How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks | Huberman Lab Podcast

Name: How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks | Huberman Lab Podcast
Uploaded: 2023-05-08T12:00:24.000Z
Duration: 4 h 18 min 2 s

Introduction

In this section, Andrew Huberman introduces the topic of psilocybin and its potential therapeutic applications.

Psilocybin Basics

Psilocybin is a psychedelic that modifies consciousness by changing perception, memories, thoughts, and feelings.

Psilocybin mimics serotonin by activating a subset of serotonin receptors in the brain leading to neuroplasticity at the level of neural circuits.

Psilocybin is one of many psychedelics such as LSD, DMT, 5meo DMT, and MDMA.

Effects of Psilocybin

Psilocybin has growing excitement for its potential therapeutic applications for mental health issues such as depression, alcohol abuse disorder, addictions of various kinds, OCD and eating disorders.

Proper psilocybin therapeutic approaches can lead to long-standing improvements in mood and tremendous insight into oneself and others.

Conditions for a Positive Journey

In this section, Andrew Huberman discusses the conditions necessary for a positive psilocybin journey.

Chemistry & Cell Biology

Silosin is the actual compound that goes into the brain to create all the changes in consciousness associated with psilocybin.

Neural circuits change over time impacting changes most people are interested in when they go on a psilocybin journey.

Factors Affecting Journey Experience

Neuroplasticity does not necessarily mean it's therapeutic. It has to be adaptive and allow someone to function better in life than they did previously.

The conditions of a psilocybin journey, including whether it's done with eyes closed or open, alternating between eyes closed and open phases, music played during the journey, and even what types of music are played will dictate whether somebody will feel better or worse in the days and weeks following that psilocybin journey.

Clinical Effects

In this section, Andrew Huberman discusses the clinical effects of psilocybin.

Dosages & Translating from Mushrooms to Psilocybin

Andrew Huberman talks about dosages and translating from psilocybin mushrooms to actual psilocybin.

Understanding how psilocybin is converted to silacin has tremendous impact on the duration of a psilocybin journey.

Positive Changes After Session

Much of the positive changes that are possible with proper psilocybin therapeutic approaches takes place after the session in which one feels all the typically associated effects of psilocybin like hallucinations and changes in thought patterns.

Improvements in Mood

Clinical studies show that just one psilocybin journey can improve mood in a long-standing way but most clinical trials involve two dosages spaced apart.

Introduction to Psilocybin

In this section, the speaker introduces psilocybin and its importance. They also discuss the topics that will be covered in the podcast.

What is Psilocybin?

The speaker discusses what psilocybin is and how it works at a chemical, cellular, neural network, and neuroplasticity level.

The speaker emphasizes that psilocybin is still a Schedule 1 drug in the United States and illegal except for rare instances such as clinical studies or decriminalized areas.

Understanding Psilocybin

The speaker talks about Oregon being an exception where psilocybin has been approved for use in particular therapeutic settings for depression and addiction.

The speaker highlights that possessing or selling psilocybin is not allowed under the law except for rare instances such as clinical studies or decriminalized areas.

The speaker discusses safety issues related to young people (25 years old or younger), dosages related to antidepressants, and people at risk of psychotic episodes.

Conclusion

The speaker encourages listeners to learn more about psilocybin's effects, therapeutic applications, dosing patterns, etc., so they can make informed decisions about whether it's right for them.

The podcast is separate from the speaker's teaching and research roles at Stanford. They thank their sponsors: Eight Sleep and Roka.

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Psilocybin as a Tryptamine

In this section, the speaker discusses psilocybin as a tryptamine. He explains what tryptamines are and how they relate to serotonin.

Tryptamines

Psilocybin is a tryptamine.

Tryptamines include psilocybin, DMT, and 5mao DMT.

They closely resemble serotonin in their chemical composition.

Serotonin

Serotonin is a neuromodulator that modifies or changes the activity of other neurons and neural circuits in the brain and body.

