Psilocybin Desynchronizes The Human Brain
This study was published just a couple of weeks ago and outlines the difference between Psilocybin's effect on the brain versus Methylphenidate (Ritalin).
Psilocybin Desynchronizes The Human Brain: What does that even mean??
To start…this is a good thing!
Psilocybin profoundly impacts brain network dynamics by disrupting functional connectivity, reducing typical synchronization within networks, and decreasing anticorrelation between networks. This leads to increased neural communication, altered perceptions, and potential therapeutic changes. Unlike methylphenidate (used for ADHD) and caffeine, which enhance wakefulness and focus by loosening the coordination of certain brain regions, psilocybin dramatically changes consciousness and perception, promoting brain network integration and mind-expanding experiences.
Psilocybin's effect on increasing connectivity across brain networks and decreasing activity in the Default Mode Network can be beneficial for those with ADHD or anxiety, as it reduces self-referential thinking and ruminations.
Ok let's break it down...
Breakdown of Findings:
Study Design:
-Healthy adults were given high doses of psilocybin (25 mg) and methylphenidate (40 mg), with MRI scans taken before, during, and up to 3 weeks after administration.
-Participants were brought back for an additional psilocybin dose 6–12 months later.
-Approximately 18 MRI sessions per participant were conducted for detailed brain mapping.
Immediate Effects of Psilocybin:
-Psilocybin caused significant disruptions in functional connectivity (FC) in the cortex and subcortex, with more than three times the change compared to methylphenidate.
-These changes were driven by brain desynchronization, dissolving network distinctions by reducing correlations within and anticorrelations between networks.
-The default mode network (DMN) experienced the strongest FC changes, connected to the anterior hippocampus and associated with the sense of space, time, and self.
Subjective Experience Correlation:
-Individual differences in FC changes correlated strongly with the intensity of the subjective psychedelic experience.
-Performing a perceptual task during the study reduced psilocybin-driven FC changes.
Persistent Effects:
-Psilocybin caused a persistent decrease in FC between the anterior hippocampus and DMN, lasting for weeks.
-This persistent reduction may be linked to the therapeutic effects of psychedelics, potentially indicating increased neuroplasticity and antidepressant effects.
Additional Observations:
-The study utilized precision functional mapping to track individual-specific brain changes.
-Psilocybin increased spatial entropy (desynchronization of brain activity), with the largest increases observed in association cortex.
-Task engagement during the psilocybin session decreased the magnitude of brain desynchronization.
-Persistent FC changes were observed 1–21 days post-psilocybin, particularly between the anterior hippocampus and DMN, but not post-methylphenidate.
Implications:
-The study provides insights into how psilocybin affects human brain networks, supporting its potential therapeutic mechanisms.
Understanding these changes could help explain the rapid and sustained therapeutic effects observed in clinical trials of psilocybin for depression, addiction, and anxiety.
OK so, what is Functional Connectivity??
Functional Connectivity (FC):
FC refers to the temporal correlation between spatially remote neurophysiological events, often measured by the correlation of the brain's activity patterns over time.
Essentially, it indicates how different regions of the brain communicate and coordinate with each other during rest or while performing tasks.
Disruptions in FC:
When psilocybin disrupts FC, it means that the usual patterns of communication between different brain regions are altered. Under normal conditions, certain brain networks exhibit strong, coordinated activity (high connectivity) within themselves and weaker, less coordinated activity (anticorrelations) with other networks.
Specific Effects of Psilocybin on FC:
Reduction of Correlations Within Networks
Reduction of Anticorrelations Between Networks
Specific Effects of Psilocybin on FC:
Reduction of Correlations Within Networks:
Typical State: In a typical state, brain networks such as the default mode network (DMN) show high internal connectivity, meaning regions within these networks are highly synchronized.
Under Psilocybin: Psilocybin reduces these internal correlations, meaning the regions within a network are less synchronized, or "desynchronized."
2. Reduction of Anticorrelations Between Networks:
Typical State: Normally, networks like the DMN and task-positive networks (involved in focused attention and task execution) show anticorrelations, meaning when one network is active, the other is suppressed.
