What Happens In Your Brain When You Take Psilocybin?

While the scientific journey of psilocybin, the main active ingredient in magic mushrooms, began when it was first identified and synthesized in the 1950s, the question of “What happens in your brain when you take psilocybin?” went unanswered. Our understanding of how psilocybin works in the brain wasn’t really possible until the introduction of brain imaging technology in the 1990s, long after psilocybin had been outlawed for medical research. 

After a bumpy few decades, drug advocates and the scientific community are increasingly forming a united front — and we are now in the midst of a psychedelic renaissance. As policies change, current research is lifting the veil on many aspects of the “trip” and showing us why this ancient drug is long revered as a tool of hope and healing. Modern technology has given us our deepest glimpse yet into how psilocybin destabilizes and resets the brain in order to repair us from within — and the science is pretty cool.

What happens in your body when you take Magic Mushrooms?

Most of the research on psilocybin uses a synthetic version of the compound since it’s much easier to control dosing and purity. The most significant chemical difference between synthetic psilocybin and psilocybin-containing mushrooms is that natural mushrooms also contain low concentrations of other alkaloids, which may or may not offer some of their own benefits. 
The most common way to consume psilocybin is orally in drinks, capsules, snacks or straight down the hatch for the bold and brave, but some research studies use an injectable form because it’s shorter acting. Upon ingestion of psilocybin, your body converts it into a compound called psilocin. Acid is important in this chemical conversion, which is why lemon teks are a popular way to enhance the effects of a dose. Psilocin works its magic because it has a chemical structure very similar to serotonin.

What exactly is Serotonin?

Serotonin is a well-known neurotransmitter, or chemical messenger, involved in various emotional and biological processes. Even though serotonin is a “neuro” transmitter, you actually have serotonin receptors throughout your body, controlling everything from bowel movements to feelings like fear or bliss. Serotonin receptors are like tiny control hubs that get activated by circulating serotonin and can trigger the release of other chemicals like dopamine, oxytocin, cortisol and even serotonin. 

Because your body is sophisticated and complicated — not all serotonin receptors are the same. To date, there are 14 known different subtypes of serotonin receptors, and they each have distinct roles. Certain receptors have been identified to play a role in many mental health disorders such as depression, addiction, anxiety, eating disorders, and sleep problems. “Playing a role” means that, similar to how a pancreas isn’t working optimally in diabetes, some serotonin receptors aren’t working optimally in mental illness. 

How Do Magic Mushrooms Affect Serotonin?

Psilocin directly affects several serotonin receptor subtypes — 5-HT1A, 5-HT2A, and 5-HT2C receptors. Neuroscientists aren’t keen on informative receptor names so let’s look at each of these in a little more detail:

• 5-HT1A: Some key functions include addiction, aggression, appetite, pupil dilation, sleep, impulsivity, heart rate, memory, and sociability
• 5-HT2A: Some key functions include addiction, anxiety, appetite, cognition, imagination, learning, mood, perception, sexual behavior, and sleep
• 5-HT2C: Some key functions include addiction, anxiety, appetite, GI motility, mood, sleep, and norepinephrine and dopamine regulation (aka heteroreceptor).

A close look at this list helps explain why in addition to the psychedelic experiences,  psilocybin causes side effects like pupil dilation and frequent bathroom trips. Most of the current research has examined the way psilocybin affects 5-HT2A receptors. One of the main findings from this research is that psilocybin’s action on these receptors helps release a chemical called brain-derived neurotrophic factor (BDNF) which is associated with healthier brain functioning. Scientists also believe this 5-HT2A action is responsible for the psychedelic experience.

Psilocybin – The Great Remodeler

Brain imaging studies allow scientists to observe and map the brain in action — giving us our first glimpse into what happens in your brain when you take psilocybin. Imaging studies have found that in addition to changing receptor activity, psilocybin also causes changes in your neural pathways. Your brain communicates through pathways that act as information highways; these highways are responsible for things like habits, reactions, and learned behaviors. 

Your brain can be fairly stubborn when it paves a highway, which also explains why habits can be so hard to break. One of the greatest struggles in mental health disorders is finding ways to alter these resistant pathways that keep people stuck in unhealthy loops and patterns.  

One well-studied series of pathways connecting several brain regions is known as the Default Mode Network (DMN). The specific brain regions involved in the DMN include: 

• Medial prefrontal cortex: A regulator known to be involved in attention, inhibition or self-regulation, habit formation and memory
• Posterior cingulate cortex: Acts as a communication hub, or switchboard, in the DMN
• Angular gyrus: Involved in various functions such as attention, self-processing, emotional regulation, out-of-body experiences, and social cognition.

Abnormalities in the DMN are associated with mental health disorders like depression, addiction, anxiety and PTSD. DMN dysfunction leads to symptoms like rumination, focusing on negative emotions, and an altered sense of self. 

Recent work has begun to show us that psilocybin appears to throw the DMN into disarray — weakening unhelpful pathways and restructuring healthier ones. 

One study at Imperial College London used two different types of brain scans to examine the effects of a moderate dose of psilocybin in 15 healthy volunteers. The researchers found that psilocybin reduces blood flow and neural activity in the DMN, specifically in the posterior cingulate cortex and the medial prefrontal cortex.  

Follow-up research using these scans mapped out the connection differences in brains without psilocybin versus when given psilocybin. In the figure, each circle depicts relationships between networks within the brain, with the lines indicating connection-rich networks. Researchers note that the changes that occur from psilocybin are actually organized and not random chaos, but more work is needed to understand the functional significance of these changes.

Another study at the University of Oxford examined brain images of nine healthy volunteers given a moderate dose of psilocybin in order to examine neural activity and create a map of brain connections, known as a “whole-brain connectome.” They found that not only did psilocybin throw well-established highways into disarray, but it also led to the creation of new pathways. 

Altogether, research is demonstrating that psilocybin creates an environment of destabilization that can help modify unhealthy brain patterns through changes in receptor activity and neural pathways. Unlike any currently available therapies, psilocybin offers the opportunity for a mini reset button that allows the brain to repair itself in various and sophisticated ways. 

Do the Changes From Magic Mushrooms Last?

Things obviously calm down when the drug wears off but there appears to be positive functional changes that stick around. One group of researchers looked at brain images of healthy volunteers pre-psilocybin and then one week and one month after dosing. They found decreased activity in brain regions responsible for negative emotional responses that rebounded at one month, and an increased response to positive emotional experiences that remained elevated at one month. They also found that increases in functional connectivity between brain regions responsible for reward-learning, attention and decision making remained increased at one month. 

Another exciting recent research finding examined a group of 24 participants with major depressive disorder who received two treatments with psilocybin dosed at 20-30mg/70kg per session. They found that psilocybin was four times more effective at treating depression than in medication studies. A 12-month follow-up with the participants revealed that 75% of the participants continued having a clinically significant reduction in symptoms, indicating the potential for sustained and long-term positive effects of psilocybin, especially when offered psychological support.

The Future of Magic Mushrooms

Much more work is needed to better understand how psilocybin can best be used as a therapeutic agent of change. Advocates and researchers alike are excited at the possibility of moving beyond current band-aid solutions in psychiatric medicine and moving toward healing. With or without a mental health diagnosis, psilocybin may offer the potential to tap into the brain’s own self-healing system and un-do programming that keeps us stuck in unhealthy life patterns. There is plenty of work ahead, but the future of psychedelic medicine continues to get brighter.

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