It's involved in many functions such as mood regulation, pleasure sensation, motivation levels etc

There are many different types of serotonin receptors which have different effects on neurons when activated by serotonin or similar molecules like psilocybin

Psilocybin and Serotonin

In this section, the speaker discusses the similarities between psilocybin and serotonin, and how psilocybin binds to the serotonin 2A receptor to trigger changes in neural circuitry that lead to improvements in mood and relief from compulsive disorders.

Psilocybin's Similarity to Serotonin

Psilocybin closely resembles serotonin.

The fact that psilocybin looks so much like serotonin raises an important question: why does psilocybin lead to specific experiences while resembling serotonin?

Psilocybin mainly binds to and activates the serotonin 2A receptor, which is expressed in particular areas of the brain and neurons.

This allows for specific types of changes in neural circuitry not just when under the influence of psilocybin but also afterwards.

Selectivity of Psilocybin

The selectivity of psilocybin binding to the serotonin 2A receptor leads to improvements in mood, relief from depression, relief from various compulsive disorders, etc.

Clinical trials show that two journeys with particular dosages of psilocybin lead to significant relief for major depression.

Psilocybin outperforms standard therapy and various antidepressants in terms of providing depression relief.

The selectivity of psilocybin binding to the serotonin 2A receptor is what makes it a therapeutic tool.

Understanding Proper Dosing Profiles

To understand how psilocybin works optimally for a given condition or goal, one needs to understand what it's actually doing.

It's important to talk about the serotonin 2A receptor - where it is in the brain, what happens when psilocybin binds it, and how those things set in motion various changes leading to neuroplasticity.

Proper dosing profiles and spacing of sessions (AKA journeys) are important to understand.

Serotonin Receptors and Psilocybin

In this section, Dr. Andrew Huberman discusses the differences between selective serotonin reuptake inhibitors (SSRIs) and psilocybin in terms of their effects on serotonin receptors in the brain. He explains how psilocybin selectively binds to serotonin 2A receptors, which are located primarily in the neocortex, including the prefrontal cortex and visual cortex.

SSRIs vs Psilocybin

SSRIs increase serotonin levels non-specifically by inhibiting reuptake at synapses.

Psilocybin selectively binds to and activates serotonin 2A receptors.

Serotonin 2A receptors are located primarily in the neocortex, including the prefrontal cortex and visual cortex.

Psilocybin triggers visual hallucinations due to its strong binding to serotonin 2A receptors in the visual cortex.

Effects of Psilocybin

Visual hallucinations occur even when eyes are closed due to high expression of serotonin 2A receptors in the visual cortex.

Having eyes closed for majority or entire psilocybin session is useful for deriving long-lasting benefits from experience.

Open-eyed experiences focus on altered perceptions of outside environment, while closed-eye experiences allow for inward exploration of thoughts, memories, and emotions.

Psilocybin Use and Safety

In this section, the speaker discusses the conditions and supports required for a psilocybin journey to be therapeutically useful. The speaker also highlights that psilocybin use is contraindicated for certain people, such as those with existing or predisposition to psychotic episodes or bipolar episodes.

Psilocybin Use and Contraindications

Psilocybin use requires certain conditions and supports to be therapeutically useful.

People with existing or predisposition to psychotic episodes or bipolar episodes should not do psilocybin.

Studies involving psilocybin are focused on adults aged 25 years old or older.

Psilocybin is a powerful drug that should only be used in the proper clinical setting.

Athletic Greens Sponsorship

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Athletic Greens Benefits

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Psilocybin Dosing

In this section, the speaker talks about dosing of psilocybin and microdosing of psilocybin. The speaker highlights that there is a lot of loose thinking around microdosing in non-clinical and non-research communities.

Psilocybin Dosing

Safe doses of psilocybin range from one milligram to 25-30 milligrams depending on the study.

Microdosing typically involves taking one to three milligrams per day repeatedly over time.

Macro or "heroic" dosing involves taking 10 milligrams or more in a single session.

Conclusion

In this section, the speaker concludes by answering a common question about how long the effects of psilocybin last.

Conclusion

The speaker answers a common question about how long the effects of psilocybin last.