Under Psilocybin: These anticorrelations are reduced, indicating that the distinct functional boundaries between networks become blurred, and they communicate more freely. In other words, a sort of balance is restored.
And in the brains of those who struggled with depression, anxiety, and ADHD, the communications between these networks is more frequently unbalanced.
Implications of These Disruptions:
1. Ego Dissolution:
Connection to Self-Perception: The DMN is closely associated with self-referential thinking and the sense of self. Disruption in its connectivity is linked to the experience of ego dissolution, where the boundary between the self and the external world becomes less distinct.
2. Altered Perception of Time and Space:
Temporal and Spatial Perception: The anterior hippocampus and its connectivity with the DMN are involved in our perception of time and space. Changes in FC in these areas can lead to altered experiences of time and space, commonly reported during psychedelic experiences.
3. Therapeutic Effects: Neuroplasticity! Boy, do we love this word!
Persistent changes in FC, particularly the reduction in connectivity between the anterior hippocampus and DMN, may enhance neuroplasticity, the brain's ability to reorganize and form new neural connections. This can underpin the rapid and sustained therapeutic effects of psilocybin, such as symptom relief in depression and anxiety.
By disrupting habitual patterns of thought and behavior that are typically governed by these brain regions. By weakening the connection between these areas, psilocybin may free the brain from its usual constraints, allowing for greater flexibility and the formation of new neural connections (aka neuroplasticity).
Mechanism Behind Disruptions:
Serotonin Receptor Agonism: Psilocybin acts on serotonin receptors, particularly the 5-HT2A receptors, which are abundant in areas like the cortex and hippocampus. Activation of these receptors is thought to cause widespread changes in neuronal activity, leading to the observed disruptions in FC.
Desynchronization: The drug induces desynchronization of neuronal activity both locally (within specific brain regions) and globally (across the whole brain), leading to increased entropy or randomness in brain activity. This desynchronization can break down the usual patterns of communication within and between networks.
Conclusion:
Psilocybin's disruption of functional connectivity reflects its profound impact on brain network dynamics. By reducing the typical synchronization within networks and the anticorrelation between networks, psilocybin facilitates a state of increased neural communication and integration, leading to altered perceptions and potentially therapeutic changes in brain function. This disruption and subsequent reorganization are crucial to understanding both the subjective experiences induced by psilocybin and its therapeutic potential.
Figure a: Shows how psilocybin changes brain communication, especially in deep areas.
Figure b: Shows how methylphenidate changes brain communication.
Figure c: Shows normal brain communication changes for comparison.
Figure d: Psilocybin changes are biggest in the Default Mode Network.
Figure e: Psilocybin causes the largest overall brain changes compared to methylphenidate and normal variation.
Figures f and g: Bigger brain changes with psilocybin are linked to more intense psychedelic experiences.
Figure h: Maps brain areas where changes are linked to the intensity of the psychedelic experience.
Figure a: Psilocybin-Associated Functional Connectivity (FC) Change
Resting Scans (Left): This part of the figure shows how psilocybin changes the way different parts of the brain connect with each other when a person is at rest (not doing any tasks).
Task Scans (Right): This part shows the changes in brain connections when a person is engaged in a task while under the influence of psilocybin.
Bar Graphs (Bottom): These graphs summarize the overall changes in brain connectivity for both resting and task conditions, comparing before and after taking psilocybin.
Figure b: Regional Normalized Global Spatial Complexity (NGSC) Change
Resting Scans (Left): This part shows how psilocybin affects the complexity of brain activity patterns when a person is at rest.
Task Scans (Right): This part shows the effects on brain activity complexity when a person is doing a task under the influence of psilocybin.
Bar Graphs (Bottom): These graphs summarize the overall changes in the complexity of brain activity for both resting and task conditions, comparing before and after taking psilocybin.
Simplified Summary:
Psilocybin Changes Brain Connectivity: Psilocybin alters the way different parts of the brain communicate, whether a person is resting or doing a task.
