus were linked to experiencing a bad trip.
“Whereas changes in [cortical] glutamate were found to be the strongest predictor of negatively experienced ego dissolution, changes in hippocampal glutamate were found to be the strongest predictor of positively experienced ego dissolution,” the researchers wrote.
More Research Needed
While it’s yet not clear if glutamate is actually related to the experience of ego-dissolution, other studies have suggested that psychedelics may decouple different regions of the brain.
“Our data add to this hypothesis, suggesting that modulations of hippocampal glutamate in particular may be a key mediator in the decoupling underlying feelings of (positive) ego dissolution,” wrote the researchers.
Although more research is needed, the discovery of psilocybin’s effect on glutamate levels could help explain how the drug can be used therapeutically for a variety of mental health conditions including depression and severe anxiety.
“Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic state, and importantly, provide a neurochemical basis for how these substances alter individuals’ sense of self, and may be giving rise to therapeutic effects witnessed in ongoing clinical trials,” the authors wrote.
The Opioid Crisis Has Plagued North America for Decades, and According to the U.S. HHS, it Kills an Estimated 130+ People Per Day in the United States Alone
Thanks to Recent Advancements in Psychedelic Medicine, There’s Renewed Hope and Optimism Surrounding the Deadly Epidemic
ATAI Life Sciences, DemeRx and MindMed Are Waging War Against Opioid Addiction By Utilizing This One Little-Known Psychedelic Substance
The opioid crisis isn’t making as many headlines these days due to the rise of the COVID-19 pandemic, which has paralyzed much of the global economy and captivated the attention of billions worldwide. While the Coronavirus continues to sweep across the globe, a different type of epidemic continues to ravage America’s communities and families. We’re talking about the Opioid Epidemic.
The U.S. Opioid Epidemic
According to the U.S. Department of Health and Human Services (HHS), the opioid epidemic was the result of gross negligence on the part of pharmaceutical companies, most notably, the now-bankrupt Purdue Pharma. Run by the now-infamous Sackler family, Purdue Pharma was the company responsible for the creation and mass promotion of the opioid pain killer Oxycotin. Certain pharmaceutical firms with Purdue leading the way assured doctors and the medical community that their opioid products were not addictive. This reassurance combined with a massive marketing campaign led to an enormous spike in the number of Oxycodone prescriptions in the U.S. Believing these new pain relievers were non-addictive, opioid use and misuse rates quickly began to soar. The truth is, opioids are highly addictive, and difficult to quit using due to the extreme withdrawal symptoms associated with it.
In 2017, the HHS finally declared the opioid epidemic a public health emergency and announced its 5-point plan to combat the crisis.
To put the opioid epidemic into perspective for you, here are some recent statistics from the Department of Health and Human Services:
130+ people died every day from opioid-related drug overdoses during 2018 and 2019
47,600 people died from overdosing on opioids in 2018
10.3 million people misused prescription opioids in 2018
2 million people had an opioid use disorder in 2018
2 million people misused prescription opioids for the first time in 2018
Source: U.S. Department of Health and Human Services
Corey Davis, a lawyer at Network for Public Health Law, recently said, “We’re now facing two deadly, concurrent declared public health emergencies: the opioid crisis and COVID-19.”
The federal government has loosened some restrictions in regards to social distancing for users of Buprenorphine (Subutex) and Methadone, the two main treatments for opioid addiction that require consistent use to prevent relapse. Opioid users are at high risk of major health conditions due to lifestyle and age (many are over 60), and there are hundreds of thousands of them. What if there was a different way to treat addiction that made opioid users less susceptible to disease and less dependent on the deadly drugs? The psychedelics industry believes it may have the answer.
Psychedelic Medicine is Showing Tremendous Promise
Several companies are working to bring a different approach to opioid addiction through the use of psychedelic medicine. Psychedelics are active compounds that have specific effects on precise parts of the brain–just like pharmaceutical drugs, but due to the U.S. federal government, have been constrained by the very outdated Controlled Substances Act.