Understanding Psilocybin Dosage

In this section, the speaker discusses the concentration of psilocybin in magic mushrooms and how it translates to dosage. They also touch on the concept of "heroic doses" and the importance of sourcing for consistent dosing.

Psilocybin Concentration in Magic Mushrooms

One gram of mushrooms contains approximately 10 milligrams of psilocybin.

A "heroic dose" typically refers to ingestion of 50 milligrams or so of psilocybin, which translates to about five grams of mushrooms.

The concentration of psilocybin can vary tremendously from batch to batch, depending on factors such as strain, age, and storage.

Importance of Sourcing for Consistent Dosing

Inconsistent dosing can occur if the concentration varies from what is expected.

As psilocybin becomes more legal and regulated, dosing will become more consistent with synthetically made psilocybin.

Components of an Effective Therapeutic Psilocybin Journey

In this section, the speaker discusses the components that make up an effective and safe psilocybin journey. They emphasize the importance of set and setting.

Set and Setting

Set refers to a person's mindset going into a journey.

Setting refers to the physical environment where a journey takes place.

Both set and setting are known to bias the probability of a beneficial journey versus a bad trip.

Variables for Safe and Effective Journeys

Safe and effective journeys are for people who are not prone to psychotic episodes, 25 years or older, and in a supportive environment.

Effective journeys involve preparation, intention setting, and integration.

Preparing for a Psilocybin Journey

In this section, the speaker discusses the importance of preparing for a psilocybin journey and how to do so safely.

Set and Setting

"Set" refers to the mindset of the person taking the psychedelic, while "setting" refers to the environment in which they are taking it.

The setting should be safe, with no opportunities for harm or danger. It is important to have responsible individuals present who are not under the influence of psychedelics.

The setting should also include an opportunity for the person on the psychedelic to be seated or lying down with their eyes covered.

Safety Concerns

People should not be on antidepressants in the weeks leading up to a psilocybin journey.

It is dangerous to stop taking medication without consulting a physician.

Taking psychedelics without considering set and setting can lead to harm or even criminalization.

The Structure of a Psychedelic Journey

In this section, the speaker discusses what a psychedelic journey entails and how it differs from recreational use.

Components of Setting

The setting must ensure safety by eliminating opportunities for harm or danger.

Responsible individuals who are not under the influence of psychedelics should be present in that environment.

The person on the psychedelic should be seated or lying down with their eyes covered.

Differences from Recreational Use

Psychedelic journeys are typically conducted in a closed environment with one or two other individuals acting as guides.

The goal of a psychedelic journey is to rewire brain circuitry and improve outcomes, rather than simply experiencing visual hallucinations.

The Role of Music in Psychedelic Therapy

In this section, the speaker discusses the role of music in psychedelic therapy and how it can impact the emotional and cognitive experience of a psilocybin journey.

Music as an Influential Factor

Music is a critical component of the set and setting for a psilocybin journey.

It is not just an incidental feature but one of the major drivers of the actual cognitive and emotional experience that somebody has on something like psilocybin.

Types of Music Used in Clinical Studies

The music used in clinical studies tends to have a particular contour that matches with and can also drive that contour of the psilocybin journey.

At the beginning, music tends to be low volume without vocalizations such as classical music.

During peak emotion, intense music with percussion such as drums are played for about 45 minutes to 90 minutes depending on the study one looks at.

Afterward, softer music such as coral type or more melodic music often female voices in particular are played before transitioning into nature sounds.

Importance of Matching Music to Experience

The reason why it is so important that music match and even contribute to the subjective experience that people have on psychedelics is because it can impact our emotions and thoughts during a psychedelic journey.

Synesthesia and Perceptual Blending Under the Influence of Psilocybin

This section discusses how psilocybin can cause synesthesia or the merging of different senses that are not ordinarily merged. It also explains how people under the influence of psilocybin often report that their pattern of breathing becomes linked to their perceptions.

Perceptual Blending and Synesthesia

Psilocybin can cause synesthesia or the merging of different senses that are not ordinarily merged.

People under the influence of psilocybin may experience perceptual blending, such as feeling a change in music when they rub their fingertips across a surface.