Task Effects: Engaging in a task while on psilocybin changes brain connectivity and activity complexity more than just resting on the drug.
Strong Effects: These changes are strong and significant, indicating that psilocybin has a profound impact on brain function, especially when tasks are involved.
Methylphenidate vs. Psilocybin
Methylphenidate (Ritalin):
What it is: Methylphenidate is a stimulant medication, commonly known by the brand name Ritalin. It is primarily used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy.
How it works: It increases the levels of certain chemicals in the brain, like dopamine and norepinephrine, which help improve focus, attention, and control of impulses.
Effects: It makes people more alert, focused, and energetic. The changes it causes in brain activity are related to increased arousal and attention.
Psilocybin:
What it is: Psilocybin is a psychedelic compound found in certain mushrooms, often referred to as "magic mushrooms."
How it works: It primarily acts on serotonin receptors in the brain, particularly the 5-HT2A receptors, leading to altered states of consciousness, changes in perception, and profound psychological experiences.
Effects: It can cause hallucinations, changes in the perception of time and space, and feelings of connectedness or ego dissolution. These effects are often described as mystical or spiritual experiences.
Similarities between Methylphenidate (Ritalin) and Caffeine
Stimulant Effects: Both methylphenidate and caffeine are stimulants. This means they increase arousal and alertness.
Brain Activity: They cause similar changes in brain activity, particularly in regions related to alertness and attention.
What This Means:
Increased Alertness: Just like drinking coffee can make you feel more awake and focused, taking methylphenidate increases alertness and concentration.
Temporary Boost: Both substances provide a temporary boost in mental and physical energy by stimulating the central nervous system.
Milder Effects: While methylphenidate is a more potent and targeted stimulant used for medical purposes, caffeine is a milder stimulant commonly found in beverages like coffee and tea.
Methylphenidate (Ritalin):
Think of methylphenidate as a powerful, prescription-strength version of caffeine. It’s used to help people with ADHD focus better by boosting certain brain chemicals that keep you alert and attentive. Just like coffee wakes you up and helps you stay focused, methylphenidate does the same but in a much stronger and more controlled way.
Methylphenidate (MTP) and Brain Networks:Within-Network Functional Connectivity (FC): Think of this as how well different parts of the same team (or network) in your brain are working together. For example, the sensory network includes all the parts of your brain that process what you see, hear, and feel.
Effects of Methylphenidate:Decrease in FC: Methylphenidate (MTP) made the teamwork within certain brain networks (like sensory, motor, and auditory networks) less synchronized. This means the parts of these networks weren't working together as closely as they usually do.
Similar to Caffeine:This effect is similar to what happens when you drink caffeine. Both MTP and caffeine cause the same kind of changes in how these brain networks function.
Psilocybin: Psilocybin, on the other hand, is like taking a trip into another world. It dramatically changes how you see and experience things, making everything look and feel different. It's not about making you more alert but rather about giving you a profound, often mind-expanding experience.
Both Methylphenidate and Caffeine
Stimulant Effects: Increase alertness and concentration by stimulating the central nervous system.
Brain Activity: Cause similar changes in brain activity, particularly reducing the synchronization within certain brain networks, like sensory, motor, and auditory regions.
Temporary Boost: Provide a temporary boost in mental and physical energy.
In essence, while methylphenidate and caffeine are about enhancing your normal wakefulness and focus, psilocybin is about altering your consciousness and perception in a deep and often transformative way.
When you take methylphenidate (a medication often used for ADHD), it makes the different parts of certain brain networks (like those that control your senses, movements, and hearing) less synchronized. This effect is similar to what happens when you drink coffee. So, both methylphenidate and caffeine cause parts of your brain to work together a bit less tightly in these specific areas.
Psilocybin
On the other hand, psilocybin from "magic mushrooms" dramatically changes perception and consciousness, disrupting brain connectivity much more and creating profound, mind-expanding experiences.
In Conclusion...Psilocybin's effect on increasing connectivity across brain networks and decreasing activity in the Default Mode Network can be beneficial for those with ADHD or anxiety, as it reduces self-referential thinking and ruminations.