DemeRx is one of ATAI’s innovating portfolio companies that’s thinking outside the box as it relates to addiction. The DemeRx website describes the company as “a clinical-stage pharmaceutical development company advancing two lead drug candidates as medication-assisted therapies for opioid addiction.”
Dr John Cunningham Lilly (January 6, 1915 – September 30, 2001) was an American physician, neuroscientist, psychoanalyst, psychonaut, philosopher, writer and inventor. He was a researcher of the nature of consciousness using mainly isolation tanks, dolphin communication, and psychedelic drugs, sometimes in combination. Lilly was a physician and psychoanalyst. He made contributions in the fields of biophysics, neurophysiology, electronics, computer science, and neuroanatomy. He invented and promoted the use of an isolation tank as a means of sensory deprivation. He also attempted communication between humans and dolphins. His work helped the creation of the United States Marine Mammal Protection Act of 1972. Lilly’s eclectic career began as a conventional scientist doing research for universities and government. Gradually, however, he began researching unconventional topics. He published several books and had two Hollywood movies based partly on his work. He also developed theories for flotation. Lilly published 19 books, including The Center of the Cyclone, which describes his own LSD experiences, and Man and Dolphin and The Mind of the Dolphin, which describe his work with dolphins. In the 1980s Lilly directed a project that attempted to teach dolphins a computer-synthesised language. Lilly designed a future “communications laboratory” that would be a floating living room where humans and dolphins could chat as equals and develop a common language. Lilly envisioned a time when all killing of whales and dolphins would cease, “not from a law being passed, but from each human understanding innately that these are ancient, sentient earth residents, with tremendous intelligence and enormous life force. Not someone to kill, but someone to learn from.” In the 1990s Lilly moved to Maui, Hawaii, where he lived most of the remainder of his life. Lilly’s literary rights and scientific discoveries were owned by Human Software, Inc., while his philanthropic endeavors were owned by the Human Dolphin Foundation. The John C. Lilly Research Institute, Inc. continues to research topics of interest to Lilly and carry on his legacy.
FDA Lists Psilocybin as “Breakthrough Therapy” for Depression Second Year in a Row
For the second year in a row, the US Food and Drug Administration (FDA) has designated psilocybin, the psychedelic compound found in many of the most popular hallucinogenic mushrooms, as a “breakthrough therapy,” for the treatment of major depressive disorder (MDD).
Treatments that are classified as breakthrough therapies are fast-tracked through the development and review process, which is often an extremely slow process filled with mountains of paperwork. This classification is not taken lightly, and is only granted in cases where a large body of evidence shows that that the new therapy is a significant improvement to its alternatives. Typically, drug companies apply for this designation, which is either approved or denied by the FDA. Last year, the first breakthrough therapy designation for psilocybin was granted to the company Compass Pathways.
Compass Pathways launched in the UK in 2016 thanks to funding from PayPal founder Peter Thiel. This year, the designation was granted to the US-based nonprofit Usona Institute, which is conducting clinical trials for treating depression with psilocybin.
Dr. Charles Raison, the director of clinical and translational research at Usona, said that psilocybin represents a vast improvement over the currently available treatments.
“What is truly groundbreaking is FDA’s rightful acknowledgement that MDD, not just the much smaller treatment-resistant depression population, represents an unmet medical need and that the available data suggest that psilocybin may offer a substantial clinical improvement over existing therapies,” Raison said in a statement.
As Truth Theory reported earlier this year, Johns Hopkins University recently announced the opening of the Center for Psychedelic and Consciousness Research, a facility within John Hopkins Medicine that will be dedicated to studying psychedelics and their potential to be used medicinally. This research center is the first of its kind in the United States, and the largest of its kind in the entire world. The unprecedented research effort is being made possible thanks to $17 million in donations from private investors.