The serotonin 2A receptor is predominantly activated by psilocybin, which leads to perceptual and emotional blending.

Pyramidal Neurons

Pyramidal neurons have dendrites that extend out into layers above them, allowing them to communicate with other neurons in their environment.

Serotonin 2A receptors on pyramidal neurons' apical dendrites increase lateral communication across brain areas, leading to a shift from modular brain function to more integrated communication.

The Default Mode Network and Ego Dissolution

This section discusses how psilocybin affects the default mode network (DMN), which is responsible for self-referential thinking. It also explains how ego dissolution can occur under the influence of psilocybin.

Default Mode Network

The DMN is responsible for self-referential thinking and is active when the mind is at rest.

Psilocybin decreases activity in the DMN, leading to a decrease in self-referential thinking.

Ego Dissolution

Ego dissolution can occur under the influence of psilocybin, which involves a loss of sense of self or identity.

The experience of ego dissolution can lead to positive changes in personality traits and increased well-being.

Psilocybin and Brain Communication

In this section, Dr. Huberman explains how psilocybin affects the communication across the brain and reduces the hierarchical organization of the brain.

Psilocybin's Effect on Brain Communication

Psilocybin increases communication across the brain.

Psilocybin broadens the flow of information from bottom-up sensory regions to higher order processing regions.

Serotonin 2A receptor activation allows for more broad, less precise, and less hierarchical activation of brain circuitry.

Reduction in Hierarchical Organization

Psilocybin reduces the hierarchical organization of the brain.

There is a shift in the flow of sensory information into the brain that can generally be described as broader and including more blending of different senses.

Activation of serotonin 2A receptors leads to far less channeled, modular, and hierarchical patterns of activation in the brain.

Effects on Perception

In this section, Dr. Huberman discusses how psilocybin affects perception by broadening sensory experiences and blending different senses together.

Broadening Sensory Experiences

Under psilocybin's influence, there is a broader flow of sensory information into the brain.

The visual cortex is very activated even in absence of any visual input under psilocybin's influence.

Patterns of activation in the brain are far less channeled than when not under psilocybin's influence.

Blending Different Senses Together

Activation of serotonin 2A receptors leads to blending of different senses.

Breathing can be linked to a sound, or a sound can be linked to something seen in the mind's eye.

Reduction in electrolyte concentrations or dehydration of the body can lead to deficits in cognitive and physical performance.

Element Electrolyte Drink

In this section, Dr. Huberman briefly talks about Element, an electrolyte drink that he uses for hydration and replenishing electrolytes.

Benefits of Electrolytes

Salt, magnesium, and potassium are critical to the function of all cells in the body.

Even slight reductions in electrolyte concentrations or dehydration of the body can lead to deficits in cognitive and physical performance.

About Element

Element is an electrolyte drink that contains a science-backed ratio of sodium, potassium, and magnesium.

It has no sugar and is useful for hydrating the body before or after physical training.

The Effects of Psilocybin on the Brain

In this section, Sam Harris discusses the default mode network and how it is thought to be rewired under conditions of psilocybin or other psychedelics. He also talks about how psilocybin expands the functional connectivity of the brain while one is under its influence.

Default Mode Network and Psychedelics

The default mode network is responsible for spontaneous imagination and daydreaming.

It reflects the base activation state of the brain when there are no drugs in our system.

The default mode network is one of the systems that is thought to be rewired under conditions of psilocybin or other psychedelics.

Expanded Functional Connectivity

Psilocybin expands the functional connectivity of the brain while one is under its influence.

Some expanded functional connectivity persists after the effects of psilocybin have worn off.

Studies have shown that psilocybin leads to more extensive communication between areas of the brain that normally are not as active at the same time.

Effects on Healthy Volunteers

A study conducted by Robin Carhart-Harris at UCSF explored what brain areas are active in a resting state.

They found more extensive connectivity between those brain areas in individuals who had taken psilocybin or MDMA compared to when they were not under their influence.

This enhanced lateral connectivity led to less hierarchical organization, effectively more interconnection and communication between different brain areas.

Adaptive Rewiring

The goal of effective psychedelic therapies is adaptive rewiring, which leads to new ideas and ways of thinking or feeling that allow people to function better in their lives.

Increasing connectivity in the brain does not necessarily lead to disruptions in memory, as studies have shown that very seldom do people who take psilocybin experience long-term issues with memory.

Creativity and Life Experience

In this section, the speaker discusses how psilocybin impacts creativity and life experience. The positive effects of psilocybin on creativity and life experience have only been explored in a narrow set of dimensions. However, where it has been explored, there are some interesting findings.

Psilocybin's Effect on Music Perception

Psilocybin changes one's experience of music not just during the psilocybin journey itself but thereafter.

Psilocybin can increase one's positive perception of music that one likes and can tone down or reduce the depressiveness or sadness of music that tends to make one sad even after the psilocybin has worn off.

People who have taken psilocybin can get a return of elevated emotionality, the positive emotions associated with music that formerly made them feel good.

Psilocybin can rewire the connections between the emotion centers in the brain and the networks that control auditory perception of music.

Impact on Depression

One common feature of major depression is that people don't derive as much pleasure from different types of experiences whether it's food, sex, or social experiences.

People with depression often feel as if music no longer has the same impact; it just doesn't really lift them up very much.

Studies show that people who have taken psilocybin according to specific parameters can get a return of elevated emotionality, including positive emotions associated with music.

Limitations

Positive effects of psychedelics on creativity and life experience have only been explored in a fairly narrow set of dimensions.

More research is needed to fully understand how psilocybin impacts creativity and life experience.

Psilocybin and Brain Connectivity

In this section, the speaker discusses a study that explores how psilocybin can rewire the brain in ways that allow individuals to experience life differently. The study focuses on changes in emotionality and responses to music.

Psilocybin's Effect on Brain Circuitry

A study shows that psilocybin can bring about structural and functional changes in brain circuitry.

The study links subjective reports of emotional changes to neuroimaging data showing changes in brain activation in response to music.

Psilocybin expands connectivity between brain areas, allowing for new learning and relationships between different sensory and emotional states.

After the psilocybin session, people's brains have rewired in a way that allows them to experience joy in response to music again.

Psilocybin's Effect on Creativity

There haven't been many studies looking specifically at the effect of psilocybin on creativity.

However, it is believed that psilocybin can invoke new patterns of learning and considerations about what might be possible, leading to actual rewiring of emotion centers in the brain with other brain areas.

This effect may lead people to consider new possibilities or evaluate things differently after their psychedelic journey.

Psilocybin's Effect on Depression

Psilocybin may help individuals with depression by invoking new patterns of learning and breaking habitual negative thinking patterns.

It allows for new contingencies and may even lead to actual rewiring of emotion centers in the brain with other brain areas.

This effect may lead people to consider new possibilities or evaluate things differently after their psychedelic journey.

Understanding the Psilocybin Experience

In this section, the speaker discusses how psilocybin works and its effects on neuroplasticity. They also introduce some of the key experiences that people tend to have during a psilocybin journey.

The Wedge Analogy

Psilocybin creates neuroplasticity that can be adaptive or maladaptive depending on whether it serves you in your daily life.

Psilocybin helps clear a path through old, ineffective patterns of thoughts or emotions using the wedge analogy.

Key Experiences During a Psilocybin Journey

People tend to experience feelings of connectedness, ego dissolution, and letting go during a psilocybin journey.

These experiences are subjective but are often described as one of the most profound or positive experiences in one's life.

However, there is also a possibility of having a bad trip while under the influence of psilocybin.

Research on Subjective Experiences

There have been scientific studies exploring subjective experiences related to positive therapeutic outcomes and general sense of positivity during a psilocybin journey.

These studies use rating scales to put numbers to these experiences and allow for comparison between different groups and studies.

Quality of Acute Psychedelic Experience

This paper explores how quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression.

Subjects underwent two different psilocybin sessions with different doses and answered an Altered States Of Consciousness questionnaire to address the quality of experiences.