Despite all of this evidence that the substance can be useful, psilocybin is still considered a Schedule I drug by the US federal government. Schedule 1 substances are defined as drugs with a high potential for abuse or drugs that have no recognized medical uses. Luckily, there are some local jurisdictions, such as Oakland and Denver, that have been making moves to decriminalize psilocybin and other psychedelic substances.
Anyone who’s went through a well-thought-out serious dose of mushrooms can tell you that psilocybin is a truly life-changing compound.
This molecule first emerged 10 to 20 million years ago, and its primary function was to repel predators from feasting on the mushrooms.
In the millions of years that followed creatures with superior sentience gradually evolved, and in humans the effects produced by psilocybin are completely different from the original purpose of this molecule.
How come some mushrooms have psilocybin?
Over two hundred species of mushrooms (which grow in almost every corner of the world) have developed psilocybin, and what’s fascinating is that this molecule seems to have evolved “separately” in each of them.
This unusual process where the beneficial genetic material jumps from species to species is called the horizontal gene transfer. This specific type of gene transfer is usually a result of a specific threat or opportunity in the environment.
It is speculated that the psilocybin-carrying genetic material “jumped” from one species to another because a great number of differing mushrooms grow on manure and rotten wood, but more importantly because in this fungi-friendly environment there’s also a lot of insects, who are the mushroom’s natural enemies.
Science has figured out (1) that unlike with humans (whose consciousness distorts in profound ways when psilocybin is introduced), psilocybin causes insects to perceive that they are full, which prevents them from eating the mushroom in question.
This sensation in the insects’ mind makes psilocybin a very sophisticated defense mechanism, because it doesn’t poison or kill them, but instead deters predatory insects from continuing to eat the mushroom.
How does psilocybin induce psychedelic effects?
Firstly, when we consume psilocybin mushrooms, the presence of water molecules in the body causes a phosphate group to detach from the psilocybin molecule.
This process is called dephosphorylation, and it converts psilocybin into psilocin, which is responsible for the mind-altering effects.
Once psilocybin is converted to psilocin, this molecule is now able to attach to specific receptors in the brain.
Because it is structurally quite similar to serotonin, psilocin prevents the reuptake (reabsorption) of serotonin on these serotonin receptors sites.
This means that psilocin temporarily “hijacks” serotonin receptors from serotonin, and stimulate them throughout numerous important regions of the brain.
This ability to stimulate serotonin receptors means that psilocin is a serotonin receptor agonist.
Serotonin is an immensely important neurotransmitter, with an extremely wide set of functions within the human body.
It’s frequently called the “happy chemical” as it’s essential for our feelings of wellbeing and happiness, but it is also intricately connected with numerous other functions such as mood, appetite, sleep cycles, sexual desire, memory and learning. Low levels of the serotonin molecule is also tightly tied with depression.
Similar to serotonin, but not the same
Psilocin molecules are capable of stimulating serotonin receptors because they are structurally similar to serotonin, and a very similar thing happens with cannabinoids from cannabis, which are able to stimulate the cellular receptors of the endocannabinoid system.
The endocannabinoid receptors have evolved to be stimulated by our endogenous endocannabinoids like anandamide. But, because cannabinoids like THC and CBD are structurally similar to our body-made endocannabinoids, endocannabinoid receptors also respond to the simulation of cannabinoids.
Just like endocannabinoids and cannabinoids are different, psilocin and serotonin are different. They don’t produce the same effects, even though they are similar in structure and fit onto the same receptors.
Since psilocybin (and subsequently psilocin) still remains a Schedule 1 substance, science is still having a hard time uncovering all of its mysteries, because the illegality cripples both the funding and volume of research.
What we know so far
Research has shown that psilocin stimulates serotonin receptors differently than serotonin, and the main difference is that psilocin activates phospholipase A2 enzymes, unlike serotonin which activates phospholipase C enzymes.
This basically means that psilocin and serotonin produce different effects when they stimulate these receptors, and other psychedelic compounds like DMT and LSD also activate phospholipase A2.