The study found that a key feature of a positive psychedelic experience is this sense of oceanic boundlessness occurring at some point during the psychedelic journey.

Psychedelic Journey and Positive Therapeutic Outcomes

The mystical experience during a psychedelic journey is positively correlated with positive therapeutic outcomes, such as relief from major depression. During the journey, there are several steps that one typically goes through, including the build-up to experiencing the effects of the drug, the peak where people often feel a sense of oceanic boundlessness, and then moving towards the second, third, fourth and fifth hour of the session.

Steps in a Psychedelic Journey

The first step is experiencing the effects of the drug about 20 to 45 minutes into the journey or trip.

The peak is when people often feel a sense of oceanic boundlessness. However, it's also often accompanied by significant increases in anxiety and fear as well as ego dissolution.

The guide's role at this point is to keep the person safe but also encourage them to let go and move through that experience.

People may temporarily feel like they lose their sense of self but then feel it restored at various intervals during or after exiting that Peak.

Correlation between Subjective Measures and Positive Clinical Outcomes

A study looked at different subjective measures such as experience of unity, spirituality, blissful state, insights gained during psilocybin treatment.

Experience of unity correlated with positive clinical outcomes for depression treatment.

Non-responders tended to report less experience of unity, spirituality or blissful state compared to responders who got relief from their depression.

Importance of Letting Go

Letting go is an important component for positive therapeutic outcomes of the psilocybin journey.

Ego dissolution and moving through anxiety are important for positive therapeutic outcomes.

The Importance of Anxiety and Ego Dissolution in Psychedelic Therapy

In this section, Dr. Andrew Huberman discusses the importance of anxiety and ego dissolution in psychedelic therapy. He explains that while letting go and experiencing anxiety is important for an effective therapeutic session, extreme levels of anxiety can be negatively correlated with positive therapeutic outcomes.

Letting Go and Anxiety

Letting go and experiencing anxiety is important for an effective therapeutic session.

Extreme levels of anxiety are negatively correlated with positive therapeutic outcomes.

Non-responders to psilocybin tended to have higher subjective ratings of anxiety than responders.

Importance of Guides

Well-trained guides who understand the contour of the psychedelic journey are crucial.

Guides should be trained in how to help someone with their anxiety in real-time during a psychedelic session.

Real-Time Tools for Anxiety Reduction

Real-time tools such as breathing techniques can reduce anxiety during a psychedelic session.

Using physiological sighing inside a psychedelic session can lead to rapid decreases in stress and anxiety levels.

Psilocybin and Neuroplasticity

In this section, the speaker discusses a paper on the therapeutic use of psilocybin and its practical considerations for dosing and administration. The paper describes the pharmacology of psilocybin, the contour of a psilocybin session, issues of dosage, contraindications, and adverse events. The speaker also talks about how psilocybin induces neuroplasticity in the brain.

Therapeutic Use of Psilocybin

Psilocybin is most effective in treating cancer-related depression, anxiety, treatment-resistant depression.

There is some evidence for improvement in alcohol use disorder independence and tobacco addiction.

Clinical trial support exists for relief or partial relief for obsessive-compulsive disorder cluster headaches and migraines and demoralization due to AIDS diagnosis.

Practical Considerations for Dosing and Administration

The paper provides detailed information on dosage translation from mushrooms to psilocybin itself to silacin.

Contraindications are discussed where it points out that women who are pregnant or breastfeeding people who have a predisposition to psychosis should avoid using psilocybin.

Adverse events are discussed as well as what sorts of bad things can happen as a consequence of psilocybin.

How Psilocybin Induces Neuroplasticity

A psilocybin journey invokes neuroplasticity by activating brain networks more broadly than they would normally be activated.

Researchers are interested in understanding what sorts of neuroplasticity psilocybin creates because there are lots of different types or processes involved with neuroplasticity for instance brain networks Behavior thinking emotion.

Neurogenesis and Neuroplasticity

In this section, the speaker discusses the role of neurogenesis and neuroplasticity in the adult human brain.