This kind of receptor activation is produces a cascading domino effect, affecting numerous regions in the brain – most importantly the default mode network.
The default mode network
When scientists first began taking brain scans of people under the influence of psilocybin, they expected to see a great increase in brain activity, corresponding with the intense sensations that people regularly report.
But unexpectedly, they saw a significant decrease of cerebral blood flow (CBF) in a specific network that is essential to our perception of self.
The default mode network (DMN) is a set of structures located in the midline of the brain, which connects structures of the frontal cortex (the most recently evolved part, home to our executive functions like planning, reasoning and problem solving), with older and deeper structures of the brain that are involved with emotions and memory.
All of this entails that the DMN is a crucial hub in the brain, involved with self-criticism, self-reflection and negative ruminating thoughts. It is also connected with our ability to think about both the past and the future, which is considered crucial for a well-developed sense of identity.
The DMN also plays a part in the theory of mind, which is the ability of humans to imagine various mental states (desires, intents, emotions and beliefs) in other people.
The ability of this molecule to temporary silence the default mode network is theorized to be responsible for the sensations of ego dissolution that many people experience on psilocybin.
This brief disconnect from the DMN results in a reconnection to everything, and the current research with psilocybin is showing astonishing results for people suffering from depression and addiction, as they are most afflicted with ruminating negative thought-patterns.
While the DMN is shut down, new neural connections are being formed, which brings us to the second important effect of psilocybin.
Novel brain connections
A 2014 study was performing functional magnetic resonance imaging (fMRI) brain scans on 15 participants who all had previous experiences with psychedelics, while they were on psilocybin.
The scans showed a significant decrease in activity in the default mode network, but more importantly, the data showed that the brain under the influence of psilocybin was creating a lot of new biologically stable neural connections.
Because the regular functioning of the default mode network is temporarily inhibited, structures within the brain that otherwise don’t directly communicate are able to connect.
This momentary rearrangement is thought to be responsible for the dramatically positive shifts in perspective that so many people experience with psilocybin, because it allows an otherwise-constricted and loop-driven brain to develop brand new insights and perspectives.
Even though these novel connections are only temporary and the functions of the brain are normalized after the psilocybin session, the study showed that the ego-dissolution in combination with new insights produces positive long-lasting neurological changes.
This occurs because the consciousness has had a chance to “experience” a different and less-constricted form of functioning, and this effect is something that isn’t easily forgotten.
Changes in the visual cortex
One of the most captivating effects of psilocybin are the vivid visual hallucinations, and scientists are currently trying to unravel how they occur.
Even though the 2019 study dealing with this correlation was performed on mice, it provided the research team with a lot of tangible insights.
A compound called DOI (2,5-Dimethoxy-4-iodoamphetamine) was used in this research, which is just like psilocybin activates phospholipase A2 enzymes.
This type of stimulation of the serotonin receptors caused the visual cortex to behave in a very disorganized fashion.
In normal states, exposure to a visual stimuli would result in an instant burst of neural activity, but for mice on DOI, this initial response was significantly obstructed.
Neurons fired with decreased intensity, and the timing of the firing was atypical. The main hypothesis is that hallucinations occur because the brain is trying to compensate for the lack of data it’s getting from the visual cortex.
The diminished input received from the main visual processing regions is possibly causing the brain to counterbalance the lack of information, which results in strange visual distortions.
This hypothesis coincides with the sensations experienced on a psilocybin trip, because the user is intellectually aware of the experienced hallucinations.
Humans have been utilizing psilocybin mushrooms for spiritual purposes for millenia, but the resurgence of interest within the scientific community for psilocybin is showing that a responsible and educated use of this molecule is extremely beneficial for both our psyche and our spirit. Contemporary research is currently verifying with factual evidence that psilocybin therapy provides a multitude of benefits for numerous disorders of the mind, including treatment-resistant depression, end-of-life depression and anxiety, and alcohol and nicotine addiction.