Neurogenesis

Adult neurogenesis is rare and not a prominent feature of learning or acquiring new skills.

Psilocybin does not induce neurogenesis as a means of changing neural circuitry in adult humans.

Neuroplasticity

Psilocybin induces neuroplasticity through the addition or strengthening of new neural connections or through the elimination or weakening of other neural connections.

The predominant theory is that psilocybin induces neuroplasticity through the growth of dendrites and dendritic spines in pyramidal neurons.

These structural and functional changes involve the addition of novel connections in pyramidal neurons in various regions of the brain, including subcortical areas like the thalamus.

Mechanisms Underlying Psilocybin-induced Neuroplasticity

In this section, the speaker discusses how psilocybin induces neuroplasticity at a mechanistic level.

Animal Models

Most studies exploring mechanisms underlying psilocybin-induced neuroplasticity have been conducted on animal models, particularly mice and rats.

These studies focus on knockout animals, imaging techniques, and real-time measurements to explore how psilocybin affects neural circuitry.

Structural Changes

Psilocybin induces structural changes in dendrites by promoting their growth and adding dendritic spines to pyramidal neurons.

Dendritic spines are mushroom-shaped protrusions that grow out from dendrites.

Functional Changes

Psilocybin-induced neuroplasticity involves both structural and functional changes.

The addition or strengthening of new neural connections leads to increased activity in certain brain areas, while the elimination or weakening of other neural connections leads to decreased activity in those areas.

Psilocybin and Neuroplasticity

In this section, the speaker discusses a paper published in the journal Neuron Cell Press Journal that shows how psilocybin induces rapid and persistent growth of dendritic spines in the frontal cortex. The speaker also talks about how these new connections persist even after the psilocybin has left the bloodstream and brain.

Psilocybin Induces Growth of Dendritic Spines

Psilocybin induces rapid and persistent growth of dendritic spines in the frontal cortex.

These measurements were done in mice, but there is growing evidence that psilocybin induces both structural and functional plasticity in the human brain as well.

Reduction in dendritic spines occurs in depressed patients, while drugs or treatments that relieve depression are correlated with increases in spine growth.

It's possible that relief from depression experienced during psilocybin journeys is due to the growth of new dendritic spines on particular neurons.

Dosages Used in Studies

Mouse studies tended to use quite high doses of psilocybin compared to therapeutic doses used for humans.

Most studies looking at changes in plasticity used dosages of psilocybin that would be about double or triple what is typically used for humans.

Nonetheless, it's clear that both animal studies and humans show that psilocybin induces both structural and functional changes in brain circuitry.

Review on Psychedelics and Neuroplasticity

A review entitled "Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics" provides more information on the neuroplasticity induced by psychedelics, including psilocybin.

The review goes into detail about intracellular signaling and how neurons change their excitability patterns based on activation of the serotonin 2A receptor.

Therapeutic Use of Psilocybin

Major depression and intractable depression show strong evidence for therapeutic use of psilocybin.

Clinical Trials and Research on Psilocybin

In this section, the speaker discusses the recent increase in clinical trials exploring how psilocybin can impact mood disorders and addictive disorders. The speaker acknowledges the researchers who have pioneered legal efforts, funding efforts, and research efforts defining the clinical data.

Pioneering Researchers

Robin Carhart-Harris, Matthew Johnson, Roland Griffis, Nolan Williams are some of the pioneering researchers in psilocybin research.

They have pioneered legal efforts, funding efforts and research efforts defining clinical data.

Clinical Data

Most of the papers published on psilocybin were published recently in journals such as New England Journal of Medicine and Journal of American Medical Association Psychiatry.

The studies involve either one or two psilocybin sessions with dosages ranging from 0mg to 30mg.

People typically receive the same dosage for both sessions if they did both sessions.

There is at least one study looking at just one single episode of psilocybin Administration.

Single Dose Psilocybin for Treatment Resistant Depression

A single dose of synthetic formulation of psilocybin was given to subjects who had treatment-resistant depression.

The dose was either 25mg, 10mg or 1mg (control).

Psychological support was provided during the study.

Results showed that people experienced more relief from depression with a higher dose (25mg) than a lower dose (1mg).

Psilocybin for Treatment-Resistant Depression Relief

In this section, the speaker discusses a study on psilocybin for treatment-resistant depression relief. The study explores adverse events and the effectiveness of different dosages.

Adverse Events

There were adverse events in every group, with the highest number of adverse events observed in the 25 milligram dose group.

Higher dosages tend to provide greater relief from depressive symptoms but also increase the chance of adverse events, some of which can be severe.

Adverse events included feelings of suicidal ideation, headaches, anxiety, and propensity for self-harm.

Effectiveness of Psilocybin

A single dose of 25 milligrams of psilocybin provided significant relief from treatment-resistant depression in this particular patient population.

The degree of relief tended to change over time but was stable at least by the read in the 25 milligram dose group.

Figure two of the paper nicely summarizes how people's levels of depression changed over time after taking psilocybin.

Studies exploring single or two-session psilocybin treatments in the 25 to 30 milligram range seem to be most effective for long-lasting relief from depression.

Clinical Trials

There have been comparisons between psilocybin and other antidepressants as well as comparisons between psilocybin plus psychoanalysis or cognitive behavioral therapy versus these therapies alone.

Approximately 60 to 75 percent of people who take a 25 milligram dose twice report good experiences with minimal adverse events and substantial positive relief from major depression.

People are asked to stop taking their antidepressants prior to participating in the trial, and they are encouraged not to suddenly start their antidepressant treatment immediately afterward.

Psilocybin Therapy for Depression

In this section, the speaker discusses the results of a study on psilocybin therapy for depression and highlights its efficacy in producing large, rapid, and sustained antidepressant effects.

Psilocybin Therapy Results

Psilocybin administered with supportive psychotherapy produced large, rapid, and sustained antidepressant effects.

Effect sizes reported in the study were approximately 2.5 times greater than those found in psychotherapy and more than four times greater than those found in psychopharmacologic depression treatment studies.

Combining drug therapy with talk therapy is more effective than either intervention alone.

Psilocybin can create an experience inside of the session that leads to neuroplastic events such as dendritic spines and enhanced activity in brain areas that normally wouldn't be talking to one another.

Role of Psilocybin

Despite the highly subjective understanding of how psilocybin exerts its effects, there is now a center of mass of data pointing to its ability to invoke neuroplasticity and changes in emotionality and perceptual experience.

Psilocybin can provide remarkable relief from major depression and other psychiatric issues for long periods after the psychedelic session.

The episode aims to put a magnifying lens on this incredible area of research happening not just in clinical trials but also trying to understand how serotonin and drugs like psilocybin can lead to enhanced ways of thinking inside short sessions.

Neuroplasticity and Psilocybin

In this section, Dr. Huberman discusses the potential of psilocybin to enhance neuroplasticity in humans. He emphasizes the importance of safety precautions when using compounds like psilocybin.

The Holy Grail of the Human Nervous System

Neuroplasticity is considered the Holy Grail of the human nervous system.

Humans are capable of long-lasting neuroplasticity throughout their lifespan.

Psilocybin can be used in a safe and controlled way to achieve maximal plasticity in a short amount of time.

Safety Precautions

People with a predisposition or history of psychosis or bipolar disorder, as well as those under 25 years old, need to be cautious when using psilocybin.

Working with a dedicated and highly trained physician is important when using these compounds.

Psilocybin is an exciting but still preliminary area of research that requires careful consideration.

Future Episodes

Dr. Huberman plans to revisit psilocybin and other psychedelics in future episodes.

Other non-classical psychedelics mentioned include LSD, DMT, 5meo DMT, ketamine, MDMA, and mescaline.

Supporting the Podcast

In this section, Dr. Huberman provides ways for listeners to support the podcast through subscriptions and sponsorships.

Subscriptions

Listeners can subscribe to the podcast on both Apple and Spotify.

Leaving a five-star review on Apple or Spotify helps support the podcast.

Subscribing to the YouTube channel is also a zero-cost way to support the podcast.